lignans and lariciresinol

Herein, the isolation of secondary metabolites from the aerial parts of

Topics: Allantoin; Anti-Inflammatory Agents; Furans; Justicia; Lignans; Molecular Structure; Nitric Oxide; Plant Extracts

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

Rheumatoid arthritis (RA) is a severe inflammatory auto-immune disorder affecting millions of people across the globe. The current therapeutic options are not adequate to address the complications of RA. Therefore, the present study was conducted to elucidate the protective effect of lariciresinol, a lignan, against Complete Freund's adjuvant (CFA)-induced arthritis in rats. The results of the study showed that lariciresinol improves paw swelling and arthritic scores in rats as compared to CFA rats. Lariciresinol also showed a significant reduction in rheumatoid factor, C-reactive protein, tumor necrosis factor-α, interleukin (IL)-17, and tissue inhibitor of metalloproteinases-3 level with a simultaneous increase in IL-4 level. The burden of oxidative stress was also reduced in CFA rats, as shown by reduced MDA levels and increased SOD and GPx after the administration of lariciresinol. In a Western blot analysis, lariciresinol showed a significant reduction of transforming growth factor-β and nuclear factor-κB (NF-κB) protein levels in CFA rats. To understand the binding characteristic of lariciresinol with NF-κB, molecular docking analysis was conducted, which showed Larciresinol interacted with the active site of NF-κB. Our study demonstrated the significant protective effect of lariciresinol against RA via multi-target action.

Topics: Animals; Arthritis, Experimental; Arthritis, Rheumatoid; Freund's Adjuvant; Lignans; Molecular Docking Simulation; NF-kappa B; Rats; Transforming Growth Factor beta; Transforming Growth Factors

Zingiber officinale Roscoe has been utilized traditionally to cure various diseases like cold, cough, diarrhoea, nausea, asthma, vomiting, toothache, stomach upset, respiratory disorders, joint pain, and throat infection. It is also consumed as spices and ginger tea.. The current study was aimed to identify the phytocompounds of traditional medicinal plants of North-Western Himalaya that could inhibit the AcrAB-TolC efflux pump activity of Salmonella typhimurium and become sensitive to antibiotic killing at reduced dosage.. Medicinal plant extracts were prepared using methanol, aqueous, and ethyl acetate and tested for efflux pump inhibitory activity of Salmonella typhimurium NKS70, NKS174, and NKS773 strains using Ethidium Bromide (EtBr)-agar cartwheel assay. Synergism was assessed by the agar well diffusion method and EPI activity by berberine uptake and EtBr efflux inhibition assays. Microdilution method and checkerboard assays were done to determine the minimum inhibitory concentration (MIC) and fractional inhibitory concentration index (FICI) respectively for a bioactive compound. To validate the phytocompound and efflux pump interaction, molecular docking with 6IE8 (RamA) and 6IE9 (RamR) targets was done using autoDock vina software. Toxicity prediction and drug-likeness were predicted by using ProTox-II and Molinspiration respectively.. Methanolic and ethyl acetate extracts of P. integerrima, O. sanctum, C. asiatica, M. charantia, Z. officinale, and W. somnifera in combination with ciprofloxacin and tetracycline showed synergistic antimicrobial activity with GIIs of 0.61-1.32 and GIIs 0.56-1.35 respectively. Methanolic extract of Z. officinal enhanced the antimicrobial potency of berberine (2 to 4-folds) and increased the EtBr accumulation. Furthermore, bioassay-guided fractionation leads to the identification of lariciresinol in ethyl acetate fraction, which decreased the MIC by 2-to 4-folds. The ΣFIC values varied from 0.30 to 0.55 with tetracycline, that indicated synergistic/additive effects. Lariciresinol also showed a good binding affinity with 6IE8 (-7.4 kcal mol. The data suggest that lariciresinol from Z. officinale could be a potential efflux pump inhibitor that could lead to effective killing of drug resistant Salmonella typhimurium at lower MIC. Molecular docking confirmed the antibacterial EPI mechanism of lariciresinol in Salmonella typhimurium and confirmed to be safe for future use.

Topics: Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Furans; Gene Expression Regulation, Bacterial; Humans; India; Lignans; Microbial Sensitivity Tests; Molecular Docking Simulation; Plant Extracts; Plants, Medicinal; Salmonella Infections; Salmonella typhimurium; Serogroup; Zingiber officinale

The aim of this study is to investigate the antidiabetic effect of lariciresinol (LSR) in C2C12 myotubes and streptozotocin (STZ)-induced diabetic mice.. To investigate antidiabetic potential of LSR, α-glucosidase inhibitory assay, molecular docking, glucose uptake assay, western blot assay on antidiabetic biomarkers are performed. STZ-induced diabetic model is used for in vivo study by calculating oral glucose tolerance test, histochemical examination, and glycogen assay. LSR inhibits α-glucosidase activity with an IC. The findings indicate a potential usefulness for oral LSR in the management and prevention of diabetes by enhancing glucose homeostasis.

