lignans and pinoresinol

This paper provides an overview on activity, stereospecificity, expression and regulation of pinoresinol-lariciresinol reductases in plants. These enzymes are shared by the pathways to all 8-8' lignans derived from pinoresinol. Pinoresinol-lariciresinol reductases (PLR) are enzymes involved in the lignan biosynthesis after the initial dimerization of two monolignols. They catalyze two successive reduction steps leading to the production of lariciresinol or secoisolariciresinol from pinoresinol. Two secoisolariciresinol enantiomers can be synthetized with different fates. Depending on the plant species, these enantiomers are either final products (e.g., in the flaxseed where it is stored after glycosylation) or are the starting point for the synthesis of a wide range of lignans, among which the aryltetralin type lignans are used to semisynthesize anticancer drugs such as Etoposide

Topics: Butylene Glycols; Furans; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Plant; Lignans; Oxidoreductases; Plant Proteins; Plants

Although lignin is the second most abundant plant substance in vascular plants, its mode of synthesis is still the subject of much debate. However, recent progress has provided crucial evidence to support the theory that lignin primary structure is controlled at the proteinaceous level. Evidence for control over lignin assembly has been demonstrated with the discovery of monomer-invariant aryl-O-ether linkages in lignins that upon alkaline cleavage release the corresponding monomers in equimolar amounts, regardless of monolignol composition. Current evidence would indicate that there are only a few native lignin primary structures, the entire sequences of which now need to be fully determined. A provisional mechanistic model is proposed to account for macromolecular lignin assembly through the participation of proteins harboring arrays of dirigent (monolignol radical binding) sites.

Topics: Binding Sites; Carbohydrate Sequence; Cell Wall; Free Radicals; Furans; Lignans; Lignin; Plants

The effects of phytochemicals (lignans and neolignans) are reviewed in a variety of insect species with special focus on the recent advances on feeding, excretion and Trypanosoma cruzi interactions with Rhodnius prolixus. Burchellin, podophyllotoxin, pinoresinol, sesamin, licarin A, and nordihydroguaiaretic acid (NDGA) added to the diet of Rhodnius prolixus larvae induce antifeedant effects only in doses up to 100 microg/ml of blood meal. Additionally, pinoresinol and NDGA significantly inhibit ecdysis (ED(50)<20 microg/ml). Simultaneous application of ecdysone (1 microg/ml) counteracts ecdysial stasis as induced by NDGA in 5th-instar larvae. Experiments in vivo demonstrate that burchellin and podophyllotoxin (100 microg/ml) diminish excretion post-feeding. Simultaneous treatment with 5-hydroxytryptamine (1 mM, 5-HT), a diuretic hormone, partially reverses this effect of burchellin. Experiments in vitro, using isolated Malpighian tubules of R. prolixus, indicate that burchellin (i) decreases diuretic hormone levels in the hemolymph but not the amount of diuretic hormone stored in the thoracic ganglionic masses (including axons); (ii) reduces the volume of urine secreted by isolated Malpighian tubules; and (iii) 5-HT therapy cannot overcome the effect of burchellin on the Malpighian tubules. In R. prolixus fed on blood containing T. cruzi epimastigotes, the number of parasites in the digestive tract decreases drastically in the presence of burchellin and NDGA (10 microg/ml). When these phytochemicals are applied 20 days after T. cruzi infection, burchellin significantly reduces the gut infection, whereas NDGA does not. However, if the insects are pretreated with both compounds 20 days before subsequent infection with epimastigotes, the parasite infection is almost completely abolished. The same holds true when 5th-instar of R. prolixus are inoculated with 0.5 microg/microl/larva of both neolignans 1 day before infection. Taken together, these findings not only provide a better understanding of the lignoid function in insects, but also offer novel insights into basic physiological processes, which make lignoids interesting candidates for new types of insecticides.

Topics: Animals; Benzofurans; Dioxoles; Feeding Behavior; Furans; Host-Parasite Interactions; Insecta; Larva; Lignans; Malpighian Tubules; Masoprocol; Molting; Podophyllotoxin; Rhodnius; Trypanosoma cruzi

Furofuran lignans, the main insecticidal ingredient in Phryma leptostachya, exhibit excellent controlling efficacy against a variety of pests. During the biosynthesis of furofuran lignans, Dirigent proteins (DIRs) are thought to be dominant in the stereoselective coupling of coniferyl alcohol to form ( ±)-pinoresinol. There are DIR family members in almost every vascular plant, but members of DIRs in P. leptostachya are unknown. To identify the PlDIR genes and elucidate their functions in lignan biosynthesis, this study performed transcriptome-wide analysis and characterized the catalytic activity of the PlDIR1 protein.. Fifteen full-length unique PlDIR genes were identified in P. leptostachya. A phylogenetic analysis of the PlDIRs classified them into four subfamilies (DIR-a, DIR-b/d, DIR-e, and DIR-g), and 12 conserved motifs were found among them. In tissue-specific expression analysis, except for PlDIR7, which displayed the highest transcript abundance in seeds, the other PlDIRs showed preferential expression in roots, leaves, and stems. Furthermore, the treatments with signaling molecules demonstrated that PlDIRs could be significantly induced by methyl jasmonate (MeJA), salicylic acid (SA), and ethylene (ETH), both in the roots and leaves of P. leptostachya. In examining the tertiary structure of the protein and the critical amino acids, it was found that PlDIR1, one of the DIR-a subfamily members, might be involved in the region- and stereo-selectivity of the phenoxy radical. Accordingly, LC-MS/MS analysis demonstrated the catalytic activity of recombinant PlDIR1 protein from Escherichia coli to direct coniferyl alcohol coupling into ( +)-pinoresinol. The active sites and hydrogen bonds of the interaction between PlDIR1 and bis-quinone methide (bisQM), the intermediate in ( +)-pinoresinol formation, were analyzed by molecular docking. As a result, 18 active sites and 4 hydrogen bonds (Asp-42, Ala-113, Leu-138, Arg-143) were discovered in the PlDIR1-bisQM complex. Moreover, correlation analysis indicated that the expression profile of PlDIR1 was closely connected with lignan accumulations after SA treatment.. The results of this study will provide useful clues for uncovering P. leptostachya's lignan biosynthesis pathway as well as facilitate further studies on the DIR family.

Topics: Chromatography, Liquid; Lignans; Molecular Docking Simulation; Phylogeny; Plant Proteins; Tandem Mass Spectrometry

We describe a novel nature-derived epoxy resin monomer (ERM) derived from the plant lignan pinoresinol. Epoxy resins are thermosetting materials in global usage owing to their excellent technical properties such as flexibility and durability. However, their adverse health effects are often not considered and affect users of epoxy resins worldwide. Components of epoxy resin systems are strong skin sensitizers and cause allergic contact dermatitis. The reported prevalence attributable to epoxy chemicals is between 11.7 and 12.5% of all cases of occupational allergic contact dermatitis. We are committed to developing epoxy resins with reduced allergenic effect, while maintaining their excellent properties. The novel ERM, pinoresinol diglycidyl ether (PinoDGE), was synthesized in one step from pinoresinol and epichlorohydrin in 88% yield. It was not classified as a skin sensitizer in the in vivo local lymph node assay, at concentrations up to 0.17 m, as it did not cause a stimulation index >3 compared to control. Pinoresinol diglycidyl ether reacted with the model peptide AcPHCKRM in a reactivity assay and was predicted to be a skin sensitizer in the KeratinoSens assay. Preliminary cross-linking studies indicate that it has promising properties compared to commercially used ERMs. Pinoresinol diglycidyl ether could be seen as a lead compound for further development of alternative ERMs with a better safety profile based on natural and renewable sources for construction of epoxy resin polymers.

Topics: Allergens; Benzhydryl Compounds; Dermatitis, Allergic Contact; Epoxy Compounds; Epoxy Resins; Furans; Humans; Lignans

Topics: Animals; Cell Proliferation; Furans; Insulin-Like Growth Factor I; Lignans; Mammals; Mice; Molecular Docking Simulation; Muscle, Skeletal; Myoblasts; Proto-Oncogene Proteins c-akt; Signal Transduction; TOR Serine-Threonine Kinases; Vanillic Acid

Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders characterized by memory deficits. Although no drug has given promising results, synaptic dysfunction-modulating agents might be considered potential candidates for alleviating this disorder. Pinoresinol, a lignan found in Forsythia suspensa, is a memory-enhancing agent with excitatory synaptic activation. In the present study, we tested whether pinoresinol reduces learning and memory and excitatory synaptic deficits in an amyloid β (Aβ)-induced AD-like mouse model. Pinoresinol enhanced hippocampal long-term potentiation (LTP) through calcium-permeable AMPA receptor, which was mediated by Akt activation. Moreover, pinoresinol ameliorated LTP deficits in amyloid β (Aβ)-treated hippocampal slices via Akt signaling. Oral administration of pinoresinol ameliorated Aβ-induced memory deficits without sensory dysfunction. Moreover, AD-like pathology, including neuroinflammation and synaptic deficit, were ameliorated by pinoresinol administration. Collectively, pinoresinol may be a good candidate for AD therapy by modulating synaptic functions.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Disease Models, Animal; Furans; Hippocampus; Lignans; Long-Term Potentiation; Male; Memory Disorders; Mice, Inbred Strains; Neuronal Plasticity; Peptide Fragments; Proto-Oncogene Proteins c-akt; Receptors, AMPA

The root of Dendropanax dentiger (Harms) Merr. has been used for centuries as an empirical treatment for rheumatoid arthritis (RA) in China without scientific validation. In our recent study, nineteen phenylpropanoids (1-19) with cyclooxygenase-2 inhibitory activities from the ethanol extract of D. dentiger roots, indicated to have a potential anti-RA effect. This study, evaluated the anti-RA effect of 19 phenylpropanoids on tumor necrosis factor (TNF)-α induced inflammation in MH7A cells and clarified their underlying mechanisms. As a result, 16 compounds remarkably suppressed nitric oxide (NO) production at a concentration of 40 μM in TNF-α-induced MH7A cells. Among them, pinoresinol (12) and dendrocoumarin A (1) were the most effective substances, which showed significant inhibitory effect on NO production, with IC

Topics: Anti-Inflammatory Agents; Araliaceae; Cell Line; Cell Survival; Coumarins; Cytokines; Furans; Humans; JNK Mitogen-Activated Protein Kinases; Lignans; NF-kappa B; Nitric Oxide; Proto-Oncogene Proteins c-akt; Signal Transduction

Pinoresinol-lariciresinol reductases (PLRs) are enzymes involved in the lignan biosynthesis after the initial dimerization of two monolignols, and this represents the entry point for the synthesis of 8-8' lignans and contributes greatly to their structural diversity. Of particular interest has been the determination of how differing substrate specificities are achieved with these enzymes. Here, we present crystal structures of IiPLR1 from Isatis indigotica and pinoresinol reductases (PrRs) AtPrR1 and AtPrR2 from Arabidopsis thaliana, in the apo, substrate-bound and product-bound states. Each structure contains a head-to-tail homodimer, and the catalytic pocket comprises structural elements from both monomers. β4 loop covers the top of the pocket, and residue 98 from the loop governs catalytic specificity. The substrate specificities of IiPLR1 and AtPrR2 can be switched via structure-guided mutagenesis. Our study provides insight into the molecular mechanism underlying the substrate specificity of PLRs/PrRs and suggests an efficient strategy for the large-scale commercial production of the pharmaceutically valuable compound lariciresinol.

Topics: Arabidopsis; Arabidopsis Proteins; Butylene Glycols; Catalytic Domain; Crystallography, X-Ray; Furans; Isatis; Lignans; Models, Molecular; Mutagenesis, Site-Directed; Oxidoreductases; Phylogeny; Plant Proteins; Protein Engineering; Protein Multimerization; Static Electricity; Substrate Specificity

Eucommia ulmoides Oliv. (E. ulmoides) is a valuable and nourishing medicinal herb in China that has been used in the treatment of hypertension. Given the fact that most traditional Chinese medicine is mainly used to treat disease, investigating the pharmacokinetics of traditional Chinese medicines in the pathological state is more useful than that in the normal state. However, the differences in the absorption kinetics of active ingredients of E. ulmoides extract between pathological and physiological conditions have not been reported. Therefore, in this study, the rat intestinal in situ circulatory perfusion model was used to investigate the differences in absorption kinetics of seven active ingredients of E. ulmoides extract in normal and spontaneously hypertensive rats, namely, genipinic acid, protocatechuic acid, neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, (+)-pinoresinol di-O-β-D-glucopyranoside and (+)-pinoresinol 4'-O-β-D-glucopyranoside. Our results indicate that the pathological state of spontaneous hypertension may change the absorption of active components of E. ulmoides extracts, and these findings may provide a reference for improving the rational use of E. ulmoides in the clinic.

Topics: Animals; Antihypertensive Agents; Body Fluids; Chlorogenic Acid; Eucommiaceae; Furans; Hydroxybenzoates; Intestinal Absorption; Lignans; Plant Extracts; Rats; Rats, Inbred SHR; Rats, Wistar

Two western red cedar pinoresinol-lariciresinol reductase (PLR) homologues were studied to determine their enantioselective, substrate versatility, and kinetic properties. PLRs are downstream of dirigent protein engendered, coniferyl alcohol derived, stereoselective coupling to afford entry into the 8- and 8'-linked furofuran lignan, pinoresinol. Our investigations showed that each PLR homolog can enantiospecifically metabolize different furofuran lignans with modified aromatic ring substituents, but where phenolic groups at both C4/C4' are essential for catalysis. These results are consistent with quinone methide intermediate formation in the PLR active site. Site-directed mutagenesis and kinetic measurements provided additional insight into factors affecting enantioselectivity and kinetic properties. From these data, PLRs can be envisaged to allow for the biotechnological potential of generation of various lignan skeleta, that could be differentially "decorated" on their aromatic ring substituents, via the action of upstream dirigent proteins.

Topics: Furans; Kinetics; Lignans; Oxidoreductases; Stereoisomerism

Topics: 4-Butyrolactone; Berberidaceae; Biotransformation; Cytochrome P-450 Enzyme System; Escherichia coli; Forsythia; Furans; Lignans; NADP; Oxidation-Reduction; Podophyllotoxin; Podophyllum peltatum

Phytochemical investigation of the whole plant of Filago vulgaris Lam. (Asteraceae) resulted in the isolation and characterization of seven compounds, including a rare methoxylated flavonol (araneol), tetrahydrofurofuranolignans (pinoresinol and syringaresinol), p-hydroxybenzaldehyde, vanillin, vanillic acid and scopoletin. The structures of the compounds were determined by NMR and mass spectroscopy. All compounds were first obtained from this species and reported for the genus Filago. Our results demonstrate that highly methoxylated flavonols lacking substituents on ring B and lignans can be regarded as taxonomic markers for the tribe Inuleae. The lipophilic extract of F. vulgaris was found to have antiproliferative activity against HeLa cells (62.1±0.9% inhibition at 30 μ/ml), and araneol was highly effective against this tumour cell line (IC

Topics: Asteraceae; Cell Line, Tumor; Cell Proliferation; Flavonoids; Flavonols; Furans; HeLa Cells; Humans; Lignans; MCF-7 Cells; Plant Extracts

Plant-derived lignans have numerous biological effects including anti-tumor and anti-inflammatory activities. Screening of purified constituents of Rubia philippinensis from human glioblastoma cells resistant to TNF-related apoptosis-inducing ligand (TRAIL) has suggested that the lignan pinoresinol was a highly active TRAIL sensitizer. Here we show that treatment with nontoxic doses of pinoresinol in combination with TRAIL induced rapid apoptosis and caspase activation in many types of glioblastoma cells, but not in normal astrocytes. Analyses of apoptotic signaling events revealed that pinoresinol enhanced the formation of TRAIL-mediated death-inducing signaling complex (DISC) and complete processing of procaspase-8 within the DISC in glioblastoma cells, in which caspase-8 was inactivated. Mechanistically, pinoresinol downregulated the expression of cellular FLICE-inhibitory protein (cFLIP

Topics: Apoptosis; CASP8 and FADD-Like Apoptosis Regulating Protein; Caspase 8; Cell Line, Tumor; Cell Membrane; Furans; Glioblastoma; Humans; Lignans; NF-kappa B; Receptors, TNF-Related Apoptosis-Inducing Ligand; Rubia; Signal Transduction; TNF-Related Apoptosis-Inducing Ligand

Acute pancreatitis (AP) is a severe inflammatory condition of the pancreas, with no specific treatment available. We have previously reported that Nardostachys jatamansi (NJ) ameliorates cerulein-induced AP. However, the specific compound responsible for this inhibitory effect has not been identified. Therefore, in the present study, we focused on a single compound, 8α-hydroxypinoresinol (HP), from NJ. The aim of this study was to determine the effect of HP on the development of pancreatitis in mice and to explore the underlying mechanism(s). AP was induced by the injection of cerulein (50 μg/kg/h) for 6 h. HP (0.5, 5 or 10 mg/kg, i.p.) was administered 1 h prior to and 1, 3 or 5 h after the first cerulein injection, with vehicle- and DMSO-treated groups as controls. Blood samples were collected to determine serum levels of amylase, lipase, and cytokines. The pancreas was removed for morphological examination, myeloperoxidase (MPO) assays, cytokine assays, and assessment of nuclear factor (NF)-κB activation. The lungs were removed for morphological examination and MPO assays. Administration of HP dramatically improved pancreatic damage and pancreatitis-associated lung damage and also reduced amylase and lipase activities in serum. Moreover, administration of HP reduced the production of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in the pancreas and serum during AP. In addition, the administration of HP inhibited degradation of inhibitory κ-Bα (Iκ-Bα), NF-κB p65 translocation into nucleus and NF-κB binding activity in the pancreas. Our results suggest that HP exerted therapeutic effects on pancreatitis and these beneficial effects may be due to the inhibition of NF-κB activation.

Topics: Animals; Ceruletide; Cytokines; Female; Furans; Inflammation; Lignans; Lung; Mice; Mice, Inbred C57BL; Nardostachys; Pancreas; Pancreatitis; Signal Transduction; Tumor Necrosis Factor-alpha

The liver X receptors (LXRs) are major regulators of lipogenesis, and their reduced activation by an inhibitor could be a treatment strategy for fatty liver disease. Small molecules originating from dietary food are considered suitable and attractive drug candidates for humans in terms of safety. In this study, an edible plant,

Topics: Acetyl-CoA Carboxylase; Animals; Benzofurans; Diet, High-Fat; Fatty Acid Synthases; Furans; Humans; Lignans; Lipogenesis; Liver; Liver X Receptors; Male; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Plant Extracts; Primulaceae; Sterol Regulatory Element Binding Protein 1; Triglycerides

Phomopsis sp. XP-8, an endophytic fungus from the bark of Tu-Chung (Eucommia ulmoides Oliv) showed capability to biosynthesize pinoresinol (Pin) and pinoresinol diglucoside (PDG) from glucose (glu) and phenylalanine (Phe). To verify the mass flow in the biosynthesis pathway, [

Topics: Ascomycota; Endophytes; Eucommiaceae; Furans; Glucose; Glycosides; Lignans; Mass Spectrometry; Phenylalanine

Eucommia ulmoides Oliver (Du-Zhong) is an ancient Chinese herbal remedy used for the treatment of various diseases. To date, the effects of its constituent lignans on influenza viruses remain to be elucidated. In the present study, a lignan glycoside was isolated and purified from Eucommia ulmoides Oliver. Its structures were identified via extensive spectroscopic analysis, and its antiviral and anti‑inflammatory activities, specifically against influenza viruses, were determined via a cytopathic effect (CPE) assay, plaque‑reduction assays, a progeny virus yield reduction assay, reverse transcription‑quantitative polymerase chain reaction analysis and a Luminex assay. Additionally, western blot analysis was performed to investigate the underlying mechanisms of its effects against influenza viruses. The chemical and spectroscopic methods determined the structure of lignan glycoside to be (+)‑pinoresinol‑O‑β‑D‑glucopyranoside. The CPE assay showed that (+)‑pinoresinol‑O‑β‑D‑glucopyranoside exerted inhibitory activities with 50% inhibition concentration values of 408.81±5.24 and 176.24±4.41 µg/ml against the influenza A/PR/8/34 (H1N1) and A/Guangzhou/GIRD07/09 (H1N1) strains, respectively. Its antiviral properties were confirmed by plaque reduction and progeny virus yield reduction assays. Additional mechanistic analyses indicated that the anti‑H1N1 virus‑induced effects of (+)‑pinoresinol‑O-β‑D-glucopyranoside were likely due to inactivation of the nuclear factor‑κB, p38 mitogen‑activated protein kinase and AKT signaling pathways. Furthermore, (+)‑pinoresinol‑O‑β‑D‑glucopyranoside exhibited pronounced inhibitory effects on the expression of influenza H1N1 virus‑induced pro‑inflammatory mediators, including tumor necrosis factor‑α, interleukin (IL)‑6, IL‑8 and monocyte chemoattractant protein 1. The data obtained suggest that (+)‑pinoresinol‑O‑β‑D-glucopyranoside may be a candidate drug for treating influenza H1N1 virus infection.

