Ebastine-mediated destabilization of E3 ligase MKRN1 protects against metabolic dysfunction-associated steatohepatitis.

ABSTRACT: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic condition encompassing metabolic dysfunction-associated steatotic liver (MASL) and metabolic dysfunction-associated steatohepatitis (MASH), which can progress to fibrosis, cirrhosis, or hepatocellular carcinoma (HCC). The heterogeneous and complex nature of MASLD complicates optimal drug development. Ebastine, an antihistamine, exhibits antitumor activity in various types of cancer. However, its effects on MASH remain unexplored. In the present study, we identified ebastine as a potential treatment for MASH. Our results indicated that ebastine acts as a novel MKRN1 inhibitor by promoting MKRN1 destabilization through self-ubiquitination, leading to AMP-activated protein kinase (AMPK) activation. Ebastine appeared

SUBMITTER: Kim S 

PROVIDER: S-EPMC11785899 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature