Targeting metabolic dysfunction-associated steatotic liver disease with phytosomal silymarin and piperine: A natural alternative to fenofibrate in a rat model

Metabolic dysfunction-associated steatotic liver disease (MASLD) is an increasing global health concern with limited effective therapies. Silymarin exhibits hepatoprotective properties, but its utility is limited by poor bioavailability. This study evaluated a novel phytosomal silymarin formulation co-administered with piperine and lecithin, compared to fenofibrate, in an oxytetracycline-induced MASLD rat model. Twenty-five male Wistar rats were allocated into five groups: healthy control, MASLD control, fenofibrate (100 mg/kg), silymarin (500 mg/kg), or silymarin-piperine-lecithin phytocomplex (500/100/3 mg/kg) for 90 days. Parameters evaluated included serum liver enzymes, lipid profiles, hepatic histology, and hepatic PPAR-α expression. The phytocomplex formulation significantly reduced serum ALT, AST, ALP, and GGT, improved lipid profiles, and restored hepatic architecture, with MASLD-AS and PPAR-α expression demonstrating a marked reduction in hepatic injury and oxidative stress. The phytocomplex outperformed both fenofibrate and silymarin alone, likely due to enhanced bioavailability and synergistic antioxidant action comparable to fenofibrate treatment. This study demonstrates the potential of a phytosomal silymarin-piperine-lecithin complex as a natural therapeutic avenue for MASLD, outperforming a conventional lipid-lowering agent in this animal model. Future clinical and pharmacokinetic studies are warranted.