Topics: A549 Cells; Animals; Anti-Inflammatory Agents; Antiviral Agents; Cell Line; Cell Line, Tumor; Dogs; Eucommiaceae; Furans; Glycosides; Humans; Influenza A Virus, H1N1 Subtype; Influenza, Human; Lignans; Madin Darby Canine Kidney Cells; Orthomyxoviridae Infections; Plant Extracts; Signal Transduction

Twenty-three resin samples have been obtained by tapping from individual Pinus pinaster adult trees grown in Corsica and submitted to acido-basic partition. Identification and quantitative determination of resin acids has been carried out using

Topics: Abietanes; Carbon-13 Magnetic Resonance Spectroscopy; Chromatography, Gas; Diterpenes; Furans; Lignans; Pinus; Plant Extracts; Plant Leaves; Principal Component Analysis; Resins, Plant

Oxidative stress contributes to the pathogenesis of many human diseases. Cinnamon is a worldwide used spice, dietary supplement and traditional medicine, and is used for the therapy of oxidative stress related diseases. A well-established concept is that the functions of cinnamon preventing oxidative stress-induced diseases are attributed to the occurrence of cinnamaldehyde and its analogues.. In our continuous searching of natural molecules with antioxidant capacity, we have found that cinnamaldehyde and its analogues in cinnamon are weak inhibitors of oxidative stress, and thus we speculate that there are novel and/or potent molecules inhibiting oxidative stress in cinnamon.. A systemic phytochemical investigation of cinnamon using column chromatography was performed to identify the chemical constituents of cinnamon, and then their capacity of inhibiting oxidative stress and action of mechanism targeting Nrf2 pathway were investigated using diverse bioassay, including NAD(P)H: quinone reductase (QR) assay, immunoblot analysis, luciferase reporter gene assay, immunofluorescence and flow cytometry.. Cinnamon improved the intracellular antioxidant capacity. A systemic phytochemical investigation of cinnamon gave the isolation of twenty-two chemical ingredients. The purified constituents were tested for their potential inhibitory effects against oxidative stress. Besides cinnamaldehyde analogues, a lignan pinoresinol (PRO) and a flavonol (-)-(2R,3R)-5,7-dimethoxy-3', 4'-methylenedioxy-flavan-3-ol (MFO) were firstly identified to be inhibitors of oxidative stress. Further study indicated that PRO and MFO activated Nrf2-mediated antioxidant response, and protected human lung epithelial cells against sodium arsenite [As(III)]-induced oxidative insults.. The lignan PRO and the flavonoid MFO are two novel Nrf2 activators protecting tissues against oxidative insults, and these two constituents support the application of cinnamon as an agent against oxidative stress related diseases.

Topics: Acrolein; Animals; Antioxidants; Arsenites; Cell Line; Cinnamomum zeylanicum; Drug Evaluation, Preclinical; Epithelial Cells; Flavonoids; Furans; Humans; Lignans; Mice; NAD(P)H Dehydrogenase (Quinone); NF-E2-Related Factor 2; Oxidative Stress; Protective Agents; Sodium Compounds

Dementia is a category of brain diseases that cause a decrease in cognitive functions. Alzheimer's disease (AD) is the most frequently mentioned neurodegenerative disease showing dementia. Although many useful drugs for dementia were developed, we still need better and safer drugs. Here, we tested pinoresinol, a lignan found in sesame seed and olive oil, whether it could be a candidate for this purpose. Pinoresinol (25 mg/kg, p.o.) ameliorated memory impairment in dementia model induced by cholinergic blockade in the passive avoidance test in a dose-dependent manner. Moreover, pinoresinol (50 μM) facilitated induction of hippocampal long-term potentiation, a cellular model of learning and memory. Pinoresinol blocked acetylcholinesterase (AchE), an acetylcholine-degrading enzyme, activity in a concentration-dependent manner. Moreover, pinoresinol (50 μM) facilitated calcium influx into neuro2a cell. These results suggest that pinoresinol improves memory impairment and facilitates hippocampal LTP induction and these results might be related to the effect of pinoresinol on AChE and calcium influx.

Topics: Acetylcholinesterase; Animals; Calcium; Cell Line; Cholinesterase Inhibitors; Cyclic AMP Response Element-Binding Protein; Dementia; Extracellular Signal-Regulated MAP Kinases; Furans; Hippocampus; Lignans; Long-Term Potentiation; Male; Memory Disorders; Mice, Inbred ICR; Neuronal Plasticity; Proto-Oncogene Proteins c-akt; Scopolamine

Pinoresinol/lariciresinol reductase (PLR), an NADPH-dependent reductase that catalyzes the sequential reduction of pinoresinol into secoisolariciresinol via Lariciresinol, can lead to the structural and stereochemical diversity of lignans. The relationship between substrate-selective reaction of PLR and sequence homology still remains unclear. In this study, we focused on the contribution of the variable region between PLRs in determining substrate selectivity. Here, two CsPLRs (CsPLR1 and CsPLR2) were identified in the tea plant (Camellia sinensis var. sinensis cv. Shuchazao). In vitro enzymatic assays showed that CsPLR1 could convert (+)- and (-)-pinoresinol into lariciresinol or secoisolariciresinol, whereas CsPLR2 catalyzed (+)-pinoresinol enantioselectively into (-)-secoisolariciresinol. Homology modeling and site-directed mutagenesis were used to examine the role of a variable loop in catalysis and substrate selectivity. The L174I mutant in CsPLR1 lost the capacity to reduce either (+)- or (-)-pinoresinol but retained the ability to catalyze the reduction of (-)-lariciresinol. These findings provide a basis for better understanding of the substrate-selective reaction of PLR.

Topics: Butylene Glycols; Camellia sinensis; Furans; Lignans; Mutagenesis, Site-Directed; Oxidoreductases; Sequence Homology, Amino Acid; Substrate Specificity

Estradiol (E2) is a first‑line drug for osteoporosis (OP) treatment via promotion of osteoblastic proliferation and differentiation. However, a long‑term use of E2 would produce side effects thus, it is imperative to discover safer and more effective drugs. Pinoresinol (PINO) has a similar chemical structure to E2. The present study aimed to investigate whether PINO could promote osteoblastic proliferation and differentiation and the potential mechanisms. After treatment with 0.1 µg/l PINO for 2 days, MC3T3‑E1 cell migration was assessed by wound healing assay. Estrogen (E2) treatment served as a positive control. RT‑qPCR and western blotting were used for mRNA and protein expression analyses. Alkaline phosphatase (ALP) activity assay and Alizarin red staining were performed to investigate the calcification and mineralization, and the cyclic AMP (cAMP) level was detected by enzyme‑linked immunosorbent assay (ELISA). H89, an inhibitor of protein kinase A (PKA), was introduced to verify the role of cAMP/PKA in the effect of PINO on MC3T3‑E1 cells. Cell viability was the highest under 48 h of 0.1 µg/l PINO treatment. After treatment with PINO, a significant increase was observed in the migration rate and the expression of collagen type I (Col‑I), ALP, osteopontin (OPN), runt‑related transcription factor 2 (Runx2) and bone morphogenetic protein‑2 (BMP‑2) (P<0.01). The ALP activity and Alizarin red size in PINO and E2 groups were notably increased. The increased cAMP, PKA and phosphorylated cAMP response element‑binding protein (CREB) levels were also observed in the PINO group. Furthermore, H89 co‑treatment abolished the positive effects of PINO on cell viability and migration. PINO had similar effects to E2 on the osteoblastic proliferation and differentiation, and these positive effects may be attributed to the regulation of the cAMP/PKA signaling pathway.

Topics: Animals; Cell Differentiation; Cell Line; Cell Proliferation; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Furans; Lignans; Mice; Osteoblasts; Osteogenesis; Signal Transduction

The effect of the composition of twelve varieties of extra virgin olive oils (EVOOs) on their differentiation based in agronomic criteria and on the antioxidant capacity was studied. Principal component analysis permitted an overview of the samples and their compositions, showing evidence of grouping and correlation between antioxidant capacity, oleuropein and ligstroside derivatives (OLD) and specific extinction at 270. Oleic and linoleic acids, 3,4-DHPEA-EA and p-HPEA-EDA (OLD), unsaturated/saturated ratio and induction time (IT) allowed the correct classification of samples according to year of harvest, ripening stage and variety. The antioxidant capacity of EVOOs was satisfactory predicted through a partial least square model based on ΔK, hydroxytyrosol, pinoresinol, oleuropein derivate and IT. Validation of the model gave a correlation R>0.83 and an error of 7% for independent samples. This model could be a useful tool for the olive industry to highlight the nutritional quality of EVOOs and improve their marketing.

Topics: Agriculture; Antioxidants; Chile; Food Analysis; Furans; Glucosides; Iridoid Glucosides; Iridoids; Least-Squares Analysis; Lignans; Olive Oil; Phenylethyl Alcohol; Principal Component Analysis; Pyrans

Pinoresinol is a dimer of two β-β'-linked coniferyl alcohol molecules. It is both a plant defense molecule synthesized through the shikimic acid pathway and a representative of several β-β-linked dimers produced during the microbial degradation of lignin in dead plant material. Until now, little has been known about the bacterial catabolism of such dimers. Here we report the isolation of the efficient (+)-pinoresinol-mineralizing

Topics: 4-Butyrolactone; Benzaldehydes; Calcification, Physiologic; Furans; Gastrointestinal Microbiome; Humans; Lignans; Lignin; Metabolic Networks and Pathways; Minerals; Pseudomonas

In this study, the chloroform-soluble extract of Cuscuta auralis was separated successfully using off-line two-dimensional high-performance countercurrent chromatography, yielding a γ-pyrone, two alkaloids, a flavonoid, and four lignans. The first-dimensional countercurrent separation using a methylene chloride/methanol/water (11:6:5, v/v/v) system yielded three subfractions (fractions I-III). The second-dimensional countercurrent separations, conducted on fractions I-III using n-hexane/ethyl acetate/methanol/water/acetic acid (5:5:5:5:0, 3:7:3:7:0, and 1:9:1:9:0.01, v/v/v/v/v) systems, gave maltol (1), (-)-(13S)-cuscutamine (2), (+)-(13R)-cuscutamine (3), (+)-pinoresinol (4), (+)-epipinoresinol (5), kaempferol (6), piperitol (7), and (9R)-hydroxy-d-sesamin (8). To the best of our knowledge, maltol was identified for the first time in Cuscuta species. Furthermore, this report details the first full assignment of spectroscopic data of two cuscutamine epimers, (-)-(13S)-cuscutamine and (+)-(13R)-cuscutamine.

Topics: Alkaloids; Chloroform; Chromatography, High Pressure Liquid; Circular Dichroism; Countercurrent Distribution; Cuscuta; Flavonoids; Furans; Hexanes; Kaempferols; Lignans; Magnetic Resonance Spectroscopy; Plant Extracts; Pyrones; Seeds; Spectrophotometry

Mycobacterium tuberculosis, Vibrio cholerae, and pathogenic Escherichia coli are global concerns for public health. The emergence of multi-drug resistant (MDR) strains of these pathogens is creating additional challenges in controlling infections caused by these deadly bacteria. Recently, we reported that Acetate kinase (AcK) could be a broad-spectrum novel target in several bacteria including these pathogens.. Here, using in silico and in vitro approaches we show that (i) AcK is an essential protein in pathogenic bacteria; (ii) natural compounds Chlorogenic acid and Pinoresinol from Piper betel and Piperidine derivative compound 6-oxopiperidine-3-carboxylic acid inhibit the growth of pathogenic E. coli and M. tuberculosis by targeting AcK with equal or higher efficacy than the currently used antibiotics; (iii) molecular modeling and docking studies show interactions between inhibitors and AcK that correlate with the experimental results; (iv) these compounds are highly effective even on MDR strains of these pathogens; (v) further, the compounds may also target bacterial two-component system proteins that help bacteria in expressing the genes related to drug resistance and virulence; and (vi) finally, all the tested compounds are predicted to have drug-like properties.. Suggesting that, these Piper betel derived compounds may be further tested for developing a novel class of broad-spectrum drugs against various common and MDR pathogens.

Topics: Acetate Kinase; Anti-Bacterial Agents; Bacterial Proteins; Carboxylic Acids; Chlorogenic Acid; Dose-Response Relationship, Drug; Drug Resistance, Multiple; Enzyme Inhibitors; Escherichia coli; Furans; Lignans; Microbial Sensitivity Tests; Molecular Docking Simulation; Molecular Structure; Mycobacterium tuberculosis; Piper betle; Piperidines; Structure-Activity Relationship

High amount of the valuable lignan pinoresinol (PR) was determined in Carduus nutans fruit (7.8mg/g) for the first time. A preparative separation method using two consecutive, identical steps of centrifugal partition chromatography (CPC) was developed in order (i) to isolate PR and (ii) to subsequently isolate PR and its 7' epimer epipinoresinol (EPR) simultaneously after an optimized acid treatment which resulted in PR epimerization forming equal amounts of PR and EPR, from C. nutans fruit. As optimal conditions, a two-phase solvent system consisting of methyl tert-butyl ether:acetone:water (4:3:3, v/v/v) for CPC separation, and an acid treatment performed at 50°C for 30min for the epimerization were applied. Thus, 33.7mg and 32.8mg PR and EPR, in as high as 93.7% and 92.3% purity, were isolated from 10.0gC. nutans fruit, representing 86.4% and 84.1% efficiency, respectively. Conversion characteristic of PR and EPR in acidic medium, determined as a function of time and temperature of acid treatment provides their unambiguous identification by on-line high performance liquid chromatography (HPLC). Antiproliferative assay of isolated PR and EPR in two different types of colon cancer cell lines (HCT116 and SW480) confirmed that both epimers caused a more significant decrease of viability in HCT116 cells than in SW480 cells, suggesting their similar mechanism of antiproliferative action.

Topics: Antineoplastic Agents, Phytogenic; Carduus; Cell Proliferation; Chromatography, High Pressure Liquid; Colonic Neoplasms; Fruit; Furans; Gas Chromatography-Mass Spectrometry; HCT116 Cells; Humans; Lignans; Plant Extracts; Stereoisomerism

Topics: Escherichia coli; Free Radical Scavengers; Furans; Genetic Enhancement; Hydrogen Peroxide; Lignans; Metabolic Engineering; Peroxidases

This study aimed to develop a specific UHPLC-ESI-MS/MS method for simultaneous determination and pharmacokinetics of pinoresinol glucoside and chlorogenic acid in rat plasma after oral administration of Eucommia ulmoides. The chromatographic separation was achieved on a Hypersil GOLD column with gradient elution by using a mixture of 0.1% formic acid aqueous solution and acetonitrile as the mobile phase at a flow rate of 200 μL/min. A tandem mass spectrometric detection was conducted using multiple-reaction monitoring via an electrospray ionization source in negative ionization mode. Samples were pre-treated by a single-step protein precipitation with acetonitrile, and bergenin was used as internal standard. After oral administration of 3 mL/kg E. ulmoides extract in rats, the maximum plasma concentrations of pinoresinol glucoside and chlorogenic acid were 57.44 and 61.04 ng/mL, respectively. The times to reach the maximum plasma concentration were 40.00 and 23.33 min for pinoresinol glucoside and chlorogenic acid, respectively. The intra- and inter-day precision (RSD) values for the two analytes were <2.46 and 5.15%, respectively, and the accuracy (RE) values ranged from -12.76 to 0.00. This is the first study on pharmacokinetics of bioactive compounds in rat plasma after oral administration of E. ulmoides extract.

Topics: Administration, Oral; Animals; Chlorogenic Acid; Chromatography, High Pressure Liquid; Eucommiaceae; Furans; Glucosides; Lignans; Limit of Detection; Linear Models; Plant Extracts; Rats; Reproducibility of Results; Tandem Mass Spectrometry

In this study, the characterization of chemical constituents and biological activity of the roots of

Topics: Antioxidants; Chromatography, High Pressure Liquid; Coumarins; Furans; Glucosides; Humans; Inhibitory Concentration 50; Inositol; Lignans; Magnetic Resonance Spectroscopy; Phenol; Plant Extracts; Plant Roots; Receptors, Scavenger; Taraxacum

Forsythiae Fructus, Lianqiao in Chinese, is one of the most fundamental herbs in Traditional Chinese Medicine. Both green Forsythia (GF) and ripe Forsythia (RF) are referred to Forsythiae Fructus in medicinal applications. In most cases, they are used without distinction. In this study, a metabolomics approach was performed to compare componential differences of two Forsythiae Fructus aqueous extracts subtypes. Principal component analysis (PCA) score plots from the UPLC-MS data showed clear separation between the two subtypes, indicating there are significant differences in the chemical components between GF and RF. Meanwhile, the anticancer activity of them was also compared. GF exhibited much stronger antitumor activity than RF against B16-F10 murine melanoma both in vitro and in vivo. 15 chemical compounds were identified as specific markers for distinguishing GF and RF. Among these marker compounds, forsythoside I, forsythoside A, forsythoside E and pinoresinol were demonstrated to be key important active compounds that account for the different anticancer efficacies of GF and RF. Our data suggest that GF and RF should be distinctively used in clinical applications, particularly in the anticancer formulas, in which GF should be preferentially prescribed.

Topics: Animals; Antineoplastic Agents, Phytogenic; Catechols; Cell Proliferation; Disaccharides; Female; Forsythia; Fruit; Furans; Glycosides; Lignans; Mass Spectrometry; Melanoma, Experimental; Metabolomics; Mice, Inbred C57BL; Phytotherapy; Plant Extracts; Skin Neoplasms; Tumor Cells, Cultured; Water

Backgroud: Pinoresinol (Pin) and pinoresinol monoglucoside (PMG) are plant-derived lignan molecules with multiple functions. We showed previously that an endophytic fungus from Eucommia ulmoides Oliv., Phomopsis sp. XP-8 is able to produce Pin and PMG.. This study was carried out to test the anti-tumor capability of the culture of XP-8 and identify the major effective compounds.. The fungal culture was added in the culture of HepG2 and K562 cells, and the viabilities of these cells were detected and the possible mechanism was analyzed.. The fungal culture showed significant capaiblity in decreasing the viability of tumor cells and induce apoptosis via up-regulation of the expression of apoptosis-related genes. It also significantly inhibited the adhesion and migration of HepG2 cells by blocking MMP-9 expression. Pin and PMG were isolated from the growth culture and shown to be the major effective components for inhibition.. The study indicated the potential application of XP-8 in the production of anti-tumour products by the bioconversion of glucose.

Topics: Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cell Movement; Endophytes; Eucommiaceae; Fungi; Furans; Gene Expression Regulation, Neoplastic; Humans; Lignans; Neoplasms

Herein we describe the influence of olive oil refining processes on the lignan profile. The detection of new isobaric lignans is suggested to reveal frauds in commercial extra-Virgin Olive Oils. We analyzed five commercial olive oils by HPLC-DAD-TOF/MS to evaluate their lignan content and detected, for the first time, some isobaric forms of natural (+)-pinoresinol and (+)-1-acetoxypinoresinol. Then we analyzed partially and fully-refined oils from Italy, Tunisia and Spain. The isobaric forms occur only during the bleaching step of the refining process and remain unaltered after the final deodorizing step. Molecular dynamic simulation helped to identify the most probable chemical structures corresponding to these new isobars with data in agreement with the chromatographic findings. The total lignan amounts in commercial olive oils was close to 2mg/L. Detection of these new lignans can be used as marker of undeclared refining procedures in commercial extra-virgin and/or Virgin Olive Oils.

Topics: Chromatography, High Pressure Liquid; Food Quality; Furans; Italy; Lignans; Olive Oil; Spain; Tunisia

Mammalian lignans or enterolignans are metabolites of plant lignans, an important category of phytochemicals. Although they are known to be associated with estrogenic activity, cell signaling pathways leading to specific cell functions, and especially the differences among lignans, have not been explored. We examined the estrogenic activity of enterolignans and their precursor plant lignans and cell signaling pathways for some cell functions, cell cycle and chemokine secretion. We used DNA microarray-based gene expression profiling in human breast cancer MCF-7 cells to examine the similarities, as well as the differences, among enterolignans, enterolactone and enterodiol, and their precursors, matairesinol, pinoresinol and sesamin. The profiles showed moderate to high levels of correlation (R values: 0.44 to 0.81) with that of estrogen (17β-estradiol or E2). Significant correlations were observed among lignans (R values: 0.77 to 0.97), and the correlations were higher for cell functions related to enzymes, signaling, proliferation and transport. All the enterolignans/precursors examined showed activation of the Erk1/2 and PI3K/Akt pathways, indicating the involvement of rapid signaling through the non-genomic estrogen signaling pathway. However, when their effects on specific cell functions, cell cycle progression and chemokine (MCP-1) secretion were examined, positive effects were observed only for enterolactone, suggesting that signals are given in certain directions at a position closer to cell functions. We hypothesized that, while estrogen signaling is initiated by the enterolignans/precursors examined, their signals are differentially and directionally modulated later in the pathways, resulting in the differences at the cell function level.

Topics: 4-Butyrolactone; Cell Cycle; Dioxoles; Estrogens; Furans; Gene Expression Profiling; Humans; Lignans; MCF-7 Cells; Oligonucleotide Array Sequence Analysis; Signal Transduction

Sixteen lignanoids were isolated from an aqueous extract of the commonly used Chinese traditional medicine Dangshen, the dried roots of Codonopsis pilosula, by using a combination of various chromatographic techniques, including silica gel, macroporous adsorbent resin, MCI resin, sephadex LH-20, and reversed phase semi-preparative HPLC. On the basis of spectral data analysis, their structures were elucidated and identified as（-）-（7R,7’R,8R,8’S）-4,4’-dihydroxy-3,3’,5,5’,7-pentamethoxy-2,7’-cyclolignane（1）,（-）-（7R,8S）- dihydrodehydrodiconiferyl alcohol 4-O-β-D-glucopyranosyl-（1’’’→2’’）-β-D-glucopyranoside（2）,（-）-（7R,8S）- dihydrodehydrodiconiferyl alcohol（3）,（+）-（7S,8R）-dehydrodiconiferyl alcohol（4）,（+）-balanophonin（5）,（+）- demethoxypinoresinol（6）,（+）-pinoresinol（7）,（+）-epipinoresinol（8）,（-）-syringaresinol（9）,（-）-medioresinol（10）,（-）-lariciresinol（11）,（-）-secoisolariciresinol（12）,（-）-ent-isolariciresinol（13）,（+）-（7S,8S）-3-methoxy-3’,7- expoxy-8,4’-neolignan-4,9,9’-triol（14）,（+）-（7S,8R）-3’,4-dihydroxy-3-methoxy-8,4’-neolignan（15）, and（-）-（7R,8R）-3’,4-dihydroxy-3-methoxy-8,4’-neolignan（16）. All these compounds were isolated from C. pilosula for the first time, while compound 1 is a new natural product of 2,7’-cyclolignan and 2 is a new 4’,7-epoxy- 8,3’-neolignan diglucoside. Compound 12 showed activity against Fe(2+)-cysteine induced rat liver microsomal lipid peroxidation with an inhibition ratio of（63.4 ± 8.3） % at 1×10(-5) mol·L(-1).

