PUBLICATION

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

Authors
Zhou, C., Chen, J., Liu, K., Maharajan, K., Zhang, Y., Hou, L., Li, J., Mi, M., Xia, Q.
ID
ZDB-PUB-230131-27
Date
2023
Source
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie   160: 114315114315 (Journal)
Registered Authors
Keywords
Anti-inflammatory effect, Gastric ulcer, Isoalantolactone, Network pharmacology, Zebrafish
MeSH Terms
  • Animals
  • Anti-Inflammatory Agents/therapeutic use
  • Ethanol/pharmacology
  • Humans
  • Inflammation/chemically induced
  • Inflammation/drug therapy
  • Inflammation/prevention & control
  • Molecular Docking Simulation
  • Phosphatidylinositol 3-Kinases/metabolism
  • Proto-Oncogene Proteins c-akt/metabolism
  • Sesquiterpenes*/pharmacology
  • Sesquiterpenes*/therapeutic use
  • Signal Transduction
  • Stomach Ulcer*/chemically induced
  • Stomach Ulcer*/drug therapy
  • Stomach Ulcer*/prevention & control
  • Zebrafish/metabolism
PubMed
36716661 Full text @ Biomed. Pharmacother.
Abstract
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. Quantitative 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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