lignans and dihydroguaiaretic-acid

The MeOH extract from leaves of Saururus cernuus L. (Saururaceae) displayed in vitro activity against trypomastigote forms of T. cruzi (100% of parasite death at 200 μg/mL), suggesting the presence of bioactive compounds. Thus, the bioactivity-guided fractionation was carried out, leading to the isolation of three related neolignan derivatives, identified as threo-austrobailignan-5 (1), threo-austrobailignan-6 (2), and threo-dihydroguaiaretic acid (3). Anti-T. cruzi activity of compounds 1-3 was performed against cell-derived trypomastigotes and intracellular amastigotes. Additionally, the mammalian cytotoxicity was investigated using NCTC cells. Compound 2 was the most effective against extracellular trypomastigotes with IC

Topics: Animals; Brazil; Cells, Cultured; Guaiacol; Lignans; Macrophages, Peritoneal; Membrane Potential, Mitochondrial; Mice, Inbred BALB C; Molecular Structure; Phytochemicals; Plant Leaves; Reactive Oxygen Species; Saururaceae; Trypanocidal Agents; Trypanosoma cruzi

The structure-activity relationship of the antifungal fluorinated dihydroguaiaretic acid derivatives was evaluated. Some of the newly synthesized lignan compounds were found to show higher antifungal activity against phytopathogenic fungi such as Alternaria alternata (Japanese pear and apple pathotypes) and A. citri than the lead compound, 3-fluoro-3'-methoxylignan-4'-ol (3). The broad antifungal spectrum of 3'-hydroxyphenyl derivative 16 was observed, and the 3'-fluoro-4'-hydroxyphenyl derivative 38 was found to show the highest activity against the A. alternata Japanese pear pathotype, with an EC

Topics: Alternaria; Fungicides, Industrial; Guaiacol; Lignans; Plant Diseases; Pyrus; Structure-Activity Relationship

Thirty-three meso-dihydroguaiaretic acid (meso-DGA) derivatives bearing esters, ethers, and amino-ethers were synthesized. All derivatives were tested against twelve drug-resistant clinical isolates of Gram-positive and Gram-negative bacteria, including sensitive (H37Rv) and multidrug-resistant Mycobacterium tuberculosis strains. Among the tested compounds, four esters (7, 11, 13, and 17), one ether (23), and three amino-ethers (30, 31, and 33) exhibited moderate activity against methicillin-resistant Staphylococcus aureus, whereas 30 and 31 showed better results than levofloxacin against vancomycin-resistant Enterococcus faecium. Additionally, nineteen meso-DGA derivatives displayed moderate to potent activity against M. tuberculosis H37Rv with minimum inhibitory concentration (MIC) values ranging from 3.125 to 50µg/mL. Seven meso-DGA derivatives bearing amino-ethers (26-31 and 33) exhibited the lowest MICs against M. tuberculosis H37Rv and G122 strains, with 31 being as potent as ethambutol (MICs of 3.125 and 6.25µg/mL). The presence of positively charged group precursors possessing steric and hydrophobic features (e.g. N-ethylpiperidine moieties in meso-31) resulted essential to significantly increase the antimycobacterial properties of parent meso-DGA as supported by the R-group pharmacophoric and field-based QSAR analyses. To investigate the safety profile of the antimycobacterial compounds, cytotoxicity on Vero cells was determined. The amino-ether 31 exhibited a selectivity index value of 23, which indicate it was more toxic to M. tuberculosis than to mammalian cells. Therefore, 31 can be considered as a promising antitubercular agent for further studies.

Topics: Animals; Anti-Bacterial Agents; Cell Survival; Chlorocebus aethiops; Dose-Response Relationship, Drug; Gram-Negative Bacteria; Gram-Positive Bacteria; Guaiacol; Lignans; Microbial Sensitivity Tests; Molecular Structure; Quantitative Structure-Activity Relationship; Vero Cells

Topics: 3T3-L1 Cells; Adipocytes; Adipogenesis; Animals; Glucose; Glucose Transporter Type 4; Guaiacol; Lignans; Mice; PPAR gamma; Up-Regulation

To investigate the chemical constituents from stems of Kadsura longipedunculata.. The constituents were isolated and purified by various chromatographic methods,and their structures were elucidated by spectroscopic analysis and comparison with literatures.. Seven compounds were isolated from the stems of Kadsura longipedunculata and were identified as longipedunin D( 1),renchangianin A( 2),renchangianin B( 3),meso-dihydroguaiaretic acid( 4),isolariciresinol-9-O-β-D-xyloside( 5),(-)-gallocatechin( 6) and( +)-catechin( 7).. Compound 1 is a novel lignan,and compounds 2,3 are isolated from this plant for the first time.

Topics: Chromatography; Guaiacol; Kadsura; Lignans; Molecular Structure; Plant Extracts; Plant Stems

meso-Dihydroguaiaretic acid (MDGA), which is a dibenzylbutane lignin isolated from the ethyl acetate fraction of Saururus chinensis, has various biological activities, including anti-oxidative, anti-inflammatory, anti-bacterial, and neuroprotective effects. However, no report has examined the potential anti-asthmatic activity of MDGA. In this study, we evaluated the protective effects of MDGA on asthmatic responses, particularly airway inflammation and mucus hypersecretion in an ovalbumin (OVA)-induced murine model of asthma. Intragastric administration of MDGA significantly lowered the productions of interleukin (IL)-4, IL-5, IL-13, tumor necrosis-α (TNF-α), eotaxin, monocyte chemoattractant protein-1 (MCP-1), vascular cell adhesion molecule-1 (VCAM-1), and immunoglobulin (Ig)E in bronchoalveolar lavage fluid (BALF), plasma, or lung tissues. Histological studies showed that MDGA inhibited OVA-induced inflammatory cell infiltration and mucus production in the respiratory tract. Moreover, MDGA markedly attenuated the OVA-induced activations of nuclear factor kappa B (NF-κB), extracellular-signal-regulated kinases 1/2 (ERK1/2), and p38 mitogen-activated protein kinase (p38 MAPK). Together, these results suggest that MDGA effectively inhibits airway inflammation and mucus hypersecretion by downregulating the levels of T helper 2 (Th2) cytokines, chemokines, and adhesion molecules, and inhibiting the activations of NF-κB and MAPKs.