Topics: Animals; Butylene Glycols; Codonopsis; Drugs, Chinese Herbal; Furans; Lignans; Microsomes, Liver; Molecular Structure; Plant Extracts; Plant Roots; Rats

To study the chemical constituents from Serissa japonica.. The constituents were isolated by various chromatographic techniques and their structures were determined on the basis of spectroscopic data,as well as literatures.. Eleven compounds were obtained and identified as 3-hydroxy-1,2-dimethoxyanthraquinone( 1),1,2,4-trimethoxy-3-hydroxy-6-methyl anthraquinone( 2),emodin( 3),pinoresinol( 4),medioresinol( 5),( 7S,8R)-balanophonin-4-O-β-D-glucopyranoside( 6),lupeol( 7),icariside F2( 8),gallic acid( 9),methyl caffeate( 10) and 4-hydroxy-3-methoxyphenyl-β-D-glucopyranoside( 11).. Compounds 4and 5 are isolated from this plant for the first time,compounds 1 ~ 3 and 6 ~ 11 are isolated from Serissa genus for the first time.

Topics: Drugs, Chinese Herbal; Furans; Lignans; Rubiaceae

To investigate the chemical constituents of Clematis aethusifolia,a traditional Mongolian medicine for resolving hard lump.. Bioactive guided isolation and purification of Clematis aethusifolia was performed by normal and reverse phase column chromatography, Sephadex LH-20 and preparation HPLC. The structures were identified by 1D,2D-NMR and MS spectral analysis and comparison with literature data. Cytotoxicity of compounds were determined by CCK-8 cell staining method for detecting growth inhibition to five kinds of human solid tumor cell lines.. Eight compounds were isolated and identified as vanillicacid( 1),protocatechuic acid( 2),( +)-pinoresinol diglucoside( 3),( +)-pinoresinol-4’-O-β-D-glucopyranoside( 4),( +)-syringaresinol-4’-O-β-Dglucopyranoside( 5),7,9,9’-trihydroxy-3,3’-dimethoxy-8-O-4’-neolignan-4-O-β-D-glucopyranoside( 6),butyl-β-D-fructopyranoside( 7),butyl-β-D-fructofuranoside( 8). Compounds 2,8 showed strong cytotoxic activity.. All the compounds are isolated from this plant for the first time, Results: Eight compounds were isolated and identified as vanillicacid( 1), protocatechuic acid( 2),( +)-pinoresinol diglucoside( 3),( +)-pinoresinol-4’-O-β-D-glucopyranoside( 4),( +)-syringaresinol-4’-O-β-Dglucopyranoside( 5),7,9,9’-trihydroxy-3,3’-dimethoxy-8-O-4’-neolignan-4-O-β-D-glucopyranoside( 6),butyl-β-D-fructopyranoside( 7),butyl-β-D-fructofuranoside( 8). Compounds 2,8 showed strong cytotoxic activity. compounds 3,6 ~ 8 are isolated from Clematis genus for the first time, compounds 6 and 8 are isolated from Ranunculaceae family for the first time. Compounds 2,8 may be the effective components in Clematis aethusifolia.

Topics: Chromatography, High Pressure Liquid; Clematis; Drugs, Chinese Herbal; Furans; Humans; Lignans; Magnetic Resonance Spectroscopy; Medicine, Mongolian Traditional

The bark of Eucommia ulmoides is a well-known Chinese herbal medicine that is used to regulate blood pressure and reduce blood sugar and fats, as well as an antioxidant and antimicrobial agent. Here we describe the development of a sensitive ultrahigh performance liquid chromatography-tandem mass spectrum method for the simultaneous determination of five major active ingredients of E. ulmoides bark extract, namely, geniposidic acid (GA), protocatechuic acid (PCA), chlorogenic acid (CA), (+)-pinoresinol di-O-β-D-glucopyranoside (PDG) and (+)-pinoresinol 4'-O-β-D-glucopyranoside (PG), in rat plasma. The preliminary steps in the plasma analysis were the addition of an internal standard and acidification (0.1 % formic acid), followed by protein precipitation with methanol. Separation of the active ingredients was performed on an ACQUITY UPLC® BEH C18 column (2.1 × 50 mm; internal diameter 1.7 µm) at a flow rate of 0.35 mL/min, with acetonitrile/water containing 0.1 % formic acid as the mobile phase. Detection was performed on a triple quadrupole tandem mass spectrometer via electrospray ionization source with positive and negative ionization modes. All calibration curves showed good linearity (r ≥ 0.997) over the concentration range with the low limit of quantification between 4.45 and 54.9 ng/mL. Precision was evaluated by intra- and inter-day assays, and the percentages of the relative standard deviation were all within 15 %. Extraction efficiency and matrix effect were 84.3-102.4 % and 98.1-112.2 %, respectively. The validated method was successfully applied to the pharmacokinetic study in rats after oral administration of E. ulmoides extract. The results indicate that the pharmacokinetic properties of GA differ from those of PCA, CA, PDG and PG, respectively.

Topics: Animals; Chlorogenic Acid; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Eucommiaceae; Furans; Hydroxybenzoates; Iridoid Glucosides; Lignans; Male; Plant Extracts; Plasma; Rats; Rats, Sprague-Dawley; Tandem Mass Spectrometry

A candidate gene for phenylcoumaran benzylic ether reductase in Arabidopsis thaliana encodes a peptide with predicted functional activity and plays a crucial role in secondary metabolism. Phenylcoumaran benzylic ether reductase (PCBER) is thought to be an enzyme crucial in the biosynthesis of 8-5'-linked neolignans. Genes of the enzyme have been isolated and characterized in several plant species. In this study, we cloned cDNA and the 5'-untranslated region of one PCBER candidate gene (At4g39230, designated AtPCBER1) from Arabidopsis thaliana. At the amino acid level, AtPCBER1 shows high sequence identity (64-71 %) with PCBERs identified from other plant species. Expression analyses of AtPCBER1 by reverse transcriptase-polymerase chain reaction and histochemical analysis of transgenic plants harboring the 5'-untranslated region of AtPCBER1 linked with gus coding sequence indicate that expression is induced by wounding and is expressed in most tissues, including flower, stem, leaf, and root. Catalytic analysis of recombinant AtPCBER1 with neolignan and lignans in the presence of NADPH suggests that the protein can reduce not only the 8-5'-linked neolignan, dehydrodiconiferyl alcohol, but also 8-8' linked lignans, pinoresinol, and lariciresinol, with lower activities. To investigate further, we performed metabolomic analyses of transgenic plants in which the target gene was up- or down-regulated. Our results indicate no significant effects of AtPCBER1 gene regulation on plant growth and development; however, levels of some secondary metabolites, including lignans, flavonoids, and glucosinolates, differ between wild-type and transgenic plants. Taken together, our findings indicate that AtPCBER1 encodes a polypeptide with PCBER activity and has a critical role in the biosynthesis of secondary metabolites in A. thaliana.

Topics: Arabidopsis; Arabidopsis Proteins; Biocatalysis; Flavonoids; Furans; Gene Expression Profiling; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Plant; Glucosinolates; Lignans; Metabolomics; Oxidoreductases; Phenols; Phylogeny; Plants, Genetically Modified; Principal Component Analysis; Reverse Transcriptase Polymerase Chain Reaction; Tandem Mass Spectrometry

Enriching oils, such as olive oil, could be one solution to tackle the worldwide epidemic of vitamin D deficiency and to better fit with omega 3 (DHA) recommendations. However, data regarding the interactions occurring at the intestinal level between vitamin D and phenols from olive oil are scarce. We first determined the effect of polyphenols from a virgin olive oil, and a virgin olive oil enriched with DHA, on vitamin D absorption in rats. We then investigated the effects of 3 main olive oil phenols (oleuropein, hydroxytyrosol and pinoresinol) on vitamin D uptake by Caco-2 cells. The presence of polyphenols in the olive oil supplemented with DHA inhibited vitamin D postprandial response in rats (-25%, p<0.05). Similar results were obtained with a mix of the 3 polyphenols delivered to Caco-2 cells. However, this inhibitory effect was due to the presence of pinoresinol only. As the pinoresinol content can highly vary between olive oils, the present results should be taken into account to formulate an appropriate oil product enriched in vitamin D.

Topics: Animals; Caco-2 Cells; Docosahexaenoic Acids; Female; Furans; Humans; Intestinal Absorption; Iridoid Glucosides; Iridoids; Lignans; Olive Oil; Phenylethyl Alcohol; Polyphenols; Rats; Rats, Wistar; Vitamin D

Pinoresinol is a high-value plant-derived lignan with multiple health supporting effects. Enantiomerically pure pinoresinol can be isolated from natural sources, but with low efficiency. Most chemical and biocatalytic approaches that have been described for the synthesis of pinoresinol furnish the racemic mixture. In this study we devised a three-step biocatalytic cascade for the production of enantiomerically pure pinoresinol from the cheap compound eugenol. Two consecutive oxidations of eugenol through vanillyl-alcohol oxidase and laccase are followed by kinetic resolution of racemic pinoresinol by enantiospecific pinoresinol reductases.. The addition of the enantiospecific pinoresinol reductase from Arabidopsis thaliana for kinetic resolution of (±)-pinoresinol to an in vitro cascade involving the vanillyl-alcohol oxidase from Penicillium simplicissimum and the bacterial laccase CgL1 from Corynebacterium glutamicum resulted in increasing ee values for (+)-pinoresinol; however, an ee value of 34% was achieved in the best case. The ee value could be increased up to ≥ 99% by applying Escherichia coli-based whole-cell biocatalysts. The optimized process operated in a one-pot "two-cell" sequential mode and yielded 876 µM (+)-pinoresinol with an ee value of 98%. Switching the reductase to the enantiospecific pinoresinol lariciresinol reductase from Forsythia intermedia enabled the production of 610 µM (-)-pinoresinol with an ee value of 97%.. A new approach for the synthesis of enantiomerically pure (+)- and (-)-pinoresinol is described that combines three biotransformation steps in one pot. By switching the reductase in the last step, the whole-cell biocatalysts can be directed to produce either (+)- or (-)-pinoresinol. The products of the reductases' activity, (-)-lariciresinol and (-)-secoisolariciresinol, are valuable precursors that can also be applied for the synthesis of further lignans.

Topics: Alcohol Oxidoreductases; Arabidopsis; Bacterial Proteins; Biocatalysis; Chromatography, Gas; Chromatography, High Pressure Liquid; Corynebacterium glutamicum; Escherichia coli; Furans; Kinetics; Laccase; Lignans; Mass Spectrometry; Oxidoreductases; Penicillium; Plasmids; Stereoisomerism

A new caffeate compound, (E)-erythro-syringylglyceryl caffeate (1), was isolated from the roots and rhizomes of Nardostachys chinensis Batal., together with nine known phenolic compounds, including (+)-licarin A (2), naringenin 4', 7-dimethyl ether (3), pinoresinol-4-O-β-D-glucoside (4), caraphenol A (5), Z-miyabenol C (6), protocatechuic acid (7), caffeic acid (8), gallic acid (9) and vanillic acid (10). Their chemical structures were elucidated on the basis of spectroscopic data and physicochemical properties. Furthermore, this is the first report of compounds 2, 5 and 6 from Nardostachys genus.

Topics: Caffeic Acids; Flavanones; Furans; Glucosides; Hydroxybenzoates; Lignans; Nardostachys; Plant Roots; Rhizome; Vanillic Acid

Consumption of virgin olive oil (VOO) has been associated with a low breast cancer incidence. Pinoresinol is a phytoestrogen that is typically found in VOO. Considering the role of oestrogen in breast cancer development and progression, we investigated the potential antitumor activity of pinoresinol in breast cancer cells.. To address this question, we treated MDA-MB-231 (oestrogen receptor [ER] negative) and MCF7 (ER+) human breast tumour cells and MCF10A human mammary epithelial cells (ER-) with different concentrations of pinoresinol. The cytotoxic activity, cell proliferation, cell cycle profile, apoptosis induction, reactive oxygen species production and DNA damage were assessed.. Pinoresinol showed cytotoxic, anti-proliferative and pro-oxidant activity in human breast tumour cells, independent of their oestrogen receptor status. In addition, pinoresinol exerted antioxidant activity and prevented DNA damage associated with oxidative stress in human mammary epithelial cells.. Overall, the results suggest that pinoresinol may have antitumor activity in human breast cancer cells independently of oestrogen receptor status. Furthermore, the results show that the pinoresinol has the typical characteristics of a chemopreventive compound.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Breast Neoplasms; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cell Survival; Furans; Humans; Lignans; Olive Oil; Phytoestrogens; Receptors, Estrogen

The Australian plant Eremophila maculata F. Muell (Scrophulariaceae) is cultivated worldwide as an ornamental plant.. This study was designed to assess the antioxidant and hepatoprotective activities of a methanol extract from E. maculata leaves (EMM) both in vitro and in vivo (rats) experiments. Detailed phytochemical study was done on the extract followed by molecular docking experiments on TNF-α ascertain the efficacy of the isolated compounds.. The antiproliferative activity was evaluated in the human cancer cell lines A-495, PC3 and HepG2 cells using the SRB method. The antioxidant activitywas evaluated in vitro using the DPPH• assay while the hepatoprotective properties were investigated by determining the amelioration of CCl. These findings highlighted for the first time that EMM could be an interesting candidate as a safe, natural liver supplement for relieving of various hepatic disorders and counteracting the effect of many xenobiotics.

Topics: Animals; Antioxidants; Australia; Carbon Tetrachloride; Cardiac Glycosides; Female; Furans; Glycosides; Hep G2 Cells; Hepatocytes; Humans; Lignans; Liver; Male; Molecular Docking Simulation; Oxidative Stress; Phytotherapy; Plant Extracts; Plant Leaves; Rats, Sprague-Dawley; Scrophulariaceae; Silymarin; Tumor Necrosis Factor-alpha

The present study was aimed to assess the in vivo acute effects of oleuropein or/and pinoresinol, polyphenols widely diffused in natural sources, on rat pial microvascular responses during transient BCCAO and reperfusion.. Rat pial microcirculation was visualized by fluorescence microscopy through a closed cranial window. Pial arterioles were classified into five orders of branching. Capillaries were assigned order 0, the smallest arterioles order 1 and the largest ones order 5.. Rats subjected to BCCAO and reperfusion showed: arteriolar diameter decrease, microvascular leakage, leukocyte adhesion in venules, and reduction in capillary perfusion. Pretreatment with oleuropein or pinoresinol, a higher dose before BCCAO determined dilation in all arteriolar orders RE. Microvascular leakage was reduced as well as leukocyte adhesion and ROS formation, while capillary perfusion was protected. Inhibition of endothelium nitric oxide synthase prior to oleuropein or pinoresinol reduced the effect of these polyphenols on pial arteriolar diameter and leakage. These substances, administered together, prevented microvascular damage to a larger extent.. Oleuropein and pinoresinol were both able to protect pial microcirculation from I-reperfusion injury, to increase nitric oxide release and to reduce oxidative stress preserving pial blood flow distribution.

Topics: Animals; Arterioles; Brain Injuries; Cerebrovascular Circulation; Furans; Iridoid Glucosides; Iridoids; Lignans; Male; Microcirculation; Rats; Rats, Wistar; Reperfusion Injury; Vasodilator Agents

Control over phenoxy radical-radical coupling reactions in vivo in vascular plants was enigmatic until our discovery of dirigent proteins (DPs, from the Latin dirigere, to guide or align). The first three-dimensional structure of a DP ((+)-pinoresinol-forming DP, 1.95 Å resolution, rhombohedral space group H32)) is reported herein. It has a tightly packed trimeric structure with an eight-stranded β-barrel topology for each DP monomer. Each putative substrate binding and orientation coupling site is located on the trimer surface but too far apart for intermolecular coupling between sites. It is proposed that each site enables stereoselective coupling (using either two coniferyl alcohol radicals or a radical and a monolignol). Interestingly, there are six differentially conserved residues in DPs affording either the (+)- or (-)-antipodes in the vicinity of the putative binding site and region known to control stereoselectivity. DPs are involved in lignan biosynthesis, whereas dirigent domains/sites have been implicated in lignin deposition.

Topics: Alcohols; Amino Acid Sequence; Catalytic Domain; Cloning, Molecular; Crystallography, X-Ray; Furans; Lignans; Lignin; Molecular Docking Simulation; Molecular Sequence Data; Pisum sativum; Plant Proteins; Protein Binding; Protein Multimerization; Protein Structure, Secondary; Stereoisomerism; Substrate Specificity

Continually exposed to potential pathogens, vascular plants have evolved intricate defense mechanisms to recognize encroaching threats and defend themselves. They do so by inducing a set of defense responses that can help defeat and/or limit effects of invading pathogens, of which the non-host disease resistance response is the most common. In this regard, pea (Pisum sativum) pod tissue, when exposed to Fusarium solani f. sp. phaseoli spores, undergoes an inducible transcriptional activation of pathogenesis-related genes, and also produces (+)-pisatin, its major phytoalexin. One of the inducible pathogenesis-related genes is Disease Resistance Response-206 (DRR206), whose role in vivo was unknown. DRR206 is, however, related to the dirigent protein (DP) family. In this study, its biochemical function was investigated in planta, with the metabolite associated with its gene induction being pinoresinol monoglucoside. Interestingly, both pinoresinol monoglucoside and (+)-pisatin were co-localized in pea pod endocarp epidermal cells, as demonstrated using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging. In addition, endocarp epidermal cells are also the site for both chalcone synthase and DRR206 gene expression. Taken together, these data indicate that both (+)-pisatin and pinoresinol monoglucoside function in the overall phytoalexin responses.

Topics: Disease Resistance; Furans; Gene Expression Regulation; Lignans; Molecular Structure; Phytoalexins; Pisum sativum; Plant Diseases; Plant Proteins; Pterocarpans; Sesquiterpenes; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Nanoparticles, including gold nanoparticles (AuNP), have been used in imaging in cancer treatment and as therapeutic agents and drug delivery vehicles. Particularly lignans, also called phytoestrogens, have strong effects on the treatment of carcinomas due to their antiestrogenic, antiangiogenic and proapoptotic mechanism. The aim of this study is to investigate the antiproliferative effects of three lignans-AuNP conjugates, pinoresinol (PINO), lariciresinol (LARI) and secoisolariciresinol (SECO), on the MCF-7 cell lines. For this purpose, first, thiolated β-cyclodextrin (β-CD) was synthesized to achieve a surface modification of AuNP, and then the β-CD modified AuNP was characterized using the transmission electron microscopy (TEM), UV-Visible and Nuclear Magnetic Resonance (NMR) spectroscopy. Then, the selected lignans were conjugated to the β-CD-modified AuNP, and the antiproliferative effect of these conjugates was monitored. The results suggest that when compared to their non-conjugated forms, the AuNP-bound lignan conjugates prevented the proliferation of the MCF-7 cells significantly. Therefore, these AuNP-conjugated derivatives can be new candidate agents for breast cancer therapy.

Topics: beta-Cyclodextrins; Butylene Glycols; Cell Proliferation; Cell Survival; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Furans; Gold; Humans; Ligands; Lignans; MCF-7 Cells; Metal Nanoparticles; Molecular Structure; Organogold Compounds; Structure-Activity Relationship; Tumor Cells, Cultured

Lignan natural products comprise a broad spectrum of biologically active secondary metabolites. Their structural diversity belies a common biosynthesis, which involves regio- and chemoselective oxidative coupling of propenyl phenols. Attempts to replicate this oxidative coupling have revealed significant challenges for controlling selectivity, and these challenges have thus far prevented the development of a unified biomimetic route to compounds of the lignan family. A practical solution is presented that hinges on oxidative ring opening of a diarylcyclobutane to intercept a putative biosynthetic intermediate. The effectiveness of this approach is demonstrated by the first total synthesis of tanegool in 4 steps starting from ferulic acid, as well as a concise synthesis of the prototypical furanolignan pinoresinol.

Topics: Biomimetics; Coumaric Acids; Furans; Lignans; Oxidation-Reduction; Phenols

Phomopsis sp. XP-8 is an endophytic fungus that has the ability to produce pinoresinol diglucoside (PDG) in vitro and thus has potential application for the biosynthesis of PDG independent of plants. When cultivated in mung bean medium, PDG production was significantly improved and pinoresinol monoglucoside (PMG) and pinoresinol (Pin) were also found in the culture medium. In this experiment, starch, protein, and polysaccharides were isolated from mung beans and separately used as the sole substrate in order to explore the mechanism of fermentation and identify the major substrates that attributed to the biotransformation of PDG, PMG, and Pin. The production of PDG, PMG, and Pin was monitored using high-performance liquid chromatography (HPLC) and confirmed using HPLC-MS. Activities of related enzymes, including phenylalanine ammonia-lyase (PAL), trans-cinnamate 4-hydroxylase (C4H), and 4-coumarate-CoA ligase (4CL) were analyzed and tracked during the cultivation. The reaction system contained the compounds isolated from mung bean in the designed amount. Accumulation of phenylalanine, cinnamic acid, p-coumaric acid, PDG, PMG, and Pin and the activities of PAL, C4H, and 4CL were measured during the bioconversion. PMG was found only when mung bean polysaccharide was analyzed, while production of PDG and Pin were found when both polysaccharide and starch were analyzed. After examining the monosaccharide composition of the mung bean polysaccharide and the effect of the different monosaccharides had on the production of PMG, PDG, and Pin, galactose in mung bean polysaccharide proved to be the major factor that stimulates the production of PMG.

Topics: Ascomycota; Biotransformation; Chromatography, High Pressure Liquid; Fabaceae; Furans; Glycosides; Lignans; Mass Spectrometry; Plant Extracts; Plant Proteins; Starch

The lignan pinoresinol is a constituent of flaxseed, sesame seeds and olive oil. Because of different molecular effects reported for this compound, e.g. antioxidative activity, pinoresinol is suggested to cause positive effects on humans. Because experimental data are limited, we have analysed the effects of the lignan on the nematode Caenorhabditis elegans: in spite of a strong antioxidative capacity detected in an in vitro assay, no antioxidative effects were detectable in vivo. In analogy to this result, no modulation of the sensitivity against thermal stress was detectable. However, incubation with pinoresinol caused an enhanced nuclear accumulation of the transcription factor DAF-16 (insulin/IGF-like signalling pathway). Using a strain with an enhanced oxidative stress level (mev-1 mutant), we clearly see an increase in stress resistance caused by this lignan, but no change in reactive oxygen species. Furthermore, we investigated the effects of pinoresinol on the life span of the nematode, but no modulation was found, neither in wild-type nor in mev-1 mutant nematodes. These results suggest that pinoresinol may exert pharmacologically interesting effects via modulation of the insulin-like signalling pathway in C. elegans as well as in other species like mammals due to the evolutionary conservation of this signalling pathway.