Topics: alpha-Glucosidases; Animals; Blood Glucose; Diabetes Mellitus, Experimental; Furans; Glucose; Glucose Transporter Type 4; Glycogen; Glycogen Synthase Kinase 3 beta; Glycoside Hydrolase Inhibitors; Hypoglycemic Agents; Insulin; Lignans; Mice; Molecular Docking Simulation; Muscle, Skeletal; Streptozocin

Chronic hepatitis induced by hepatitis B virus (HBV) infection is a serious public health problem, leading to hepatic cirrhosis and liver cancer. Although the currently approved medications can reliably decrease the virus load and prevent the development of hepatic diseases, they fail to induce durable off-drug control of HBV replication in the majority of patients. The roots of

Topics: Animals; Furans; Hepatitis B virus; Humans; Isatis; Lignans; RNA; Viral Transcription

Based on the transcriptome data of Isatis indigotica, a total of 110 putative glycosytransferases were identified. Through prokaryotic expression and enzymic activity assay in vitro, a novel lignan glycosyltransferase gene was screened out and named IiUGT349, which catalyzed lariciresinol into lariciresinol-4-O-β-D-glucoside and lariciresinol-4'-O-β-D-glucoside. Bioinformatics analysis suggested that IiUGT349 contained an open reading frame(ORF) of 1 401 bp encoding a protein of 467 amino acids. A protein analysis indicated that IiUGT349 have a predecited molecular weight of 52.77 kDa and pI of 5.96. Phylogenetic analysis showed that IiUGT349 belonging to UGT90 family shared low amino acid sequence identity with the reported lignan glycosyltransferases, which may represent a novel type of lignan glycosyltransferases. Quantitative real-time PCR(qRT-PCR) analysis showed that IiUGT349 was expressed in roots, stems, young leaves and leaves, with the highest expression level in stems. Further biochemical analysis showed that the optimal reaction time of IiUGT349 recombinant protein was 12 h and the optimal temperature was 45 ℃. Subcellular localization demonstrated that IiUGT349 was located in the cytoplasm and nucleus of plants. In this study, a new glucosyltransferase gene IiUGT349 from I. indigotica belonging to the UGT90 family was cloned, which laid a foundation to further investigate its' function and elucidate the lignan glycosides biosynthesis pathway and plays an important role for great significance for the synthetic biology of active lignan glycosides.

Topics: Cloning, Molecular; Glucosides; Glycosyltransferases; Isatis; Lignans; Phylogeny

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

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

Humans perceive bitterness via around 25 different bitter receptors. Therefore, the identification of antagonists remains a complex challenge. We previously demonstrated several bitter-tasting compounds such as caffeine to induce acid secretion in the stomach and in a human gastric tumor cell line (HGT-1). Here, the results of a fluorescent-based in vitro assay using HGT-1 cells and a human sensory panel testing nine selected potential bitter modulators, with or without the bitter compounds caffeine or theobromine, were compared. Of the bitter-modulating compounds tested, eriodictyol, matairesinol, enterolacton, lariciresinol, and homoeriodictyol reduced the effect of caffeine on proton secretion by -163 ± 14.0, -152 ± 12.4, -74 ± 16.4, -58 ± 7.2, and -44.6 ± 16.5%, respectively, and reduced the bitter intensity of caffeine in the human sensory panel. In contrast, naringenin and 5,7-dihydroxy-4(4-hydroxyphenyl)chroman-2-one neither reduced the caffeine-induced proton secretion in HGT-1 cells nor showed an effect on bitter intensity perceived by the sensory panel. Results for theobromine were not as pronounced as those for caffeine, but followed a similar trend. The results demonstrate that the HGT-1 in vitro assay is a useful tool to identify potential bitter-masking compounds. Nevertheless, a sensory human panel is necessary to quantify the bitter-masking potency.

Topics: Caffeine; Cell Line; Flavanones; Flavones; Furans; Gastric Mucosa; Humans; Lignans; Parietal Cells, Gastric; Protons; Taste

Lariciresinol (LA) is one of the main active ingredients in many traditional medicinal plants such as Patrinia, and has the role of anti-liver cancer. However, the precise mechanisms are unclear. This study investigated the molecular mechanisms of LA against HepG2 cells. LA anti-tumor activity was assessed with the CCK-8, Ki-67, and immunofluorescence staining. Cells apoptotic ratio was evaluated by Annexin V/PI double-staining assay. A proteomic approach was used to identify differentially expressed proteins after LA treatment. JC-1 staining was carried out to detect the mitochondrial membrane potential (ΔΨm), and the Western blot analysis was used to analyse the apoptosis-associated proteins. Our results suggested that LA significantly suppressed the viability of HepG2 cells. The CCK-8 and Ki-67 expression indicated dose-dependent decreases in cell proliferation. Flow cytometry analysis showed that LA exhibited a apoptosis-inducing effect. The proteomic study observed the presence of apoptosis-associated proteins and mitochondrial dysfunction in HepG2 cells after LA-treatment. Further analysis showed that LA could trigger the mitochondrial-mediated apoptosis pathway, based on a decrease in ΔΨm; deliver of cytochrome c; activation of caspase-9/-3 and poly(ADP-ribose) polymerase; and decrease of the proportion of Bcl-2/Bax. Collectively, our studies found that LA exhibits significant cytotoxic effects by inhibiting cell proliferation, inducing apoptosis, possibly via activation of the mitochondrial-mediated apoptosis pathway.

