A Novel Supramolecular Complex-Based Therapeutic Strategy for Metabolic Dysregulation in Non-Alcoholic Fatty Liver Disease (Nafld)

Abstract

This study aimed to design and evaluate novel supramolecular complexes (SCs) as potential therapeutic agents for non-alcoholic fatty liver disease (NAFLD). Three complexes of glycyrrhizic acid (or its salts) and gallic acid (2:1 ratio)—SC1, SC2 (monopotassium salt), and SC3 (monoammonium salt)—were synthesized. Their hepatoprotective efficacy was assessed in a high-fat diet (HFD)-induced NAFLD model in male Wistar rats over a 20-week period, with interventions administered during the final four weeks. Systemic effects were evaluated through biochemical profiling (liver enzymes, lipid profile, glucose, protein metabolism), biometric measurements, and histopathological analysis. The HFD successfully induced characteristic metabolic and hepatic damage. All SCs significantly mitigated these alterations, with SC2 demonstrating superior efficacy. It most effectively normalized liver enzymes, improved lipid and glucose homeostasis, restored serum protein and urea levels, reduced weight gain and liver index, and induced near-complete histopathological restoration of liver architecture, outperforming silymarin. In conclusion, the supramolecular complex SC2 exhibits potent multi-target therapeutic effects in experimental NAFLD, validating the supramolecular approach as a promising strategy for enhancing the bioactivity of natural compounds toward developing advanced phytopharmaceuticals for NAFLD management.