Topics: Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Cell Nucleus; Forkhead Transcription Factors; Free Radical Scavengers; Furans; Lignans; Longevity; Oxidative Stress; Reactive Oxygen Species; Signal Transduction; Stress, Physiological; Temperature

An integrated omics approach using genomics, transcriptomics, metabolomics (MALDI mass spectrometry imaging, MSI), and bioinformatics was employed to study spatiotemporal formation and deposition of health-protecting polymeric lignans and plant defense cyanogenic glucosides. Intact flax (Linum usitatissimum) capsules and seed tissues at different development stages were analyzed. Transcriptome analyses indicated distinct expression patterns of dirigent protein (DP) gene family members encoding (-)- and (+)-pinoresinol-forming DPs and their associated downstream metabolic processes, respectively, with the former expressed at early seed coat development stages. Genes encoding (+)-pinoresinol-forming DPs were, in contrast, expressed at later development stages. Recombinant DP expression and DP assays also unequivocally established their distinct stereoselective biochemical functions. Using MALDI MSI and ion mobility separation analyses, the pinoresinol downstream derivatives, secoisolariciresinol diglucoside (SDG) and SDG hydroxymethylglutaryl ester, were localized and detectable only in early seed coat development stages. SDG derivatives were then converted into higher molecular weight phenolics during seed coat maturation. By contrast, the plant defense cyanogenic glucosides, the monoglucosides linamarin/lotaustralin, were detected throughout the flax capsule, whereas diglucosides linustatin/neolinustatin only accumulated in endosperm and embryo tissues. A putative biosynthetic pathway to the cyanogens is proposed on the basis of transcriptome coexpression data. Localization of all metabolites was at ca. 20 μm resolution, with the web based tool OpenMSI enabling not only resolution enhancement but also an interactive system for real-time searching for any ion in the tissue under analysis.

Topics: Butylene Glycols; Flax; Furans; Glucosides; Glycosides; Lignans; Molecular Structure; Nitriles; Seeds; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Potato, tomato, eggplant and pumpkin were deep fried, sautéed and boiled in Mediterranean extra virgin olive oil (EVOO), water, and a water/oil mixture (W/O). We determined the contents of fat, moisture, total phenols (TPC) and eighteen phenolic compounds, as well as antioxidant capacity in the raw vegetables and compared these with contents measured after cooking. Deep frying and sautéing led to increased fat contents and TPC, whereas both types of boiling (in water and W/O) reduced the same. The presence of EVOO in cooking increased the phenolics identified in the raw foods as oleuropein, pinoresinol, hydroxytyrosol and tyrosol, and the contents of vegetable phenolics such as chlorogenic acid and rutin. All the cooking methods conserved or increased the antioxidant capacity measured by DPPH, FRAP and ABTS. Multivariate analyses showed that each cooked vegetable developed specific phenolic and antioxidant activity profiles resulting from the characteristics of the raw vegetables and the cooking techniques.

Topics: Antioxidants; Benzothiazoles; Chlorogenic Acid; Chromatography, High Pressure Liquid; Cluster Analysis; Cooking; Cucurbita; Dietary Fats; Furans; Iridoid Glucosides; Iridoids; Lignans; Multivariate Analysis; Olive Oil; Phenols; Phenylethyl Alcohol; Rutin; Solanum lycopersicum; Solanum melongena; Solanum tuberosum; Sulfonic Acids; Vegetables

Investigation on the fruits of Melia toosendan afforded seven new lignans (1-7), along with seventeen known compounds (8-24). The structures of the new compounds, involving four neo-lignans (1-4), two sesquilignans (5-6), and a nor-lignan (7), were elucidated based on extensive spectroscopic analyses (high-resolution electrospray ionization mass spectra, ultraviolet, infrared, one-dimensional and two-dimensional nuclear magnetic resonance). Compound 24 exhibited activity on melatonin receptor type 1 with an agonistic rate of 57.77% at 1.02 mM according to the assay on HEK293 cell lines in vitro.

Topics: Drug Evaluation, Preclinical; Furans; HEK293 Cells; Humans; Lignans; Magnetic Resonance Spectroscopy; Melia; Molecular Structure; Neuroprotective Agents; Plants, Medicinal; Receptor, Melatonin, MT1; Spectrometry, Mass, Electrospray Ionization

Pinoresinol diglucoside (PDG) and pinoresinol (Pin) are normally produced by plant cells via the phenylpropanoid pathway. This study reveals the existence of a related pathway in Phomopsis sp. XP-8, a PDG-producing fungal strain isolated from the bark of the Tu-chung tree (Eucommiaulmoides Oliv.). After addition of 0.15 g/L glucose to Phomopsis sp. XP-8, PDG and Pin formed when phenylalanine, tyrosine, leucine, cinnamic acid, and p-coumaric acid were used as the substrates respectively. No PDG formed in the absence of glucose, but Pin was detected after addition of all these substrates except leucine. In all systems in the presence of glucose, production of PDG and/or Pin and the accumulation of phenylalanine, cinnamic acid, or p-coumaric acid correlated directly with added substrate in a time- and substrate concentration- dependent manner. After analysis of products produced after addition of each substrate, the mass flow sequence for PDG and Pin biosynthesis was defined as: glucose to phenylalanine, phenylalanine to cinnamic acid, then to p-coumaric acid, and finally to Pin or PDG. During the bioconversion, the activities of four key enzymes in the phenylpropanoid pathway were also determined and correlated with accumulation of their corresponding products. PDG production by Phomopsis sp. exhibits greater efficiency and cost effectiveness than the currently-used plant-based system and will pave the way for large scale production of PDG and/or Pin for medical applications.

Topics: Amino Acids; Ascomycota; Furans; Glucose; Lignans; Propionates

To study the chemical constituents in the stem bark of Styrax perkinsiae.. The chemical constituents were separated and purified by chromatographic methods after solvent extraction and identified by spectroscopic analyses.. Ten lignans were isolated from the stem bark of Styrax perkinsiae and identified as following: pinoresinol 4-O-β-D-glucopyranoside (1), matairesinoside (2), styraxlignolide B (3), 3- (β-D-glucopyranosyloxymethyl)-2-(4-hydroxy-3-methoxyphenyl)-5-(3-hydroxypropyl )-7-methoxy-(2R , 3S) -dihydrobenzofuran (4), burselignan (5), (+) -neo-olivil (6), threo-1-(4-hydroxy-3-methoxyphenyl )-2-[ 4-(3-hydroxypropyl)-2-methoxyphenoxy]-1, 3-propanediol (7), erythro-1-(4-hydroxy-3-methoxyphenyl )-2-[ 4-(3-hydroxypropyl )-2-methoxyphenoxy ] -1 ,3-propanediol (8), isolariciresinol(9) and (+) -lariciresinol (10).. Compounds 5 - 10 are isolated from the plants of Styrax genus for the first time.

Topics: Furans; Lignans; Lignin; Naphthols; Plant Bark; Plant Extracts; Styrax

To study the chemical constituents of Eucommia ulmoides in Guizhou Province.. Silica gel, Sephadex LH-20, RP-18, MCI and semi-preparative HPLC were used to study the chemical constituents of Eucommia ulmoides, and the chemical structures were elucidated by application of spectral data.. 16 compounds were isolated from the bark of Eucommia ulmoides. Their structures were identified as β-sitosterol (1), cycloeucalenol (2), betulinic acid (3), 24-methylenecycloartenone (4), cycloeucalenone (5), salicifoliol (6), pinoresinol (7), genipin (8) , alternariol (9), balanophonin (10), eucommidiol (11), pinoresinol-4'-O-β-D-glucopyranoside (12), eucommiol (13), deoxyeucommiol (14), 8-hydroxypinoresinol (15), and dehydrodiconiferyl alcohol -γ'-O-β-D-glucopyranoside (16).. Seven compounds, including compounds 2,4 - 6,9, 10 and 15 are isolated from Eucommia ulmoides for the first time, and compound 14 is isolated from the bark of Eucommia ulmoides for the first time.

Topics: Betulinic Acid; Chromatography, High Pressure Liquid; Eucommiaceae; Furans; Lignans; Pentacyclic Triterpenes; Phenols; Phytochemicals; Plant Bark; Sitosterols; Triterpenes

To study the chemical constituents of stem of Camellia oleifera.. The chemical constituents were isolated and purified by column chromatography on silica gel, ODS, Sephadex LH-20 and MPLC. Their structures were elucidated on the basis of physicochemical properties and special analysis.. Seven compounds were isolated from the stem of Camellia oleifera, whose structures were elucidated as (-) -pinoresinol (1), (-) -medioresinol (2), skullcapflavone II (3), betulinic acid (4), ursolic acid (5), 3-O-β-D-glucopyranosyl- (1 --> 2) -β-D-xylopyransoyl-(1 --> 3) -[β-D-glucopyranosyl- (1 --> 2)] -β-D-glucuronopyranosyl-22α-angeloyloxyolean-12-ene-15α,16α,28-triol (6) and oleanolic acid (7).. Compounds 1 - 6 are isolated from this plant for the first time, and compounds 1 - 3 are isolated from this genus for the first time.

Topics: Betulinic Acid; Camellia; Drugs, Chinese Herbal; Flavonoids; Furans; Lignans; Oleanolic Acid; Pentacyclic Triterpenes; Phytochemicals; Plant Stems; Plants, Medicinal; Triterpenes; Ursolic Acid

The invasive emerald ash borer (EAB) beetle is a significant threat to the survival of North American ash. In previous work, we identified putative biochemical and molecular markers of constitutive EAB resistance in Manchurian ash, an Asian species co-evolved with EAB. Here, we employed high-throughput high-performance liquid chromatography with photodiode array detection and mass spectrometry (HPLC-PDA-MS) to characterize the induced response of soluble phloem phenolics to EAB attack in resistant Manchurian and susceptible black ash under conditions of either normal or low water availability, and the effects of water availability on larval performance. Total larval mass per tree was lower in Manchurian than in black ash. Low water increased larval numbers and mean larval mass overall, but more so in Manchurian ash. Low water did not affect levels of phenolics in either host species, but six phenolics decreased in response to EAB. In both ashes, pinoresinol A was induced by EAB, especially in Manchurian ash. Pinoresinol A and pinoresinol B were negatively correlated with each other in both species. The higher accumulation of pinoresinol A in Manchurian ash after attack may help explain the resistance of this species to EAB, but none of the responses measured here could explain increased larval performance in trees subjected to low water availability.

Topics: Analysis of Variance; Animals; Chromatography, High Pressure Liquid; Chromatography, Liquid; Coleoptera; Fraxinus; Furans; Larva; Lignans; Linear Models; Mass Spectrometry; Multivariate Analysis; Phenols; Phloem; Plant Leaves; Principal Component Analysis; Statistics, Nonparametric; Water

In the present study, we evaluated the anti-inflammatory properties of several plant lignans most commonly distributed in foods. 7-Hydroxymatairesinol (HMR) and its major isomer 7-hydroxymatairesinol 2 (HMR2), lariciresinol, secoisolariciresinol, and pinoresinol, isolated from Norway spruce knots were examined.. We investigated the anti-inflammatory effects of lignans on tumor necrosis factor-α-treated human aortic endothelial cells by measuring the expression of intracellular adhesion molecule-1 and vascular cell adhesion molecule-1 by cell ELISA and the adhesion of U937 monocytes to activated endothelial cells using a cell adhesion assay. Among the lignans studied, HMR and HMR2 significantly reduced intracellular adhesion molecule-1 and vascular cell adhesion molecule-1 levels as well as the adhesion of U937 to endothelial cells. To further characterize the molecular mechanisms involved in this regulation, the effect of HMR and HMR2 on nuclear factor-κB, SAPK/c-Jun NH2-terminal kinase and extracellular signal regulated kinase phosphorylation was assessed.. Our results demonstrated that the lignans HMR and HMR2, dominant in cereals such as in wheat, triticale, oat, barley, millet, corn bran, and in amaranth whole grain, exhibit strong anti-inflammatory properties in endothelial cells, at least in part, through attenuation of nuclear factor-κB and extracellular signal regulated kinase phosphorylation.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Aorta; Butylene Glycols; Cell Adhesion; Cells, Cultured; Endothelial Cells; Furans; Humans; Intercellular Adhesion Molecule-1; Lignans; MAP Kinase Kinase 4; Monocytes; NF-kappa B; Picea; PPAR gamma; Receptors, Estrogen; Vascular Cell Adhesion Molecule-1

Lignans, a class of dimeric phenylpropanoid derivative found in plants, such as whole grains and sesame and flax seeds, have anticancer activity and can act as phytoestrogens. The lignans secoisolariciresinol and matairesinol can be converted in the mammalian proximal colon into enterolactone and enterodiol, respectively, which reduce the risk of breast and colon cancer. To establish an efficient bioconversion system to generate matairesinol from pinoresinol, the genes encoding pinoresinol-lariciresinol reductase (PLR) and secoisolariciresinol dehydrogenase (SDH) were cloned from Podophyllum pleianthum Hance, an endangered herb in Taiwan, and the recombinant proteins, rPLR and rSDH, were expressed in Escherichia coli and purified. The two genes, termed plr-PpH and sdh-PpH, were also linked to form two bifunctional fusion genes, plr-sdh and sdh-plr, which were also expressed in E. coli and purified. Bioconversion in vitro at 22°C for 60 min showed that the conversion efficiency of fusion protein PLR-SDH was higher than that of the mixture of rPLR and rSDH. The percent conversion of (+)-pinoresinol to matairesinol was 49.8% using PLR-SDH and only 17.7% using a mixture of rPLR and rSDH. However, conversion of (+)-pinoresinol by fusion protein SDH-PLR stopped at the intermediate product, secoisolariciresinol. In vivo, (+)-pinoresinol was completely converted to matairesinol by living recombinant E. coli expressing PLR-SDH without addition of cofactors.

Topics: Biotransformation; Escherichia coli; Furans; Lignans; Metabolic Engineering; Molecular Sequence Data

Lignans are a group of diphenolic compounds with anticancer and antioxidant properties which are present in various grains, although their effect on toxigenic fungi has been poorly examined to date. In this study, the impact of the plant lignans pinoresinol and secoisolariciresinol on growth and trichothecene biosynthesis by five Fusarium graminearum strains of different chemotypes was examined in vitro. Both tested lignans exhibited radial growth inhibition against the fungal strains. RT-qPCR analyses of tri4, tri5 and tri11 genes encoding the first steps of the trichothecene biosynthesis pathway revealed a decrease in tri mRNA levels in lignan-treated fungal cultures. Correspondingly, decreased accumulation of toxins in lignan-treated cultures was confirmed by GC-MS analysis. This is the first study to demonstrate the inhibitory effect of both pinoresinol and secoisolariciresinol on growth and trichothecene biosynthesis in F. graminearum.. Knowledge of the regulation of trichothecene production in Fusarium graminearum by environmental cues is key to the design of novel strategies to reduce mycotoxin levels in grains. Here, we show that the lignans pinoresinol and secoisolariciresinol, which occur in wheat grains, inhibit radial growth and decrease trichothecene levels in five F. graminearum strains. RT-qPCR analysis reveals that the reduction in trichothecene level in lignan-treated fungal cultures is associated with decreased mRNA transcript levels for the tri4, tri5 and tri11 genes that are involved in the trichothecene biosynthesis pathway.

Topics: Antifungal Agents; Butylene Glycols; Edible Grain; Furans; Fusarium; Gene Expression; Genes, Fungal; Lignans; Microbial Sensitivity Tests; RNA, Messenger; Transcription, Genetic; Trichothecenes; Triticum

To investigate the chemical constituents of Selaginella sinensis (Desv.) Spring.. Chromatographic separations on Diaion HP-20, silica gel, and Sephadex LH-20 were used. The structures of the isolates were elucidated on the basis of spectroscopic analysis, as well as chemical methods.. Eight compounds were obtained and their structures were identified as sinensioside A (1), syringaresinol-4- O-β-D-glucopyranoside (2), (+)-medioresinol-4-O-β-D-glucopyranoside (3), pinoresinol-4, 4'-di-O-β-D-glucopyranoside (4), quercetin (5), eucomic acid (6), shikimic acid (7), and 2, 3-dihydroamentoflavone (8).. Compound 1 is a new dihydrobenzofuran sesquilignan glycoside from Selaginella sinensis.

Topics: Benzofurans; Furans; Glucosides; Lignans; Molecular Structure; Plant Extracts; Plant Stems; Quercetin; Selaginellaceae

Systematic studies of physico-chemical and stability-related properties, and chemical composition, of extra virgin olive oils (EVOOs) obtained from drupes cropped in specific regions are of special agricultural interest. This is particularly so with new production areas, where careful selection of the most suitable olive varieties for EVOO production is required. This paper reports the first comprehensive chemical characterisation of EVOOs obtained from three different olive varieties (viz., Picual, Morisca and Manzanilla de Sevilla) grown in a new cultivation area in Galicia (NW Spain). The Morisca variety was that providing the highest industrial oil yield (21%). However, the three types of EVOO exhibited no statistically significant differences in standard quality-related indices other than acidity. Morisca EVOO was that with the lowest content in oleic acid (mean=68%) and highest content in linoleic acid (mean=13%). Also, Morisca EVOO exhibited the highest sterol levels (mean=1,616 mg/kg) and Picual EVOO the lowest (mean=1,160 mg/kg). Picual EVOO contained greater amounts of the phenolic compounds luteolin and pinoresinol than both Morisca and Manzanilla de Sevilla EVOOs. Finally, Manzanilla de Sevilla EVOO exhibited differential attributes, with banana and olive fruit aromatic series prevailing predominantly over bitter-like, pungent-like and leaf series.

Topics: Food Quality; Fruit; Furans; Lignans; Olea; Oleic Acid; Olive Oil; Phenols; Plant Oils; Spain; Taste

RNAi technology was applied to down regulate LuPLR1 gene expression in flax (Linum usitatissimum L.) seeds. This gene encodes a pinoresinol lariciresinol reductase responsible for the synthesis of (+)-secoisolariciresinol diglucoside (SDG), the major lignan accumulated in the seed coat. If flax lignans biological properties and health benefits are well documented their roles in planta remain unclear. This loss of function strategy was developed to better understand the implication of the PLR1 enzyme in the lignan biosynthetic pathway and to provide new insights on the functions of these compounds. RNAi plants generated exhibited LuPLR1 gene silencing as demonstrated by quantitative RT-PCR experiments and the failed to accumulate SDG. The accumulation of pinoresinol the substrate of the PLR1 enzyme under its diglucosylated form (PDG) was increased in transgenic seeds but did not compensate the overall loss of SDG. The monolignol flux was also deviated through the synthesis of 8-5' linked neolignans dehydrodiconiferyl alcohol glucoside (DCG) and dihydro-dehydrodiconiferyl alcohol glucoside (DDCG) which were observed for the first time in flax seeds.

Topics: Butylene Glycols; Flax; Furans; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Plant; Gene Knockdown Techniques; Glucosides; Lignans; Oxidoreductases; Plant Proteins; Plants, Genetically Modified; RNA Interference; Seeds

Lignans are important biologically active dietary polyphenolic compounds. Consumption of foods that are rich in lignans is associated with positive health effects. Using modeling tools to probe the ligand-binding pockets of molecular receptors, we found that lignans have high docking affinity for the human thyroid hormone receptor β. Follow-up experimental results show that lignans (-) arctigenin and (+) pinoresinol are antagonists of the human thyroid hormone receptor β. The modeled complexes show key plausible interactions between the two ligands and important amino acid residues of the receptor.

Topics: Furans; Humans; Hydrogen Bonding; Lignans; Molecular Docking Simulation; Protein Structure, Tertiary; Thyroid Hormone Receptors beta

To study the chemical constituents from the crop pathogenic fungus active fraction of Wisteria sinensis tumor.. The chemical constituents were extracted of different concentrations and isolated by silica gel and Sephadex LH-20 column. The chemical structures of components were further elucidated by the physicochemical characters and MS, NMR spectral data.. Ten compounds were isolated and identified as dibutyl phthalate (1), diacetonealcohol (2), pinoresinol (3), stellasterol (4), oleanolic acid (5), olean-12-ene-3-oxo-22,24-diol (6), betulinic acid (7), 2',4',4-hydroxy-chalcone (8), avicularin (9) and quercetin-3-O-β-D-glucopyranoside (10).. All the compounds are isolated from the genus for the first time.

Topics: Betulinic Acid; Flavonoids; Fungi; Furans; Lignans; Oleanolic Acid; Pentacyclic Triterpenes; Plant Diseases; Triterpenes; Wisteria

To study the chemical constituents from Daphne acutiloba.. The constituents were separated by column chromatography, and their structures were elucidated by spectroscopic data analyses.. Fifteen compounds were isolated from the EtOAc extract and identified as wikstroelide M (1), vesiculosin (2), prostratin (3), 7-hydroxy-coumarin (4), 7,8-di-hydroxy-coumarin (5), isodaphnoside (6), daphnorine (7), rutamontine (8), daphnolin (9), daphneticin (10), (+)-pinoresinol-beta-D-glucoside (11), oleodapnone (12), oleodaphnal (13), ergosterol peroxide (14) and cholest-5-en-3beta-ol (15).. All the compounds except for 4, 5 and 14 were obtained from the stems of this plant for the first time.

