Sulforaphane regulation autophagy-mediated pyroptosis in autoimmune hepatitis via AMPK/mTOR pathway

作者：Weijian Yang, Shiyi Zeng, Rongrong Shao, Ru Jin, Jiayin Huang, Xinyu Wang, Enqian Liu, Tenghui Zhou, Fangyuan Li, Yongping Chen, Dazhi Chen · 发表于：International Immunopharmacology · 年份：2024 · DOI：10.1016/j.intimp.2024.113826 · 被引用次数：7 · 研究领域：Inflammasome and immune disorders、Genomics, phytochemicals, and oxidative stress、Adenosine and Purinergic Signaling

• Sulforaphane (SFN) mitigates pyroptosis by inhibiting the NLRP3 inflammasome. • SFN improves autophagic flux, alleviating experimental autoimmune hepatitis (EAH). • The autophagy inhibitor, 3-MA, negates SFN effects against pyroptosis. • SFN activates the AMPK/mTOR signaling pathway, protecting S100-induced EAH. • Inhibition of AMPK suppressed autophagic flux and protected against pyroptosis. Autoimmune hepatitis (AIH) is a liver disease marked by inflammation of unknown origin. If untreated, it can progress to cirrhosis or liver failure, posing a significant health risk. Currently, effective drug therapies are lacking in clinical practice. Sulforaphane (SFN), a natural anti-inflammatory and antioxidant compound found in various cruciferous vegetables, alleviate pyroptosis and improve impaired autophagic flux, both of which contribute to AIH progression. However, whether SFN modulates autophagic flux and pyroptosis in S100-induced EAH through the AMPK/mTOR pathway remains unclear. Therefore, this study aims to investigate whether SFN can regulate AIH and elucidate its potential mechanisms of action. In this study, experimental AIH (EAH) was induced in male C57BL/6 J mice through intraperitoneal (i.p.) injection of S100. SFN was administered intraperitoneally every other day. After 28 days, the mice were euthanized, and their livers and serum were collected for histological and biochemical analyses. AML12 cells were used for the in vitro studies. The results showed that SFN ...