lignans and osthol

With the features of multiple-components and targets as well as multifunction, traditional Chinese medicine (TCM) has been widely used in the prevention and treatment of various diseases for a long time. During the application of TCM, the researches about bioavailability enhancement of the bioactive constituents in formula are flourishing. Bushen-Yizhi formula (BSYZ), a TCM prescription with osthole (OST) as one of the main bioactive ingredients, have been widely used to treat kidney deficiency, mental retardation and Alzheimer's disease. However, the underlying biological mechanism and compound-enzyme interaction mediated bioavailability enhancement of OST are still not clearly illuminated.. The aim of this study is to explore the material basis and molecular mechanism from BSYZ in the bioavailability enhancement of OST. Screening the potential CYP3A4 inhibitors using theoretical prediction and then verifying them in vitro, and pharmacokinetics study of OST in rat plasma under co-administrated of screened CYP3A4 inhibitors and BSYZ were also scarcely reported.. Screening of CYP3A4 inhibitors from BSYZ was performed with molecular docking simulation from systems pharmacology database. The screened compounds were verified by using P450-Glo Screening Systems. A multiple reaction monitoring (MRM) mass spectrometry method was established for OST quantification. Male Sprague-Dawley rats divided into four groups and six rats in each group were employed in the pharmacokinetics study of OST. The administrated conditions were group I, OST (20 mg/kg); group II, BSYZ (containing OST 1 mg/mL, at the dose of 20 mg/kg OST in BSYZ); group III, co-administration of ketoconazole (Ket, 75 mg/kg) and OST (20 mg/kg); group IV, co-administration of CYP3A4 inhibitor (10 mg/kg) and OST (20 mg/kg). They were determined by using HPLC-MS/MS (MRM) and statistical analysis was performed using student's t-test with p < 0.05 as the level of significance.. Schisantherin B, a profoundly effective CYP3A4 inhibitor screened from BSYZ antagonized the metabolism of CYP3A4 on OST via activity inhibition, therefore significantly enhanced the bioavailability of OST in rat plasma. The results of this study will be helpful to explain the rationality of the compatibility in TCM formula, and also to develop new TCM formula with more reasonable drug compatibility.

Topics: Animals; Antifungal Agents; Biological Availability; Coumarins; Cyclooctanes; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inhibitors; Dioxoles; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Gene Expression Regulation, Enzymologic; Herb-Drug Interactions; Ketoconazole; Lignans; Male; Polycyclic Compounds; Random Allocation; Rats; Rats, Sprague-Dawley

Understanding the mechanism of action of antifungal drugs is vital for better control of mycosis, which kills >1.3 million lives every year thus remains a major health problem worldwide. In this study, we investigate the activities of three different categories of plant-derived antifungal compounds (resveratrol, honokiol and osthole) via transcriptomics and bioinformatics analysis, with the goal of discovering the common Mode-of-Action (MoA) at molecular level. The result shows that a common transcriptional response (72 gene are up-regulated while 10 genes are down-regulated, commonly) are triggered by above representative antifungal compounds in Schizosaccharomyces pombe (S. pombe) yeast. By virtue of gene set enrichment analysis (GSEA) and gene functional annotation study, we identify that the genes involved in oxidative stress response, sugar metabolism, fatty acid metabolism, amino acid metabolism and glycolysis are significantly up-regulated, while the genes involved in nucleosome assembly, transcription and RNA processing are down-regulated, by any of these antifungal compounds. These observations demonstrate that the common MoA includes a strengthened anti-oxidative cell adaptation, a faster metabolic rate and a generally suppressed gene transcriptional activity. It implies a genetically encoded common redistribution of intracellular energy flux and molecules synthesis, after the challenging of antifungal compounds.

Topics: Antifungal Agents; Biphenyl Compounds; Coumarins; Gene Expression Profiling; Gene Expression Regulation, Fungal; Lignans; Oxidative Stress; Plant Extracts; Resveratrol; Schizosaccharomyces; Stilbenes; Transcription, Genetic; Up-Regulation

To study the chemical constituents of the dichloromethane extract from pine needles of Cedrus deodara.. The chemical constituents were isolated and purified from the dichloromethane extract of pine needles by chromatography on silica gel and Sephadex LH-20. Their structures were elucidated by analysis of spectral data and chemical properties.. Seven compounds were isolated and their chemical structures were identified as ferulic acid (1), osthole (2), beta-phenylacrylic acid (3), paeonol (4), beta-sitosterol (5), magnolol (6) and honokiol (7).. Compounds 1 - 4, 6 and 7 are isolated from this plant for the first time.

Topics: Acetophenones; Biphenyl Compounds; Cedrus; Chromatography, Thin Layer; Coumaric Acids; Coumarins; Lignans; Methylene Chloride; Molecular Structure; Plant Leaves