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Antioxidants
Volume 13
Issue 4
10.3390/antiox13040468
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Article

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

by
Cui Ma
1,
Fuxi Wang
1,2,
Jiawei Zhu
1,
Shiyi Wang
1,3,
Yaqing Liu
1,4,
Jianfang Xu
1,
Qingyu Zhao
1,
Yuchang Qin
1,
Wei Si
1,* and
Junmin Zhang
1,*
1
State Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Sciences of Chinese Academy of Agricultural Sciences, Beijing 100193, China
2
College of Animal Science and Technology, Shanxi Agricultural University, Jinzhong 030801, China
3
College of Food Science and Engineering, Qingdao Agricultural University, Qingdao 266109, China
4
College of Animal Science and Technology, Qingdao Agricultural University, Qingdao 266109, China
*
Authors to whom correspondence should be addressed.
Antioxidants 2024, 13(4), 468; https://doi.org/10.3390/antiox13040468
Submission received: 5 March 2024 / Accepted: 6 April 2024 / Published: 16 April 2024
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
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Abstract

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.
Keywords: 18beta-glycyrrhetinic acid; oxidative stress; PI3K/Akt pathway; molecular docking 18beta-glycyrrhetinic acid; oxidative stress; PI3K/Akt pathway; molecular docking
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MDPI and ACS Style

Ma, C.; Wang, F.; Zhu, J.; Wang, S.; Liu, Y.; Xu, J.; Zhao, Q.; Qin, Y.; Si, W.; Zhang, J. 18Beta-Glycyrrhetinic Acid Attenuates H2O2-Induced Oxidative Damage and Apoptosis in Intestinal Epithelial Cells via Activating the PI3K/Akt Signaling Pathway. Antioxidants 2024, 13, 468. https://doi.org/10.3390/antiox13040468

AMA Style

Ma C, Wang F, Zhu J, Wang S, Liu Y, Xu J, Zhao Q, Qin Y, Si W, Zhang J. 18Beta-Glycyrrhetinic Acid Attenuates H2O2-Induced Oxidative Damage and Apoptosis in Intestinal Epithelial Cells via Activating the PI3K/Akt Signaling Pathway. Antioxidants. 2024; 13(4):468. https://doi.org/10.3390/antiox13040468

Chicago/Turabian Style

Ma, Cui, Fuxi Wang, Jiawei Zhu, Shiyi Wang, Yaqing Liu, Jianfang Xu, Qingyu Zhao, Yuchang Qin, Wei Si, and Junmin Zhang. 2024. "18Beta-Glycyrrhetinic Acid Attenuates H2O2-Induced Oxidative Damage and Apoptosis in Intestinal Epithelial Cells via Activating the PI3K/Akt Signaling Pathway" Antioxidants 13, no. 4: 468. https://doi.org/10.3390/antiox13040468

APA Style

Ma, C., Wang, F., Zhu, J., Wang, S., Liu, Y., Xu, J., Zhao, Q., Qin, Y., Si, W., & Zhang, J. (2024). 18Beta-Glycyrrhetinic Acid Attenuates H2O2-Induced Oxidative Damage and Apoptosis in Intestinal Epithelial Cells via Activating the PI3K/Akt Signaling Pathway. Antioxidants, 13(4), 468. https://doi.org/10.3390/antiox13040468

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