Non-alcoholic fatty liver disease (NAFLD) has emerged as a dominant contributor to chronic liver disease and hepatocellular carcinoma worldwide. Defined by pathological triglyceride deposition in hepatocytes, its pathogenesis involves a complex interplay of insulin resistance, metabolic syndrome, and emerging molecular mechanisms—particularly the I148M polymorphism in PNPLA3, which disrupts hepatic lipid metabolism, and dysregulated redox signaling pathways such as Nrf2.
Flavonoids, a structurally diverse group of polyphenolic compounds derived from natural products, exhibit promising adjunctive therapeutic potential for NAFLD management. Characterized by a benzopyran core structure, these bioactive compounds demonstrate:
● Modulatory effects on lipid metabolism (via PNPLA3 regulation)
● Redox-balancing properties through Nrf2 pathway activation
● Synergistic benefits when combined with standard therapies
● Improve insulin sensitivity, thereby reducing, at the source, the transport and deposition of lipids to the liver
● Inhibit the transcription of pro-inflammatory cytokines, downregulate the expression of inflammation-related enzymes
This work explores flavonoids’ complementary role in NAFLD, bridging natural product chemistry with hepatic pathophysiology. While not yet established as primary therapeutics, their multi-target mechanisms position them as valuable candidates for adjunctive intervention in this metabolic disorder.
Wang, X.Y. et al. / J. Chin. Pharm. Sci. 2025, 34 (9), 801–820.
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