Topics: Apoptosis; Apoptosis Regulatory Proteins; Cell Proliferation; Cell Survival; Cells, Cultured; Furans; Hep G2 Cells; Humans; Lignans; Membrane Potential, Mitochondrial; Mitochondria; Proteomics; Signal Transduction

The aim of the present study was to examine the antioxidative activity of (+)-lariciresinol (LRSL), an optically active lignan isolated from Rubia philippinensis in several in vitro assays. LRSL was also subjected to evaluate its inhibitory effect against the generation of reactive oxygen species (ROS) in murine macrophage (RAW 264.7) cells. The results showed that LRSL possessed very strong radical scavenging activity and reducing power, as well as inhibited ROS generation in a dose-dependent manner without showing any cytotoxicity. The transcriptional and translational levels of superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) were markedly higher in the sample treated group. LRSL treatment also increased the transcriptional and translational activities of NF-E2-related factor-2 (Nrf-2) with a corresponding increase in the transcriptional and translational activities of the heme oxygenase-1 (HO-1). LRSL activated p38 and treatments with SB239063 (a p38 inhibitor) suppressed the LRSL-induced activation of Nrf2, resulting in a decrease in HO-1 expression. Collectively, the data demonstrated that LRSL has potent antioxidative activity, decreasing ROS generation in RAW 264.7 cells and increasing the transcriptional and translational levels of antioxidant enzymes by activating Nrf2-mediated HO-1 induction via p38 signaling.

Topics: Amidines; Animals; Antioxidants; Cell Nucleus; Cell Survival; Enzyme Activation; Free Radical Scavengers; Furans; Heme Oxygenase-1; Lignans; Metabolic Detoxication, Phase II; Mice; NF-E2-Related Factor 2; Oxidative Stress; p38 Mitogen-Activated Protein Kinases; Phosphorylation; RAW 264.7 Cells; Reactive Oxygen Species; Rubia; Up-Regulation

Ten new glycosides, 6,10-O-di-trans-feruloyl catalpol (1), 6,6'-O-di-trans-feruloyl catalpol (2), 3,4-dihydro-6-O-di-trans-feruloyl catalpol (10), (8R,7'S,8'R)-lariciresinol 9'-O-β-d-(6-O-trans-feruloyl)glucopyranoside (17), and ovatosides A-F (18-22, 24), were isolated from the stem bark of Catalpa ovata along with 19 known compounds. All isolates, except 6 (catalposide) and 9 (6-O-veratroyl catalpol), were found to scavenge peroxynitrite (ONOO

Topics: Bignoniaceae; Furans; Glucosides; Glycosides; Inhibitory Concentration 50; Iridoid Glucosides; Iridoids; Lignans; Molecular Structure; Peroxynitrous Acid; Plant Stems

The influenza A virus is an acute contagious pathogen that affects the human respiratory system and can cause severe lung disease and even death. Lariciresinol-4-β-D-glucopyranoside is a lignan that is extracted from Isatis indigotica, which is a medicinal herb plant that was commonly applied to treat infections, the common cold, fever and inflammatory diseases. Our previous study demonstrated that lariciresinol-4-β-D-glucopyranoside possesses anti-viral and anti-inflammatory properties. However, the comprehensive and detailed mechanisms that underlie the effect of lariciresinol-4-β-D-glucopyranoside interventions against influenza virus infection remain to be elucidated. In this study, we employed high-throughput RNA sequencing (RNA-seq) to investigate the transcriptomic responses of influenza A virus-infected lung epithelial (A549) cells with lariciresinol-4-β-D-glucopyranoside treatment. The transcriptome data show that infection with influenza A virus prompted the activation of 368 genes involved in RIG-I signalling, the inflammatory response, interferon α/β signalling and gene expression that was not affected by lariciresinol-4-β-D-glucopyranoside treatment. Lariciresinol-4-β-D-glucopyranoside exerted its pharmacological actions on the immune system, signal transduction, cell cycle and metabolism, which may be an underlying defense mechanism against influenza virus infection. In addition, 166 differentially expressed genes (DEGs) were uniquely expressed in lariciresinol-4-β-D-glucopyranoside-treated cells, which were concentrated in the cell cycle, DNA repair, chromatin organization, gene expression and biosynthesis domains. Among them, six telomere-associated genes were up-regulated by lariciresinol-4-β-D-glucopyranoside treatment, which have been implicated in telomere regulation and stability. Collectively, we employed RNA-seq analysis to provide comprehensive insight into the mechanism of lariciresinol-4-β-D-glucopyranoside against influenza virus infection.

Topics: A549 Cells; Cluster Analysis; Computational Biology; Epithelial Cells; Furans; Gene Expression Profiling; Gene Expression Regulation; High-Throughput Nucleotide Sequencing; Humans; Influenza A virus; Lignans; Transcriptome

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

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

Lariciresinol (LA) is a traditional Chinese medicine possessing anticancer activity, but its mechanism of action remains unclear. The present study explored the effects of LA on human HepG2 cells and the underlying mechanism. Our data indicated that LA inhibited cell proliferation and induced cell cycle arrest in S phase, subsequently resulting in apoptosis in HepG2 cells. Using a proteomics approach, eight differentially expressed proteins were identified. Among them, three proteins, glyceraldehyde-3-phosphate, UDP-glucose 4-epimerase, and annexin A1, were upregulated, while the other five proteins, heat shock protein 27, haptoglobin, tropomodulin-2, tubulin alpha-1A chain, and brain acid soluble protein 1, were downregulated; all of these proteins are involved in cell proliferation, metabolism, cytoskeletal organization, and movement. Network analysis of these proteins suggested that the ubiquitin-conjugating enzyme (UBC) plays an important role in the mechanism of LA. Western blotting confirmed downregulation of heat shock protein 27 and upregulation of ubiquitin and UBC expression levels in LA-treated cells, consistent with the results of two-dimensional electrophoresis and a STRING software-based analysis. Overall, LA is a multi-target compound with anti-cancer effects potentially related to the ubiquitin-proteasome pathway. This study will increase our understanding of the anticancer mechanisms of LA.