Topics: Coumarins; Daphne; Drugs, Chinese Herbal; Furans; Lignans; Mass Spectrometry

Podophyllotoxin, an aryltetralin lignan, is the source of important anticancer drugs etoposide, teniposide, and etopophos. Roots/rhizome of Podophyllum hexandrum form one of the most important sources of podophyllotoxin. In order to understand genes involved in podophyllotoxin biosynthesis, two suppression subtractive hybridization libraries were synthesized, one each from root/rhizome and leaves using high and low podophyllotoxin-producing plants of P. hexandrum. Sequencing of clones identified a total of 1,141 Expressed Sequence Tags (ESTs) resulting in 354 unique ESTs. Several unique ESTs showed sequence similarity to the genes involved in metabolism, stress/defense responses, and signalling pathways. A few ESTs also showed high sequence similarity with genes which were shown to be involved in podophyllotoxin biosynthesis in other plant species such as pinoresinol/lariciresinol reductase. A full length coding sequence of pinoresinol/lariciresinol reductase (PLR) has been cloned from P. hexandrum which was found to encode protein with 311 amino acids and show sequence similarity with PLR from Forsythia intermedia and Linum spp. Spatial and stress-inducible expression pattern of PhPLR and other known genes of podophyllotoxin biosynthesis, secoisolariciresinol dehydrogenase (PhSDH), and dirigent protein oxidase (PhDPO) have been studied. All the three genes showed wounding and methyl jasmonate-inducible expression pattern. The present work would form a basis for further studies to understand genomics of podophyllotoxin biosynthesis in P. hexandrum.

Topics: Alcohol Oxidoreductases; Amino Acid Sequence; Base Sequence; Biosynthetic Pathways; Cloning, Molecular; Expressed Sequence Tags; Furans; Gene Expression Profiling; Gene Expression Regulation, Plant; Gene Library; Genes, Plant; Lignans; Molecular Sequence Data; NAD (+) and NADP (+) Dependent Alcohol Oxidoreductases; Oxidoreductases; Phylogeny; Plant Proteins; Podophyllotoxin; Podophyllum; Sequence Alignment; Sequence Analysis, DNA; Stress, Physiological

Different grades of genuine and counterfeit Fraxinus excelsior exudates, marketed as natural sweeteners or mild laxatives, were evaluated for their proximate composition and for saccharidic, organic acids, lipidic and phenolic profile by means of GC-MS and (1)H NMR. Genuine samples contained mannitol (39-48 g/100 g, according to the grade), fructose (9-16 g/100 g), glucose (2-3.7 g/100 g), sorbitol (0,5-0,6 g/100 g), galactose (0.02-0.74 g/100 g), oligosaccharides as mannotriose (13-22 g/100 g) and stachyose (1-11 g/100 g), and traces of myo-inositol, mannose, sucrose. On the contrary, counterfeit samples contained mostly mannitol and sorbitol, with traces of fructose, glucose and mannose. Differences in ash, total polyphenolic content and fatty acid composition allowed a quick identification of counterfeit products, confirmed by a distinct mono-, oligosaccharidic and phenolic pattern. Elenolic acid (63-1628 mg/kg), tyrosol (15-774 mg/kg), homovanillic acid (2,39-52.8 mg/Kg), dopaol (0.8-63 mg/kg), pinoresinol (4.2-18.5 mg/kg) and fraxetin (0.25-11.64 mg/kg), albeit showing a wide concentration range, were the most abundant substances detected in the phenolic fraction of Fraxinus manna, while esculetin, p-hydroxybenzoic acid, 4-hydroxyphenacetic acid, 3,4 hydroxybenzoic acid, hydroxy-pinoresinol, medioresinol and siringaresinol were present in low amounts. The polyphenolic profile may be used as a marker for authentication and should be considered in the evaluation of nutritional and health properties ascribed to Fraxinus manna.

Topics: Coumarins; Fatty Acids; Fraxinus; Furans; Hexoses; Homovanillic Acid; Lignans; Oligosaccharides; Phenylethyl Alcohol; Plant Extracts; Plant Exudates; Polyphenols; Pyrans; Sugar Alcohols

Three new 7,8-secolignans, schisandlignans A-C (1, 2, and 4), one new dibenzocyclooctadiene lignan, schisandlignan D (5), together with nine known lignans 3',4'-dimethoxybenzoic acid (3″,4″-dimethoxyphenyl)-2-methyl-3-oxobutyl ester (3), gomisin J (6), rubrisandrin A(1b) (7), interiotherin B (8), schisantherin D (9), ( - )-machilusin (10), ganschisandrine (11), henricine A (12), and (+)-1-hydroxy pinoresinol (13), were isolated from the rattan of Schisandra sphenanthera. Their structures were determined by analysis of 1D and 2D NMR spectroscopic data.

Topics: Cyclooctanes; Furans; Lignans; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Polycyclic Compounds; Schisandra

Pinoresinol (PIN), one of the simplest lignans, is the precursor of other dietary lignans that are present in whole-grain cereals, legumes, fruits, and other vegetables. Several experimental and epidemiological evidences suggest that lignans may prevent human cancer in different organs. In this study we investigated the chemopreventive properties of PIN on cell lines derived from different sites either expressing or not the functional tumor suppressor protein p53. It was found that PIN inhibited the proliferation of p53 wild type colon and prostate tumor cells (HCT116 and LNCaP) while in breast cells the inhibition of growth was observed only in p53 mutant cells (MDA-MB-231). A potent antiproliferative activity of PIN was also observed on p53 null cells HL60 (IC50% 8 μM), their multidrug resistant variant HL60R (IC50% 32 μM) and K562. On HL60 cells, PIN caused a block of cell cycle in the G0/G1 phase, induced a weak proapoptotic effect but it was a good trigger of differentiation (NBT reduction and CD11b expression). PIN caused an upregulation of the CDK inhibitor p21(WAF1/Cip1) both at mRNA and protein levels so suggesting that this could be a mechanism by which PIN reduced proliferation and induced differentiation on HL60 cells.

Topics: Antineoplastic Agents; Apoptosis; Cell Differentiation; Cell Line, Tumor; Cell Proliferation; Cyclin-Dependent Kinase Inhibitor p21; Drug Resistance, Neoplasm; Furans; G1 Phase; HL-60 Cells; Humans; Inhibitory Concentration 50; Lignans; S Phase; Tumor Suppressor Protein p53

The aim of this work was to study the chemical characteristics of two Tunisian cultivars, namely Dhokar and Gemri-Dhokar, to analyse the fatty acids, sterols, triacylglycerols, triterpenic alcohols, and to determine the phenolic composition and oxidative stability.. Among the rare varieties, Gemri-Dhokar olive oil had the highest value of oleic acid (69.39%) whereas Dhokar oil was noteworthy for its lower content of phenolic compounds (94.56 mg kg(-1) gallic acid equivalents of oil) and presented the highest level of palmitic acid (19.37%). The main sterols found in all olive oil samples were β-sitosterol and Δ5-avenasterol, whereas cholesterol and 24-methylenecholesterol were also found in all samples but in lower amounts. Two triterpenic dialcohols (erythrodiol and uvaol) were also detected and their content ranged from 1.45 to 2.30%, in Gemri-Dhokar and Dhokar olive oil, respectively. Ten phenolic compounds were identified. In all samples, the main phenols found were oleuropein aglycon and pinoresinol. These phenolic compounds showed significant correlations with oxidative stability.. The analytical parameters of two oils that were determined in this study were greatly influenced by genetic factors (cultivar).

Topics: Alcohols; Drug Stability; Fatty Acids; Furans; Iridoid Glucosides; Iridoids; Lignans; Oleanolic Acid; Olive Oil; Oxidation-Reduction; Palmitic Acid; Phenols; Phytosterols; Plant Oils; Pyrans; Sitosterols; Species Specificity; Triglycerides; Triterpenes; Tunisia

The characterisation of virgin olive oils from two Tunisian cultivars, growing in the Tataouin zone, namely Jemri-Bouchouka, a rare olive cultivar, and Chemlali-Tataouin, was carried out. Several analytical parameters were evaluated; these include quality index, fatty acids, phenolic, chlorophyll, carotenoid, squalene, α-tocopherol compositions and oxidative stability.. Jemri-Bouchouka olive oil had the highest value of oleic acid (74.50%) while Chemlali-Tataouin olive oil had the highest value of oleic acid (69.39 %) and also was characterized by a high percentage of palmitic acid (14.75 %) which makes this oil freeze at a low temperature [corrected]. On the other hand, Jemri-Bouchouka oil was characterised by a low phenolic and α-tocopherol content (267.72 mg GAE kg⁻¹ and 278.34 mg kg⁻¹, respectively). Ten phenolic compounds were identified. The main phenols found in the two olive oils were oleuropein aglycon and pinoresinol. All phenolic compounds showed significant correlations with oxidative stability.. The analytical parameters of virgin olive oil that were determined in this study were greatly influenced by cultivar.

Topics: alpha-Tocopherol; Antioxidants; Fatty Acids; Food Quality; Food Storage; Fruit; Furans; Hydrogen-Ion Concentration; Iridoid Glucosides; Iridoids; Lignans; Lipid Peroxides; Olea; Oleic Acid; Olive Oil; Oxidation-Reduction; Palmitic Acid; Phenols; Pigments, Biological; Plant Oils; Pyrans; Species Specificity; Transition Temperature; Tunisia

Phenoxy radical coupling reactions are involved in the biosynthesis of lignans in planta. Interestingly, the reaction can be guided by dirigent proteins, which mediate the stereoselective formation of either (+) or (-)-pinoresinol from coniferyl alcohol. So far, the mechanism is poorly understood, and for detailed mechanistic studies, a heterologous expression platform which allows the cost-effective, fast, and robust expression in high yields is needed. We established a reliable, high-yield fed-batch fermentation process with Pichia pastoris resulting in 47 mg L⁻¹ of the dirigent protein AtDIR6, which represents a more than 250-fold increase compared to previous studies. Biochemical characterization of AtDIR6 produced with P. pastoris showed an overall agreement in protein structure, N-glycosylation sites, and dirigent activity compared to AtDIR6 produced by plant cell cultures of Solanum peruvianum. CD spectroscopy verified the β-barrel structure proposed by earlier studies and bioconversion experiments revealed similar activities to plant-derived protein, validating P. pastoris as a suitable expression system for dirigent proteins. Compared to the complex glycan structures of most plant cells, proteins produced with P. pastoris have the advantage that they can be enzymatically deglycosylated under non-denaturating conditions. With this study, we demonstrate that the glycan structures of AtDIR6 are essential for structure, solubility, and function of the protein as deglycosylation induced conformational changes leading to the complete loss in dirigent activity and subsequent protein aggregation.

Topics: Arabidopsis; Arabidopsis Proteins; Circular Dichroism; Furans; Gene Expression; Glycosylation; Lignans; Phenols; Pichia; Protein Conformation; Recombinant Proteins

Bacterial genes for the degradation of major dilignols produced in lignifying xylem are expected to be useful tools for the structural modification of lignin in plants. For this purpose, we isolated pinZ involved in the conversion of pinoresinol from Sphingobium sp. strain SYK-6. pinZ showed 43-77% identity at amino acid level with bacterial NmrA-like proteins of unknown function, a subgroup of atypical short chain dehydrogenases/reductases, but revealed only 15-21% identity with plant pinoresinol/lariciresinol reductases. PinZ completely converted racemic pinoresinol to lariciresinol, showing a specific activity of 46±3 U/mg in the presence of NADPH at 30°C. In contrast, the activity for lariciresinol was negligible. This substrate preference is similar to a pinoresinol reductase, AtPrR1, of Arabidopsis thaliana; however, the specific activity of PinZ toward (±)-pinoresinol was significantly higher than that of AtPrR1. The role of pinZ and a pinZ ortholog of Novosphingobium aromaticivorans DSM 12444 were also characterized.

Topics: Arabidopsis; Arabidopsis Proteins; Bacterial Proteins; Furans; Genes, Bacterial; Lignans; Lignin; Molecular Structure; Oxidoreductases; Recombinant Fusion Proteins; Sequence Homology, Amino Acid; Species Specificity; Sphingomonadaceae; Substrate Specificity

Higher intake of lignans, diphenolic plant compounds, may reduce the risk of certain types of cancer and cardiovascular diseases. We assessed the dietary intake of four lignans: matairesinol, secoisolariciresinol, lariciresinol and pinoresinol. Furthermore, for the breads we supplemented the data with two more lignans: syringaresinol and medioresinol. Study subjects were 172 men and 97 women aged 40-75 years, residing in Riga, the capital of Latvia, all living at home, eating habitual food. Median total lignan intake was 2259 (range 1169-5759) μg/day. Secoisolariciresinol contributed 58% and syringaresinol 22% of lignan intake. Bread was the major food source of lignans in men (86%), whereas in women it was bread (57%) and flaxseed (35%).

Topics: Adult; Aged; Bread; Butylene Glycols; Cardiovascular Diseases; Diet; Feeding Behavior; Female; Flax; Furans; Humans; Latvia; Lignans; Male; Middle Aged; Neoplasms; Phenols; Phytoestrogens; Plant Extracts; Sex Factors

Secoisolariciresinol diglucoside (SDG), the main phytoestrogenic lignan of Linum usitatissimum, is accumulated in the seed coat of flax during its development and pinoresinol-lariciresinol reductase (PLR) is a key enzyme in flax for its synthesis. The promoter of LuPLR1, a flax gene encoding a pinoresinol lariciresinol reductase, contains putative regulatory boxes related to transcription activation by abscisic acid (ABA). Gel mobility shift experiments evidenced an interaction of nuclear proteins extracted from immature flax seed coat with a putative cis-acting element involved in ABA response. As ABA regulates a number of physiological events during seed development and maturation we have investigated its involvement in the regulation of this lignan synthesis by different means. ABA and SDG accumulation time courses in the seed as well as LuPLR1 expression were first determined in natural conditions. These results showed that ABA timing and localization of accumulation in the flax seed coat could be correlated with the LuPLR1 gene expression and SDG biosynthesis. Experimental modulations of ABA levels were performed by exogenous application of ABA or fluridone, an inhibitor of ABA synthesis. When submitted to exogenous ABA, immature seeds synthesized 3-times more SDG, whereas synthesis of SDG was reduced in immature seeds treated with fluridone. Similarly, the expression of LuPLR1 gene in the seed coat was up-regulated by exogenous ABA and down-regulated when fluridone was applied. These results demonstrate that SDG biosynthesis in the flax seed coat is positively controlled by ABA through the transcriptional regulation of LuPLR1 gene.

Topics: Abscisic Acid; Butylene Glycols; Flax; Furans; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Plant; Genes, Plant; Lignans; Oxidoreductases; Plant Growth Regulators; Plants, Genetically Modified; Seeds

Dirigent proteins impart stereoselectivity on the phenoxy radical-coupling reaction, yielding optically active lignans from two molecules of coniferyl alcohol. By an unknown mechanism, they direct the coupling of two phenoxy radicals toward the formation of optically active (+)- or (-)-pinoresinol. We show here that the dirigent protein AtDIR6 from Arabidopsis thaliana is a homodimeric all-beta protein in the superfamily of calycins. Based on its homology with calycins, the structure of AtDIR6 was modeled using allene oxide cyclase as template. The structural model of AtDIR6 was supported experimentally by confirmation of a predicted disulfide bridge and by the characterization of two N-linked glycans at the solvent-exposed protein surface. The model shows AtDIR6 as an eight-stranded antiparallel β-barrel with a central hydrophobic cavity for substrate binding, suggesting that dirigent proteins evolved from hydrophobic ligand-binding proteins. The data are fully consistent with the current view of the dirigent protein mode of action, according to which each subunit of the homodimer captures one of the substrate radicals and orients them in a way that precludes undesired reaction channels, thus favoring the formation of the optically pure coupling product.

Topics: Amino Acid Sequence; Arabidopsis; Arabidopsis Proteins; Binding Sites; Furans; Hydrophobic and Hydrophilic Interactions; Intramolecular Oxidoreductases; Lignans; Lipocalins; Models, Molecular; Molecular Sequence Data; Phenols; Protein Binding; Protein Multimerization; Protein Structure, Secondary; Sequence Homology, Amino Acid; Stereoisomerism; Structural Homology, Protein

A new orthoquinone, berryammone A (1), and four new naphthalenone derivatives, berryammone B (2), berryammone C (3), 6-O-methylberryammone C (4), and 4-O-methylberryammone C (5), have been isolated from the stem of Berrya ammonilla, together with eleven known compounds (6-16). The structures of these new compounds were determined through spectroscopic and MS analyses. Among the isolates, compounds 1-3, 5, (+)-pinoresinol (6), and betulinic acid (12) exhibited inhibition (IC50 ≤ 4.41 µM) of superoxide anion generation by human neutrophils in response to formyl-L-methionyl-L-leucyl-L-phenylalanine/cytochalasin B (fMLP/CB). Compounds 1, 2, and 5 also inhibited fMLP/CB-induced elastase release with IC50 values ≤ 3.95 µM.

Topics: Anti-Inflammatory Agents; Betulinic Acid; Drug Evaluation, Preclinical; Furans; Humans; Inhibitory Concentration 50; Lignans; Magnetic Resonance Spectroscopy; Malvaceae; Molecular Structure; N-Formylmethionine Leucyl-Phenylalanine; Naphthalenes; Naphthoquinones; Neutrophils; Pancreatic Elastase; Pentacyclic Triterpenes; Superoxides; Triterpenes

Lignan-rich diets have been associated with favorable health effects through improved metabolic profile. In this study, we hypothesized that dietary lignan intake could be also associated with childhood obesity.. We studied prevalent obesity in relation to lignan intake within the enKid study that involved 3438 children, adolescents and young adults (2-24 years old). Participant's dietary records were used to calculate lignan dietary intake using a lignan composition database adapted to the Spanish diet.. The mean intake of the dietary lignans was calculated as ~1 mg/day, corresponding mainly (37%) to pinoresinol. No gender differences were found, but lignan intake was positively associated with age, physical activity level and dietary fiber intake, and negatively with the intake of polyunsaturated and saturated fatty acids. The main sources of dietary lignans were refined wheat, olive oil and whole-wheat bread. A strong association between dietary lignan intake and prevalent obesity was found only for boys, with odds ratio (highest versus lowest quartile of lignan intake) of 0.34 (95% confidence interval, 0.17-0.70) after adjusting for main confounders, including dietary fiber.. Boys with the highest lignan-rich products including cereals, whole-grain products and olive oil, presented less cases of obesity in this representative sample of Spanish children and adolescents. It is unknown whether this association implies an active role of dietary lignans on obesity development, or is merely an indicator of a healthier lifestyle.

Topics: Adolescent; Adult; Age Factors; Bread; Child; Child, Preschool; Confidence Intervals; Diet; Dietary Fiber; Exercise; Fatty Acids; Female; Furans; Humans; Life Style; Lignans; Male; Obesity; Odds Ratio; Olea; Olive Oil; Phytotherapy; Plant Extracts; Plant Oils; Prevalence; Sex Factors; Spain; Triticum; Young Adult

Refined edible oils (viz., oils from maize, soya, high-oleic sunflower, sunflower, olive, and rapeseed) enriched at two concentration levels (200 and 400 μg/mL total phenolic content) with phenolic extracts isolated from olive pomace and leaves have been characterized and compared with nonenriched oils and extra virgin olive oil (EVOO). Enriched oils were analyzed by LC-TOF/MS to generate representative fingerprints and compared with nonenriched oils and EVOO by unsupervised principal component analysis (PCA). The two raw materials reported enriched oils with profiles which were compared with those provided by EVOOs. Correlation analysis enabled us to establish the enriched oils with a composition more similar to EVOO. Discrimination according to the enrichment level depended on the raw material for extracts, and a global discussion about the enrichment on relevant phenolic compounds present in EVOO has reported quantitative results concerning the enrichment level for those significant compounds with known nutraceutical properties.

Topics: Antioxidants; Flavonoids; Furans; Iridoids; Lignans; Mass Spectrometry; Olea; Olive Oil; Phenols; Phenylethyl Alcohol; Plant Extracts; Plant Leaves; Plant Oils; Principal Component Analysis

To study the chemical constituents of the roots of Dendropanax chevalieri.. The constituents were isolated by column chromatography with silica gel, Sephadex LH-20 gel and RP-18. Their structures were elucidated by analysis of spectral data and physicochemical properties.. Eight compounds were isolated and identified as palmitic acid (1), dibutylphthalate (2), beta-sitosterol (3), coniferaldehyde (4), scopoletin (5), beta-hydroxypropiovanillone (6), (+)-pinoresinol (7), (+)-syringaresinol (8).. Compounds 1-2, 4-8 are obtained from this genus for the first time.

Topics: Acrolein; Araliaceae; Dibutyl Phthalate; Furans; Lignans; Magnetic Resonance Spectroscopy; Molecular Structure; Palmitic Acid; Plant Roots; Scopoletin

To separate and identify chemical constituents from Coptis chinensis.. The compounds were separated and purified by various chromatographic techniques. Their structures were identified on the basis of their physicochemical properties using spectral techniques such as NMR and MS.. Thirteen compounds were separated from ethanol extracts of C. chinensis, including seven lignans, three simple phenylpropanoids, two flavones and one phenolic acid, and identified as erythro-guaiacylglycerol-8-O-4'-(coniferyl alcohol) ether (1), threo-guaiacylglycerol-8-O-4'-(coniferyl alcohol) ether (2), (+)-pinoresinol (3), (+)-medioresinol (4), (+)-lariciresinol (5), (+)-5'-methoxylariciresinol (6), (+)-isolariciresinol (7), chlorogenic acid (8), ferulic acid (9), Z-octadecyl caffeate (10), rhamnetin (11), wogonin (12), and vanillic acid (13).. Compounds 1, 2, 4, 6, 10-13 were separated from the genus Coptis for the first time.

Topics: Caffeic Acids; Chlorogenic Acid; Coptis; Coumaric Acids; Ethanol; Flavanones; Flavones; Furans; Hydroxybenzoates; Lignans; Lignin; Naphthols; Quercetin; Vanillic Acid

Defatted sesame seeds have been reported for hypoglycemic effect in mice and T2DM women. An attempted to identify active components responsible for this effect was conducted using α-glucosidase-guided fractionation, resulting in the isolation of various lignans. Of compounds isolated, only (+)-pinoresinol showed inhibitory activity against rat intestinal maltase with an IC(50) value of 34.3 μM. The kinetic study indicated that enzymatic hydrolysis of maltose is inhibited by (+)-pinoresinol through competitive and noncompetitive manners. However, a lower dissociation constant (k(i) 288 M) of EI complex suggested that competitive inhibition is predominant over noncompetitive mode (k'(i) 1342 M).

