The role of p38 MAPK in acteoside-mediated gastric ulcer protection

TL;DR

This study explores how acteoside, a compound from Anisomeles indica, protects against stomach ulcers by reducing inflammation through the p38 MAPK pathway.

Contribution

The study identifies acteoside's gastroprotective mechanism via p38 MAPK suppression in both in vivo and in vitro models.

Findings

Acteoside reduced ulcer index and inflammatory markers in pyloric ligation-induced rat ulcers.

Acteoside increased cell viability and suppressed inflammatory gene expression in indomethacin-treated cells.

p38 MAPK knockdown enhanced acteoside's protective effects, confirming its role in the mechanism.

Abstract

Stomach ulcers are a significant health concern, with epidemiological studies indicating multiple forms and causes. Current treatments often lead to various side effects and may require additional medical resources. Therefore, there is an urgent need to identify safer natural extracts with fewer side effects. In this study, we established two models: an in vivo model, where gastric ulcer was induced through pyloric ligation in Wistar rats, and an in vitro model, where indomethacin treatment in RGM1 gastric mucosal cells was used to evaluate the gastroprotective effects of Anisomeles indica (L.) Kuntze HP813 powder (AIHP) in vivo, and its major functional component, acteoside, protective effects mechanisms in vitro. The preventive gastroprotective effect of AIHP was assessed in Wistar rats with pyloric ligation-induced ulcers. We evaluated the ulcer index, gastric acidity, and the immunohistochemical expression of anti-inflammatory markers in gastric tissues. We evaluated the protective effects and the underlying mechanism of acteoside in indomethacin-treated RGM1 cells, utilizing transient transfection with shRNA targeting p38 mitogen-activated protein kinase (p38 MAPK) to specifically examine its role. Results showed AIHP significantly reduced ulcer index and downregulated TNF-α, IL-1β, NF-κB, and p38 MAPK expression in gastric tissue. Acteoside significantly increased the cell viability and down-regulated TNF-α, IL-1β, IL-6, NF-κB, and p38 MAPK expression of RGM1 cells after indomethacin treatment. Following p38 MAPK knockdown via shRNA, acteoside reduced the indomethacin-induced expression of p38 MAPK and IL-6 in RGM1 cells. These effects are mediated through the suppression of inflammatory mediators via the p38 MAPK pathway. Our findings support acteoside's potential as a pharmacological agent for the management of gastric ulcers.

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