AutophagyMay 19, 2026

Byakangelicin may improve liver inflammation and fat buildup by targeting a specific cell growth pathway

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated May 23, 2026

Abstract

Byakangelicin (Bya) selectively inhibited MTORC1-mediated phosphorylation of TFEB in a mouse model of metabolic dysfunction-associated steatohepatitis (MASH).

Bya did not affect canonical MTORC1 substrates while targeting TFEB.
Knockout of hepatic TFEB blocked the positive effects of Bya on liver issues like steatosis and inflammation.
Reintroduction of TFEB restored the beneficial effects of Bya in the liver.
Bya was found to bind directly to specific sites on FLCN, inhibiting its complex with FNIP1/FNIP2.
Mutation of FLCN eliminated the protective effects of Bya against MASH.

Simplified

Metabolic dysfunction-associated steatohepatitis (MASH) is emerging as a leading cause of chronic liver disease. MTOR (mechanistic target of rapamycin kinase) complex 1 (MTORC1) is a potential therapeutic target, whereas suppression of total MTORC1 activity can lead to unwanted effects. Here, we found that byakangelicin (Bya), a natural compound, selectively inhibited MTORC1-mediated phosphorylation of TFEB (transcription factor EB), without affecting canonical MTORC1 substrates. Knockout of hepaticblocked the alleviation effects of Bya on hepatic steatosis, inflammation, insulin resistance, and fibrosis in mice, while reintroduction of TFEB restored these effects. We identified Bya directly bound to MET370 and PHE552 of FLCN (folliculin), suppressing the function of the FLCN-FNIP1 (folliculin interacting protein 1)/FNIP2 complex, which in turn inhibited MTORC1-mediated cytoplasmic sequestration of TFEB. Mutation of FLCN (M370A and F552A) in the liver abolished Bya-induced protection against MASH. Thus, Bya is a promising therapeutic natural compound for MASH, and selective inhibition of MTORC1 is a potential approach to treat this disease. Tfeb

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Byakangelicin may improve liver inflammation and fat buildup by targeting a specific cell growth pathway

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