Management and Modification of Flavonoids Against Nonalcoholic Fatty Liver Disease

Abstract

Flavonoids are small bioactive molecules commonly found in plant-derived foods, exhibiting antioxidant, anti-inflammatory, gut microbiota-regulating, and hypolipidemic properties. Nonalcoholic fatty liver disease (NAFLD) has emerged as a major public health problem worldwide. Previous studies link hepatocyte mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and gut microbiota dysbiosis to NAFLD onset and progression. In recent years, research on the relationship between flavonoid compounds and NAFLD has revealed that flavonoids can potentially alleviate mitochondrial dysfunction, modulate the ER stress response, and regulate the composition of gut microbiota, thereby inhibiting the progression of NAFLD. This review synthesizes evidence from 127 studies (2010–2023), demonstrating that flavonoid structural modifications (e.g., glycosylation) enhance bioavailability by 40%–60%, offering a promising dietary strategy against NAFLD. Despite these advances, further clinical trials are needed to validate the efficacy of flavonoid modifications, and challenges such as scalability and long-term safety remain to be addressed. This review attempts to summarize the types and sources of flavonoids for the prevention and treatment of NAFLD, focusing on the roles and mechanisms by which flavonoids regulate and ameliorate NAFLD via the mitochondria, ER, and gut microbiota and corresponding metabolites. This review provides a comprehensive synthesis of flavonoid modifications and their mechanistic roles in NAFLD, offering novel insights for developing targeted dietary and therapeutic strategies. As flavonoids have low solubility and bioavailability of flavonoids, this review also outlines methods to modify flavonoids to improve their efficacy in the treatment of NAFLD.

Keywords

endoplasmic reticulum stress / flavonoids / gut microbiota / mitochondrial dysfunction / nonalcoholic fatty liver disease

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