Multicomponent Ayurveda formulation Lodhrasavam ameliorates steatosis and lipotoxicity in HepG2 cell model of NAFLD

BackgroundMetabolic-dysfunction associated steatotic liver disease (MASLD) is a complex, multifactorial condition and a leading cause of liver-related morbidity worldwide. Due to its heterogeneous pathogenesis, conventional single-target therapies often show limited efficacy. Multicomponent ayurveda formulations offer a promising alternative through their multitargeted actions. This study explores the therapeutic potential and underlying mechanisms of Lodhrasavam (LS), a classical, polyherbal ayurveda formulation, in both in vitro and in vivo models of MASLD. MethodsLS was evaluated for its anti-steatotic and anti-obesogenic potential using in vitro (HepG2, 3T3-L1) and in vivo (HF-HFD-induced rat) models. Antioxidant, lipase inhibition, cytotoxicity, anti-steatotic, and anti-adipogenic activities were assessed via DPPH, MTT, ORO/BODIPY staining, triglyceride quantification, ROS assay, and qPCR. Lipidomic profiling was done in HepG2 cells. Biochemical analyses (GLP-1, insulin, lipid panel), histopathology and OGTT further validated efficacy. Data were statistically analyzed by one-way ANOVA (p<0.05). Results/discussion: In HepG2 cells, LS reduced PA-induced lipid accumulation, ROS, triglycerides, and restored viability, while downregulating lipogenic genes (PPAR{gamma}, SREBP-1c, FASN). Lipidomics confirmed lipid modulation. In 3T3-L1 cells, LS suppressed adipogenesis and key adipogenic genes. In HFD-fed rats, LS reduced weight gain, hepatic steatosis, serum lipids, and improved liver histology. LS enhanced insulin and GLP-1 secretion, improved glucose tolerance, and restored pancreatic islet structure. These findings highlight the multitargeted potential of LS in ameliorating MASLD by modulating lipid metabolism, oxidative stress, inflammation, and glucose homeostasis. ConclusionLodhrasavam ameliorates MASLD by modulating the liver-adipose-pancreas axis, improving lipid metabolism, reducing inflammation, and enhancing insulin and GLP-1 secretion through multitargeted mechanisms.