Comprehensive chemical profiling of monascus-fermented rice product and screening of lipid-lowering compounds other than monacolins.

ETHNOPHARMACOLOGICAL RELEVANCE: Monascus-fermented rice product (MFRP) has been regarded as a dietary supplement and traditional medicine with circulation-promoting effects in China and other countries for centuries. AIM OF THE STUDY: This study was carried out to profile the chemical components in MFRP, and provide available information for elucidating the potential lipid-lowering compounds other than monacolins. MATERIALS AND METHODS: High-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC-QTOF MS) and gas chromatography coupled with mass spectrometry (GC-MS) methods were applied to comprehensive analysis of chemical components in MFRP. Potential small molecules were identified by comparing with reference standards, or tentatively characterized by comparing their retention time and high-resolution mass spectral data with previous literature. The lipid-lowering properties of ten major non-monacolin compounds were evaluated in cholesterol-fed zebrafish larvae. And one with optimum lipid-lowering activity was subsequently evaluated in high fat diet-fed C57BL/6 J mice, with the dyslipidemia and ectopic lipid deposition being investigated. RESULTS: A total of 99 compounds were characterized in MFRP, including 38 monacolins, 5 decalins, 6 isoflavones, 13 pigments, 8 azaphilonoids, 11 amino acids, 4 nucleosides, 9 lipid acids, 4 phytosterols and glycerol. The preliminary screening showed that ergosterol remarkably reduced cholesterol levels in zebrafish larvae. Moreover, ergosterol delayed body weight gain and decreased circulating total cholesterol, triglyceride, low density lipoprotein cholesterol levels in high fat diet-fed mice. Ectopic lipid accumulation was also ameliorated in the liver and heart of obese mice. CONCLUSION: Global analysis of chemical components and screening of lipid-lowering non-monacolin compounds in MFRP have improved our understanding of its therapeutic material basis.

Integration of Multiple Analytical and Computational Tools for the Discovery of High-Potency Enzyme Inhibitors from Herbal Medicines.

Herbal medicines (HMs) are an important source of drugs. In this study, an efficient strategy integrating ultrafiltration LC-MS, microplate bioassays, and molecular docking was proposed to screen high-potency enzyme inhibitors from HMs. Using this strategy, the structure-activity relationships (SARs) including binding-affinity-based SAR, enzymatic-activity-based SAR, and structural-complementarity-based SAR of compounds in an HM can be analyzed to provide abundant information for drug discovery. A prominent advantage of the approach is that it offers a multidimensional perspective to understand enzyme-ligand interactions, which could help to avoid false-positive screening results brought by a single method. By using xanthine oxidase (XOD) as an illustrative case, two types of potent XOD inhibitors, including flavones and coumarins, were successfully screened out from an HM of Ginkgo biloba. The study is expected to set a solid foundation for multidisciplinary cooperation in drug discovery.