The Protective Effects Of On Acute Liver And Kidney Injury Of 20(R)- Ginsenoside Rg3 On Liver And Kidney Injury Were Explored,Based On PI3K/AKT/NF-?B Signaling Pathway

In this study,the panaxadiol saponin Rd was selected for transformation,and the optimal process conditions were selected to prepare 20(R)-Rg3.Then,the mice models of APAPinduced acute liver injury and cisplatin-induced acute kidney injury were established,and the biochemical kits,Elisa detections,immunohistochemical staining,immunofluorescence staining and western blots were used to investigate the protective effects of 20(R)-Rg3 on druginduced liver and kidney injuries and further elucidated its possible molecular mechanism.The details are as follows:1.Optimization of preparation process of 20(R)-Rg3.In this experiment,the hightemperature acid hydrolysis method was used to efficiently convert the ginseng diol saponin Rd into a rare ginsenoside Rg3.The process conditions of ginsenoside Rd conversion to secondary ginsenoside Rg3 were optimized by different factors of acidity,ratio of material to liquid and conversion time.The optimum conditions are: 95?,0.1% formic acid,reaction for 3 h,and 20(R)-Rg3 can be obtained to the utmost by means of recrystallization.This process has short reaction time,easy operation and few by-products.The research provides a material basis and a theoretical basis for the study of rare ginsenoside Rg3.2.The protective effects and molecular mechanism of 20(R)-ginsenoside Rg3 on APAP-induced acute liver injury.The results showed that 20(R)-Rg3 pretreatment for 7 days significantly reduced alanine aminotransferase(ALT),aspartate aminotransferase(AST),malondialdehyde(MDA)and increased glutathione(GSH)levels.At the same time,the over expression of cytochrome P450 E1(CYP2E1)and a lipid peroxidation end product,4-hydroxynonenal(4-HNE),caused by APAP exposure were also inhibited by 20(R)-Rg3.In addition,H&E,Hoechst 33258 and TUNEL staining showed that 20(R)-Rg3 could protect hepatocytes against APAP-induced cell necrosis and apoptosis,and the PI3K/AKT pathway was inhibited after toxic doses of APAP treatment,and 20(R)-Rg3 pretreatments for 7 days could restore,and inhibited the expression of pro-apoptotic protein(Bax)and increase the expression of anti-apoptotic protein(Bcl-2).Furthermore,in terms of inflammation,TNF-? and IL-1? levels in serum were significantly reduced by pretreatment with 20(R)-Rg3 compared with the APAP group.Western blot analysis showed that 20(R)-Rg3 inhibited NF-?B activation by inhibiting the activation of IKK?,IKK? and I-?B?.In conclusion,this experiment clearly demonstrates that 20(R)-Rg3 can inhibits oxidative stress,improves inflammatory response,reduces apoptosis and necrosis,and regulates PI3K/AKT signaling pathway-associated proteins.It plays an important role in APAP-induced acute liver injury.3.The protective effects and molecular mechanism of 20(R)-ginsenoside Rg3 on Cisplatin-induced Nephrotoxicity.The experimental data showed that after 10 days of pretreatment of 20(R)-Rg3,the blood urea nitrogen(BUN),serum creatinine(CRE),malondialdehyde(MDA)levels were reduced,and glutathione(GSH),superoxide dismutase(SOD),and catalase(CAT)levels were increased.These results indicate that the model was successfully established and oxidative stress damage was improved.H&E,Hoechst 33258 and TUNEL staining and the immunohistochemical staining of Cyclooxygenase-2(COX-2)and inducible nitric oxide synthase(iNOS)showed that 20(R)-Rg3 could effectively improve renal tissue structural degeneration and significantly reduce renal cell apoptosis by Cisplatin-induced.The results showed that 20(R)-Rg3 inhibition Apoptosis and inflammatory responses in mice.In addition,Western blot was used to analyze the PI3K/AKT signaling pathway and its downstream target proteins Bcl-2,Bax,as well as NF?B signaling pathway-related proteins.In conclusion,this experiment clearly demonstrates that 20(R)-Rg3 can play an important role in Cisplatin-induced acute kidney injury by inhibiting oxidative stress,improving inflammatory response,reducing apoptosis and necrosis,and regulating PI3K/AKT signaling pathwayassociated proteins,and proved that 20(R)-Rg3 does not affect the anticancer activity of Cisplatin under the premise of protecting kidney damage.In summary,this article provides a reliable theoretical basis for the clinical prevention of hepato-renal toxicity in the treatment of 20(R)-Rg3,thereby expanding the clinical application of 20(R)-Rg3 and also having a significant impact on the clinical treatment of cancer.