Screening of the optimal therapeutic dose of Gynostemma pentaphyllum gypenosides and the mechanism on lowering lipids and hepatic and renal protection
DENG Meng-yue
YANG Chang-xin
FENG Bao-wen
SHI He-min
XIA Die
DING Yu-zhen
YAN Zi-jun
WEI Pan-pan
HE Bo
CHEN Tong
Abstract：Objective:To investigate the effect of lipid-lowering,hepatic and renal protection of different doses of Gynostemma pentaphyllum gypenosides(GPs)in hyperlipidemia rats and its preliminary mechanism to screen the optimal therapeutic dose.Methods:A hyperlipidemia rat model was constructed by high-fat diet,and treated by different doses of GPs.The efficacy of GPs on the rats was examined by measuring blood lipids,liver lipids,liver and kidney function and oxidative stress.The secretion levels of proprotein convertase subtilisin/kexin 9(PCSK9),3-hydroxy-3-methyl glutaryl coenzyme a reductase(HMGR),and peroxisome proliferators-activated receptors(PPAR-α and PPAR-γ)in serum were detected to preliminarily explore its mechanism of action.Results:GPs significantly reduced total cholesterol(TC),triglyceride(TG)and low-density lipoprotein cholesterol(LDL-C)in serum and liver homogenate,and increased the level of high-density lipoprotein cholesterol(HDL-C).120～240 mg·kg-1 GPs and 20 mg·kg-1 fenofibrate showed similar hypolipidemic effects,and GPs indicated a better effect on down-regulating liver lipids.120～240 mg·kg-1 GPs also reduced the content of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in liver homogenate,significantly reduced hepatocyte steatosis and ballooning,and reduced the degree of liver lesions,significantly reduced blood urea nitrogen(BUN)and creatinine(CRE),reduced renal tubular degeneration and necrosis,cytoplasmic cavitation and lysis in hyperlipidemia rats.At the same time,GPs also enhanced the activity of antioxidant enzymes(SOD,CAT and GSH-Px)in rats,reduced oxidative stress and lipid peroxidation(MDA),and significantly reduced the secretion of PCSK9 and increased the expression of PPAR receptor.Conclusion:GPs can exert a lipid-lowering effect,and the efficacy is positively dose-dependent.The dose range of 120～240 mg·kg-1 GPs has the best therapeutic effect,which may be related to its inhibition of PCSK9 secretion and enhancement of PPAR expression;and GPs can effectively reduce liver and kidney injury and lipid peroxidation damage caused by hyperlipidemia,providing a reliable theoretical basis for further development of the clinical application of Gynostemma pentaphyllum gypenosides.
Keywords：gypenosidesdose screeninghyperlipidemialiver and kidney protectionantioxidantproprotein convertase subtilisin/kexin 9peroxisome proliferators-activated receptors
Publication Date：2024-03-15
Online Publishing Date：2026-08-14(First online date of this platform, not the publication date of the document)
Pages：11( 458-468 )