Topics: Animals; Anti-Asthmatic Agents; Asthma; Cell Movement; Chemokine CCL2; Cytokines; Female; Guaiacol; Humans; Immunoglobulin E; Lignans; MAP Kinase Signaling System; Mice; Mice, Inbred BALB C; NF-kappa B; Pneumonia; Saururaceae; Th2 Cells; Vascular Cell Adhesion Molecule-1

meso-Dihydroguaiaretic acid (MDGA) is a major component of Myristica fragrans and Machilus thunbergii that is traditionally used as a spice and for medicinal purposes. Despite reports of various biological activities exerted by MDGA, there is no information regarding its metabolic properties. The purpose of this study was to determine the metabolic stability and cytochrome P450 (CYP) inhibitory potential of MDGA, using pooled human liver microsomes (HLMs) to characterize its metabolic properties. In addition, pharmacokinetic analysis was performed in mice treated intravenously (5 mg/kg) or orally (20 mg/kg) with MDGA for comparison with our in vitro results. The half-life of MDGA in HLMs and mouse liver microsomes incubated with NADPH, UDPGA or NADPH plus UDPGA was 25.41 and 22.74, 0.39 and 0.20 or 0.28 and 0.22 min, respectively. In our pharmacokinetic study, MDGA rapidly declined in plasma and had low bioavailability, which was attributable to extensive metabolism by UDP-glucuronosyltransferases and CYPs. Among CYP isoforms, CYP2E1 activity was selectively inhibited by MDGA through a competitive inhibitory mode, with an inhibitory constant (Ki) value of 13.1 µM. These results suggest that MDGA can be used as a selective CYP2E1 inhibitor in vitro, which warrants evaluation of the pharmacological significance of MDGA-induced CYP2E1 inhibition.

Topics: Animals; Cytochrome P-450 CYP2E1 Inhibitors; Cytochrome P-450 Enzyme System; Glucuronosyltransferase; Guaiacol; Half-Life; Humans; Lauraceae; Lignans; Male; Mice; Mice, Inbred ICR; Microsomes, Liver

(-)-Dihydroguaiaretic acid (DGA) and its derivatives having 3-hydroxyphenyl (3-OH-DGA) and variously substituted phenyl groups instead of 3-hydroxy-4-methoxyphenyl groups were synthesized to measure their larvicidal activity against the mosquito Culex pipiens Linnaeus, 1758 (Diptera: Culicidae). Compared with DGA and 3-OH-DGA (LC50 (M), 3.52 × 10(-5) and 4.57 × 10(-5), respectively), (8R,8'R)-lignan-3-ol (3) and its 3-Me (10), 2-OH (12), 3-OH (13), and 2-OMe (15) derivatives showed low potency (ca. 6-8 × 10(-5) M). The 4-Me derivative (11) showed the lowest potency (12.1 × 10(-5) M), and the 2-F derivative (4) showed the highest (2.01 × 10(-5) M). All of the synthesized compounds induced an acute toxic symptom against mosquito larvae, with potency varying with the type and position of the substituents. The 4-F derivative (6), which killed larvae almost completely within 45 min, suppressed the O2 consumption of the mitochondrial fraction, demonstrating that this compound inhibited mitochondrial O2 consumption contributing to a respiratory inhibitory activity.

Topics: Animals; Culex; Guaiacol; Insecticides; Larva; Lignans; Molecular Structure; Oxygen

Meso-dihydroguaiaretic acid (MDA) is known for its anti-inflammatory, anti-oxidant, anti-bacterial, and anti-tumor activity. However, the anti-breast cancer effect and the mechanism of MDA remain undefined.. In this study, we examined the anti-cancer activity and the mechanisms of action of MDA in breast cancer cell lines, 4T-1 and MCF-7 cells; and 4T-1 bearing mouse model.. MDA showed cytotoxic effects on 4T-1 and MCF-7 cells in a dose-dependent manner. Moreover, MDA increased the amount of Annexin V-positive apoptotic bodies, phosphorylated JNK and p38 in 4T-1 cells. MDA also down-regulated cell-cycle dependent proteins, CDK-4 and cyclin D1; and induced cleaved caspase-3 in MDA-treated 4T-1 cells. We further verified that MDA-induced apoptosis is mediated by p38 and caspase-3 activation in 4T-1 cells. Next, we studied the effect of MDA treatment on cell migration and found that MDA significantly reduced cell migration. Moreover, MDA reduced EGFR and intergrin β3 expression, and dephosphorylated Src in a dose-dependent manner in 4T-1 cells. Furthermore, we observed in vivo effect of MDA in 4T-1 cell inoculated mice. MDA (20mg/kg/day) significantly suppressed mammary tumor volume and activated caspase-3 in tumor tissues.. These results suggest novel targets of MDA in breast cancer in vitro and in vivo, making it a potential candidate as a chemotherapeutic drug.

Topics: Animals; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cell Movement; Cell Survival; Dose-Response Relationship, Drug; Down-Regulation; Enzyme Activation; ErbB Receptors; Female; Genes, src; Guaiacol; Humans; Integrin beta3; Lignans; Mammary Neoplasms, Experimental; MCF-7 Cells; Mice; p38 Mitogen-Activated Protein Kinases

Cytotoxic activities of synthesized lignan derivatives were estimated by WST-8 reduction assay against HL-60 and HeLa cells to show the structure-activity relationship. The activities of some effective compounds were examined against Colon 26 and Vero cells. Dietary secoisolariciresinol (SECO, 1) and its metabolite, 9,9'-anhydrosecoisolariciresinol (2), did not show the cytotoxic activity. On the other hand, all stereoisomers of dihydroguaiaretic acid (DGA, 9,9'-dehydroxysecoisolariciresinol, 3-5) exhibited the activity (IC50: around 30 μM). The IC50 value of (8R,8'R)-9-butyl DGA derivative 13 was around 6 μM. This fact means that the hydrophobic group was advantageous for higher activity at 9- and 9'-positions. By the evaluation of the effect of 7and 7'-aryl group on the activity, we discovered the highest activity of (8R,8'R)-7-(3-hydroxy-4-methoxyphenyl)-7'-(2-ethoxyphenyl) DGA derivative 47 showing around 1 μM of IC50 value, which is about 24-fold higher activity than that of natural (8R,8'R)-DGA. The derivative of dietary lignan showed the high cytotoxic activity.

