Ginsenoside Rh4 Ameliorates Cisplatin-Induced Intestinal Toxicity via PGC-1[Formula: see text]-Mediated Mitochondrial Autophagy and Apoptosis Pathways.
{"title":"Ginsenoside Rh4 Ameliorates Cisplatin-Induced Intestinal Toxicity via PGC-1[Formula: see text]-Mediated Mitochondrial Autophagy and Apoptosis Pathways.","authors":"Wei Liu, Meng Sun, Wen-Ting Wang, Jian Song, Chun-Mei Wang, Neng-Yan Mou, Tian-Qi Shao, Zhi-Hong Zhang, Meng-Yang Wang, Hai-Ming Sun","doi":"10.1142/S0192415X24500848","DOIUrl":null,"url":null,"abstract":"<p><p>Cisplatin-evoked profound gastrointestinal symptomatology is one of the most common side effects of chemotherapy drugs, causing further gastrointestinal cell and intestinal mucosal injury. Ginsenoside Rh4 (G-Rh4), an active component extracted from red ginseng, possesses beneficial anti-oxidative and anti-apoptosis effects. This study aimed to assess the effectiveness of pharmacological intervention with G-Rh4 mitigating intestinal toxicity evoked by cisplatin in a murine model and in IEC-6 cells <i>in vitro</i>. Following oral administration for 10 days, G-Rh4 (10[Formula: see text]mg/kg and 20[Formula: see text]mg/kg) significantly increased the indicators of diamine oxidase (DAO) affected by cisplatin (20[Formula: see text]mg/kg) in mice, and histopathological analysis further indicated that G-Rh4 could effectively improve intestinal tissue morphology, as well as the expression of peroxisome proliferator-activated receptor-gamma coactivator 1 [Formula: see text] (PGC-1[Formula: see text] pathway and autophagy-related proteins. Moreover, <i>in vitro</i> experiments demonstrated that G-Rh4 exerted a concentration-dependent increase in cell viability, while also inhibiting cytotoxicity and abnormal rise of reactive oxygen species (ROS). Notably, ROS also activate PGC-1[Formula: see text] protein and mediate the occurrence of mitochondrial autophagy and apoptosis pathways. The molecular docking approach was employed to dock G-Rh4 with PGC-1[Formula: see text] and AMPK, revealing a binding energy of [Formula: see text]7.3[Formula: see text]kcal/mol and [Formula: see text]8.1[Formula: see text]kcal/mol and indicating a tight interaction between the components and the target. G-Rh4 could reduce the expression of autophagy-related protein p62/p53, reduce the accumulation of autophagy products, and promote the flow of autophagy. In conclusion, G-Rh4 exerted protective effects against cisplatin-induced intestinal toxicity, at least partially through PGC-1[Formula: see text]-mediated autophagy and apoptosis.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"2187-2209"},"PeriodicalIF":0.0000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"The American journal of Chinese medicine","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1142/S0192415X24500848","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/11/19 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Cisplatin-evoked profound gastrointestinal symptomatology is one of the most common side effects of chemotherapy drugs, causing further gastrointestinal cell and intestinal mucosal injury. Ginsenoside Rh4 (G-Rh4), an active component extracted from red ginseng, possesses beneficial anti-oxidative and anti-apoptosis effects. This study aimed to assess the effectiveness of pharmacological intervention with G-Rh4 mitigating intestinal toxicity evoked by cisplatin in a murine model and in IEC-6 cells in vitro. Following oral administration for 10 days, G-Rh4 (10[Formula: see text]mg/kg and 20[Formula: see text]mg/kg) significantly increased the indicators of diamine oxidase (DAO) affected by cisplatin (20[Formula: see text]mg/kg) in mice, and histopathological analysis further indicated that G-Rh4 could effectively improve intestinal tissue morphology, as well as the expression of peroxisome proliferator-activated receptor-gamma coactivator 1 [Formula: see text] (PGC-1[Formula: see text] pathway and autophagy-related proteins. Moreover, in vitro experiments demonstrated that G-Rh4 exerted a concentration-dependent increase in cell viability, while also inhibiting cytotoxicity and abnormal rise of reactive oxygen species (ROS). Notably, ROS also activate PGC-1[Formula: see text] protein and mediate the occurrence of mitochondrial autophagy and apoptosis pathways. The molecular docking approach was employed to dock G-Rh4 with PGC-1[Formula: see text] and AMPK, revealing a binding energy of [Formula: see text]7.3[Formula: see text]kcal/mol and [Formula: see text]8.1[Formula: see text]kcal/mol and indicating a tight interaction between the components and the target. G-Rh4 could reduce the expression of autophagy-related protein p62/p53, reduce the accumulation of autophagy products, and promote the flow of autophagy. In conclusion, G-Rh4 exerted protective effects against cisplatin-induced intestinal toxicity, at least partially through PGC-1[Formula: see text]-mediated autophagy and apoptosis.