Selection and evaluation of quality markers from Yinlan capsule and its LXRα-mediated therapy for hyperlipidemia
| Autor: | Xu Aili, Chen Zhao, Haoliang Guo, Dongmei Sun, Dake Cai, Luo Wenhui, Lizhong Cao, Chen Weitao, Jie-yi Jiang, Xiaoli Bi |
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| Rok vydání: | 2018 |
| Předmět: |
Quality Control
Ginsenosides Metabolite Pharmaceutical Science Capsules Hyperlipidemias Pharmacology Cholesterol 7 alpha-hydroxylase Diet High-Fat Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Pharmacokinetics Tandem Mass Spectrometry Drug Discovery Animals Liver X receptor Triglycerides 030304 developmental biology Lupeol Hypolipidemic Agents Liver X Receptors 0303 health sciences Bioavailability Cholesterol Complementary and alternative medicine chemistry Gene Expression Regulation Liver Ginsenoside 030220 oncology & carcinogenesis Pharmacodynamics Molecular Medicine Pentacyclic Triterpenes Biomarkers Drugs Chinese Herbal |
| Zdroj: | Phytomedicine : international journal of phytotherapy and phytopharmacology. 59 |
| ISSN: | 1618-095X |
| Popis: | Background The selection of active compounds for the quality evaluation of traditional Chinese medicine (TCM), specifically complex formulas, remains a challenge for researchers, as components selected as indexes usually have no clear relation with the therapeutic effects of interest. As a suggested resolution, quality control markers (Q-markers) showed good perspective for discriminating numerous compounds found for specific efficacies. In the presented study, the components of the Yinlan (YL) capsule, a TCM patent formula comprising four ingredients, were evaluated and selected for their lipid regulatory effects using principles for Q-marker selection. Purpose The mechanism of TCM therapeutic effects involves several pathways and targets that combine to become an integrated action in the body. Therefore, it is assumed that specific compounds in YL should have good affinity for related targets and obvious effects (both up- and downregulating). Thus, a series of experiments, including cytobiology, animal-based pharmacodynamics, computer-assisted drug design, conventional content determination and pharmacokinetics, would be helpful for the selection and final confirmation of Q-markers. Methods The capsule was first administered to Wistar mice fed a high-fat diet and tested for their triglycerides (TG) and total cholesterol (TC) values to evaluate the effectiveness of YL. Then, liver tissue was extracted for gene expression. According to the results, the compounds in YL with good affiliation were selected and determined using UHPLC-MS-MS, and those with adequate results in the capsule were chosen as Q-marker candidates. Finally, pharmacokinetics research was performed; the candidates with desirable metabolite and bioavailability parameters were confirmed as Q-markers of YL. Results YL capsule was capable of lowering TG and TC levels. For target selection, the expression of LXR mRNA increased significantly at all three tested dosages. Downstream genes, such as LCAT, CYP7A1, and ABCA1, and intestinal FXR mRNA also showed significant increases in expression. For screening of the Q-marker candidates, 5 compounds were selected according to abovementioned results. The pharmacokinetics research demonstrated that the rats exploited lupeol and ginsenoside Rb3 in a desirable pattern with adequate bioavailability, which confirmed their roles as lipid regulatory Q-markers. Conclusion The YL capsule was demonstrated to have obvious lipid regulatory effects, which are mainly exerted by targeting LXR and its related pathway. Lupeol and ginsenoside Rb3 were validated as Q-markers that represent the anti-hyperlipidemia activity of the capsule. |
| Databáze: | OpenAIRE |
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