基于HCBP6靶点的8种常用中草药调节糖脂代谢作用及其潜在活性成分的探讨

Regulatory effect of eight Chinese herbal medicines on glucose and lipid metabolism and their potential active components based on HCBP6 target

随着生活水平的提高和工作方式的改变,现代社会人类糖脂代谢异常的发病率越来越高。临床上常通过调整生活方式和/或应用降糖降脂药进行治疗,但目前并没有专门针对糖脂代谢紊乱的药物。丙型肝炎病毒核心蛋白结合蛋白6(HCBP6)是一个新发现的靶点,可依据体内水平振荡调节甘油三酯及胆固醇的含量,从而调节糖脂代谢异常。相关研究表明,人参皂苷Rh2可显著上调HCBP6的表达,但关于中药对HCBP6作用的研究几乎为空白,且HCBP6三维结构信息也未被确定,作用于HCBP6的潜在活性成分的发现研究较为缓慢。因此,该研究首先选择8种常用的调节糖脂代谢异常的中药的总皂苷部位为研究对象,观察其对HCBP6表达的影响,然后采用预测获得的HCBP6三维结构与8种中草药中皂苷类成分进行分子对接,以期快速获取潜在活性单体。结果表明,8种总皂苷部位均有上调HCBP6 mRNA及蛋白表达的作用趋势。其中,绞股蓝总皂苷组上调HCBP6 mRNA的作用最好;人参总皂苷组上调HCBP6蛋白表达的效果最好。利用Robetta网站对蛋白质结构进行预测并通过SAVES对预测的结构进行评估后得到可靠的蛋白结构。同时搜集网站及文献中的皂苷类化合物与预测的蛋白进行对接,发现皂苷类成分与HCBP6蛋白具有良好的结合活性。研究结果为从中药中发现调节糖脂代谢的新药提供了思路和方法。

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 Rh2can 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.