Hepatocellular Interactions of Potential Nutraceuticals in the Management of Inflammatory NAFLD.

Numerous studies highlight the potential of natural antioxidants, such as those found in foods and plants, to prevent or treat nonalcoholic fatty liver disease (NAFLD). Inflammation is a key factor in the progression from high‐fat diet‐induced NAFLD to nonalcoholic steatohepatitis (NASH). Injured liver cells and immune cells release inflammatory cytokines, activating hepatic stellate cells. These cells acquire a profibrogenic phenotype, leading to extracellular matrix accumulation and fibrosis. Persistent fibrosis can progress to cirrhosis. Fatty infiltration, oxidative stress, and inflammation exacerbate fatty liver diseases. Thus, many plant‐derived antioxidants, like silymarin, silibinin, curcumin, resveratrol, berberine, and quercetin, have been extensively studied in experimental models and clinical patients with NAFLD. Experimentally, these compounds have shown beneficial effects in reducing lipid accumulation, oxidative stress, and inflammatory markers by modulating the ERK, NF‐κB, AMPKα, and PPARγ pathways. They also help decrease metabolic endotoxemia, intestinal permeability, and gut inflammation. Clinically, silymarin and silibinin have been found to reduce transaminase levels, while resveratrol and curcumin help alleviate inflammation in NAFLD patients. However, these phytocompounds exhibit poor water solubility, leading to low oral bioavailability and hindering their biological efficacy. Additionally, inconclusive clinical results highlight the need for further trials with larger populations, longer durations, and standardized protocols. Significance Statement: This review explores hepatoprotective phytochemicals for nonalcoholic fatty liver disease at the molecular level. Existing literature supports that silymarin, silibinin, resveratrol, curcumin, and berberine exhibit antioxidant and anti‐inflammatory properties by inhibiting inflammatory pathways, while also mitigating metabolic endotoxemia, intestinal permeability, and gut inflammation. However, their poor solubility and limited oral bioavailability in clinical settings reduce their potential benefits for patients with nonalcoholic fatty liver disease. [ABSTRACT FROM AUTHOR]