Xanthohumol alleviates oxidative stress and impaired autophagy in experimental severe acute pancreatitis through inhibition of AKT/mTOR

Yaru Huangfu; Xiuxian Yu; Chengyu Wan; Yuda Zhu; Zeliang Wei; Fan Li; Yilan Wang; Kun Zhang; Shiyi Li; Yuman Dong; Yangying Li; Hai Niu; Guang Xin; Wen Huang

doi:10.3389/fphar.2023.1105726

Xanthohumol alleviates oxidative stress and impaired autophagy in experimental severe acute pancreatitis through inhibition of AKT/mTOR

Front Pharmacol. 2023 Jan 18:14:1105726. doi: 10.3389/fphar.2023.1105726. eCollection 2023.

Authors

Yaru Huangfu¹, Xiuxian Yu¹, Chengyu Wan¹, Yuda Zhu¹, Zeliang Wei¹, Fan Li¹, Yilan Wang¹, Kun Zhang¹, Shiyi Li¹, Yuman Dong¹, Yangying Li¹, Hai Niu¹, Guang Xin¹, Wen Huang¹

Affiliation

¹ Laboratory of Ethnopharmacology, Tissue-orientated Property of Chinese Medicine Key Laboratory of Sichuan Province, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, China.

Abstract

Severe acute pancreatitis (SAP) is a lethal gastrointestinal disorder, yet no specific and effective treatment is available. Its pathogenesis involves inflammatory cascade, oxidative stress, and autophagy dysfunction. Xanthohumol (Xn) displays various medicinal properties, including anti-inflammation, antioxidative, and enhancing autophagic flux. However, it is unclear whether Xn inhibits SAP. This study investigated the efficacy of Xn on sodium taurocholate (NaT)-induced SAP (NaT-SAP) in vitro and in vivo. First, Xn attenuated biochemical and histopathological responses in NaT-SAP mice. And Xn reduced NaT-induced necrosis, inflammation, oxidative stress, and autophagy impairment. The mTOR activator MHY1485 and the AKT activator SC79 partly reversed the treatment effect of Xn. Overall, this is an innovative study to identify that Xn improved pancreatic injury by enhancing autophagic flux via inhibition of AKT/mTOR. Xn is expected to become a novel SAP therapeutic agent.

Keywords: acute pancreatitis; autophagy; inflammation; oxidative stress; xanthohumol.

Grants and funding

The National Natural Science Foundation of China (Grant No.81973580, 81803866); The Key Technology Research and Development Program of Sichuan Province of China (Grant No. 2022YFS0425, 2022YFS0426); The 1·3·5 project for disciplines of excellence, West China Hospital, Sichuan University (ZYXY21002); The Innovative Chinese Medicine Preclinical Research Fund of “Liqing No. 2”; West China Hospital, Sichuan University (161200012); The Sichuan Province COVID-19 Science and Technology Emergency Project (2021YFS0408); Innovative Chinese Medicine and Health Products Research Academician Workstation of Academician Boli KZ and Academician Beiwei YZ, West China Hospital, Sichuan University (HXYS19001, HXYS19002).