摘要Cisplatin and its metabolites can cause severe gastrointestinal mucosal damage,leading to varying degrees of intestinal injury in nearly all patients following administration.Although the anti-tumor effectiveness of R-ginsenoside Rg3(R-Rg3,a key chemical component of Shen Yi Capsule)as the first-line drug is widely recognized in the clinic,there is less concern about the improved effects of R-Rg3 against intestinal toxicity caused by concurrent cisplatin chemotherapy.This study aimed to investigate the protective effects of R-Rg3 against cisplatin-induced intestinal toxicity and to explore its potential molecular targets and mechanisms.Rats in the R-Rg3 treatment group were treated with R-Rg3(7,14 mg·kg-1,p.o.)for 7 days,and a single dose of cisplatin(14 mg·kg-1,i.p.)was administered via intraperitoneal injection to rats in the cisplatin group and R-Rg3 treatment group on the 7th day.Intestinal epithelial cell line 6(IEC-6)were pretreated with R-Rg3(1.25,2.5,5 μmol·L-1)for 24 h followed by cis-platin treatment(3 μmol·L-1,24 h).The in vivo results showed that,R-Rg3 treatment for 7 days markedly alleviated cisplatin-induced oxidative stress and mitochondrial dysfunction in vivo,while suppressing excessive autophagy and reducing intestinal damage.In IEC-6 cells,R-Rg3 pretreatment inhibited mitophagy and promoted the restoration of lysosomal function.Autophagy inhibitors 3-methyladenine(autophagosome formation inhibitor,1 μmol·L-1)and Bafilomycin A1(proton pump inhibitor,8 μmol·L-1)were used to verify the mechanism of R-Rg3 action.Importantly,application of 3-methyladenine and Bafilomycin A1 verified that R-Rg3 could alleviate gastrointestinal dysfunction by restoring the cisplatin-induced autophagic flux blockade.In conclusion,this study identifies a previously underappreciated protective role of R-Rg3 against cisplatin-induced intestinal injury.Furthermore,it suggests that phar-macological modulation of the mitochondria-lysosome axis by R-Rg3 may effectively mitigate oxidative stress-mediated autophagic flux impairment caused by cisplatin.