Topics: alpha-Glucosidases; Animals; Diabetes Mellitus, Type 2; Enzyme Inhibitors; Female; Furans; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemic Agents; Intestines; Kinetics; Lignans; Mice; Rats; Seeds; Sesamum; Stereoisomerism

Two new compounds, (2S,3R)-methyl 7-hydroxy-2-(4-hydroxy-3-methoxy-phenyl)-3-(hydroxymethyl)-2,3-dihydrobenzofuran-5-carboxylate (1) and (4R,5S)-5-(3-hydroxy-2,6-dimethylphenyl)-4-isopropyldihydrofuran-2-one (2), tentatively named norcurlignan and limlactone, respectively, were isolated from Liriope muscari, together with the known compound (-)-pinoresinol (3). The structures of these compounds were elucidated and characterized on the basis of 1D NMR, 2D NMR, CD and MS data. The in vitro antioxidant activities of compounds 1-3 were assessed by the DPPH and ABTS scavenging methods.

Topics: Benzofurans; Benzothiazoles; Biphenyl Compounds; Chromatography, Gel; Free Radical Scavengers; Free Radicals; Furans; Lignans; Liriope Plant; Magnetic Resonance Spectroscopy; Medicine, Chinese Traditional; Molecular Conformation; Molecular Structure; Picrates; Sulfonic Acids

How stereoselective monolignol-derived phenoxy radical-radical coupling reactions are differentially biochemically orchestrated in planta, whereby for example they afford (+)- and (-)-pinoresinols, respectively, is both a fascinating mechanistic and evolutionary question. In earlier work, biochemical control of (+)-pinoresinol formation had been established to be engendered by a (+)-pinoresinol-forming dirigent protein in Forsythia intermedia, whereas the presence of a (-)-pinoresinol-forming dirigent protein was indirectly deduced based on the enantiospecificity of downstream pinoresinol reductases (AtPrRs) in Arabidopsis thaliana root tissue. In this study of 16 putative dirigent protein homologs in Arabidopsis, AtDIR6, AtDIR10, and AtDIR13 were established to be root-specific using a β-glucuronidase reporter gene strategy. Of these three, in vitro analyses established that only recombinant AtDIR6 was a (-)-pinoresinol-forming dirigent protein, whose physiological role was further confirmed using overexpression and RNAi strategies in vivo. Interestingly, its closest homolog, AtDIR5, was also established to be a (-)-pinoresinol-forming dirigent protein based on in vitro biochemical analyses. Both of these were compared in terms of properties with a (+)-pinoresinol-forming dirigent protein from Schizandra chinensis. In this context, sequence analyses, site-directed mutagenesis, and region swapping resulted in identification of putative substrate binding sites/regions and candidate residues controlling distinct stereoselectivities of coupling modes.

Topics: Arabidopsis; Binding Sites; Furans; Lignans; Plant Proteins; Plant Roots; Schisandra; Sequence Homology, Amino Acid; Species Specificity; Substrate Specificity

Dietary lignans show some promising health benefits, but little is known about their fate and activities in the small intestine. The purpose of this study was thus to investigate whether plant lignans are taken up by intestinal cells and modulate the intestinal inflammatory response using the Caco-2 cell model. Six lignan standards [secoisolariciresinol diglucoside (SDG), secoisolariciresinol (SECO), pinoresinol (PINO), lariciresinol, matairesinol (MAT), and hydroxymatairesinol] and their colonic metabolites [enterolactone (ENL) and enterodiol] were studied. First, differentiated cells were exposed to SDG, SECO, PINO, or ENL at increasing concentrations for 4 h, and their cellular contents (before and after deconjugation) were determined by HPLC. Second, in IL-1β-stimulated confluent and/or differentiated cells, lignan effects were tested on different soluble proinflammatory mediators quantified by enzyme immunoassays and on the NF-κB activation pathway by using cells transiently transfected. SECO, PINO, and ENL, but not SDG, were taken up and partly conjugated by cells, which is a saturable conjugation process. PINO was the most efficiently conjugated (75% of total in cells). In inflamed cells, PINO significantly reduced IL-6 by 65% and 30% in confluent and differentiated cells, respectively, and cyclooxygenase (COX)-2-derived prostaglandin E(2) by 62% in confluent cells. In contrast, MAT increased significantly COX-2-derived prostaglandin E(2) in confluent cells. Moreover, PINO dose-dependently decreased IL-6 and macrophage chemoattractant protein-1 secretions and NF-κB activity. Our findings suggest that plant lignans can be absorbed and metabolized in the small intestine and, among the plant lignans tested, PINO exhibited the strongest antiinflammatory properties by acting on the NF-κB signaling pathway, possibly in relation to its furofuran structure and/or its intestinal metabolism.

Topics: 4-Butyrolactone; Anti-Inflammatory Agents; Butylene Glycols; Caco-2 Cells; Cell Differentiation; Chemokine CCL2; Chromatography, High Pressure Liquid; Cyclooxygenase 2; Furans; Glucosides; Humans; Interleukin-1beta; Interleukin-6; Interleukin-8; Intestines; Lignans; NF-kappa B; Plant Extracts; Signal Transduction

Pinoresinol structures, featuring a β-β'-linkage between lignin monomer units, are important in softwood lignins and in dicots and monocots, particularly those that are downregulated in syringyl-specific genes. Although readily detected by NMR spectroscopy, pinoresinol structures largely escaped detection by β-ether-cleaving degradation analyses presumably due to the presence of the linkages at the 5 positions, in 5-5'- or 5-O-4'-structures. In this study, which is aimed at helping better understand 5-linked pinoresinol structures by providing the required data for NMR characterization, new lignin model compounds were synthesized through biomimetic peroxidase-mediated oxidative coupling reactions between pre-formed (free-phenolic) coniferyl alcohol 5-5'- or 5-O-4'-linked dimers and a coniferyl alcohol monomer. It was found that such dimers containing free-phenolic coniferyl alcohol moieties can cross-couple with the coniferyl alcohol producing pinoresinol-containing trimers (and higher oligomers) in addition to other homo- and cross-coupled products. Eight new lignin model compounds were obtained and characterized by NMR spectroscopy, and one tentatively identified cross-coupled β-O-4'-product was formed from a coniferyl alcohol 5-O-4'-linked dimer. It was demonstrated that the 5-5'- and 5-O-4'-linked pinoresinol structures could be readily differentiated by using heteronuclear multiple-bond correlation (HMBC) NMR spectroscopy. With appropriate modification (etherification or acetylation) to the newly obtained model compounds, it would be possible to identify the 5-5'- or 5-O-4'-linked pinoresinol structures in softwood lignins by 2D HMBC NMR spectroscopic methods. Identification of the cross-coupled dibenzodioxocin from a coniferyl alcohol 5-5'-linked moiety suggested that thioacidolysis or derivatization followed by reductive cleavage (DFRC) could be used to detect and identify whether the coniferyl alcohol itself undergoes 5-5'-cross-linking during lignification.

Topics: Cross-Linking Reagents; Furans; Lignans; Lignin; Magnetic Resonance Spectroscopy; Phenols

A phytochemical investigation of Chromolaena odorata resulted in the isolation of five new compounds, 5aα,6,9,9aβ,10-pentahydro-10β-hydroxy-7-methylanthra[1,2-d][1,3]dioxol-5-one (1), 1,2-methylenedioxy-6-methylanthraquinone (2), 3-hydroxy-1,2,4-trimethoxy-6-methylanthraquinone (3), 3-hydroxy-1,2-dimethoxy-6-methylanthraquinone (4), and 7-methoxy-7-epi-medioresinol (5), together with 12 known compounds, odoratin (6), 3β-acetyloleanolic acid (7), ursolic acid (8), ombuin (9), 4,2'-dihydroxy-4',5',6'-trimethoxychalcone (10), (-)-pinoresinol (11), austrocortinin (12), tianshic acid (13), cleomiscosin D (14), (-)-medioresinol (15), (-)-syringaresinol (16), and cleomiscosin A (17). All the compounds were evaluated for their PPARγ transactivation activity, and compound 6 showed moderate activity with an EC(50) value of 3.10 μM.

Topics: Anthraquinones; Chromolaena; Dioxoles; Drugs, Chinese Herbal; Flavonoids; Furans; Hepatocytes; Humans; Lignans; Luciferases; Molecular Structure; PPAR gamma; Sesquiterpenes; Stereoisomerism

To study the chemical constituents of the roots of Vaccinium bracteatum.. The constituents were separated and purified with chromatographic methods (including silica gel, Sephadex LH-20 and RP-18 column chromatography), and their structures were determined by spectroscopic methods (including MS, 1H-NMR and 13C-NMR).. 10 compounds were isolated from the roots of Vaccinium bracteatu and were elucidated as chlorogenic acid (1), pinoresinol (2), ferulic acid (3), kaempferol (4), trans-caffeic acid (5), beta-sitosterol (6), quercetin (7), oleanolic acid (8), apigenin (9) and luteolin (10).. Compounds 1 -3 are obtained from this plant for the first time.

Topics: Chlorogenic Acid; Coumaric Acids; Furans; Kaempferols; Lignans; Magnetic Resonance Spectroscopy; Plant Roots; Quercetin; Solvents; Vaccinium

The first phytochemical study of Simira eliezeriana Peixoto (Rubiaceae) allowed the isolation and structural determination of two new diterpenes named simirane A [(5R,6R,8R,9R,10S,11S,13S)-6β,11β-dihydroxy-2,4(18),15-erythroxylatrien-1-one] (1) and simirane B [(5S,8R,9R,10S,11S,13S)-11β-hydroxy-2,4(18),15-erythroxylatrien-1-one] (2), together with seven known compounds: sitosterol (3), stigmasterol (4), campesterol (5), coniferaldehyde (6), vanillin (7), pinoresinol (8) and harman (9) from the bark of the plant. The structures of the compounds were established on the basis of spectroscopic methods, including 1-D and 2-D NMR, HRESI-MS and CD analysis and comparisons with available literature data of known compounds.

Topics: Acrolein; Benzaldehydes; Cholesterol; Diterpenes; Ethanol; Furans; Harmine; Lignans; Magnetic Resonance Spectroscopy; Molecular Structure; Phytosterols; Plant Bark; Plant Extracts; Rubiaceae; Sitosterols

It has been suggested that lignan intake may decrease the risk for cardiovascular disease (CVD) by modifying traditional risk factors as well as aortic stiffness. However, the role of dietary lignans on the vascular system is largely unknown. The objective was to investigate whether dietary intake of plant lignans in a free-living population was associated with markers of vascular inflammation and function.. We performed a cross-sectional study in 242 (151 males) men and post-menopausal women. Anthropometric characteristics and lignan intake were evaluated. Soluble intercellular adhesion molecule-1 (sICAM-1), insulin, high-sensitive C-reactive protein, glucose, total cholesterol, HDL-cholesterol and triacylglycerols were measured in fasting blood samples. Brachial flow-mediated dilation (FMD) measurements were available for 101 subjects (56 males). Median (interquartile range) daily intake of matairesinol (MAT), secoisolariciresinol (SECO), pinoresinol (PINO), lariciresinol (LARI), and total lignans was 20.9 microg (17.4), 335.3 microg (289.1), 96.7 microg (91.1), 175.7 microg (135.8), and 665.5 microg (413.7), respectively, as assessed by 3-day weighed food record. Plasma concentrations of sICAM-1 (whole sample) significantly decreased (mean (95%CI) = 358 microg/L (320-401), 276 microg/L (252-303), 298 microg/L (271-326), and 269 microg/L (239-303), P per trend 0.013) and FMD values (FMD sub-group) significantly increased (4.1% (2.2-6.0), 5.7% (4.3-7.2), 6.4% (4.9-7.8), and 8.1% (6.3-10.0), P per trend 0.016) across quartiles of energy-adjusted MAT intake, even after adjustment for relevant clinical and dietary variables. Intake of SECO was also inversely related to plasma sICAM-1 (P per trend 0.018), but not to FMD values. No relationship between intake of PINO, LARI or total lignans and either sICAM-1 or FMD values was observed.. Higher MAT intakes in the context of a typical Northern Italian diet are associated to lower vascular inflammation and endothelial dysfunction, which could have some implications in CVD prevention.

Topics: Aged; Biomarkers; Butylene Glycols; Cardiovascular Diseases; Cross-Sectional Studies; Diet; Diet Records; Diet, Mediterranean; Endothelium, Vascular; Female; Furans; Hemodynamics; Humans; Inflammation; Italy; Lignans; Male; Middle Aged; Phytoestrogens; Surveys and Questionnaires; Vascular Diseases

Topics: Amino Acid Sequence; Arabidopsis Proteins; Biocatalysis; Furans; Laccase; Lignans; Molecular Sequence Data; Oxidation-Reduction; Phenols; Plant Proteins; Sequence Alignment; Sequence Homology, Amino Acid; Stereoisomerism

Forsythiae Fructus is known to have diuretic, anti-bacterial, and anti-inflammatory activities. This study examined the hepatoprotective effects of pinoresinol, a lignan isolated from Forsythiae Fructus, against carbon tetrachloride (CCl(4))-induced liver injury. Mice were treated intraperitoneally with vehicle or pinoresinol (25, 50, 100, and 200 mg/kg) 30 min before and 2 h after CCl4 (20 microl/kg) injection. In the vehicle-treated CCl(4 )group, serum aminotransferase activities were significantly increased 24 h after CCl4 injection, and these increases were attenuated by pinoresinol at all doses. Hepatic glutathione contents were significantly decreased and lipid peroxidation was increased after CCl4 treatment. These changes were attenuated by 50 and 100 mg/kg of pinoresinol. The levels of protein and mRNA expression of inflammatory mediators, including tumor necrosis factor-alpha, inducible nitric oxide synthase, and cyclooxygenase-2, were significantly increased after CCl4 injection; and these increases were attenuated by pinoresinol. Nuclear translocation of nuclear factor-kappaB (NF-kappaB) and phosphorylation of c-Jun, one of the components of activating protein 1 (AP-1), were inhibited by pinoresinol. Our results suggest that pinoresinol ameliorates CCl4)-induced acute liver injury, and this protection is likely due to anti-oxidative activity and down-regulation of inflammatory mediators through inhibition of NF-kappaB and AP-1.

Topics: Animals; Carbon Tetrachloride Poisoning; Forsythia; Furans; Lignans; Liver; Liver Diseases; Male; Mice; Mice, Inbred ICR; Oxidative Stress; Plant Extracts; Signal Transduction

The activation of microglia plays an important role in a variety of brain disorders by the excessive production of inflammatory mediators such as nitric oxide (NO), prostaglandin E(2) (PGE(2)) and proinflammatory cytokines. We investigated here whether pinoresinol isolated from the fruits of Forsythia koreana Nakai inhibits the inflammatory responses in LPS-activated microglia. Pinoresinol inhibited the production of NO, PGE(2), TNF-alpha, IL-1beta and IL-6 in LPS-activated primary microglia. Also, pinoresinol attenuated mRNA and protein levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and proinflammatory cytokines in LPS-activation. However, most of these inhibitory effects of pinoresinol have been mediated by extracellular-signal-regulated kinase (ERK) 1/2 mitogen-activated protein kinase (MAPK) phosphorylation and the NF-kappaB dependent. The results suggest that pinoresinol attenuates inflammatory responses of microglia and could be potentially useful in modulation of inflammatory status in brain disorders.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cells, Cultured; Cytokines; Dinoprostone; Forsythia; Furans; Gliosis; Inflammation Mediators; Lignans; Lipopolysaccharides; Microglia; Nitric Oxide; Plant Extracts; Rats; Rats, Sprague-Dawley

In this study, we investigated the antifungal activity and mechanism of action of (+)-pinoresinol, a biphenolic compound isolated from the herb Sambucus williamsii,used in traditional medicine. (+)-Pinoresinol displays potent antifungal properties without hemolytic effects on human erythrocytes. To understand the antifungal mechanism of (+)-pinoresinol, we conducted fluorescence experiments on the human pathogen Candida albicans. Fluorescence analysis using 1,6-diphenyl-1,3,5-hexatriene (DPH) indicated that the (+)-pinoresinol caused damage to the fungal plasma membrane. This result was confirmed by using rhodamine-labeled giant unilamellar vesicle (GUV) experiments. Therefore, the present study indicates that (+)-pinoresinol possesses fungicidal activities and therapeutic potential as an antifungal agent for the treatment of fungal infectious diseases in humans.

Topics: Antifungal Agents; Candida albicans; Cell Membrane; Erythrocytes; Furans; Humans; Lignans; Mycoses; Plants, Medicinal; Sambucus

To study the chemical constituents from Solanum nigrum.. Compounds were isolated and purified by silica gel, Sephadex LH-20 and preparative HPLC. Their structures were identified by physicochemical properties and spectral analysis.. Six compounds were isolated and identified as (+)-pinoresinol (I), (+)-syringaresinol (II), (+)-medioresinol (III), scopoletin (IV), tetracosanoic acid (V) and beta-sitosterol (VI).. Compounds I - III are isolated from this genus for the first time, while compounds IV and V are isolated from this plant for the first time.

Topics: Anti-Inflammatory Agents; Chromatography, High Pressure Liquid; Fatty Acids; Furans; Lignans; Plants, Medicinal; Scopoletin; Sitosterols; Solanum nigrum

To study the chemical constituents from Pachysandra terminalis and their antioxidant activity.. Chemical constituents were isolated by repeated column chromatography (silica gel, Toyopearl HW-40C and preparative HPLC). The structures of isolated compounds were elucidated on the basis of spectral data analysis. DPPH method was used to evaluate the free radical scavenging activity of the isolated compounds.. Six compounds were isolated and their structures were identified as follow: 2-Phenylethyl-beta-D-glucopyranoside (1), (+)Pinoresinol-4'-O-beta-D-glucopyranoside (2), Pinoresinol (3), cis-Syringin (4), 4-hydroxy-4-(3-oxo-l-butenyl)-3,5,5-trimethylcyclohex-2-en-l-one (5), 3alpha-hydroxy-5,6-epoxy-7-megastigmen-9-one (6). Compounds 2, 4, 5 showed obviously antioxidant activity, their DPPH free radical scavenging rates were 82.50%, 87.36%, and 84.56% on the concentration of 50 micromol/L, respectively.. Compounds 1-6 are isolated from this genus for the first time. Compounds 2, 4, and 5 showed significant antioxidant activities.

Topics: Antioxidants; Biphenyl Compounds; Chromatography, High Pressure Liquid; Free Radical Scavengers; Furans; Glucosides; Glycosides; Lignans; Magnetic Resonance Spectroscopy; Molecular Structure; Pachysandra; Phenylethyl Alcohol; Phenylpropionates; Picrates; Plant Extracts; Plants, Medicinal

Lignans are a large class of secondary metabolites in plants, with numerous biological effects in mammals, including antitumor and antioxidant activities. Sesamin, the most abundant furofuran-class lignan in sesame seeds (Sesamum plants), is produced by the cytochrome P450 enzyme CYP81Q1 from the precursor lignan, pinoresinol. In contrast, Forsythia plants produce dibenzylbutyrolactone-class lignans, such as matairesinol, from pinoresinol via the catalysis of pinoresinol/lariciresinol reductase (PLR) and secoisolariciresinol dehydrogenase. Here we present the engineering of lignan biosynthesis in Forsythia cell suspension cultures for the development of an efficient production method of beneficial lignans. A suspension cell culture prepared from leaves of Forsythia koreana produced lignans, mainly pinoresinol and matairesinol glucosides, at levels comparable with that obtained from the leaves. In an attempt to increase the pinoresinol content in Forsythia, we generated a transgenic cell line overexpressing an RNA interference (RNAi) construct of PLR (PLR-RNAi). Down-regulation of PLR expression led to a complete loss of matairesinol and an accumulation of approximately 20-fold pinoresinol in its glucoside form in comparison with the non-transformant. Moreover, the Forsythia transgenic cells co-expressing CYP81Q1 and PLR-RNAi exhibited production of sesamin as well as accumulation of pinoresinol glucoside. These data suggest Forsythia cell suspension to be a promising tool for the engineering of lignan production. To the best of our knowledge, this is the first report on transgenic production of an exogenous lignan in a plant species.

Topics: Cell Culture Techniques; Cells, Cultured; Dioxoles; Forsythia; Furans; Gene Expression Regulation, Plant; Genetic Engineering; Lignans; Molecular Structure; Plant Leaves; Plants, Genetically Modified; RNA Interference; Transformation, Genetic

To study the chemical constituents of the stems of Clematis parviloba.. The compounds were isolated and purified by repeated column chromatography with silica gel, Sephadex LH-20 and HPLC. Their structures were identified by spectroscopic data together with physical and chemical property.. Ten compounds have been isolated from the stems of C. parviloba, and identified as: (+) pinoresionol (1), (+) pinoresionol-4'-O-p-D-glucopyranoside (2), ( +) pinoresionol4, 4'-O-bis-beta-D-glucopyranoside (3), (-) syringaresinol (4), (+) syringaresinol-4'-O-beta-D-glucopyranoside (5), (-)episyringaresinol (6), (+) medioresinol-4'-O-beta-D-glucopyranoside (7), (+) lariciresinol-4-O-beta-D-glucopyranoside (8), (+) lariciresinol-4'-O-beta-D-glucopyranoside (9), (+) lariciresinol-4, 4'-O-bis-beta-D-glucopyranoside (10), respectively.. Compounds 6, 7 were isolated from this genus for the first time, and the other ones were isolated from this plant for the first time.