Topics: Animals; Cell Proliferation; Cell Survival; Chlorocebus aethiops; Cytotoxins; Guaiacol; HL-60 Cells; Humans; Lignans; Molecular Structure; Structure-Activity Relationship; Vero Cells

Collaborative regulation of liver X receptor (LXR) and sterol regulatory element binding protein (SREBP)-1 are main determinants in hepatic steatosis, as shown in both animal models and human patients. Recent studies indicate that selective intervention of overly functional LXRα in the liver shows promise in treatment of fatty liver disease. In the present study, we evaluated the effects of meso-dihydroguaiaretic acid (MDGA) on LXRα activation and its ability to attenuate fatty liver in mice. MDGA inhibited activation of the LXRα ligand-binding domain by competitively binding to the pocket for agonist T0901317 and decreased the luciferase activity in LXRE-tk-Luc-transfected cells. MDGA significantly attenuated hepatic neutral lipid accumulation in T0901317- and high fat diet (HFD)-induced fatty liver. The effect of MDGA was so potent that treatment with 1mg/kg for 2 weeks completely reversed the lipid accumulation induced by HFD feeding. MDGA reduced the expression of LXRα co-activator protein RIP140 and LXRα target gene products associated with lipogenesis in HFD-fed mice. These results demonstrate that MDGA has the potential to attenuate nonalcoholic steatosis mediated by selective inhibition of LXRα in the liver in mice.

Topics: Animals; Base Sequence; Cell Line, Tumor; Diet, High-Fat; DNA Primers; Fatty Liver; Guaiacol; Humans; Lignans; Lipogenesis; Liver X Receptors; Mice; Mice, Inbred C57BL; Molecular Docking Simulation; Non-alcoholic Fatty Liver Disease; Orphan Nuclear Receptors

Abnormal proliferation of vascular smooth muscle cells (VSMCs) plays an essential functional role in the pathogenesis of vascular disorders, such as atherosclerosis, restenosis, and neointimal hyperplasia. In this study, we examined the effects of meso-dihydroguaiaretic acid (MDGA) on platelet-derived growth factor (PDGF)-BB-induced proliferation and the molecular basis of its underlying mechanism of action in rat aortic VSMCs. Incubation of resting VSMCs with MDGA for 24 h significantly diminished PDGF-BB-induced DNA synthesis in a dose-dependent manner. We also examined the effects of MDGA on PDGF-BB signal transduction. Pre-treatment of VSMCs with MDGA inhibited PDGF-BB-induced phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2), p38, and C-Jun N-terminal kinase (JNK). MDGA also effectively inhibited phosphorylation of Akt, phospholipase C gamma 1 (PLCγ1), and PDGF receptor beta (PDGFRβ). These results indicate that MDGA may inhibit proliferation of VSMCs by suppressing autophosphorylation of PDGFRβ, and may be useful in the treatment of VSMC-associated vascular disease such as atherosclerosis, restenosis, and neointimal hyperplasia after angioplasty.

Topics: Animals; Aorta; Becaplermin; Cell Proliferation; Cells, Cultured; Extracellular Signal-Regulated MAP Kinases; Guaiacol; JNK Mitogen-Activated Protein Kinases; Lignans; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; p38 Mitogen-Activated Protein Kinases; Phospholipase C gamma; Phosphorylation; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-sis; Rats; Signal Transduction

The isolation and characterization of the lignan meso-dihydroguaiaretic acid (MDGA) from Larrea tridentata and its activity against Mycobacterial tuberculosis has been demonstrated, but no information regarding its mechanism of action has been documented. Therefore, in this study we carry out the gene expression from total RNA obtained from M. tuberculosis H37Rv treated with MDGA using microarray technology, which was validated by quantitative real time polymerase chain reaction. Results showed that the alpha subunit of coenzyme A transferase of M. tuberculosis H37Rv is present in both geraniol and 1-and 2-methylnaphthalene degradation pathways, which are targeted by MDGA. This assumption was supported by molecular docking which showed stable interaction between MDGA with the active site of the enzyme. We propose that inhibition of coenzyme A transferase of M. tuberculosis H37Rv results in the accumulation of geraniol and 1-and 2-methylnaphtalene inside bacteria, causing membrane destabilization and death of the pathogen. The natural product MDGA is thus an attractive template to develop new anti-tuberculosis drugs, because its target is different from those of known anti-tubercular agents.

Topics: Antitubercular Agents; Binding Sites; Down-Regulation; Gene Expression Regulation, Bacterial; Genes, Bacterial; Guaiacol; Lignans; Microbial Sensitivity Tests; Molecular Docking Simulation; Mycobacterium tuberculosis; Oligonucleotide Array Sequence Analysis; Real-Time Polymerase Chain Reaction; Up-Regulation

To study the chemical constituents of K. oblongifolia, silica gel column chromatography, MCI and Sephadex LH-20 were used to separate the 70% acetone extract of the stems of K. oblongifolia. The structures of the isolated compounds have been established on the basis of physicochemical and NMR spectroscopic evidence as well as ESI-MS in some cases. Twenty compounds were obtained and identified as heteroclitalignan A (1), kadsulignan F (2), kadoblongifolin C (3), schizanrin F (4), heteroclitalignan C (5), kadsurarin (6), kadsulignan O (7), eburicol (8), meso-dihydroguaiaretic acid (9), kadsufolin A (10), tiegusanin M (11), heteroclitin B (12), (7'S)-parabenzlactone (13), angeloylbinankadsurin B (14), propinquain H (15), quercetin (16), kadsulignan P (17), schizanrin G (18), micrandilactone C (19) and (-)-shikimic acid (20). Compouds 1, 5, 8, 11-15, 18 and 20 were isolated from this plant for the first time. Toxicity of compounds 1-10 were evaluated with zebrafish model to observe the effect on its embryonic development and heart function. The results showed that compounds 7, 9 and 10 caused edema of zebrafish embryo and decreased the heart rate of zebrafish, which exhibited interference effect on heart development of zebrafish.

Topics: Animals; Embryo, Nonmammalian; Guaiacol; Kadsura; Lignans; Plant Extracts; Quercetin; Triterpenes; Zebrafish

To separate and identify the chemical constituents from the stem of Schisandra chinensis.. Various chromatographic techniques were used to separate and purify the chemical constituents from 95% ethanol extraction of the stem of Schisandra chinensis. Their structures were elucidated based on the physico-chemical properties and spectral data.. Ten compounds were obtained and elucidated as (+)-deoxyschizandrin (1), γ-schizandrin (2), wuweizisu C (3), gomisin N (4), schizandrin (5), anwuweizic acid (6), (-)-dihydroguaiaretic acid (7), tetradecanoic acid (8), β-sitosterol (9) and daucosterol (10).. Compounds 6-8 are obtained from the stem of Schisandra chinensis for the first time.

