2. Academic Validation
  3. Hinokitiol protects gastric injury from ethanol exposure via its iron sequestration capacity

Hinokitiol protects gastric injury from ethanol exposure via its iron sequestration capacity

  • Eur J Pharmacol. 2024 Jan 18:176340. doi: 10.1016/j.ejphar.2024.176340.
Mengran Zhao 1,  Chen Qiao 1,  Shuyue Yang 1,  Yefeng Tang 2,  Wenjing Sun 1,  Shanshan Sun 3,  Qingdong Guo 1,  Feng Du 1,  Nan Zhang 1,  TingTing Ning 1,  Jing Wu 1,  Junxuan Xu 4,  Peng Li 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Digestive Health, Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing, 100050, China.
  • 2 School of Pharmaceutical Sciences, MOE Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Tsinghua University, Beijing, 100084, China.
  • 3 National Institute of Food and Drug Control (NIFDC), Beijing, 100050, China.
  • 4 State Key Laboratory of Digestive Health, Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing, 100050, China. Electronic address: junxuan.xu.jerry@mail.ccmu.edu.cn.
  • 5 State Key Laboratory of Digestive Health, Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing, 100050, China. Electronic address: lipeng@ccmu.edu.cn.
PMID: 38244759 DOI: 10.1016/j.ejphar.2024.176340
Abstract

Hinokitiol is a natural bioactive tropolone derivative isolated from Chamaecyparis obtusa and Thuja plicata, which exhibits promising potential in terms of antioxidant and anti-inflammatory properties and possesses potent iron-binding capacity. In this study, we aimed to investigate the potential role of hinokitiol in protecting against ethanol-induced gastric injury and elucidate the underlying mechanism. Our results demonstrated that hinokitiol effectively attenuated hemorrhagic gastric lesions, epithelial cell loss, and inflammatory response in mice with ethanol-induced gastric injury. Intriguingly, we found that ethanol exposure affects iron levels both in vivo and in vitro. Moreover, the disturbed iron homeostasis was involved in the development of ethanol-induced injury. Iron depletion was found to enhance defense against ethanol-induced damage, while iron repletion showed the opposite effect. To further explore the role of iron sequestration in the protective effects of hinokitiol, we synthesized methylhinokitiol, a compound that shields the iron binding capacity of hinokitiol with a methyl group. Interestingly, this compound significantly diminishes the protective effect against ethanol-induced injury. These findings collectively demonstrated that hinokitiol could potentially be used to prevent or improve gastric injury induced by ethanol through regulating cellular iron homeostasis.

Keywords

Anti-inflammation; Ethanol-induced gastric injury; Gastric ulcer; Hinokitiol; Iron homeostasis.

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