ReferenceID 5131
Dioscin ameliorates cisplatin-induced intestinal toxicity by mitigating oxidative stress and inflammation
Int Immunopharmacol
Cisplatin is the most widely prescribed drug in chemotherapy, but its gastrointestinal toxicity reduces therapeutic efficacy. Oxidative stress and inflammation are considered to be the main pathogenesis of cisplatin-indu
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Record Fields
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- Reference Id
- 5131
- Evidence Id
- 21721
- Core Evidence Id
- 21721
- Source Reference Id
- 3542
- Herb2 Reference Id
- HBREF004339
- Subject Paper Key
- HBIN024134_35933746
- Pubmed Id
- 35933746
- Doi
- 10.1016/j.intimp.2022.109111
- Paper Title
- Dioscin ameliorates cisplatin-induced intestinal toxicity by mitigating oxidative stress and inflammation
- Paper Abstract
- Cisplatin is the most widely prescribed drug in chemotherapy, but its gastrointestinal toxicity reduces therapeutic efficacy. Oxidative stress and inflammation are considered to be the main pathogenesis of cisplatin-induced intestinal toxicity. Dioscin is a steroidal saponin with potential anti-cancer, antioxidant, and anti-inflammatory activities. In this study, we established a rat model of intestinal injury by tail vein injection of cisplatin, and intragastrically administered dioscin to evaluate its effect on intestinal injury. Biochemical markers, western blotting, qRT-PCR and histopathological staining were used to analyze intestinal injury according to various molecular mechanisms. The results revealed that dioscin significantly inhibited cisplatin-induced intestinal mucosal damage and decreased DAO levels in rats. Furthermore, dioscin activated the Nrf2/HO-1 pathway to increase the level of antioxidant enzymes and reduce the levels of MDA and H 2 O 2 . In addition, dioscin pretreatment significantly reduced ileum epithelial NLRP3 inflammasome formation and decreased the levels of inflammatory factors compared with the cisplatin group. In parallel, Nrf2 inhibitor ML385 blocked the therapeutic effect of dioscin in rat with cisplatin-induced intestinal toxicity. In terms of mechanisms, dioscin reversed cisplatin-induced up-regulation of MAPKs and up-regulated p-PI3K and p-AKT levels. Meanwhile, dioscin potently promoted Wnt3A/β-catenin signaling to relieve cisplatin-induced proliferation inhibition. In conclusion, our study suggests that dioscin could ameliorate the cisplatin-induced intestinal toxicity by reducing oxidative stress and inflammation.
- Journal
- Int Immunopharmacol
- Publish Year
- 2022
- Experiment Subject
- rat
- Experiment Type
- Animal Experiment
- Phenotype Related
- Intestinal Injury; Cisplatin-induced Intestinal Toxicity; Inflammation
- Paper Title Cn
- Paper Title En
- Dioscin ameliorates cisplatin-induced intestinal toxicity by mitigating oxidative stress and inflammation
- Bilingual Status
- semi_complete