Topics: Chromatography, Gel; Chromatography, High Pressure Liquid; Clematis; Drugs, Chinese Herbal; Furans; Glucosides; Lignans; Magnetic Resonance Spectroscopy; Plant Stems; Spectrometry, Mass, Electrospray Ionization

The Mediterranean diet is rich in extra virgin olive oil (EVOO) and associated with a lower incidence of colorectal cancer. EVOO contains phenolic extracts with potential anticarcinogenic activity.. To assess the anticancer properties of EVOO phenolic extracts using in vitro models.. Phenolic profiles of two different EVOOs (A and B) were determined. RKO and HCT116 (both p53 proficient), SW480 (p53 mutant) and HCT116(p53-/-) (p53 knocked out) cell lines were treated with EVOO extracts and assessed for cell viability. Apoptosis was determined by terminal deoxynucleotidyl transferase nick end labeling (TUNEL) assay and changes in Bax transcript levels. Cell cycle analysis was determined by flow cytometry and western blots. To confirm the data, analysis of cell viability and cell cycle was performed with purified pinoresinol.. Chemical characterization showed that pinoresinol is the main phenol in EVOO-A, and oleocanthal predominates in EVOO-B. Only EVOO-A affected cell viability, which was significantly more pronounced in p53-proficient cells. At a concentration of 200 nM, p53-proficient cells showed increased apoptosis and G(2)/M arrest. In p53-proficient cells, ataxia telangiectasia mutated (ATM) and its downstream-controlled proteins were upregulated after treatment, with a parallel decrease of cyclin B/cdc2. Identical results on cell viability and cell cycle were obtained with purified pinoresinol, but this required a higher concentration than in EVOO-A.. Our results demonstrate that pinoresinol-rich EVOO extracts have potent chemopreventive properties and specifically upregulate the ATM-p53 cascade. This result was achieved at substantially lower concentrations in EVOO than with purified pinoresinol, indicating a possible synergic effect between the various polyphenols in olive oil.

Topics: Anticarcinogenic Agents; Ataxia Telangiectasia Mutated Proteins; Blotting, Western; Cell Cycle Proteins; Cell Line, Tumor; Colonic Neoplasms; DNA-Binding Proteins; Flow Cytometry; Furans; Humans; In Situ Nick-End Labeling; Lignans; Olive Oil; Plant Oils; Protein Serine-Threonine Kinases; Tumor Suppressor Protein p53; Tumor Suppressor Proteins

Enantiopure chiral amidic derivatives of sinapic acid were oxidised with hydrogen peroxide using horseradish peroxidase (HRP) as the catalyst to give the aryltetraline dilignol thomasidioic acid. Trans-diastereoselectivity and enantioselectivity in the formation of thomasidioic acid was observed. Computational methods show that the enantioselectivity is controlled by the beta-beta oxidative coupling step, while the diastereoselectivity is controlled by the stability of the reactive conformation of the intermediate quinomethide.

Topics: Benzoates; Biomimetics; Biphenyl Compounds; Furans; Hydrolysis; Lignans; Molecular Conformation; Oxidation-Reduction; Phenols; Stereoisomerism; Thermodynamics

Due to their peculiar stereochemistry and numerous biological activities, lignans are of widespread interest. As only a few biosynthetic steps have been clarified to date, we aimed to further resolve the molecular basis of lignan biosynthesis. To this end, we first established that the biologically active lignan (-)-hinokinin could be isolated from in vitro cultures of Linum corymbulosum. Two hypothetical pathways were outlined for the biosynthesis of (-)-hinokinin. In both pathways, (+)-pinoresinol serves as the primary substrate. In the first pathway, pinoresinol is reduced via lariciresinol to secoisolariciresinol by a pinoresinol-lariciresinol reductase, and methylenedioxy bridges are formed later. In the second pathway, pinoresinol itself is the substrate for formation of the methylenedioxy bridges, resulting in consecutive production of piperitol and sesamin. To determine which of the proposed hypothetical pathways acts in vivo, we first isolated several cDNAs encoding one pinoresinol-lariciresinol reductase (PLR-Lc1), two phenylcoumaran benzylic ether reductases (PCBER-Lc1 and PCBER-Lc2), and two PCBER-like proteins from a cDNA library of L. corymbulosum. PLR-Lc1 was found to be enantiospecific for the conversion of (+)-pinoresinol to (-)-secoisolariciresinol, which can be further converted to give (-)-hinokinin. Hairy root lines with significantly reduced expression levels of the plr-Lc1 gene were established using RNAi technology. Hinokinin accumulation was reduced to non-detectable levels in these lines. Our results strongly indicate that PLR-Lc1 participates in (-)-hinokinin biosynthesis in L. corymbulosum by the first of the two hypothetical pathways via (-)-secoisolariciresinol.

Topics: 4-Butyrolactone; Amino Acid Sequence; Benzodioxoles; Butylene Glycols; Cells, Cultured; Cloning, Molecular; Dioxoles; DNA, Complementary; Flax; Furans; Gene Expression; Gene Library; Genes, Plant; Lignans; Molecular Sequence Data; Oxidoreductases; Phylogeny; Plant Proteins; RNA, Plant; Sequence Alignment; Sequence Homology, Amino Acid

A cDNA encoding a pinoresinol-lariciresinol reductase PLR (PLR-Lp1) was isolated from a cell culture of Linum perenne Himmelszelt accumulating the arylnaphthalene lignan justicidin B. The recombinant PLR-Lp1 prefers (+)-pinoresinol in the first reaction step, but (-)-lariciresinol in the second step. Therefore, it is the first PLR described with opposite enantiospecificity within the two reaction steps catalysed by PLRs. Hairy root lines transformed with an ihpRNAi construct to suppress plr gene expression show less mRNA accumulation for the plr-Lp1 gene and PLR enzyme activity. Justicidin B accumulation was reduced down to 24% in comparison to control lines showing the involvement of PLR-Lp1 in the biosynthesis of justicidin B.

Topics: Base Sequence; Blotting, Southern; Catalysis; Cloning, Molecular; Dioxolanes; DNA, Plant; Escherichia coli; Flax; Furans; Gene Expression Regulation, Plant; Gene Silencing; Genes, Plant; Genome, Plant; Lignans; Plant Proteins; Plant Roots; RNA, Messenger

Four new diepoxylignan glycosides, pinoresinol-4'-O-[6' '-O-(E)-feruloyl]-beta-D-glucopyranoside (1), pinoresinol-4'-O-[4' ',6' '-O-(E)-diferuloyl]-beta-D-glucopyranoside (2), pinoresinol-4'-O-[3' ',6' '-O-(E)-diferuloyl]-beta-D-glucopyranoside (3), and syringaresinol- 4'-O-[4' ',6' '-O-(E)-diferuloyl]-beta-D-glucopyranoside (4), together with three known compounds, pinoresinol (5), syringaresinol (6), and pinoresinol-4'-O-beta-D-glucopyranoside (7), were isolated from the n-butanol extract of Rhus javanica var. roxburghiana, and their structures were established using various spectroscopic techniques. Three glycosides (2-4) of the lignans showed moderate inhibition of multiplication of the tobacco mosaic virus.

Topics: Furans; Glycosides; Lignans; Plant Roots; Rhus; Tobacco Mosaic Virus; Virus Replication

To isolate and identify the chemical constituents from the whole plant of Pyrethrum tatsienense, which has been used as traditonal herb medicine in the treatment of some diseases.. The compounds were isolated by column chromatography and their structures were elucidated through spectroscopic analysis (NMR).. Six compounds were isolated and identified as: linoeic acid, pinoresinol, (+)-pinoresinol-4'-O-beta-D- glucopyranoside, betulabuside A, dihydrosyringin.. All these compounds were obtained from Pyrethrum tatsienense for the first time.

Topics: Chrysanthemum cinerariifolium; Drugs, Chinese Herbal; Furans; Glucosides; Lignans; Linoleic Acids; Magnetic Resonance Spectroscopy; Molecular Structure; Monoterpenes; Plants, Medicinal

The health-promoting effects of whole-grain consumption have been attributed in part to their unique phytochemical contents and profiles. Wheat is an important component of the human diet; however, little is known about the phytochemical profiles of different wheat varieties, especially of old wheats. The objective of this study was to investigate the distribution of lignans, a class of phytochemicals with proved health benefit effects, of four modern and six old Italian soft wheat (Triticum aestivum L.) cultivars. In this work, we describe the first analytical method involving CE coupled to MS (CE-MS) used to identify and quantify lignan compounds in grains of different cultivars of wheat. Total lignan content determined by CE-ESI-MS was 2.60+/-0.21 and 5.00+/-1.30 microg/g dry seed weight for modern and old cultivars, respectively. Secoisolariciresinol and pinoresinol were detected in all ten investigated soft wheat cultivars, whereas arctigenin, hinokinin, and syringaresinol were exclusively detected in old genotypes. Significant differences between modern and old cultivars were also observed for the number of glycosidic forms. Results highlighted the high content and unique composition in lignans of old cultivars suggesting their uses into a wide range of regular and specialty food products naturally enriched with health-promoting compounds.

Topics: 4-Butyrolactone; Benzodioxoles; Butylene Glycols; Dioxoles; Electrophoresis, Capillary; Furans; Italy; Lignans; Seeds; Tandem Mass Spectrometry; Triticum

Plant lignans are converted to enterolignans that have antioxidant and weak estrogen-like activities, and therefore they may lower cardiovascular disease and cancer risks.. We investigated whether the intakes of 4 plant lignans (lariciresinol, pinoresinol, secoisolariciresinol, and matairesinol) were inversely associated with coronary heart disease (CHD), cardiovascular diseases (CVD), cancer, and all-cause mortality.. The Zutphen Elderly Study is a prospective cohort study in which 570 men aged 64-84 y were followed for 15 y. We recently developed a database and used it to estimate the dietary intakes of 4 plant lignans. Lignan intake was related to mortality with the use of Cox proportional hazards analysis.. The median total lignan intake in 1985 was 977 microg/d. Tea, vegetables, bread, coffee, fruit, and wine were the major sources of lignan. The total lignan intake was not related to mortality. However, the intake of matairesinol was inversely associated with CHD, CVD, and all-cause mortality (P

Topics: Aged; Aged, 80 and over; Butylene Glycols; Cardiovascular Diseases; Cause of Death; Cohort Studies; Coronary Disease; Diet; Diet Surveys; Furans; Humans; Lignans; Male; Middle Aged; Multivariate Analysis; Neoplasms; Netherlands; Proportional Hazards Models; Prospective Studies; Wine

Pinoresinol, a lignan of wide distribution in plants, is found to occur as a minor component in the defensive secretion produced by glandular hairs of caterpillars of the cabbage butterfly, Pieris rapae. The compound or a derivative is appropriated by the larva from its normal food plant (the cabbage, Brassica oleracea). Pinoresinol was shown to be absent from the secretion if the larva was given a cabbage-free diet but present in the effluent if that diet was supplemented with pinoresinol. Pinoresinol is shown to be a feeding deterrent to ants (Formica exsectoides), indicating that it can complement the defensive action of the primary components of the secretion, a set of previously reported lipids called mayolenes. In the test with F. exsectoides, pinoresinol proved to be more potent than concomitantly tested mayolene-16.

Topics: Animals; Ants; Brassica; Butterflies; Diet; Fatty Acids, Unsaturated; Furans; Glycosides; Larva; Lignans; Molecular Structure; Plant Extracts; Plants

Phytochemical investigation of plants used in traditional Indonesian medicine (Jamu) yielded lignans (pinoresinol, 9 alpha-hydroxypinoresinol and salicifoliol), flavonoids (3-O-beta-(D)-glucopyranosyl-(1-->6)-beta-(D)-glucopyranosylkaempferol, luteolin and apigenin) and coumarins (coumarin, 8-hydroxycoumarin and 5-hydroxycoumarin). The beneficial effects of the respective plants for human health are thought to be associated with antioxidative activity. In the present study, the antioxidative capacity of the isolated compounds was determined in an in-vitro assay. Luteolin and kaempferol (cleavage product of 3-O-beta-(D)-glucopyranosyl-(1-->6)-beta-(D)-glucopyranosylkaempferol, which is thought to be formed in the intestine) showed strong antioxidant activity; pinoresinol and 9 alpha-hydroxypinoresinol showed only minor antioxidative effects. The coumarins, as well as apigenin and 3-O-beta-(D)-glucopyranosyl-(1-->6)-beta-(D)-glucopyranosylkaempferol were inactive. The antioxidative effects of luteolin, kaempferol and pinoresinol were further investigated in H4IIE rat hepatoma cells. A strong protective effect of kaempferol and luteolin was found against H2O2-mediated intracellular reactive oxygen species formation measured using the dichlorofluorescein assay and H2O2-mediated DNA strand breaks. Pinoresinol did not have a protective effect against H2O2-mediated DNA-damage, but in the dichlorofluorescein assay, an antioxidative effect was detectable. During studies with H4IIE cells, kaempferol, luteolin and pinoresinol were taken up by the cells within 60 min. The flavonoids were found to be relatively toxic at higher concentrations, while pinoresinol was less cytotoxic. In conclusion, kaempferol and luteolin, at low concentrations (< or = 50 microM), protect H4IIE cells against oxidative stress but are cytotoxic at higher concentrations; the biological effects of pinoresinol are less prominent in comparison. These results are important for the identification of pharmacologically active substances from traditional Indonesian medicinal plants.

Topics: Animals; Antioxidants; Apigenin; Carcinoma, Hepatocellular; Cell Death; Cell Line, Tumor; Coumarins; DNA Damage; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Flavonoids; Furans; Germany; Hydrogen Peroxide; Indonesia; Kaempferols; Lignans; Luteolin; Malvaceae; Medicine, Traditional; Molecular Structure; Phenols; Plant Bark; Plant Extracts; Plant Leaves; Plants, Medicinal; Polyphenols; Rats; Reactive Oxygen Species

In the continuous search for antifungal compounds from plants, the hydroxycoumarin scopoletin (1) was isolated from seed kernels of Melia azedarach L. from which three other compounds, vanillin (2), 4-hydroxy-3-methoxycinnamaldehyde (3), and (+/-) pinoresinol (4), have also been isolated. Guided fractionation through autobiography on TLC using Fusarium verticillioides (Saccardo) Nirenberg as test organism led to the isolation of 1, which exhibited a minimum inhibitory concentration (MIC) of 1.50 mg/mL in the microbroth dilution method. Despite its own weak activity, when the coumarin was combined with the above-mentioned compounds, a strong enhancement of the antifungal effect was observed, even showing a complete inhibition in the growth of the pathogen when 1 was added at a concentration of up to 5% of its MIC value. The same level of effectiveness was observed when the synthetic antifungal agents Mancozeb and Carboxin were each combined with compounds 1-4, in which cases it became possible to decrease the effective concentrations of these commercial compounds by up to 2.5 and 3%, respectively.

Topics: Acrolein; Benzaldehydes; Drug Synergism; Fruit; Fungicides, Industrial; Furans; Fusarium; Lignans; Melia; Melia azedarach; Scopoletin

Enterolignans (enterolactone and enterodiol) are phytoestrogens that are formed by the colonic microflora from plant lignans. They may reduce the risk of certain types of cancer and cardiovascular diseases. Initially, only secoisolariciresinol and matairesinol were considered to be enterolignan precursors, but recently, new precursors such as lariciresinol and pinoresinol were identified. We recently developed a lignan database including 4 major enterolignan precursors. We used this database to estimate lignan intake in a representative sample of Dutch men and women participating in the Dutch Food Consumption Survey, carried out in 1997-1998. Median total lignan intake among 4660 adults (19-97 y old) was 979 microg/d. Total lignan intake did not differ between men and women; thus, the lignan density of the diet was significantly higher (P < 0.001) in women than in men. Lignan intake was strongly skewed toward higher values (range 43-77584 microg/d, mean 1241 microg/d). Lariciresinol and pinoresinol contributed 75% to lignan intake, whereas secoisolariciresinol and matairesinol contributed only 25%. The major food sources of lignans were beverages (37%), vegetables (24%), nuts and seeds (14%), bread (9%), and fruits (7%). Lignan intake was significantly (P < 0.001) correlated with intake of dietary fiber (r = 0.46), folate (r = 0.39), and vitamin C (r = 0.44). Older persons, nonsmokers, vegetarians, and persons with a low BMI or a high socioeconomic status had higher lignan intakes than their counterparts. In brief, this study shows that the amount of enterolignan precursors in the diet has previously been largely underestimated.

Topics: Adult; Aged; Beverages; Bread; Butylene Glycols; Diet; Female; Fruit; Furans; Humans; Lignans; Male; Middle Aged; Netherlands; Nuts; Vegetables

Enterolignans (enterodiol and enterolactone) can potentially reduce the risk of certain cancers and cardiovascular diseases. Enterolignans are formed by the intestinal microflora after the consumption of plant lignans. Until recently, only secoisolariciresinol and matairesinol were considered enterolignan precursors, but now several new precursors have been identified, of which lariciresinol and pinoresinol have a high degree of conversion. Quantitative data on the contents in foods of these new enterolignan precursors are not available. Thus, the aim of this study was to compile a lignan database including all four major enterolignan precursors. Liquid chromatography-tandem mass spectrometry was used to quantify lariciresinol, pinoresinol, secoisolariciresinol and matairesinol in eighty-three solid foods and twenty-six beverages commonly consumed in The Netherlands. The richest source of lignans was flaxseed (301,129 microg/100 g), which contained mainly secoisolariciresinol. Also, lignan concentrations in sesame seeds (29,331 microg/100 g, mainly pinoresinol and lariciresinol) were relatively high. For grain products, which are known to be important sources of lignan, lignan concentrations ranged from 7 to 764 microg/100 g. However, many vegetables and fruits had similar concentrations, because of the contribution of lariciresinol and pinoresinol. Brassica vegetables contained unexpectedly high levels of lignans (185-2321 microg/100 g), mainly pinoresinol and lariciresinol. Lignan levels in beverages varied from 0 (cola) to 91 microg/100 ml (red wine). Only four of the 109 foods did not contain a measurable amount of lignans, and in most cases the amount of lariciresinol and pinoresinol was larger than that of secoisolariciresinol and matairesinol. Thus, available databases largely underestimate the amount of enterolignan precursors in foods.

Topics: Beverages; Butylene Glycols; Databases, Factual; Edible Grain; Food Analysis; Fruit; Furans; Humans; Lignans; Netherlands; Plants, Edible; Seeds; Vegetables

A capillary zone electrophoresis method has been carried out to determine and quantitate some compounds of the polyphenolic fraction of virgin olive oil which have never previously been determined before using capillary electrophoresis, such as elenolic acid, ligstroside aglycon, oleuropein aglycon, and (+)-pinoresinol. The compounds were identified using standards obtained by semipreparative high-performance liquid chromatography (HPLC). A detailed method optimization was performed to separate the phenolic compounds present in olive oil using a methanol-water extract of Picual extra-virgin olive oil, and different extraction systems were compared (C18-solid phase extraction (SPE), Diol-SPE, Sax-SPE and liquid-liquid extraction). The optimized parameters were 30 mM sodium tetraborate buffer (pH 9.3) at 25 kV with 8 s hydrodynamic injection, and the quantitation was carried out by the use of two reference compounds at two different wavelengths.

Topics: Chromatography, High Pressure Liquid; Electrophoresis, Capillary; Flavonoids; Furans; Glucosides; Iridoid Glucosides; Iridoids; Lignans; Olive Oil; Phenols; Phenylethyl Alcohol; Plant Oils; Polyphenols; Pyrans

An essential step in lignan and lignin formation in planta is one electron oxidation of (E)-coniferyl alcohol (CA) to generate the radical intermediate (CA(*)), which can then undergo directed radical-radical couplings in vivo. For lignan formation in vitro and in vivo, stereoselective coupling of CA(*) only occurs to afford (+)-pinoresinol in the additional presence of (+)-pinoresinol forming dirigent protein (DP). Presented herein is a kinetic and thermodynamic study which reveals the central mechanistic details of the coupling process involved in DP-mediated coupling. DP activity was maximal between pH 4.25 and pH 6.0, with activity being maintained at temperatures below 33 degrees C. Equilibrium binding assays revealed that coniferyl alcohol was only weakly bound to the DP, with a K(D) of 370 +/- 65 microM. On the other hand, the enantiomeric excess of (+)-pinoresinol formed was dependent on both DP concentration and rate of CA oxidation and, thus, on apparent steady-state [CA(*)]. The data obtained could best be explained using a kinetic model where radical-radical coupling via DP competes with that occurring in open solution. Using this model, an apparent K(M) of about 10 nM was estimated from the saturation behavior of (+)-pinoresinol formation with respect to apparent steady-state [CA(*)]. These data strongly suggest that CA(*), rather than CA, is the substrate for DP, in agreement with earlier predictions. A mechanism of directed radical-radical coupling, where two coniferyl alcohol radical substrates are bound per protein dimer, is proposed.

Topics: Binding, Competitive; Dimerization; Free Radicals; Furans; Hydrogen-Ion Concentration; Kinetics; Lignans; Models, Chemical; Phenols; Plant Proteins; Protein Binding; Stereoisomerism; Temperature

A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the quantification of the four major enterolignan precursors [secoisolariciresinol, matairesinol, lariciresinol, and pinoresinol] in foods. The method consists of alkaline methanolic extraction, followed by enzymatic hydrolysis using Helix pomatia (H. pomatia) beta-glucuronidase/sulfatase. H. pomatia was selected from several enzymes based on its ability to hydrolyze isolated lignan glucosides. After ether extraction samples were analyzed and quantified against secoisolariciresinol-d8 and matairesinol-d6. The method was optimized using model products: broccoli, bread, flaxseed, and tea. The yield of methanolic extraction increased up to 81%, when it was combined with alkaline hydrolysis. Detection limits were 4-10 microg/(100 g dry weight) for solid foods and 0.2-0.4 microg/(100 mL) for beverages. Within- and between-run coefficients of variation were 6-21 and 6-33%, respectively. Recovery of lignans added to model products was satisfactory (73-123%), except for matairesinol added to bread (51-55%).

Topics: Butylene Glycols; Chromatography, Liquid; Food Analysis; Furans; Hydrolysis; Lignans; Mass Spectrometry; Plants; Sensitivity and Specificity

[structure: see text]Derivatization with (+)- and (-)-chloromenthoxydiphenylsilane was used to determine the absolute configuration of the insect defensive agent pinoresinol (1). Although the (1)H NMR chemical shift differences of the resulting two diastereomers are small, (1)H NMR spectroscopy provided for the unambiguous assignment of the natural product's configuration. For this purpose, a new approach involving NMR spectra of mixtures of diastereomers was used. Our method resembles coinjecting mixtures of samples of known and unknown configuration in GC and HPLC.