Topics: Amino Acid Sequence; Antineoplastic Agents, Phytogenic; Apoptosis; Carcinoma, Hepatocellular; Cell Cycle; Cell Proliferation; Furans; Hep G2 Cells; Hepatocytes; Humans; Lignans; Liver Neoplasms; Patrinia; Protein Interaction Maps; Proteome; Proteomics

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

A lignan, lariciresinol, is an important efficacious compound for the antiviral effect of Isatis indigotica, a widely used herb for the treatment of colds, fever, and influenza. Although some rate-limiting steps of the lariciresinol biosynthetic pathway are well known, the specific roles of gene family members in I. indigotica in regulating lariciresinol production are poorly understood. In the present study, a correlation analysis between the RNA sequencing (RNA-Seq) expression profile and lignan content by using I. indigotica hairy roots treated with methyl jamonate (0.5 μM) at different time points as a source implicated that I. indigotica pinoresinol/lariciresinol reductase 1 (IiPLR1), but not IiPLR2 or IiPLR3, contributed greatly to lariciresinol accumulation. Gene silencing by RNA interference (RNAi) demonstrated that IiPLR1 indeed influenced lariciresinol biosynthesis, whereas suppression of IiPLR2 or IiPLR3 did not change lariciresinol abundance significantly. IiPLR1 was thus further characterized; IiPLR1 was constitutively expressed in roots, stems, leaves, and flowers of I. indigotica, with the highest expression in roots, and it responds to different stress treatments to various degrees. Recombinant IiPLR1 reduces both (±)-pinoresinol and (±)-lariciresinol efficiently, with comparative K cat/K m values. Furthermore, overexpression of IiPLR1 significantly enhanced lariciresinol accumulation in I. indigotica hairy roots, and the best line (ovx-2) produced 353.9 μg g(-1) lariciresinol, which was ~6.3-fold more than the wild type. This study sheds light on how to increase desired metabolites effectively by more accurate or appropriate genetic engineering strategies, and also provides an effective approach for the large-scale commercial production of pharmaceutically valuable lariciresinol by using hairy root culture systems as bioreactors.

Topics: Furans; Isatis; Lignans; Molecular Sequence Data; Phylogeny; Plant Proteins; Sequence Analysis, DNA; Transcriptome

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

Chemical investigation from roots of Enkleia siamensis (Kurz) Nervling resulted in the isolation of 10 compounds. Their structures were established on the basis of 1D and 2D NMR spectroscopic data as linobiflavonoid (1), chamaejasmin (2), 7-O-β-D-glucopyranosylchamaejasmin (3), ormocarpin (4), (-)-wikstromol (5), matairesinol (6), (+)-lariciresinol (7), umbelliferone (8), daphnoretin (9) and carthamidin (10). Compounds 2 and 8 showed cytotoxicity against KB, MCF-7 and NCI-H187 cancer cell lines. Compounds 1, 2 and 5 showed weak minimum inhibitory requirements to acetylcholinesterase with values ranging from 50 to 1000 ng. In addition, compound 2 exhibited antimalarial activity against Plasmodium falciparum with an IC50 value of 2.32 μg/mL.

Topics: Antimalarials; Antineoplastic Agents, Phytogenic; Biflavonoids; Cholinesterase Inhibitors; Coumarins; Drug Screening Assays, Antitumor; Flavonoids; Furans; Humans; KB Cells; Lignans; Nuclear Magnetic Resonance, Biomolecular; Plant Roots; Plasmodium falciparum; Thailand; Thymelaeaceae

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

Phyto-oestrogens have been suggested to have a protective effect on hormone-sensitive cancers. However, few studies have investigated the association between dietary phyto-oestrogens and gynaecological cancers. In the present study, we analysed data from two population-based case-control studies of ovarian (1366 cases and 1414 controls) and endometrial (1288 cases and 1435 controls) cancers. Dietary intake information was obtained using a 135-item FFQ, and phyto-oestrogen intake was estimated using published food composition databases. Unconditional logistic regression was used to estimate adjusted OR and 95% CI. In multivariable analyses, there was a suggestive pattern of inverse associations between increasing intakes of total phyto-oestrogens, isoflavones and enterolignans and the risk of ovarian cancer. However, the results only reached statistical significance for the lignan compounds matairesinol and lariciresinol, where the OR for the highest v. the lowest intake category was 0.72 (95% CI 0.54, 0.96; P for trend = 0.02) for matairesinol and 0.72 (95% CI 0.55, 0.96; P for trend = 0.03) for lariciresinol. When the risk of ovarian cancer was assessed by subtype, there was an indication that increasing intakes of phyto-oestrogens may be associated with a decreased risk of mucinous (cases n 158) ovarian tumours (OR for the highest v. the lowest intake category: 0.47 (95% CI 0.24, 0.93); P for trend = 0.04). However, there were no significant associations with other histological subtypes. In contrast, dietary phyto-oestrogens (total or any subclass) were unrelated to the risk of endometrial cancer cases overall or by subtype.

Topics: Adenocarcinoma, Mucinous; Aged; Australia; Case-Control Studies; Diet; Diet Surveys; Endometrial Neoplasms; Female; Furans; Humans; Isoflavones; Lignans; Lignin; Logistic Models; Middle Aged; Odds Ratio; Ovarian Neoplasms; Phytoestrogens; Surveys and Questionnaires

Phytochemical investigation on the stems of Trigonostemonheterophyllus led to the isolation of a new lariciresinol-based lignan glycoside, trigonoheteran (1), together with a known lignan glycoside, aviculin (2). Their structures were elucidated by spectroscopic methods including 1D and 2D NMR (HMQC, (1)H-(1)H COSY, HMBC, and NOESY).

