Capsaicin (CAP) exerts a protective effect against ethanol-induced oxidative gastric mucosal injury by modulating the chemokine receptor 4 (CCR4)/Src/p47phox signaling pathway both in vitro and in vivo

Zhiru Yang , Haolin Guo , Pengfei Zhang , Kairui Liu , Junli Ba , Xue Bai , Shiti Shama , Bo Zhang , Xiaoning Gao , Jun Kang

Chinese Journal of Natural Medicines ›› 2025, Vol. 23 ›› Issue (2) : 191 -202.

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Chinese Journal of Natural Medicines ›› 2025, Vol. 23 ›› Issue (2) :191 -202. DOI: 10.1016/S1875-5364(25)60823-5
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Capsaicin (CAP) exerts a protective effect against ethanol-induced oxidative gastric mucosal injury by modulating the chemokine receptor 4 (CCR4)/Src/p47phox signaling pathway both in vitro and in vivo

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Abstract

Ethanol (EtOH) is a common trigger for gastric mucosal diseases, and mitigating oxidative stress is essential for attenuating gastric mucosal damage. Capsaicin (CAP) has been identified as a potential agent to counteract oxidative damage in the gastric mucosa; however, its precise mechanism remains unclear. This study demonstrates that CAP alleviates EtOH-induced gastric mucosal injuries through two primary pathways: by suppressing the chemokine receptor 4 (CCR4)/Src/p47phox axis, thereby reducing oxidative stress, and by inhibiting the phosphorylation and nuclear translocation of nuclear factor-κB p65 (NF-κB) p65, resulting in diminished inflammatory responses. These findings elucidate the mechanistic pathways of CAP and provide a theoretical foundation for its potential therapeutic application in the treatment of gastric mucosal injuries.

Keywords

Capsaicin / Gastric mucosal damage / Chemokine signaling / NF-κB p65

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Zhiru Yang, Haolin Guo, Pengfei Zhang, Kairui Liu, Junli Ba, Xue Bai, Shiti Shama, Bo Zhang, Xiaoning Gao, Jun Kang. Capsaicin (CAP) exerts a protective effect against ethanol-induced oxidative gastric mucosal injury by modulating the chemokine receptor 4 (CCR4)/Src/p47phox signaling pathway both in vitro and in vivo. Chinese Journal of Natural Medicines, 2025, 23(2): 191-202 DOI:10.1016/S1875-5364(25)60823-5

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