Topics: Cyclooctanes; Guaiacol; Lignans; Phytochemicals; Plant Stems; Polycyclic Compounds; Schisandra; Sitosterols

The insecticidal activity of (-)-(8R,8'R)-3,3'-dimethoxy-9,9'-epoxylignane-4,4'-diol (1) against houseflies was clarified for the first time. The activities of other stereoisomers were weaker than that of the (8R,8'R)-stereoisomer. In the course of research into structure-activity relationships involving 30 newly synthesized (8R,8'R)-derivatives, 5-fold higher activity (ED50 = 0.91 nmol/fly) was observed for (-)-(8R,8'R)-3,3',4-trimethoxy-9,9'-epoxylignan-4'-ol (21) than for the naturally occurring compound (1). The activity of 1 was weaker than that of (-)-(8R,8'R)-dihydroguaiaretic acid ((-)-DGA) (4); however, compound 21 showed almost the same level of activity as 4.

Topics: Animals; Epoxy Compounds; Guaiacol; Houseflies; Insecticides; Lignans; Plant Extracts; Stereoisomerism; Structure-Activity Relationship

The relationship between antifungal activity against Alternaria alternata and structure on the 7-phenyl group of (+)-dihydroguaiaretic acid ((+)-DGA) was clarified by employing 38 synthesized (+)-DGA derivatives. The results were identified by quantitative structure-activity relationship (QSAR) analysis employing the Hansch-Fujita method. Some compounds showed higher activity than (+)-DGA. The compound showing highest activity was 3,5-difluorophenyl derivative 37. It was suggested that the small electron-withdrawing group at the meta-position of the 7-phenyl group is important for the higher activity by antifungal test and Hansch-Fujita analysis. The whitening activity of 3-hydroxy-4-methoxyphenyl derivative 28, 3-hydroxy-4-ethoxyphenyl derivative 29, and 3-hydroxy-4-isopropoxyphenyl derivative 30 against A. alternata Japanese pear pathotype was also discovered.

Topics: Alternaria; Fungicides, Industrial; Guaiacol; Lignans; Quantitative Structure-Activity Relationship

The larvicidal activity against Culex pipiens of all stereoisomers of dihydroguaiaretic acid (DGA) and secoisolariciresinol was measured, and these DGAs were found to be potent. Sixteen (-)-DGA derivatives were then newly synthesized to analyze their structure-activity relationship. Two derivatives monohydroxylated at the 3- or 4-position of the 7-phenyl group of DGA induced acute paralytic activity in the mosquitoes. Derivatives with several hydroxyl groups had lower activity than the natural compound, suggesting that hydrophobicity was probably an important factor for their insecticidal activity.

Topics: Animals; Butylene Glycols; Culex; Disease Vectors; Guaiacol; Hydrophobic and Hydrophilic Interactions; Hydroxylation; Insect Control; Insecticides; Larva; Lethal Dose 50; Lignans; Stereoisomerism; Structure-Activity Relationship

Hepatic lipid accumulation is a major risk factor for dyslipidemia, nonalcoholic fatty liver disease, and insulin resistance. The present study was conducted to evaluate hypolipidemic effects of meso-dihydroguaiaretic acid (MDA), anti-oxidative and anti-inflammatory compound isolated from the Myristica fragrans HOUTT., by oil red O staining, reverse transcription-polymerase chain reaction (RT-PCR), and Western blot. MDA significantly inhibited insulin-induced hepatic lipid accumulation in a dose-dependent manner. The lipid-lowering effect of MDA was accompanied by increased expression of proteins involved in fatty acid oxidation and decreased expression of lipid synthetic proteins. In addition, MDA activated AMP-activated protein kinase (AMPK) as determined by phosphorylation of acetyl-CoA carboxylase (ACC), a downstream target of AMPK. The effects of MDA on lipogenic protein expression were suppressed by pretreatment with compound C, an AMPK inhibitor. Taken together, these findings show that MDA inhibits insulin-induced lipid accumulation in human HepG2 cells by suppressing expression of lipogenic proteins through AMPK signaling, suggesting a potent lipid-lowering agent.

Topics: Acetyl-CoA Carboxylase; AMP-Activated Protein Kinases; Cell Culture Techniques; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Dyslipidemias; Enzyme Activation; Enzyme Inhibitors; Fatty Liver; Guaiacol; Hep G2 Cells; Humans; Hypolipidemic Agents; Insulin Resistance; Lignans; Lipid Metabolism; Liver; Molecular Targeted Therapy; Myristica; Non-alcoholic Fatty Liver Disease; Phosphorylation; Phytotherapy; Plant Extracts; Pyrazoles; Pyrimidines

Plant active components characterized of many different structures and activities on multiple targets, have made them to be the important sources of inhibitors on HIV-1. For finding leading compounds with new structure against HIV-1, three key HIV-1 replicative enzymes (reverse transcriptase, protease and integrase) were used as screening models. The in vitro activities of 45 plant derived components isolated from Schisandraceae, Rutaceae and Ranunculaceae were reported. Within twelve triterpene components isolated, eight compounds were found to inhibit HIV-1 protease, in these eight active compounds, kadsuranic acid A (7) and nigranoic acid (8), inhibited both HIV-1 protease and integrase; Among fifteen lignans, meso-dihydroguaiaretic acid (15) and kadsurarin (16) were active on HIV-1 reverse transcriptase, and 4, 4-di(4-hydroxy-3-methoxyphenly)-2, 3-dimethylbutanol (13) active on HIV-1 integrase. All of the six alkaloids, seven flavones, and five others compounds were not active or only with low activities against HIV-1 replicative enzymes. Further studies of the triterpene components showing strong inhibitory activities on HIV-1 were warranted.