Topics: Euphorbiaceae; Furans; Glycosides; Lignans; Molecular Structure

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

The syntheses of 55 lariciresinol derivatives containing derivatives on the 9-position and an aryl group at both 7- and 7'-positions were successful to examine the effect of structure of (-)-lariciresinol (1) on plant growth regulatory activity. (-)-(7R,8R,8'S)-9-Dehydroxylariciresinol 9 showed activity 2-fold more potent than that of natural (-)-lariciresinol (1) and -95% growth inhibitory activity to negative control against rye grass root at 1 mM. The derivatives bearing hydrophobic and smaller groups at the 9-position showed higher activity. The importance of 4- and 4'-hydroxy groups and 3- and 3'-small hydrophobic groups on 7- and 7'-phenyl groups for higher activity was also suggested.

Topics: Furans; Herbicides; Lignans; Lolium; Structure-Activity Relationship

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

Linum album has been shown to accumulate anti-tumor podophyllotoxin (PTOX) and its related lignans. In the present study, we examined the effects of five fungal extracts on the production of lignans in L. album cell cultures. Fusarium graminearum extract induced the highest increase of PTOX [140μgg(-1) dry weight (DW) of the L. album cell culture] which is seven-fold greater than the untreated control, while Rhizopus stolonifer extract enhanced the accumulation of lariciresinol, instead of PTOX, up to 365μgg(-1) DW, which was 8.8-fold greater than the control. Quantitative PCR analyses showed that expression of the enzyme genes responsible for the PTOX biosynthesis cascade, such as pinoresinol-lariciresinol reductase (PLR), phenylalanine ammonia-lyase (PAL), cinnamoyl-CoA reductase (CCR) and cinnamyl-alcohol dehydrogenase (CAD) genes, were also up-regulated in a fungal extract-selective fashion. These results provide evidence that the fungal extracts used in this study differentially increase the production of PTOX or larisiresinol via the up-regulation of the genes in lignan biosynthesis in L. album cell cultures, and suggest that such selective actions of fungal elicitors on the lignan synthesis will lead to more efficient metabolic engineering-based production of PTOX and other beneficial lignans using L. album cell cultures.

Topics: Aldehyde Oxidoreductases; Biosynthetic Pathways; Cells, Cultured; Flax; Furans; Fusarium; Gene Expression Regulation, Plant; Genes, Plant; Lignans; Oxidoreductases; Phenylalanine Ammonia-Lyase; Podophyllotoxin; Rhizopus

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

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

Lariciresinol is an enterolignan precursor isolated from the herb Sambucus williamsii, a folk medicinal plant used for its therapeutic properties. In this study, the antifungal properties and mode of action of lariciresinol were investigated. Lariciresinol displays potent antifungal properties against several human pathogenic fungal strains without hemolytic effects on human erythrocytes. To understand the antifungal mechanism of action of lariciresinol, the membrane interactions of lariciresinol were examined. Fluorescence analysis using the membrane probe 3,3'-diethylthio-dicarbocyanine iodide (DiSC(3)-5) and 1,6-diphenyl-1,3,5-hexatriene (DPH), as well as a flow cytometric analysis with propidium iodide (PI), a membrane-impermeable dye, indicated that lariciresinol was associated with lipid bilayers and induced membrane permeabilization. Therefore, the present study suggests that lariciresinol possesses fungicidal activities by disrupting the fungal plasma membrane and therapeutic potential as a novel antifungal agent for the treatment of fungal infectious diseases in humans.

Topics: Antifungal Agents; Benzothiazoles; Candida albicans; Carbocyanines; Cell Membrane; Cells, Cultured; Diphenylhexatriene; Erythrocytes; Flow Cytometry; Fluorescent Dyes; Furans; Hemolysis; Hemolytic Agents; Humans; Lignans; Propidium; Sambucus

All stereoisomers of lariciresinol were synthesized to examine the effect of stereochemistry on plant growth. Configuration of benzylic 7-positions was constructed through S(N)1 or S(N)2 intramolecular etherification. 8- and 8'-position configurations were established from the starting material except for all cis stereoisomers, the 8-position configurations of which were achieved by employing stereoselective hydroboration. (-)-Lariciresinol and its 7S,8S,8'R stereoisomer inhibited the root growth of Italian ryegrass to 51-55% relative to the negative control, whereas other stereoisomers had less effect. These results demonstrate that the stereochemistry of lignans is one of the important factors influencing their inhibitory activity.

Topics: Furans; Germination; Lactuca; Lignans; Lolium; Plant Development; Plant Roots; Plants; Seeds; Stereoisomerism; Structure-Activity Relationship

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

Chemical investigation of the EtOH extract of the fresh stem of Aquilaria sinensis collected in Hainan Province of China resulted in the isolation of a new benzenoid, named aquilarin A (1), together with two known compounds balanophonin (2) and (+)-lariciresinol (3). Their structures were elucidated by a study of their physical and spectral data. Compounds 2 and 3 exhibited cytotoxicity against SGC-7901 and SMMC-7721 cell lines.

