Zhai Lixiang, Ning Zi-Wan, Huang Tao, Wen Bo, Liao Cheng-Hui, Lin Cheng-Yuan, Zhao Ling, Xiao Hai-Tao, Bian Zhao-Xiang
School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong.
Shenzhen Research Institute and Continuing Education, Hong Kong Baptist University, Shenzhen, China.
Front Pharmacol. 2018 Aug 28;9:973. doi: 10.3389/fphar.2018.00973. eCollection 2018.
Hyperlipidemia and hepatic steatosis afflict over 75% of patients with type 2 diabetes, causing diabetic dyslipidemia. (CP) leaf is a herbal tea which has long been consumed by the Chinese population, particularly people suffering from obesity and diabetes. CP appears to exhibit a hypolipidemic effect in lipid loaded mice (Kurihara et al., 2003), although the detailed mechanisms and active ingredients for this hypolipidemic effect have not yet been answered. In this study, we investigated the beneficial effects of CP and predicted the mechanisms by utilizing lipidomics, serum-pharmacochemistry and network pharmacology approaches. Our results revealed that serum and hepatic levels of total triglyceride (TG), total cholesterol (T-CHO), low-density lipoproteins (LDL) and high-density lipoproteins (HDL), as well as 30 lipids including cholesterol ester (CE), diglyceride (DG), phosphatidylethanolamine (PE), phosphatidylcholine (PC), and sphingomyelin (SM) in CP-treated mice were improved in comparison with untreated diabetic mice. In parallel, 14 phytochemical compounds of CP were determined in mice serum after CP administration. Mechanistically, the network pharmacology analysis revealed the predicted targets of CP's active ingredients ALOX12, APP, BCL2, CYP2C9, PTPN1 and linked lipidome targets PLD2, PLA2G(s), and PI3K(s) families could be responsible for the CP effects on diabetic dyslipidemia. In conclusion, this study revealed the beneficial effects of CP on diabetic dyslipidemia are achieved by reducing accumulation of hepatic lipid droplets and regulating circulatory lipids in diabetic mice, possibly through PI3K signaling and MAPK signaling pathways. GRAPHICAL ABSTRACTWork flow of the evaluation of the effects and mechanisms of leaves tea on dyslipidemia in diabetic mice.
高脂血症和肝脂肪变性困扰着超过75%的2型糖尿病患者，导致糖尿病血脂异常。(CP)叶是一种长期以来被中国人饮用的草药茶，尤其是肥胖和糖尿病患者。CP在脂质负荷小鼠中似乎具有降血脂作用（栗原等人，2003年），尽管这种降血脂作用的详细机制和活性成分尚未明确。在本研究中，我们利用脂质组学、血清药理学和网络药理学方法研究了CP的有益作用并预测其机制。我们的结果显示，与未治疗的糖尿病小鼠相比，CP治疗小鼠的血清和肝脏中总甘油三酯（TG）、总胆固醇（T-CHO）、低密度脂蛋白（LDL）和高密度脂蛋白（HDL）水平，以及包括胆固醇酯（CE）、甘油二酯（DG）、磷脂酰乙醇胺（PE）、磷脂酰胆碱（PC）和鞘磷脂（SM）在内的30种脂质均有所改善。同时，在给予CP后，在小鼠血清中测定了CP的14种植物化学化合物。从机制上讲，网络药理学分析显示，CP活性成分ALOX12、APP、BCL2、CYP2C9、PTPN1的预测靶点以及脂质组靶点PLD2、PLA2G(s)和PI3K(s)家族可能是CP对糖尿病血脂异常产生作用的原因。总之，本研究表明，CP对糖尿病血脂异常的有益作用是通过减少糖尿病小鼠肝脏脂质滴的积累和调节循环脂质来实现的，可能是通过PI3K信号通路和MAPK信号通路。图摘要糖尿病小鼠叶茶对血脂异常影响及机制评估的工作流程。