Topics: Alkaloids; Anti-HIV Agents; Drugs, Chinese Herbal; Flavones; Guaiacol; HIV Integrase; HIV Protease; HIV Reverse Transcriptase; Lignans; Plants, Medicinal; Ranunculaceae; Rutaceae; Schisandraceae; Triterpenes

Chemical investigations of the DCM extract from the roots of Endiandra anthropophagorum resulted in the isolation of a new cyclobutane lignan endiandrin B (1), together with the known natural products, endiandrin A (2), and (-)-dihydroguaiaretic acid (3). The structure of 1 was determined by extensive spectroscopic analyses, and confirmed by single crystal X-ray crystallography. Methylation of 1 using diazomethane afforded the previously reported natural product, cinbalansan (4). All compounds were evaluated for their cytotoxicity towards human lung carcinoma cells (A549) using high-content screening. (-)-Dihydroguaiaretic acid (3) was found to be the most potent cytotoxin against the A549 lung carcinoma cell line, with an IC(50) value of 7.49 microM.

Topics: Antineoplastic Agents, Phytogenic; Australia; Cell Line, Tumor; Crystallography, X-Ray; Cyclobutanes; Guaiacol; Humans; Inhibitory Concentration 50; Lauraceae; Lignans; Magnetic Resonance Spectroscopy; Plant Roots; Plants, Medicinal

The relationship between the stereochemistry and antimicrobial activity of butane-type lignans was clarified. All stereoisomers of dihydroguaiaretic acid (DGA) showed both antibacterial and antifungal activity. The (+)- and (-)-7,7'-dioxodihydroguaiaretic acid (ODGA) also showed both antibacterial and antifungal activity, while meso-ODGA did not show antibacterial activity, but showed antifungal activity. No activity of any stereoisomer of secoisolariciresinol (SECO) was apparent.

Topics: Anti-Infective Agents; Bacteria; Butanes; Foodborne Diseases; Fungi; Guaiacol; Lignans; Plant Diseases; Stereoisomerism; Structure-Activity Relationship; Substrate Specificity

The antioxidant activity of butane-type lignans was evaluated. Secoisolariciresinol (SECO) and dihydroguaiaretic acid (DGA) showed higher radical scavenging activity than that of 7,7'-dioxodihydroguaiaretic acid (ODGA). SECO and DGA inhibited the oxidation of unsaturated fatty acid. Both enantiomers of DGA were also lipoxygenase inhibitors, but neither enantiomer of SECO inhibited the lipoxygenase activity.

Topics: Butanes; Butylene Glycols; Free Radical Scavengers; Guaiacol; Lignans; Lipoxygenase Inhibitors; Oxidation-Reduction; Stereoisomerism

Meso-dihydroguaiaretic acid (MDGA) is a medicinal herbal product isolated from the aerial parts of Saururus chinensis that inhibits the cyclooxygenase-2 (COX-2)-dependent phase of prostaglandin D(2) (PGD(2)) generation in bone marrow-derived mast cells (BMMC) (IC(50) 9.8 microM). However, this compound did not inhibit COX-2 protein expression in BMMC at concentrations up to 30 microM, indicating that MDGA directly inhibits COX-2 activity. In addition, this compound consistently inhibited the production of leukotriene C(4) (IC(50) 1.3 microM). These results demonstrate that MDGA inhibits both COX-2 and 5-lipoxygenase. Furthermore, this compound strongly inhibited the degranulation reaction in BMMC (IC(50) 11.4 microM). Therefore, this compound might provide a basis for novel anti-inflammatory drug development.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arachidonic Acid; Bone Marrow Cells; Cells, Cultured; Cyclooxygenase 2 Inhibitors; Guaiacol; Lignans; Lipoxygenase Inhibitors; Male; Mast Cells; Mice; Mice, Inbred BALB C; Saururaceae

Neutrophil apoptosis is an important physiological process in the resolution of pulmonary inflammation. Previous studies have shown that eicosapentaenoic acid (EPA; 20:5n-3) increases the rate of apoptosis in a concentration- and time-dependent manner in HL-60 cells. However, it is not known if the EPA-induced apoptosis involves the lipoxygenase (LO) and cyclooxygenase (COX) enzymes or the downstream metabolic products of these enzymes. Thus, the objective of this study was to determine the effects of inhibitors LO and COX enzymes on apoptosis, viability, and necrosis in EPA-treated HL-60 cells.. Cells were incubated with 50 mum EPA in the presence of an enzyme inhibitor (1-10 microm) for 12 h. Compounds were used to inhibit COX 1 and 2 (ibuprofen), 5-, 12-, 15-LO (NDGA), 12-LO (baicalein), 5-LO (AA-861), and 5-LO activating protein (MK-886). Eicosanoid (0.001-1.0 mum) add-back experiments were also conducted; LTB(4) and 5-HETE with 5-LO inhibition and 12-HETE with 12-LO inhibition. Flow cytometry was used to assess apoptosis.. Inhibition of COX 1 and 2 had no effect on apoptosis. Inhibition of 5-LO and 12-LO significantly increased apoptosis in EPA-treated HL-60 cells. Addition of LTB(4) reduced apoptosis to levels significantly lower than in HL-60 cells treated with EPA alone; 5-HETE and 12-HETE also lowered apoptosis to control levels.. These data indicate that inhibition of LO, particularly 5-LO, increased apoptosis in EPA-treated HL-60 cells. Furthermore, this study demonstrated that the products of the LO enzymes, particularly LTB(4), are critical in the regulation of apoptosis in EPA-treated HL-60 cells.

Topics: Apoptosis; Arachidonate 12-Lipoxygenase; Arachidonate 15-Lipoxygenase; Arachidonate 5-Lipoxygenase; Cyclooxygenase Inhibitors; Eicosapentaenoic Acid; Enzyme Inhibitors; Fatty Acids, Unsaturated; Flavanones; Guaiacol; HL-60 Cells; Humans; Hydroxyeicosatetraenoic Acids; Ibuprofen; Indoles; Leukotriene B4; Lignans; Lipoxygenase Inhibitors; Neutrophils; Respiratory Distress Syndrome

In a search for plant extracts with potent in vivo antifungal activity against various plant diseases, we found that treatment with a methanol extract of Myristica fragrans Houttyn (nutmeg) seeds reduced the development of various plant diseases. The objectives of the present study were to isolate and determine antifungal substances from My. fragrans and to evaluate their antifungal activities.. Three antifungal lignans were isolated from the methanol extract of My. fragrans seeds and identified as erythro-austrobailignan-6 (EA6), meso-dihydroguaiaretic acid (MDA) and nectandrin-B (NB). In vitro antimicrobial activity of the three lignans varied according to compound and target species. Alternaria alternata, Colletotrichum coccodes, C. gloeosporioides, Magnaporthe grisea, Agrobacterium tumefaciens, Acidovorax konjaci and Burkholderia glumae were relatively sensitive to the three lignans. In vivo, all three compounds effectively suppressed the development of rice blast and wheat leaf rust. In addition, EA6 and NB were highly active against the development of barley powdery mildew and tomato late blight, respectively. Both MDA and NB also moderately inhibited the development of rice sheath blight.. This is the first study to demonstrate the in vitro and in vivo antifungal activities of the three lignans from My. fragrans against plant pathogenic fungi.