Topics: Antinematodal Agents; Benzene Derivatives; Cell Line, Tumor; Furans; Humans; Lignans; Magnetic Resonance Spectroscopy; Molecular Structure; Plant Stems; Thymelaeaceae

X-ray structures of two compounds isolated from wood knots of coniferous trees, namely dihydrokaempferol (3,5,8,13-tetrahydroxyflavanon) and lariciresinol (3,14-dimetoxy-7,10-epoxylignan-4,15,19-triol), are presented here. Diffraction data for the Dihydrokaempferol crystals were collected on a CAD4 diffractometer and on a synchrotron for the lariciresinol crystal. The investigated compounds inhibit lipid peroxidation and lariciresinol is additionally a good scavenger of superoxide radicals. The structural data presented in this work provide a useful basis for designing more active compounds with potential use as antioxidants.

Topics: Abies; Europe; Flavonoids; Furans; Lignans; Molecular Structure; Phenols; Polyphenols; Populus; X-Ray Diffraction

Lariciresinol is a dietary lignan that accounts for a significant portion of the total phytoestrogen intake from Western foods. Recent epidemiological studies suggest that high dietary intake of lignans and lariciresinol is associated with reduced breast cancer risk. However, no causal relationship between lariciresinol intake and breast cancer development has been established. In this study, we investigated for the first time the effects and possible mechanisms of action of lariciresinol on hormone responsive mammary cancer in vivo in dimethylbenz[a]anthracene induced mammary cancer in rats, and in human MCF-7 breast cancer xenografts in athymic mice. For tumor bearing rats, lariciresinol (3 or 15 mg/kg of body weight) or vehicle was administered p.o. daily for 9 weeks. For E2-maintained ovariectomized athymic mice bearing orthotopic MCF-7 tumors, control diet (AIN-93G) or lariciresinol containing diet (AIN-93G supplemented with 20 or 100 mg of lariciresinol/kg of diet) was administered for 5 weeks. In both models, lariciresinol administration inhibited the tumor growth and tumor angiogenesis. In MCF-7 cells, enterolactone significantly inhibited the E2-stimulated VEGF secretion. Moreover, in MCF-7 xenografts, lariciresinol administration enhanced tumor cell apoptosis and increased estrogen receptor beta expression. Lariciresinol and its further metabolites secoisolariciresinol, enterodiol and enterolactone were found in serum of both rats and athymic mice confirming a similar lignan metabolism pattern as in humans. These findings indicate conceivable importance of dietary lignan lariciresinol in inhibition of breast cancer development.

Topics: 4-Butyrolactone; 9,10-Dimethyl-1,2-benzanthracene; Angiogenesis Inhibitors; Animals; Antineoplastic Agents; Apoptosis; Butylene Glycols; Carcinogens; Cell Proliferation; Dietary Supplements; Estrogen Receptor alpha; Estrogen Receptor beta; Female; Furans; Gene Expression Regulation, Neoplastic; Humans; Lignans; Mammary Neoplasms, Experimental; Mice; Mice, Nude; Ovariectomy; Phytoestrogens; Rats; Receptors, Progesterone; Transplantation, Heterologous

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

To study the chemical constituents in the root of Isatis indigotica.. The constituents root were separated through various chromatographic techniques and their structures were elucidated by means of physicochemical properties and the analysis of their spectral data.. Eleven compounds were isolated and identified as (+) -isolariciresinol (1), lariciresinol (2), lariciresinol-9-O-beta-D-glucopyranoside (3), lariciresinol-4'-O-beta-D-glucopyranoside (4), lariciresinol-4,4'-bis-O-beta-D-glucopyranoside (5), 3-formylindole (6), 1-methoxy-3-indolecarbaldehyde (7), 1-methoxy-3-indoleacetonitrile (8), deoxyvasicinone (9), epigoitrin (10), adenosine (11).. Compounds 4-8 were isolated from I. indigotica for the first time.

Topics: Furans; Glucosides; Indoles; Isatis; Lignans; Lignin; Naphthols; Plant Extracts; Plant Roots; Plants, Medicinal; Spectrometry, Mass, Electrospray Ionization

To study the chemical constituents of Sambucus adnata.. Compounds were isolated by silica gel chromatography. Their structures were elucidated by means of spectral analysis.. Five compounds were isolated and identified as: 1-(3-hydroxy4-methoxyphenyl)-1',2'-ethanediol (1), ursolic acid (2 ), 1-( 3,4,5 -trimethoxyphenyl) -1', 2'-ethanediol (3), lariciresinol (4), 5, 7, 3', 4'-tetramethoxyflavone-3-O-rhamnopyranosyl-(1 --> 6)-glucopyranoside(5).. Compounds 1, 3, 4 and 5 were obtained from this plant for the first time.

Topics: Disaccharides; Flavones; Furans; Lignans; Magnetic Resonance Spectroscopy; Molecular Structure; Plant Extracts; Plants, Medicinal; Sambucus; Triterpenes; Ursolic Acid

