Liver cirrhosis represents a critical global health burden, characterized by the progressive replacement of healthy liver parenchyma with fibrous scar tissue, leading to architectural distortion and functional failure. The pathogenesis of cirrhosis is intricately linked to chronic inflammation and oxidative stress, which drive hepatocyte apoptosis and the activation of hepatic stellate cells (HSCs). Silybin, the most biologically active flavonolignan isolated from Silybum marianum (milk thistle), has garnered significant attention for its dual hepatoprotective and antioxidant capabilities. This study provides a comprehensive comparative analysis of silybin’s mechanisms of action, evaluating its efficacy in mitigating liver injury through membrane stabilization, anti-inflammatory modulation, and direct scavenging of reactive oxygen species (ROS). By synthesizing data from preclinical models and clinical trials, we delineate the relative contributions of its hepatoprotective versus antioxidant properties. Our analysis suggests that while silybin’s antioxidant activity is fundamental in halting the initiation of fibrogenesis via the Nrf2 pathway, its hepatoprotective effects are crucial for preserving cellular integrity and improving synthetic liver function in established cirrhosis. Despite promising results, challenges regarding bioavailability and standardization persist. This review underscores the potential of silybin as an adjunctive therapy in multidisciplinary management strategies for liver cirrhosis, highlighting the need for advanced delivery systems to maximize therapeutic outcomes.

Silybin, Liver Cirrhosis, Hepatoprotection, Oxidative Stress, Antioxidant Therapy, Nrf2 Pathway, Fibrosis, Silybum marianum.

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