Protective Roles and Mechanism of Action of Plant Flavonoids against Hepatic Impairment: Recent Developments

Background The liver is one of the crucial organs in humans and is responsible for the regulation of diverse processes, including metabolism, secretion, and detoxification. Ingestion of alcohol and drugs, environmental pollutants, and irradiation are among the risk factors accountable for oxidative stress in the liver. Plant flavonoids have the potential to protect the liver from damage caused by a variety of chemicals. Objective The present study aims to summarize up-to-date information on the protective roles of plant flavonoids against liver damage. Methodology The literature information on the hepatoprotective plant flavonoids was assessed through various databases, which were searched from their respective inception until March 2022. Results More than 70 flavonoids with hepatoprotective activity against a variety of models of liver toxicity have been reported across the literature. Among these are flavones (19), flavonols (30), flavanones (9), isoflavonoids (5), and biflavonoids (2). Several hepatoprotective mechanisms of action were reported in various classes of flavonoids, including flavones and flavonols (upregulation of the pro-survival ERK1/2 pathway; downregulation of apoptotic proteins, including Bax, Bcl-2, Bax, BH3, caspase-3, 8, 9, etc.), flavanones (downregulation of NF-kappa B, TNF-alpha, IL-1 beta, IL-6, iNOS, etc.), isoflavonoids (downregulation of lipogenesis genes, such as SREBP-1c, LXR alpha, RXR alpha, PPAR gamma and ACC2, with concomitant upregulation of genes involved in beta-oxidation, including AMPK and PPAR alpha; inhibition of CYPs, such as CYP1A1, CYP1A2, CYP2B1, CYP2D6, CYP2E1 and CYP3A1/2). Conclusion The present work demonstrated the effectiveness of plant flavonoids against hepatic damage. However, more studies need to be performed regarding the cytotoxicity, pharmacokinetics, and mechanisms of action of these very important cytoprotective flavonoids.