18Beta-Glycyrrhetinic Acid Attenuates H2O2-Induced Oxidative Damage and Apoptosis in Intestinal Epithelial Cells via Activating the PI3K/Akt Signaling Pathway

文献类型： 外文期刊

第一作者： Ma, Cui

作者： Ma, Cui;Wang, Fuxi;Zhu, Jiawei;Wang, Shiyi;Liu, Yaqing;Xu, Jianfang;Zhao, Qingyu;Qin, Yuchang;Si, Wei;Zhang, Junmin;Wang, Fuxi;Wang, Shiyi;Liu, Yaqing

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关键词： 18beta-glycyrrhetinic acid; oxidative stress; PI3K/Akt pathway; molecular docking

期刊名称：ANTIOXIDANTS （ 影响因子：7.0； 五年影响因子：7.3 ）

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年卷期： 2024 年 13 卷 4 期

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收录情况： SCI

摘要： Oxidative stress causes gut dysfunction and is a contributing factor in several intestinal disorders. Intestinal epithelial cell survival is essential for maintaining human and animal health under oxidative stress. 18beta-Glycyrrhetinic acid (GA) is known to have multiple beneficial effects, including antioxidant activity; however, the underlying molecular mechanisms have not been well established. Thus, the present study evaluated the therapeutic effects of GA on H2O2-induced oxidative stress in intestinal porcine epithelial cells. The results showed that pretreatment with GA (100 nM for 16 h) significantly increased the levels of several antioxidant enzymes and reduced corresponding intracellular levels of reactive oxidative species and malondialdehyde. GA inhibited cell apoptosis via activating the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathway, as confirmed by RNA sequencing. Further analyses demonstrated that GA upregulated the phosphorylation levels of PI3K and Akt and the protein level of B cell lymphoma 2, whereas it downregulated Cytochrome c and tumor suppressor protein p53 levels. Moreover, molecular docking analysis predicted the binding of GA to Vasoactive intestinal peptide receptor 1, a primary membrane receptor, to activate the PI3K/Akt signaling pathway. Collectively, these results revealed that GA protected against H2O2-induced oxidative damage and cell apoptosis via activating the PI3K/Akt signaling pathway, suggesting the potential therapeutic use of GA to alleviate oxidative stress in humans/animals.

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