Topics: Antifungal Agents; Guaiacol; Lignans; Mass Spectrometry; Microbial Sensitivity Tests; Myristica; Plants; Seeds

The effect of meso-dihydroguaiaretic acid (MDGA) on the staurosporine-induced neuronal apoptosis and its potential mechanism were investigated using primary cultures of rat cortical cells as an assay system. Treatment of MDGA at the concentrations of 0.1, 1.0 and 10 microM significantly protected neuronal cells against Staurosporine-induced apoptosis. The neuroprotective activity of MDGA was the most potent at the concentration of 1.0 microM and was not increased at higher concentration. MDGA reduced apoptotic characteristics induced by STS; MDGA reduced the condensed nuclei in staurosporine-injured rat cortical cells. MDGA diminished the calcium influx that accompanies the staurosporine-induced apoptosis, and inhibited the subsequent overproduction of reactive oxygen species and peroxide to the level of control cells. It also preserved cellular activity of superoxide dismutase, an antioxidative enzyme reduced by staurosporine insult. In addition, MDGA significantly inhibited caspase-3/7 activation and cytochrome c release. Taken together, these results suggested that MDGA protected neuronal cells against staurosporine-induced apoptosis through the inhibition of Ca(2+) influx, cellular oxidation, cytochrome c release and caspase-3/7 activation.

Topics: Analysis of Variance; Animals; Apoptosis; Calcium; Caspase 3; Caspases; Cells, Cultured; Cerebral Cortex; Cytochromes c; Dansyl Compounds; Dose-Response Relationship, Drug; Drug Interactions; Embryo, Mammalian; Galactosamine; Guaiacol; Lignans; Neurons; Neurotoxins; Peroxides; Rats; Rats, Sprague-Dawley; Staurosporine

Inhibition of protein tyrosine phosphatase 1B (PTP1B) has been proposed as one of the drug targets for treating type 2 diabetes and obesity. Bioassay-guided fractionation of a MeOH extract of the semen of Myristica fragrans Houtt. (Myristicaceae) afforded PTP1B inhibitory compounds, meso-dihydroguaiaretic acid (1) and otobaphenol (2). Compounds 1 and 2 inhibited PTP1B with IC(50) values of 19.6 +/- 0.3 and 48.9 +/- 0.5 microM, respectively, in the manner of non-competitive inhibitors. Treatment with compound 1 on 32D cells overexpressing the insulin receptor (IR) resulted in a dose-dependent increase in the tyrosine phosphorylation of IR. These results indicate that compound 1 can act as an enhancing agent in intracellular insulin signaling, possibly through the inhibition of PTP1B activity.

Topics: Animals; Cell Line; Chemical Fractionation; Enzyme Inhibitors; Granulocytes; Guaiacol; Inhibitory Concentration 50; Lignans; Mice; Myristica; Phosphorylation; Plant Extracts; Pollen; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Protein Tyrosine Phosphatases; Receptor, Insulin

Ethanol and aqueous extracts of Machilus thunbergii Sieb et Zucc (Lauraceae) used traditionally for the treatment of a variety of diseases were screened in vitro for MMP-1 inhibitory actions. Meso-dihydroguaiaretic acid (MDGA) from the stem bark of M. thunbergii showed a significant inhibition of matrix metalloproteinase (MMP)-1 in primary human fibroblasts by heat shock-induced. This study investigated the effect of MDGA isolated from M. thunbergii on heat shock-induced premature skin aging. MDGA reduced the expression of MMP-1 at the protein level in a dose-dependent manner in heat shock-induced cultured primary human fibroblasts. Taken together, these results show that MDGA can prevent the harmful effects of heat (and/or IR) that lead to skin aging.

Topics: Cell Proliferation; Cells, Cultured; Fibroblasts; Guaiacol; Heat-Shock Response; Hot Temperature; Humans; Lauraceae; Lignans; Matrix Metalloproteinase 1; Plant Extracts

Two DNA cleavage agents, meso-dihydroguaiaretic acid (1) and isobavachalcone (2) together with the known alpha-ylangene, beta-sitosterol, daucosterol, pentacosane, hexacosanic acid and cerotic acid 1-monoglyceride were isolated from the stem barks of Kadsura ananosma Kerr for the first time. Compounds 1 and 2 showed relaxation of supercoiled DNA to nicked DNA. 1 represented a new structural type of DNA cleavage agent, while 2 was reported to show DNA strand-scission activity for the first time. 1 also showed significant cytotoxic effect on Hela and Leukemia cells in vitro.

Topics: Cell Line, Tumor; Chalcones; DNA; DNA, Superhelical; Guaiacol; HeLa Cells; Humans; Kadsura; Leukemia; Lignans; Magnetic Resonance Spectroscopy; Mass Spectrometry; Nucleic Acid Conformation; Plant Bark; Plant Stems

meso-dihydroguaiaretic acid (DGA), naturally occurring in plants such as Machilus thunbergii and Myristica fragrans, exhibits a neuroprotective effect and also exerts cytotoxicity to certain cancer cells. Activated hepatic stellate cells (HSCs) play an important role in liver fibrogenesis through the production of transforming growth factor beta1 (TGF-beta1) after injuries. TGF-beta1 mediates the deposition of extracellular matrix and the inhibition of collagenase activity in the liver. This study has investigated the inhibitory effect of DGA on the activation of rat HSCs in culture and TGF-beta1 production from HSCs. The level of alpha-smooth muscle actin (alpha-SMA), a representative marker of stellate cell transdifferentiation, was decreased upon treatment of activated HSCs with DGA (1 - 10 microM). Immunoblot analysis revealed that DGA inhibited the expression of TGF-beta1 in activated HSCs. Consistently, DGA down-regulated the transactivation of the TGF-beta1 promoter linked to the luciferase reporter gene in HSCs. Promoter deletion analysis revealed that the region located between -731 bp and -323 bp in the TGF-beta1 promoter, which is comprised of AP-1 response elements, conferred the inhibition of TGF-beta1 expression by DGA. DGA also inhibited AP-1-mediated gene transactivation in HSCs to a comparable extent, indicating that down-regulation of the TGFbeta1 gene by DGA might result from its inhibition of AP-1 activity. We found in addition that DGA inhibited DNA synthesis in HSCs stimulated by platelet-derived growth factor. The data provide evidence that DGA directly inhibits activation of HSCs and down-regulates TGF-beta1 gene expression through inhibition of AP-1 activity.

