Hongjam, an edible silkworm-derived food, attenuates steatohepatitis and fibrosis via multi-axis modulation of metabolic stress, inflammation, and fibrogenic signaling.

Introduction: Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease characterized by sustained inflammation and fibrosis, for which effective disease-modifying therapies remain limited. In this study, we investigated the hepatoprotective effects of Hongjam, a processed edible silkworm-derived food, in a methionine-choline-deficient (MCD) diet-induced mouse model of MASH. Methods: Histological analysis, plasma biochemical assessments, western blotting, quantitative PCR analyses, and in vitro experiments using macrophages and HepG2 hepatocyte-derived cells were performed to evaluate the effects of Hongjam and silk fibroin peptides associated with Hongjam. Results: Hongjam markedly alleviated hepatic injury, as evidenced by improved histological features, normalization of plasma biochemical parameters, and reduced collagen deposition. Mechanistically, Hongjam suppressed activation of the TGF-β/Smad signaling pathway, inhibited NF-κB-mediated inflammatory signaling, and attenuated MCD-associated metabolic stress signaling, including changes in AMPK phosphorylation and the expression of genes involved in fatty acid oxidation and lipid transport. Consistent with the in vivo findings, silk fibroin peptides associated with Hongjam attenuated NF-κB-mediated inflammatory signaling in macrophages and modulated TGF-β/Smad-associated signaling in HepG2 hepatocyte-derived cells in vitro. Discussion: Collectively, these results demonstrate that Hongjam attenuates experimental MASH by concurrently modulating metabolic stress, inflammation, and fibrotic remodeling. These findings highlight Hongjam as a food-derived candidate with potential relevance for dietary strategies targeting metabolic liver diseases.