Regulatory effect of eight Chinese herbal medicines on glucose and lipid metabolism and their potential active components based on HCBP6 target / 中国中药杂志

With the improvement of living standards and changes in working style, the prevalence of abnormal glucose and lipid metabolism in humans is increasing in modern society. Clinically, the related indicators are often improved by changing the lifestyle and/or taking hypoglycemic and lipid-lowering drugs, but there are no therapeutic drugs for disorders of glucose and lipid metabolism at present. Hepatitis C virus core protein binding protein 6(HCBP6) is a newly discovered target that can regulate triglyceride and cholesterol content according to level oscillations in the body, thereby regulating abnormal glucose and lipid metabolism. Relevant studies have shown that ginsenoside Rh_2 can significantly up-regulate the expression of HCBP6, but there are few studies on the effect of Chinese herbal medicines on HCBP6. Moreover, the three-dimensional structural information of HCBP6 has not been determined and the discovery of potential active components acting on HCBP6 is not rapidly advanced. Therefore, the total saponins of eight Chinese herbal medicines commonly used to regulate abnormal glucose and lipid metabolism were selected as the research objects to observe their effect on the expression of HCBP6. Then, the three-dimensional structure of HCBP6 was predicted, followed by molecular docking with saponins in eight Chinese herbal medicines to quickly find potential active components. The results showed that all total saponins tended to up-regulate HCBP6 mRNA and protein expression, where gypenosides showed the optimum effect on up-regulating HCBP6 mRNA and ginsenosides showed the optimum effect on up-regulating HCBP6 protein expression. Reliable protein structures were obtained after the prediction of protein structures using the Robetta website and the evaluation of the predicted structures by SAVES. The saponins from the website and literature were also collected and docked with the predicted protein, and the saponin components were found to have good binding activity to the HCBP6 protein. The results of the study are expected to provide ideas and methods for the discovery of new drugs from Chinese herbal medicines to regulate glucose and lipid metabolism.

The regulation mechanism of HCBP6 mimic phosphorylation on triglyceride synthesis in hepatocytes / 西安交通大学学报(医学版)

【Objective】 To investigate the regulation of HCBP6 mimic phosphorylation on triglyceride synthesis in hepatocytes so as to provide a molecular target for the treatment of metabolism-associated fatty liver disease. 【Methods】 We used site-directed mutagenesis to mimic constitutive phosphorylation and dephosphorylation of HCBP6 Ser-10 and Ser-151. Oil red O staining and triglyceride content determination were used to detect triglyceride levels in hepatocytes. The expressions of SREBP1c, ACC1 and FASN were detected by qRT-PCR and Western blotting. The Dual-Luciferase Report Gene System was used to detect SREBP1c promoter activity. 【Results】 HCBP6 Ser-10 phosphorylation promoted triglyceride synthesis. HCBP6 Ser-10 phosphorylation upregulated the expressions of SREBP1c, ACC1and FASN genes; HCBP6 Ser-10 phosphorylation enhanced the SREBP1c promoter activity. 【Conclusion】 HCBP6 Ser-10 phosphorylation can significantly enhance the activity of the SREBP1c promoter, upregulate the SREBP1c-FASN signal pathway transduction, and promote the synthesis of triglycerides.