Silybum marianum L., commonly known as milk thistle, is traditionally recognized for its hepatoprotective properties. This is primarily due to silymarin, a mixture of flavonolignans with strong antioxidant and anti-inflammatory activities. Although many studies have reported on its biological activities, critical syntheses that compare extraction technologies and highlight its protective roles beyond liver health remain limited. Despite the abundant literature, the protective effects of milk thistle against skin damage remain largely unexplored. To address this gap, we performed a comprehensive literature search across PubMed, Scopus, Web of Science, and Google Scholar. Our research covered publications up to February 2025 and used predefined keywords, including extraction methods for the release of silymarin, in vitro, in vivo, and clinical studies relevant to its protective effects against skin damage. The evidence indicates that silymarin exerts protective effects on the skin, including the prevention of photoaging, the management of acne, the promotion of wound healing, and the defense against UV-induced damage, through the activation of Nrf2 and the preservation of the extracellular matrix. These results highlight the promising dermatological benefits of silymarin, as well as the need for further clinical studies and the optimization of environmentally sustainable extraction techniques for large-scale production.

While nickel is required in trace amounts for human health, excessive exposure can be harmful. It can cause significant damage to the liver, kidneys, and other organs, depending on the route of exposure. The aim of this study is to investigate the protective effect of the Silybum marianum L. seeds and leaves on the liver and kidneys as well as blood parameters. The purpose is to examine whether a one-month dietary supplementation with Silybum marianum L. seeds and leaves could prevent and prepare the body to resist nickel-induced damage. Seed and leaf extracts were administered orally to albino rats for one month. The rats were then exposed intraperitoneally to nickel chloride NiCl₂ for 10 days. Hematological and biochemical parameters as well as biomarkers for oxidative stress were measured in this investigation. Injection of Nickel-chloride showed significant alterations along the period of exposure. Seed extract exerted a marked protective effect on the biochemical, hematological, and oxidative stress parameters. In contrast, the leaf extract showed only partial protection for some parameters, while other parameters showed no significant protection, which highlights the differences in efficacy among plant parts. These results were supported by histological analysis which demonstrated that exposure to NiCl₂ resulted in notable renal and hepatic lesions, such as hydropic degeneration, necrosis, sinusoidal congestion, and tubular damage. Seed extract has completely prevented these alterations, whereas leaf extract has conferred only partial protection. Molecular docking analysis confirms that Silybin predominantly modulates AMPK and that Silydianin preferentially engages SIRT1, whereas Silychristin exhibits a dual-target modulatory activity.