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

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

JOURNAL=Frontiers in Pharmacology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1105726

DOI=10.3389/fphar.2023.1105726

ISSN=1663-9812

ABSTRACT=<p>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,</p><p>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) <italic>in vitro</italic> and <italic>in vivo</italic>. 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 <italic>via</italic> inhibition of AKT/mTOR. Xn is expected to become a novel SAP therapeutic agent.</p>