Topics: Animals; DNA Primers; Dose-Response Relationship, Drug; Down-Regulation; Guaiacol; Immunoblotting; Immunohistochemistry; Lauraceae; Lignans; Liver; Male; Phytotherapy; Plant Bark; Plant Extracts; Protective Agents; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; RNA; Transforming Growth Factor beta; Transforming Growth Factor beta1

1 We previously reported that four lignans isolated from the bark of Machilus thunbergii Sieb. et Zucc. (Lauraceae) protected primary cultures of rat cortical neurons from neurotoxicity induced by glutamate. 2 Among the lignans, meso-dihydroguaiarectic acid (MDGA) and licarin A significantly attenuated glutamate-induced neurotoxicity when added prior to or right after the excitotoxic glutamate challenge. 3 The neuroprotective activities of two lignans appeared to be more effective in protecting neurons against neurotoxicity induced by NMDA than that induced by kainic acid. 4 MDGA and licarin A diminished the calcium influx that routinely accompanies with the glutamate-induced neurotoxicity, and inhibited the subsequent overproduction of cellular nitric oxide and peroxide to the level of control cells. They also preserved cellular activities of antioxidative enzymes such as superoxide dismutase, glutathione peroxidase and glutathione reductase reduced in the glutamate-injured neuronal cells. 5 Thus, our results suggest that MDGA and licarin A significantly protect primary cultured neuronal cells against glutamate-induced oxidative stress, via antioxidative activities.

Topics: Animals; Calcium; Cells, Cultured; Cerebral Cortex; Glutamic Acid; Glutathione; Guaiacol; Lauraceae; Lignans; Nitric Oxide; Peroxides; Rats; Rats, Sprague-Dawley

Ethanol and aqueous extracts of Machilus thunbergii used traditionally for the treatments a wide variety of diseases were screened in vitro for the matrix metalloproteinase (MMP)-9 inhibitor actions. Meso-dihydroguaiaretic acid from the stems bark of Machilus thunbergii showed significant MMP-9 inhibition in human keratinocyte cells cause by ultraviolet irradiation. Here we investigated the effect of meso-dihydroguaiaretic acid, which was isolated from Machilus thunbergii, on UV-induced premature skin aging. We studied the effect of meso-dihydroguaiaretic acid on UV-induced MMP-9 expression in an immortalized human keratinocyte cell line, HaCaT, in vitro. Acute UV irradiation induced MMP-9 expression at both the mRNA and protein levels and meso-dihydroguaiaretic acid suppressed this UV-induced MMP-9 expression in a dose-dependent manner. Taken together, these results show that meso-dihydroguaiaretic acid can prevent the harmful effects of UV that lead to skin aging. Therefore, we suggest that meso-dihydroguaiaretic acid should be viewed as a potential therapeutic agent for preventing and/or treating premature skin aging.

Topics: Cell Line; Gene Expression Regulation, Enzymologic; Glyceraldehyde-3-Phosphate Dehydrogenases; Guaiacol; Humans; Keratinocytes; Lauraceae; Lignans; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Nitroblue Tetrazolium; Reverse Transcriptase Polymerase Chain Reaction; RNA; Ultraviolet Rays

Four lignans were isolated from the petrol extract of Myristica argentea mace (Myristicaceae) and their structures were elucidated by means of NMR and mass spectrometry. Although they have been previously described, NMR data are only available for threo-austrobailignan-5, which has been isolated only once, and is incomplete. Three of them, erythro-austrobailignan-6, meso-dihydroguaiaretic acid and nectandrin-B, exert an antiproliferative effect on MCF-7 cells as well as antioxidant activity on the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, but not the threo-austrobailignan-5. Nectandrin-B also possesses anti-17beta-hydroxysteroid dehydrogenase and anti-aromatase activities.

Topics: 17-Hydroxysteroid Dehydrogenases; Antineoplastic Agents, Phytogenic; Antioxidants; Aromatase Inhibitors; Cell Division; Guaiacol; Humans; Lignans; Magnetic Resonance Spectroscopy; Myristicaceae; Plant Extracts; Tumor Cells, Cultured

Two diarylbutane derivatives of dihydroguaiaretic acid have been isolated from emergent portions of the southeastern United States freshwater angiosperm Saururus cernuus L. (Saururaceae). Bioassay-guided fractionation of organic extracts of S. cernuus led to the compounds, sauriols A and B, in addition to five previously known lignoids. These metabolites deter feeding by the omnivorous crayfish Procambarus clarkii. The two lignans were identified by analysis of nuclear magnetic resonance and mass spectral data, and by comparison with spectral data of dihydroguaiaretic acid.

Topics: Animals; Astacoidea; Feeding Behavior; Fresh Water; Guaiacol; Lignans; Magnoliopsida; Models, Molecular; Molecular Conformation; Molecular Structure

The effect of dihydroguaiaretic acid (DHGA), isolated from the aryls of Myristica fragrans, on the transcription factor (fos-jun dimer) action was investigated via in vitro assay. DHGA showed an inhibitory effect against the complex formation of the fos-jun dimer and the DNA consensus sequence with an IC50 value of 0.21 micromol. Nordihydroguaiaretic acid (NDGA) and curcumin also inhibited fos-jun dimer action showing IC50 values of 7.9 and 6.9 nmol, respectively. DHGA and NDGA suppressed leukemia, lung cancer and colon cancer in an in vitro bioassay. The in vitro experiment suggested that inhibition of fos-jun-DNA complex formation could be due to the direct interference of fos-jun dimer binding onto the DNA consensus sequence by NDGA and curcumin.

