Isoalantolactone protects against ethanol-induced gastric ulcer via alleviating inflammation through regulation of PI3K-Akt signaling pathway and Th17 cell differentiation

被引：16
作者：
Zhou, Chaoyi [1 ,2 ]
Chen, Jing [3 ]
Liu, Kechun [2 ]
Maharajan, Kannan [2 ]
Zhang, Yun [2 ]
Hou, Linhua [1 ,2 ]
Li, Jianheng [1 ]
Mi, Ma [3 ]
Xia, Qing [2 ]
机构：
[1] Hebei Univ, Sch Pharm, Baoding 071002, Peoples R China
[2] Qilu Univ Technol, Shandong Acad Sci, Biol Inst, Jinan 250103, Peoples R China
[3] Tibetan Tradit Med Coll, Lhasa 850000, Peoples R China
来源：
BIOMEDICINE & PHARMACOTHERAPY | 2023年 / 160卷
关键词：
Isoalantolactone; Gastric ulcer; Anti-inflammatory effect; Network pharmacology; Zebrafish; ZEBRAFISH;
D O I：
10.1016/j.biopha.2023.114315
中图分类号：
R-3 [医学研究方法]; R3 [基础医学];
学科分类号：
1001 ;
摘要：
Gastric ulcer (GU) is one of the most prevalent digestive system diseases in humans, and it has been linked to inflammation. Previous studies have demonstrated the anti-inflammatory potential of isoalantolactone (IAL), a sesquiterpene lactone isolated from Radix Inulae. However, the pharmacological effects of IAL on GU and its mechanism of action are still unclear. Hence, the present study is aimed to investigate the anti-inflammatory potential of IAL on GU. Firstly, we assessed the effect of IAL on ethanol-induced injury of human gastric epithelial cells and the levels of inflammatory cytokines in cell culture supernatants. Then, the anti-inflammatory effects of IAL were confirmed in vivo using zebrafish inflammation models. Furthermore, the mechanism of IAL against GU was preliminarily discussed through network pharmacology and molecular docking studies. Quan-titative real-time PCR assays were also used to confirm the mechanism of IAL action. ALB, EGFR, SRC, HSP90AA1, and CASP3 were found for the first time as the key targets of the IAL anti-GU. PI3K-Akt signaling pathway and Th17 cell differentiation were identified to play a crucial role in the anti-GU effects of IAL. In conclusion, we found that IAL has anti-inflammatory effects both in vitro and in vivo, and showed potential protective effects against ethanol-induced GU.
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页数：12
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