Treatment with saponins from Panax japonicus decreases jejunal inflammation in mice fed a high-fat diet.

BACKGROUND/OBJECTIVES: Chronic high-fat diet (HFD) consumption induces low-grade intestinal inflammation. Although saponins from Panax japonicus (SPJs) have anti-inflammatory properties, the mechanisms by which they mitigate HFD-induced jejunal inflammation remain unclear. This study examined whether SPJs alleviate inflammation by modulating lipid metabolism and endoplasmic reticulum stress (ERS) in the jejunum. MATERIALS/METHODS: HFD-fed mice were administered high-dose SPJs extract. The jejunal triglyceride (TG) levels, gene expression related to TG synthesis (glycerol-3-phosphate acyltransferase 3 [Gpat3] and diacylglycerol O-acyltransferase 2 [Dgat2]) and lipolysis (adipose triglyceride lipase [Atgl]), cytosolic lipid droplets (CLDs) deposition, ERS markers, and inflammatory responses were assessed. RESULTS: HFD feeding induced TG accumulation, upregulated Gpat3 and Dgat2, downregulated Atgl, and promoted CLDs deposition in jejunal epithelial cells. High-dose SPJs attenuated these changes. Furthermore, SPJs suppressed HFD-induced ERS and inflammation in the jejunum. In particular, short-term HFD exposure initially enhanced the antioxidant responses without significant ERS activation. CONCLUSION: SPJs ameliorate HFD-induced jejunal inflammation by modulating lipid metabolic genes, reducing intracellular lipid accumulation, and alleviating ERS. These findings highlight the role of lipid-driven ERS in gut inflammation and the potential of SPJs as a therapeutic intervention.