Therapeutic Potential of Quercetin, Silibinin, and Crocetin in a High-Fat Diet-Induced Mouse Model of MASLD: The Role of CD36 and PLIN3.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent and progressive liver disorder linked to metabolic syndrome affecting over 30% of global population, currently lacking effective pharmacological treatment. Natural compounds like quercetin, silibinin, and crocetin have shown hepatoprotective potential. This study investigates their therapeutic effect in a high-fat diet (HFD)-induced mouse model of MASLD. METHODS: Ninety-five C57BL/6J (wild type) mice were fed an HFD for 12 weeks to induce hepatic steatosis and were then randomized into eight groups for a 4-week therapeutic intervention. Liver histopathology was assessed using the NAFLD Activity Score (NAS), and immunohistochemistry was conducted to quantify CD36 and PLIN3 expressions. RESULTS: Both quercetin groups significantly reduced the prevalence of steatohepatitis (p-value < 0.05) and showed an increased PLIN3 expression. Silibinin also improved steatohepatitis, with the high-dose group reaching statistical significance (p-value 0.020), and demonstrated upregulation of PLIN3 along with significant CD36 downregulation. Crocetin groups markedly improved disease severity and showed the highest PLIN3 expression, though without significant changes in CD36. CONCLUSIONS: Quercetin, silibinin, and crocetin mitigate MASLD progression by reducing steatohepatitis. These effects are associated with distinct modulations of CD36 and PLIN3 protein expression, suggesting that these pathways are promising therapeutic targets in MASLD management. Natural compounds offer a multi-targeted hepatoprotective approach warranting further clinical investigation.