Progressive Metabolic Changes During High-Cholesterol Diet Feeding and Attenuation by PNBio in a Rabbit Model of MASLD

Abstract

Background: prolonged dietary cholesterol exposure can progressively disrupt lipid and glucose metabolism and promote hepatic lipid accumulation; metabolic features associated with metabolic dysfunction-associated steatotic liver disease (MASLD). The present study evaluated the preventive effect of a polyherbal nutraceutical preparation (PNBio) during ongoing exposure to a high-cholesterol diet (HCD). Methods: Male New Zealand White rabbits were allocated to control, HCD, HCD + PNBio, and HCD + atorvastatin groups (n = 6/group) and followed for 90 days. Body weight and serum biochemical parameters, including total cholesterol, triglycerides, LDL-C, HDL-C, glucose, ALT, and AST, were monitored at baseline and monthly. At the end of the feeding period, hepatic cholesterol and triglyceride contents, ApoA-I, ApoB, ApoE levels, ApoA-I and ApoE gene expression, HMG-CoA reductase activity, and LDLR expression were assessed. Results: Continuous HCD exposure produced progressive increases in serum total cholesterol, triglycerides, LDL-C, glucose, ALT, and AST, accompanied by reductions in HDL-C and increases in hepatic cholesterol and triglyceride accumulation. HCD also altered hepatic apolipoprotein levels and reduced HMG-CoA reductase activity and LDLR expression. PNBio attenuated these metabolic and hepatic alterations and partially restored the apolipoprotein profile, HMG-CoA reductase activity, and LDLR expression toward control levels. Conclusion: PNBio attenuated progressive metabolic and hepatic abnormalities during sustained HCD exposure. These findings support its potential as a preventive nutritional intervention against diet-induced metabolic disturbances associated with MASLD.