Flavonoids of Silybum marianum (Milk thistle): Their multifaceted hepatoprotective effects against oxidative stress: A comprehensive review of preclinical and clinical evidence

Abstract

The oxidative stress within liver cells, the imbalance between oxidants and antioxidants, is one of the main pathological mechanisms involved in a number of liver diseases such as non-alcoholic fatty liver disease, alcoholic liver disease, cirrhosis, and hepatocellular carcinoma. This is relevant because the liver is an important target organ in metabolic and detoxification processes and is very sensitive to oxidative damage, necessitating effective therapeutic interventions. The plant Silybum marianum (L.) is a species of Silybum. S. marianum (L.) is a variety of Silybum . The medicinal plant, G. Scleranthus L., has been extensively studied over the years because of its potent hepatoprotective activity, which is mainly attributed to its active flavonolignan compound, silymarin. This systematic review provides an extensive overview of the current clinical and preclinical evidence and highlights the complex molecular mechanisms underlying the anti-oxidative effects of silymarin on the liver. Silymarin’s protective effects include direct antioxidant activity against free radicals, enhancement of endogenous antioxidant enzymes (e.g., glutathione, superoxide dismutase), modulation of inflammatory pathways (e.g., Nuclear factor-kappa B, inflammasomes), anti-fibrotic activity (by blocking the activation of hepatic stellate cells), and membrane-stabilizing properties. There is a large preclinical base of support for efficacy, but safety and effectiveness in humans have not been proven, and more standardized and rigorous clinical trials with longer follow-up are needed to assure optimal dosage, further long-term studies, and wider systemic use. This review underscores the importance of further investigation of more complex formulations, better understanding of the mechanism of action of silymarin (with a particular focus on the pharmacokinetics of the individual components), and the potential benefits of silymarin in liver health and beyond, which requires more rigorous and well-designed randomized controlled trials to be able to allocate a role in evidence-based medicine.