1. Ginsenoside Re Attenuates Cisplatin-Induced Intestinal Toxicity via Suppressing GSK-3β-Dependent Wnt/β-Catenin Signaling Pathway In Vivo and In Vitro.
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Wang, Jian-Qiang, Dong, Yu, Feng, Zi-Meng, Fan, Mei-Ling, Yang, Jia-Yu, Hu, Jun-Nan, Cai, En-Bo, Zhu, Hong-Yan, Li, Wei, and Wang, Zi
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PROTEIN kinases , *IN vitro studies , *BIOLOGICAL models , *IN vivo studies , *CELL culture , *ANIMAL experimentation , *WESTERN immunoblotting , *GLYCOSIDES , *SIGNAL peptides , *CYTOSKELETAL proteins , *CHEMICAL reagents , *APOPTOSIS , *RISK assessment , *CELLULAR signal transduction , *CISPLATIN , *INTESTINAL diseases , *RESEARCH funding , *DESCRIPTIVE statistics , *CELL surface antigens , *DATA analysis software , *DRUG toxicity , *GINSENG , *CASPASES , *IMMUNODIAGNOSIS , *MICE , *DISEASE risk factors - Abstract
Previous reports have confirmed that crude saponins (ginsenosides) in Panax ginseng have a preventive effect on chemotherapy-induced intestinal injury. However, the protective effects and possible mechanisms of ginsenoside Re (G-Re, a maker saponin in ginseng) against chemotherapy-induced intestinal damage have not been thoroughly studied. In this work, a series of experiments in vivo and in vitro on the intestinal toxicity caused by cisplatin have been designed to verify the improvement effect of G-Re, focusing on the levels of Wnt3a and β -catenin. Mice were intragastric with G-Re for 10 days, and intestinal injury was induced by intraperitoneal administration of cisplatin at a dose of 20 mg/kg. Histopathology, gastrointestinal digestive enzyme activities, inflammatory cytokines, and oxidative status were evaluated to investigate the protective effect. Furthermore, in IEC-6 cells, G-Re statistically reverses cisplatin-induced oxidative damage and cytotoxicity. The TUNEL and Hoechst 33258 staining demonstrated that G-Re possesses protective effects in cisplatin-induced apoptosis. Additionally, pretreatment with G-Re significantly alleviated the apoptosis via inhibition of over-expressions of B-associated X (Bax), as well as the caspase family members, such as caspase 3 and 9, respectively, in vivo and in vitro. Notably, western blotting results showed that G-Re treatment decreased Wnt3a, Glycogen synthase kinase 3 β (GSK- 3 β), and β -catenin expression, suggesting that nuclear accumulation of β -catenin was attenuated, thereby inhibiting the activation of GSK- 3 β -dependent Wnt/ β -catenin signaling, which was consistent with our expected results. Therefore, the above evidence suggested that G-Re may be a candidate drug for the treatment of intestinal injury. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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