Topics: Dimerization; Guaiacol; Humans; Lignans; Masoprocol; Proto-Oncogene Proteins c-fos; Proto-Oncogene Proteins c-jun; Transcription Factor AP-1; Tumor Cells, Cultured

The methanol extract from Machilus thunbergii showed a suppressive effect on umu gene expression of the SOS response in Salmonella typhimurium TA1535/pSK1002 against the mutagen, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), which requires liver metabolizing enzymes. The methanol extract from M. thunbergii was successively re-extracted with chloroform, butanol and water. A suppressive compound in the chloroform extract fraction was isolated by SiO2 column chromatography and identified as meso-dihydroguaiaretic acid by GC-MS, and 1H- and 13C-NMR spectroscopy. Meso-dihydroguaiaretic acid inhibited of the SOS-inducing activity of Trp-P-1 in the umu test. Gene expression was suppressed by 62% at less than 0.18 mumol/ml, the ID50 value being 0.08 mumol/ml. Compound 1 was also assayed with aflatoxin B1 (AfB1) and showed a suppressive effect.

Topics: Aflatoxin B1; Carbolines; Chloroform; DNA Damage; Gas Chromatography-Mass Spectrometry; Guaiacol; Lauraceae; Lignans; Magnetic Resonance Spectroscopy; Mutagens; Plant Extracts; Salmonella typhimurium; SOS Response, Genetics

The modifying effects of the naturally occurring antioxidants n-tritriacontane-16,18-dione (TTAD), curcumin, dihydroguaiaretic acid (DHGA), chlorophyllin, tannic acid and phytic acid on the initiation stage in a rat multi-organ carcinogenesis model were examined in male F344 rats. Animals were initiated with two i.p. injections of 2,2'-dihydroxy-di-n-propylnitrosamine (DHPN), followed by two i.g. administrations of N-ethyl-N-hydroxyethylnitrosamine (EHEN), and then three s.c. injections of 3,2'-methyl-4-aminobiphenyl (DMAB) during the first 3 weeks. Starting 1 day before the first carcinogen application, groups of rats received diet containing one of the antioxidants (0.2% TTAD, the others at 1% each) until 1 week after the last carcinogen exposure. Surviving animals were killed and complete autopsies were performed at the end of week 36. Histological examination revealed no inhibitory effects in terms of the multiplicities and/or incidences of neoplastic lesions in any of the organs examined, other than a significant increase in seminal vesicle atypical hyperplasia observed in rats treated with tannic acid. Thus, the antioxidants, with the exception of tannic acid, did not show any modifying effects on the initiation stage in the present multi-organ carcinogenesis model and at the present dose levels applied.

Topics: Aminobiphenyl Compounds; Animals; Antimutagenic Agents; Antineoplastic Agents; Antioxidants; Carcinogens; Chlorophyllides; Curcumin; Diethylnitrosamine; Guaiacol; Hydrolyzable Tannins; Lignans; Liver Neoplasms; Lung Neoplasms; Male; Neoplasms, Experimental; Nitrosamines; Paraffin; Phytic Acid; Precancerous Conditions; Rats; Rats, Inbred F344

Aluminum (Al3+) intoxication is thought to play a major role in the development of Alzheimer's disease and in certain pathologic manifestations arising from long-term hemodialysis. Although the metal does not present redox capacity, it can stimulate tissue lipid peroxidation in animal models. Furthermore, in vitro studies have revealed that the fluoroaluminate complex induces diacylglycerol formation, 43-kDa protein phosphorylation and aggregation. Based on these observations, we postulated that Al(3+) -induced blood platelet aggregation was mediated by lipid peroxidation. Using chemiluminescence (CL) of luminol as an index of total lipid peroxidation capacity, we established a correlation between lipid peroxidation capacity and platelet aggregation. Al3+ (20-100 microM) stimulated CL production by human blood platelets as well as their aggregation. Incubation of the platelets with the antioxidants nor-dihydroguaiaretic acid (NDGA) (100 microM) and n-propyl gallate (NPG) (100 microM), inhibitors of the lipoxygenase pathway, completely prevented CL and platelet aggregation. Acetyl salicylic acid (ASA) (100 microM), an inhibitor of the cyclooxygenase pathway, was a weaker inhibitor of both events. These findings suggest that Al3+ stimulates lipid peroxidation and the lipoxygenase pathway in human blood platelets thereby causing their aggregation.

Topics: Adult; Aluminum; Guaiacol; Humans; L-Lactate Dehydrogenase; Lignans; Lipid Peroxidation; Luminescent Measurements; Platelet Aggregation; Propyl Gallate; Ristocetin; Salicylates

Topics: Animals; Antineoplastic Agents, Phytogenic; Caenorhabditis elegans; Decapoda; Guaiacol; Humans; Lignans; Plant Stems; Plants, Medicinal; Trees; Tumor Cells, Cultured

beta-Keto ester(5) was obtained from vanilin through etherification, oxidation and condensation with acetoacetic ester, (5) on oxidative coupling reaction by NaOEt/I2 produced dimer (6) in high yield. Acid catalyzed cyclodehydration of (6) gave the furan derivative(7), and by a series of selective hydrogenation nordihydroguaiaretic acid, furoguaiacin dimethyl ether and dihydroguaiaretic acid dimethyl ether were synthesized.

Topics: Furans; Guaiacol; Lignans; Masoprocol; Molecular Structure; Plants, Medicinal

Investigations on croconazole, a novel imidazole compound, suggested antiphlogistic properties in vitro. Hence, its anti-inflammatory capacity was tested in vivo using the arachidonic acid-induced mouse ear swelling test, which is a suitable model for screening inhibitors of the lipoxygenase and/or the cyclooxygenase. Topical application of croconazole (1%/0.01%) to the mouse ear induced a maximal inhibition of edema (inhibition: 39%/33%; p = 0.01) which was as strong as the reference nordihydroguaiaretic acid (inhibition: 38.9%; p = 0.01). These results justify further investigations on croconazole to study potential inhibitory effects on proinflammatory arachidonic acid metabolites.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antifungal Agents; Arachidonic Acid; Ear, External; Edema; Female; Guaiacol; Imidazoles; Lignans; Lipoxygenase Inhibitors; Mice; Mice, Inbred Strains

Topics: Chemical Phenomena; Chemistry; Guaiacol; Lignans; Medicine, Chinese Traditional; Medicine, East Asian Traditional; Plant Extracts; Plants, Medicinal; Platelet Membrane Glycoproteins; Receptors, Cell Surface; Receptors, G-Protein-Coupled

Topics: Guaiac; Guaiacol; Humans; Hypersensitivity; Lignans