To study the bioactive constituents of the fresh rhizome of Pinellia ternata, and provide the scientific basis for quality control.. Various chromatographic techniques were used to separate and purify the chemical constituents, and their chemical structures were determined on the basis of physical-chemical properties and spectroscopic analysis. The inhibitory effects of the isolated compounds on tumor necrosis factor (TNF)-alpha production in the peritoneal macrophages of mice stimulated with lipopolysaccharide (LPS) were assayed in vitro by microplate colorimetric method.. Nine compounds were isolated and identified as (E)-p-coumaryl alcohol (1), 3, 4-dihydroxycinnamyl alcohol (2), ferulic acid (3), lariciresinol (4), erythro-guaiacylglycerol-beta-O-4'-sinapyl ether (5), dehydrodiconiferyl alcohol (6) , isolariciresinol (7) , sachaliside 1 (8) and coniferin (9). The inhibitory effect of compounds 1, 2, 3, 8, and 9 were 24.1% , 57.6% , 40.2% , 82.7% , and 62.0% , respectively, against the TNF-alpha production in the peritoneal macrophages of mice stimulated with LPS at a concentration of 10(-5) mol L(-1) in vitro.. The compounds 1, 2 and 4-8 from genera Pinellia Ten. and compound 9 from P. ternata were isolated for the first time. The compounds 1, 2, 8 and 9 were phenylpropanoids, and 4-7 were lignanoids. The anti-inflammatory effects of the rhizome of P. ternata might relate at the least to compounds 1, 2, 3, 8 and 9.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cells, Cultured; Cinnamates; Coumaric Acids; Furans; Lignans; Macrophages, Peritoneal; Male; Mice; Mice, Inbred C57BL; Molecular Structure; Pinellia; Plants, Medicinal; Rhizome; Tumor Necrosis Factor-alpha

The paper describes a method for the determination of selected lignans in plant foods. First, samples were submitted to methanolysis resulting in cleavage of ester bonds between lignan glycosides and organic acids. Glycosidic linkages were then broken by enzymatic hydrolysis using cellulase. The released aglycones were separated isocratically (acetonitrile/10 mM sodium acetate buffer, pH 4.8, 225:775, v:v) by reversed phase high performance liquid chromatography (RP-HPLC) and the compounds were detected coulometrically at four electrodes set on potentials between +260 and +330 mV against palladium reference electrodes. The selectivity and sensitivity of the method allowed quantitation of the lignans secoisolariciresinol, lariciresinol and isolariciresinol in various foodstuffs down to the upper ppb-range with recoveries between 44.7 and 97.0%. Unidentified peaks displaying similar current-voltage curves (CVCs) as the investigated lignans indicated the presence of further possible lignan representatives. In addition, investigation of various foodstuffs involving enzymatic hydrolysis with and without preceding methanolysis showed that the degree of esterification of lignans in plant foods is species dependent.

Topics: Butylene Glycols; Calibration; Chromatography, High Pressure Liquid; Electrochemistry; Electrodes; Furans; Hydrolysis; Lignans; Lignin; Molecular Structure; Naphthols; Plants, Edible; Reproducibility of Results

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

To study the chemical constituents of the leaves of Isatis indigotica.. The leaves of I. indigotica were extracted with 80% ethanol. The EtOH extract was dispersed in H20 and extracted with petroleum, EtOAc and BuOH successively. The EtOAc fraction was isolated and purified by column chromatography on silica gel, Sephadex LH -20 and Rp-8, Rp-18. All the compounds were identified on the basis of spectral analyses (including MS, 1H-NMR, 13 C-NMR) , RESULT: Eleven compounds were isolated from the leaves of I. indigotica, and structures were characterized as 10H-indolo [3, 2-b] quinoline (1), indirubin (2), 4 (3H)-quinazo-linone (3), (E)-3-(3', 5'-dimethoxy-4'-hydroxybenzylidene) -2-indolinone (4), 2, 3-dihydropyrrolo [2, 1-b] quinazolin-9(1H) -one (5) , benzoic acid (6) , o-droxy-benzoic acid (7), ( - ) -lariciresinol (8) , ( + ) -isolariciresinol (9), isovitexin (10), 6-f-D-glucopyranosyldiosmetin (11).. 1, 4, 5, 8, 9, 11 were obtained from the leaves of I. indigotica for the first time.

Topics: Furans; Indole Alkaloids; Isatis; Lignans; Lignin; Naphthols; Plant Leaves; Plants, Medicinal; Quinolines

To study the chemical constituents in bark of Larix olgensis var. koreana.. The compounds were isolated with silica gel column chromatography and their structures were elucidated on the basis of spectral analysis (IR, EI-MS, 1H-NMR, 13C-NMR).. Eight compounds were isolated and identified as isopimaric acid (I), beta-sitosterol (II), 24R,5alpha-stigmast-3,6-dione (III), larixol (IV), ferulic acid (V), lariciresinol (VI), secroisolariciresinol (VII) and isolariciresinol (VIII).. All the compounds were isolated from this plant for the first time.

Topics: Carboxylic Acids; Furans; Larix; Lignans; Phenanthrenes; Plant Bark; Plants, Medicinal; Sitosterols

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

Six new lignans (2-7) were isolated from the bark of Larix olgensis var. koreana, and their structures were determined on the basis of their spectroscopic data. Seven known lignans were also obtained and identified as (+)-lariciresinol 9'-p-coumarate (1), (+)-lariciresinol, (-)-secoisolariciresinol, (+)-isolariciresinol, vladinol D, sesquipinsapol B, and ehletianol C. Compound 1 showed weak inhibition against K562, SHG44, HCT-8, A549, and PC-3M tumor cells with IC50 values of 2.9, 21.4, 32.9, 33.8, and 28.0 microg/mL, respectively.

