Bergenin promotes mitochondrial biogenesis via the AMPK/SIRT1 axis in hepatocytes

Aging and obesity trigger liver mitochondrial decline, impairing liver function and energy metabolism. Effective hepatic mitochondrial biogenesis helps maintain and restore hepatocyte function. The effects of bergenin, a polyphenol with various pharmacological effects, on hepatic mitochondrial biogenesis remain unclear. Therefore, we aimed to determine its effects on mitochondrial biogenesis in hepatocytes. We measured mitochondrial content in human HepG2 hepatocytes using MitoTracker Green FM ; intracellular ATP content using an ATP assay kit ; and mitochondrial DNA (mtDNA) using the ratio of mtDNA to nuclear DNA by qPCR. Protein levels were analyzed using immunoblotting. Nuclear translocation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) was assessed by immunofluorescence staining and immunoblotting. In human HepG2 hepatocytes, bergenin increased mitochondrial content, elevated mitochondrial DNA and constituent proteins, and enhanced intracellular ATP levels and PGC-1α nuclear translocation, possibly promoting mitochondrial biosynthesis. SIRT1 expression was induced in bergenin-treated cells and may be responsible for bergenin-inducible mitochondrial biogenesis, which was abolished by the SIRT1 inhibitor EX-527. Furthermore, bergenin activated AMP-activated protein kinase (AMPK). Compound C, an AMPK inhibitor, abolished bergenin-induced SIRT1 expression and mitochondrial biogenesis. Overall, bergenin activates hepatic mitochondrial biogenesis through the AMPK / SIRT1 axis, which could help to prevent and ameliorate serious aging- and obesity-related liver diseases. J. Med. Invest. 72 : 66-75, February, 2025.