Topics: Animals; Butterflies; Furans; Lignans; Magnetic Resonance Spectroscopy; Molecular Structure; Siloxanes; Stereoisomerism

Total extract of resin from Araucaria angustifolia was analyzed by gas chromatography/mass spectrometry and 32 lignans were identified. Lignan acetates are present in the resin and consist of four secoisolariciresinol acetates, six lariciresinol acetates, two 7'-hydroxylariciresinol acetates and an isolariciresinol acetate, which have hitherto not been reported in the plant kingdom. Shonanin and 7'-hydroxylariciresinol type lignans are also present in A. angustifolia resin. Lignans containing syringyl moieties, characteristic for angiosperms, occur in the resin and consist of 5-methoxylariciresinol-9-acetate, 5'-methoxylariciresinol-9-acetate, 5-methoxypinoresinol dimethyl ether and 5-methoxypinoresinol. This is noteworthy because syringyl moieties have only been reported for Thuja species (Cupressaceae) among the gymnosperms. The mass spectra of the various lignan trimethylsilyl derivatives are discussed with the interpretations of the fragmentation patterns.

Topics: Butylene Glycols; Furans; Gas Chromatography-Mass Spectrometry; Lignans; Lignin; Naphthols; Phenols; Pinus; Resins, Plant; Trimethylsilyl Compounds

Phytoestrogens of the lignan type are widely distributed in plant-derived food items and are believed to protect against hormone-dependent cancer. The richest known dietary source of lignans is flaxseed. Flaxseed has been reported to contain glycosides of secoisolariciresinol as the major lignan, together with small amounts of matairesinol, isolariciresinol, and pinoresinol. Secoisolariciresinol, but none of the other lignans, has so far been identified in pumpkin seeds. In the present study, two different methods for the hydrolysis of lignan glycosides are compared. Artifact formation and loss of lignans under acidic conditions were observed. Lariciresinol was identified by GC-MS analysis in two different types of flaxseed (Linum usitatissimum L. and Linum flavum L.) and in pumpkin seeds (Cucurbita pepo L.) for the first time. Likewise, the novel lignan demethoxy-secoisolariciresinol was tentatively identified in the flaxseed samples. Stereochemical analysis by chiral HPLC of several lignans isolated from flaxseed showed that secoisolariciresinol, matairesinol, and lariciresinol consisted predominantly of one enantiomer.

Topics: Butylene Glycols; Chromatography, High Pressure Liquid; Cucurbita; Flax; Furans; Gas Chromatography-Mass Spectrometry; Hydrogen-Ion Concentration; Hydrolysis; Lignans; Lignin; Seeds; Stereoisomerism

Despite the importance of plant lignans and isoflavonoids in human health protection (e.g. for both treatment and prevention of onset of various cancers) as well as in plant biology (e.g. in defense functions and in heartwood development), systematic studies on the enzymes involved in their biosynthesis have only recently begun. In this investigation, three NADPH-dependent aromatic alcohol reductases were comprehensively studied, namely pinoresinol-lariciresinol reductase (PLR), phenylcoumaran benzylic ether reductase (PCBER), and isoflavone reductase (IFR), which are involved in central steps to the various important bioactive lignans and isoflavonoids. Of particular interest was in determining how differing regio- and enantiospecificities are achieved with the different enzymes, despite each apparently going through similar enone intermediates. Initially, the three-dimensional x-ray crystal structures of both PLR_Tp1 and PCBER_Pt1 were solved and refined to 2.5 and 2.2 A resolutions, respectively. Not only do they share high gene sequence similarity, but their structures are similar, having a continuous alpha/beta NADPH-binding domain and a smaller substrate-binding domain. IFR (whose crystal structure is not yet obtained) was also compared (modeled) with PLR and PCBER and was deduced to have the same overall basic structure. The basis for the distinct enantio-specific and regio-specific reactions of PCBER, PLR, and IFR, as well as the reaction mechanism and participating residues involved (as identified by site-directed mutagenesis), are discussed.

Topics: Amino Acid Sequence; Crystallography, X-Ray; Escherichia coli; Furans; Lignans; Models, Chemical; Models, Molecular; Molecular Sequence Data; Mutagenesis, Site-Directed; NADP; Oxidoreductases; Oxidoreductases Acting on CH-CH Group Donors; Plasmids; Protein Binding; Protein Conformation; Protein Structure, Secondary; Protein Structure, Tertiary; Sequence Homology, Amino Acid; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Ultracentrifugation

Based on results from 2D NMR studies, both pinoresinol and secoisolariciresinol structures were found to be present in native lignin from spruce wood as well as in spruce kraft lignin and residual kraft pulp lignin. These two structures constitute the major types of beta-beta inter-unit linkages present in spruce lignin, but their formation in the lignin polymer may follow different pathways leading to their different bonding patterns with the rest of the lignin polymer. The mechanisms involved are discussed.

Topics: Butylene Glycols; Carbohydrate Conformation; Carbohydrates; Furans; Lignans; Lignin; Models, Chemical; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Wood

The (+)-pinoresinol-forming dirigent protein is the first protein capable of stereoselectively coupling two coniferyl alcohol derived radical species, in this case to give the 8-8' linked (+)-pinoresinol. Only dimeric cross-linked dirigent protein structures were isolated when 1-ethyl-3-[3-(dimethylamino)-propyl]carbodiimide was used as cross-linking agent, whereas the associated oxidase, presumed to generate the corresponding free radical substrate, was not detected. Native Forsythia intermedia dirigent protein isoforms were additionally subjected to MALDI-TOF and ESI-MS analyses, which established the presence of both monomeric masses of 23-25 kDa and dimeric dirigent protein species ranging from 46 to 49 kDa. Analytical ultracentrifugation, sedimentation velocity, and sedimentation equilibrium analyses of the native dirigent protein in open solution confirmed further its dimeric nature as well as a propensity to aggregate, with the latter being dependent upon both temperature and solution ionic strength. Circular dichroism analysis suggested that the dirigent protein was primarily composed of beta-sheet and loop structures.

Topics: Chromatography, Gel; Circular Dichroism; Furans; Lignans; Plant Proteins; Protein Conformation; Protein Structure, Quaternary; Protein Structure, Secondary; Spectrometry, Mass, Electrospray Ionization; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Spectrophotometry, Ultraviolet

Ipomoea cairica cell cultures produced a tetrahydrofuran lignan, (+)-pinoresinol, identified by UV, IR, MS and NMR methods, not yet found in the intact plant, and new in the Convolvulaceae family. Pinoresinol was found to have antioxidant and Ca2+ antagonist properties. As it could be requested for its biological activity, we examined the possibility to raise the pinoresinol yield of I. cairica cultures, as well as we continued investigations on lignans' response to optimization.

Topics: Antioxidants; Calcium; Cells, Cultured; Culture Media, Conditioned; Furans; Ipomoea; Lignans; Magnetic Resonance Spectroscopy; Molecular Structure

A new isoflavone, 4',5,7-trihydroxy-6,8-dimethylisoflavone (1), and a new sesterterpenoic acid (2), together with five known compounds, lichexanthone (3), (-)-pinoresinol (4), betulinic acid, palmitic acid, and beta-sitosterol, were isolated from a dichloromethane extract of the branches of Henriettella fascicularis. Their structures were established by extensive spectroscopic methods. An attempt to determine the absolute stereochemistry of (2E,6S)-6-[(1R,5Z,3aS,9R,10Z,12aR)-1,2,3,3a,4,7,8,9,12,12a-decahydro-9-hydroxy-3a,6,10-trimethylcyclopentanocycloundecen-1-yl]-2-methylhept-2-enoic acid (2) was performed by single-crystal X-ray analysis, using Cu Kalpha radiation. Compound 1 showed significant competitive binding to estrogen receptor beta and moderate antiestrogenic activity with cultured Ishikawa cells.

Topics: Alkaline Phosphatase; Binding Sites; Cell Line; Crystallography, X-Ray; Endometrium; Estrogen Antagonists; Estrogen Receptor Modulators; Female; Furans; Humans; Isoflavones; Lignans; Melastomataceae; Methylation; Molecular Conformation; Molecular Structure; Palmitic Acid; Panama; Phytosterols; Plant Shoots; Plants, Medicinal; Sitosterols; Stereoisomerism; Terpenes

Intramolecular radical cyclization of suitably substituted epoxy ethers 4a-g using bis(cyclopentadienyl)titanium(III) chloride as the radical source resulted in trisubstituted tetrahydrofurano lignans and 2,6-diaryl-3,7-dioxabicyclo[3.3.0]octane lignans depending on the reaction conditions. The titanium(III) species was prepared in situ from commercially available titanocene dichloride and activated zinc dust in THF. Upon radical cyclization followed by acidic workup, epoxy olefinic ethers 4a-g afforded furano lignans dihydrosesamin 1a, lariciresinol dimethyl ether 1b, acuminatin methyl ether 1e, and sanshodiol methyl ether 1g directly and lariciresinol 1h, acuminatin 1i, and lariciresinol monomethyl ether 1j after removal of the benzyl protecting group by controlled hydrogenolysis of the corresponding cyclized products. The furofuran lignans sesamin 2a, eudesmin 2b, and piperitol methyl ether 2e were also prepared directly by using the same precursors 4a-f on radical cyclization followed by treatment with iodine and pinoresinol 2h, piperitol 2i, and pinoresinol monomethyl ether 2j after controlled hydrogenolysis of the benzyl protecting group of the corresponding cyclized products. Two naturally occurring acyclic lignans, secoisolariciresinol 5h and secoisolariciresinol dimethyl ether 5b, have also been prepared by exhaustive hydrogenolysis of 2h and 2b, respectively.

Topics: Alkylation; Catalysis; Chemistry, Organic; Cyclization; Dioxoles; Epoxy Compounds; Ethers, Cyclic; Flavonoids; Furans; Glycosides; Lignans; Lignin; Magnetic Resonance Spectroscopy; Molecular Structure; Stereoisomerism

The chemical constituents of the herb of Cuscuta chinensis Lam. were investigated. Five compounds were isolated from petroleum ether and chloroform fraction. Their structures were identified as beta-sitosterol, d-sesamin, 9(R)-hydroxy-d-sesamin, d-pinoresinol and daucosterol by chemical and spectroscopical methods. All these compounds were isolated from the stem for the first time.

Topics: Chemical Fractionation; Cuscuta; Dioxoles; Drugs, Chinese Herbal; Furans; Lignans; Sitosterols; Spectrum Analysis

Three lignans, pinoresinol (1), 8-hydroxypinoresinol (2) and olivil (3) have been isolated from the leaves of Strophanthus gratus by reversed-phase HPLC.

Topics: Chromatography, High Pressure Liquid; Furans; Humans; Lignans; Plant Extracts; Plants, Medicinal

Coptis japonica Makino (Ranunculaceae) is known to possess several biological activities such as anti-inflammatory effects. In this study, five lignans, isolariciresinol (1), lariciresinol glycoside (2), pinoresinol (3), pinoresinol glycoside (4) and syringaresinol glycoside (5), isolated from the rhizomes of C. japonica were tested to evaluate their in vitro anti-inflammatory effects. Pinoresinol and isolariciresinol showed higher inhibitory effects on TNF-alpha production, whereas syringaresinol glycoside strongly suppressed lymphocyte proliferation. The results indicate that the lignans may differentially modulate inflammatory cell responses, suggesting that these compounds may participate in anti-inflammatory processes by C. japonica.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; CD4-Positive T-Lymphocytes; Cells, Cultured; Furans; Glucosides; Glycosides; Interferon-gamma; Interleukin-2; Lignans; Lignin; Lipopolysaccharides; Macrophages; Male; Medicine, Traditional; Mice; Mice, Inbred BALB C; Molecular Structure; Naphthols; Nitric Oxide; Plants, Medicinal; Spleen; Tumor Necrosis Factor-alpha

To study the chemical constituents in the twigs and leaves of Ligustrum obtusifolium.. Seven compounds were isolated from the ethanol extract of the twigs and leaves by polystyrene resin RA and silica gel column chromatography. The structures were identified by spectral analysis.. Of the seven compounds isolated six were identified as luteolin, luteolin-4'-O-beta-D-glucopyranoside, (+)-pinoresinol, (+)-pinoresinol-4'-O-beta-D-glucopyranoside, (+)-medioresinol and (-)-olivil.. luteolin, luteolin-4'-O-beta-D-glucopyranoside, (+)-pinoresinol, (+)-medioresionnol and (-)-olivil were isolated from this plant for the first time.

Topics: Flavonoids; Furans; Lignans; Ligustrum; Luteolin; Plant Leaves; Plants, Medicinal

Because olive oil is an important component of the Mediterranean diet, it is necessary to establish unequivocal identification of the major potential antioxidant phenolic compounds it contains.. The major phenolic antioxidants in extra virgin olive oil were isolated and purified. Structural analysis was conducted using several spectroscopic techniques, including mass spectrometry and nuclear magnetic resonance (NMR). In particular, detailed (1)H and (13)C NMR data are presented, and several assignment errors in the literature are corrected.. The data show for the first time that the lignans (+)-1-acetoxypinoresinol and (+)-pinoresinol are major components of the phenolic fraction of olive oils. These lignans, which are potent antioxidants, are absent in seed oils and virtually absent in refined virgin oils but are present at concentrations of up to 100 mg/kg (mean +/- SE, 41.53+/-3.93 mg/kg; range, 0.65-99.97 mg/kg) in extra virgin oils. As with the simple phenols and secoiridoids, there is considerable interoil variation in lignan concentrations. Foods containing high amounts of lignan precursors have been found to be protective against breast, colon, and prostate cancer.. Lignans, as natural components of the diet, may be important modulators of cancer chemopreventive activity.

Topics: Chromatography, High Pressure Liquid; Dietary Fats, Unsaturated; Furans; Gas Chromatography-Mass Spectrometry; Lignans; Magnetic Resonance Spectroscopy; Olive Oil; Phenols; Plant Oils

The effects of six lignans and neolignans as inhibitors of ecdysis and on the water balance in fourth-instar larvae of Rhodnius prolixus were studied by oral, topical and continuous contact treatments. The main results may be summarised as follows: (i) burchellin, pinoresinol, sesamin, licarin A and nordihydroguaiaretic acid (NDGA) did not cause feeding inhibition at doses of 100 micrograms/ml blood; podophyllotoxin had no antifeedant effect but caused a high moulting inhibition and significant toxicity when applied either orally or topically; (ii) the highest ecdysis inhibitory effects were observed with pinoresinol and NDGA when applied orally at a dose of 100 micrograms/ml (58% and 50% of moulting inhibition, respectively); burchellin inhibited 30% of the moulting at this concentration; (iii) by topical treatment none of the compounds presented any influence on the moulting cycle; and (iv) podophyllotoxin and burchellin significantly reduced the excretion of the insect in 24 h; the other compounds had no effect on excretion. The implications of these findings in relation to the pertinent biological events in R. prolixus are discussed.

Topics: Animals; Benzofurans; Dioxoles; Feeding Behavior; Furans; Larva; Lauraceae; Lignans; Masoprocol; Plants, Medicinal; Podophyllotoxin; Rhodnius

Pinoresinol-lariciresinol and isoflavone reductase classes are phylogenetically related, as is a third, the so-called "isoflavone reductase homologs." This study establishes the first known catalytic function for the latter, as being able to engender the NADPH-dependent reduction of phenylcoumaran benzylic ethers. Accordingly, all three reductase classes are involved in the biosynthesis of important and related phenylpropanoid-derived plant defense compounds. In this investigation, the phenylcoumaran benzylic ether reductase from the gymnosperm, Pinus taeda, was cloned, with the recombinant protein heterologously expressed in Escherichia coli. The purified enzyme reduces the benzylic ether functionalities of both dehydrodiconiferyl alcohol and dihydrodehydrodiconiferyl alcohol, with a higher affinity for the former, as measured by apparent Km and Vmax values and observed kinetic 3H-isotope effects. It abstracts the 4R-hydride of the required NADPH cofactor in a manner analogous to that of the pinoresinol-lariciresinol reductases and isoflavone reductases. A similar catalytic function was observed for the corresponding recombinant reductase whose gene was cloned from the angiosperm, Populus trichocarpa. Interestingly, both pinoresinol-lariciresinol reductases and isoflavone reductases catalyze enantiospecific conversions, whereas the phenylcoumaran benzylic ether reductase only shows regiospecific discrimination. A possible evolutionary relationship among the three reductase classes is proposed, based on the supposition that phenylcoumaran benzylic ether reductases represent the progenitors of pinoresinol-lariciresinol and isoflavone reductases.

Topics: Amino Acid Sequence; Base Sequence; Cloning, Molecular; DNA, Complementary; Furans; Lignans; Lignin; Molecular Sequence Data; Oxidoreductases; Oxidoreductases Acting on CH-CH Group Donors; Sequence Homology, Amino Acid; Stereoisomerism; Trees

The isolation and characterization of the lignans, isolariciresinol, pinoresinol, secoisolariciresinol, and matairesinol, potent phytoestrogens, from flaxseed meal are described. This is the first report of isolariciresinol and pinoresinol being detected in a food. The extraction method selected combined the removal of the lignan glycosides from the plant matrix with an alcoholic solvent system, followed by acid hydrolysis to release the aglycons. A reversed-phase high-performance liquid chromatography with diode array detection system was used for initial separation and detection of the lignans at 280 nm in the acid-hydrolyzed methanolic extract. Lignan trimethylsilyl ether derivatives were characterized by gas chromatography/mass spectrometry. Secoisolariciresinol is the major lignan in flaxseed; isolariciresinol, pinoresinol, and matairesinol were identified as minor lignan components.

Topics: Chromatography, High Pressure Liquid; Flax; Flour; Furans; Gas Chromatography-Mass Spectrometry; Lignans; Lignin; Naphthols; Seeds

Four compounds were isolated from the roots of Pimpinella thellungiana Wolff., their structures were identified as palmitic acid(I), 4-propenylphenol(II), pinoresinol(III), 2-methyl-2-hydroxy-5-methoxy berzo(d) hydrofuran-3-one(IV) by physicochemical constants and spectral analysis (UV, IR, MS, 1HNMR, 13CNMR, 13C-1HCOSY, DEPT), IV of them is a new compound, Pharmacological tests showed IV has a hypotensive effect.

Topics: Furans; Lignans; Palmitic Acid; Pimpinella; Plant Roots; Plants, Medicinal; Spectrophotometry; Spectroscopy, Near-Infrared

The regio- and stereospecificity of bimolecular phenoxy radical coupling reactions, of especial importance in lignin and lignan biosynthesis, are clearly controlled in some manner in vivo; yet in vitro coupling by oxidases, such as laccases, only produce racemic products. In other words, laccases, peroxidases, and comparable oxidases are unable to control regio- or stereospecificity by themselves and thus some other agent must exist. A 78-kilodalton protein has been isolated that, in the presence of an oxidase or one electron oxidant, effects stereoselective bimolecular phenoxy radical coupling in vitro. Itself lacking a catalytically active (oxidative) center, its mechanism of action is presumed to involve capture of E-coniferyl alcohol-derived free-radical intermediates, with consequent stereoselective coupling to give (+)-pinoresinol.

Topics: Dimerization; Flavin Mononucleotide; Flavin-Adenine Dinucleotide; Free Radicals; Furans; Kinetics; Laccase; Lignans; Molecular Conformation; Oxidation-Reduction; Oxidoreductases; Phenols; Plant Proteins; Stereoisomerism

Microbial transformation of (+/-)-eudesmin by Aspergillus niger was investigated. Enantioselective accumulation of (--)-pinoresinol was shown through O-demethylation of (+/-)-eudesmin. This fungus O- demethylated both enantiomers of eudesmin, but the conversion rates for each enantiomer were clearly different.

Topics: Aspergillus niger; Biotransformation; Furans; Lignans; Methylation; Stereoisomerism

Bioassay-guided fractionation of the EtOAc extract of both Allamanda cathartica and Himatanthus fallax (Apocynaceae) using the Sc-7 yeast strain resulted in the isolation of the weakly cytotoxic isoplumericin and plumericin. In addition, the new lignan 7(R)-methoxy-8-epi-matairesional and three known compounds, plumieride, matairesinol, and pinoresinol, were isolated from H. fallax.

Topics: Animals; Antineoplastic Agents, Phytogenic; Drug Screening Assays, Antitumor; Furans; Lignans; Magnetic Resonance Spectroscopy; Mass Spectrometry; Mice; Plants, Medicinal; Saccharomyces cerevisiae; Spiro Compounds; Suriname; Tumor Cells, Cultured

The furofuran lignans in sesame seed have an unusual oxygen insertion between their furan and aryl rings. In our continuing investigations on the isolation and characterization of the enzyme(s) involved, the diastereoselective syntheses of various substrate analogues for the oxygen insertion step were developed for future substrate specificity and inhibitor studies. This synthetic strategy also provided entry to so-called furofuranone epoxy-lignans, such as salicifoliol from Bupleurum sp., and acuminatolide from Helichrysum sp.

Topics: Dioxoles; Furans; Lignans; Magnoliopsida; Oxygen; Seeds; Sesame Oil; Stereoisomerism

Nine compounds were isolated from the roots of Euphorbia pekinensis Rupr., a traditional Chinese medicine. By combination of chemical methods and spectral analyses, the structures of the compounds were identified as lanosterol (I), octadecanyl-3-methoxy-4-hydroxybenzeneacrylate (II), beta-sitosterol (III), 7-hydroxycoumarin (IV), 2, 2'-dimethoxy-3, 3'-dihydroxy-5, 5'-oxygen-6, 6'-biphenylformic anhydride (V), d-pinoresinol (VI), quercetin (VII), 3, 4-dimethoxybenzoic acid (VIII) and 3, 4-dihydroxybenzoic acid (IX). II and V are new compounds which have not been reported in the literature. The other compounds were isolated for the first time from this plant. VI is a lignan which was first isolated from the plants of genus of Euphorbia.

Topics: Drugs, Chinese Herbal; Euphorbiaceae; Furans; Lignans; Molecular Structure; Plant Roots; Saponins; Triterpenes

Topics: Furans; Lignans