Molecular mechanisms of the hepatoprotective action of silymarin in toxic and metabolic liver injury

Introduction. Chronic liver diseases, including viral hepatitis, non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease, and drug-induced liver injury, remain a significant global health concern. Oxidative stress, chronic inflammation, and activation of fibrogenesis play key roles in their pathogenesis. Plant-derived bioactive compounds, particularly silymarin from milk thistle, are considered promising agents for adjunctive therapy of liver diseases of various origins.

Aim. To analyze current data on the hepatoprotective, antioxidant, and anti-inflammatory mechanisms of silymarin in toxic and metabolic liver injury.

Materials and methods. A literature search was conducted in the PubMed database for the period 2020–2025 using the keywords: "silymarin", "silybin", "NAFLD", "liver fibrosis", "oxidative stress", "clinical trial". A quantitative assessment of publication activity and descriptive statistical analysis of the data (frequency of effect detection, proportion of clinical studies) were performed. A targeted selection of the fifteen most relevant and recent original publications was carried out, followed by a detailed analysis of the data presented in these articles.

Results and discussion. The initial search identified 210 publications; after removing duplicates and excluding irrelevant sources, 48 studies were included in the analysis, comprising 17 randomized clinical trials. In 71 % of the analyzed studies, a statistically significant reduction in ALT and AST levels was observed. Experimental studies confirm the inhibition of NF-κB, modulation of MAPK signaling pathways, reduction in TNF-α and IL-6 production, as well as a decrease in the severity of fibrosis in models of CCl 4 -induced liver injury.

Conclusion. Silymarin exerts multifactorial hepatoprotective effects, including antioxidant, anti-inflammatory, antifibrotic, and anticancer activities. Modern pharmaceutical formulations (phospholipid complexes, water-soluble derivatives, nanoparticles) aim to enhance its bioavailability and therapeutic efficacy. Further well-designed clinical studies are required to determine optimal dosing regimens and long-term outcomes.

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