Topics: Antineoplastic Agents, Phytogenic; Butylene Glycols; Drug Screening Assays, Antitumor; Drugs, Chinese Herbal; Furans; Inhibitory Concentration 50; Larix; Lignans; Molecular Structure; Plants, Medicinal; Stereoisomerism; Tumor Cells, Cultured

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

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

By anaerobic incubation of pinoresinol diglucoside (1) from the bark of Eucommia ulmoides with a fecal suspension of humans, eleven metabolites were formed, and their structures were identified as (+)-pinoresinol (2), (+)-lariciresinol (3), 3'-demethyl-(+)-lariciresinol (4), (-)-secoisolariciresinol (5), (-)-3-(3", 4"-dihydroxybenzyl)-2-(4'-hydroxy-3'-methoxybenzyl)butane-1, 4-diol (6), 2-(3', 4'-dihydroxybenzyl)-3-(3", 4"-dihydroxybenzyl)butane-1, 4-diol (7), 3-(3"-hydroxybenzyl)-2-(4'-hydroxy-3'-methoxybenzyl)butane-1, 4-diol (8), 2-(3', 4'-dihydroxybenzyl)-3-(3"-hydroxybenzyl)butane-1, 4-diol (9), (-)-enterodiol (10), (-)-(2R, 3R)-3-(3", 4"-dihydroxybenzyl)-2-(4'-hydroxy-3'-methoxybenzyl)butyrolactone (11), (-)-(2R, 3R)-2-(3', 4'-dihydroxybenzyl)-3-(3", 4"-dihydroxybenzyl)butyrolactone (12), (-)-(2R, 3R)-3-(3"-hydroxybenzyl)-2-(4'-hydroxy-3'-methoxybenzyl)butyrolactone (13), 2-(3', 4'-dihydroxybenzyl)-3-(3"-hydroxybenzyl)butyrolactone (14), 2-(3'-hydroxybenzyl)-3-(3", 4"-dihydroxybenzyl)butyrolactone (15) and (-)-(2R, 3R)-enterolactone (16) by various spectroscopic means, including two dimensional (2D)-NMR, mass spectrometry and circular dichroism. A possible metabolic pathway was proposed on the basis of their structures and time course experiments monitored by thin-layer chromatography. Furthermore, a bacterial strain responsible for the transformation of (+)-pinoresinol to (+)-lariciresinol was isolated from a human fecal suspension and identified as Enterococcus faecalis strain PDG-1.

Topics: Anticarcinogenic Agents; Biotransformation; Chromatography, High Pressure Liquid; Circular Dichroism; Dealkylation; Enterococcus faecalis; Feces; Furans; Humans; Intestines; Lignans; Magnetic Resonance Spectroscopy; Mass Spectrometry; Plant Bark; Plants, Medicinal; Spectrophotometry, Ultraviolet

To study the lignans from Patrinia scabra Bunge.. The constituents were separated and purified by column chromatography with silical gel, RP-silical gel and Sephadex LH-20. Their structures were identified on the basis of spectral data (IR, MS, 1HNMR, 13CNMR, HMQC and HMBC).. A new lignan was obtained and its structure was elucidated as 4-[1-ethoxyl-1-(4-hydroxy-3-methoxy)benzyl]methyl- 2-(4-hydroxy-3-methoxy)benzyl-3-hydroxymethyl-tetrahydro-furan (2), along with three known lignans, lariciresinol (1), isolariciresinol (3) and nortracheloside (4).

Topics: Furans; Guaiacol; Lignans; Lignin; Molecular Structure; Naphthols; Patrinia; Plant Roots; Plants, Medicinal

Five compounds were isolated from the roots of Patrinia scabra Bunge separated and purified on sillica gel column chromatography. Their structures were elucidated on the physico-chemical properties and spectral data as lariciresinol(I), syringaresinol(II), scopoletin(III), quercetin(IV), ferulaic acid(V). All compounds were obtained from P. scabra for the first time. In vitro biological test of these compounds showed that syringaresinol was able to stimulate T and B lymphocyte proliferation.

Topics: B-Lymphocytes; Cell Division; Drugs, Chinese Herbal; Furans; Lignans; Patrinia; Plant Roots; Plants, Medicinal; Scopoletin; T-Lymphocytes

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

(+)-Lariciresinol 3a-acetate [(+)-(3S)-acetyloxymethyl-(2S)-(4-hydroxy-3-methoxyphenyl)-(4R)-[(4-hydroxy-3-methoxyphenyl)methyl]tetrahydrofuran] (1), a metabolite of A. elaeagnoidea was synthesized starting from (-)-lariciresinol (2) in three steps with an overall yield of 66%.

Topics: Furans; Guaiacol; Lignans; Lignin; Magnetic Resonance Spectroscopy; Magnoliopsida; Models, Chemical

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 mammalian lignans enterolactone and enterodiol are regular constituents of human urine and are excreted daily in mumol amounts. They are produced by metabolic action of intestinal bacteria from natural plant lignan precursors which are constituents of various food plants. However, natural plant lignans seem to occur very seldom in detectable amounts in human urine. The present investigation shows that only in 5% of the 150 diphenolic fractions extracted from the urine of women plant lignans other than the previously identified matairesinol could be found. The lignans lariciresinol, isolariciresinol and secoisolariciresinol were identified for the first time by comparison of their GC characteristics and mass spectra with the corresponding results of authentic synthesized reference compounds. Secoisolariciresinol is one natural precursor of the mammalian lignan enterodiol. Of the two other plant lignans, no animal or human metabolic products are known. The occurrence of chemically unchanged plant lignans in some cases in human urine could be a result of an insufficient metabolic capacity of intestinal bacteria, resulting in a decreased detoxification of phenolic plant products.

Topics: Adult; Butylene Glycols; Chemical Phenomena; Chemistry; Female; Furans; Gas Chromatography-Mass Spectrometry; Humans; Lignans; Lignin; Naphthols; Plant Extracts