Ginsenoside Re Attenuates Cisplatin-Induced Intestinal Toxicity via Suppressing GSK-3ß-Dependent Wnt/ß-Catenin Signaling Pathway In Vivo and In Vitro.
Am J Chin Med
; 51(2): 407-424, 2023.
Article
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| MEDLINE
| ID: mdl-36575152
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 [Formula see text]-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 [Formula see text] (GSK-[Formula see text]), and [Formula see text]-catenin expression, suggesting that nuclear accumulation of [Formula see text]-catenin was attenuated, thereby inhibiting the activation of GSK-[Formula see text]-dependent Wnt/[Formula see text]-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.
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Base de datos:
MEDLINE
Asunto principal:
Saponinas
/
Ginsenósidos
/
Antineoplásicos
Idioma:
En
Revista:
Am J Chin Med
Año:
2023
Tipo del documento:
Article