Animal models suggest that silymarin confers hepatoprotection via downregulation of extracellular matrix proteins such as collagen ⁽²⁾. It may also be useful against liver carcinogenesis by inhibiting mast cells, a source of matrix metalloproteins that are involved in invasion and angiogenesis ⁽²⁹⁾. In addition, silymarin reduced cisplatin-induced kidney damage in rats without diminishing the drug’s antitumor activity ⁽⁷⁾, and suppressed formation of amyloid beta-proteins and neurotoxicity in mice ⁽³⁰⁾.

Silibinin, one of the flavonoids, demonstrated antioxidant and anti-inflammatory effects by inhibiting release of hydrogen peroxide and production of tumor necrosis factor alpha ⁽³¹⁾. Another study showed improvement in endothelial dysfunction via reduction in circulating and vascular asymmetric dimethylarginine (ADMA) levels. ADMA is an endogenous inhibitor of nitric oxide synthase (NOS) and is believed to play a role in endothelial dysfunction, associated with cardiovascular disease ⁽³²⁾. Silibinin also inhibits the early phase of hepatitis C viral infection by affecting endosomal trafficking of virions ⁽³⁴⁾.

Other studies indicate milk thistle flavonoids exert anticancer effects by arresting G1 and S phases of the cell cycle ⁽⁸⁾. Silybin inhibited hepatocellular carcinoma cell growth via the Notch signaling pathway ⁽³⁶⁾. Silibinin suppressed the epidermal growth factor receptor (EGFR)-induced expression of CD44, the transmembrane receptor for hyaluronan implicated in tumor cell invasion and metastasis by inhibiting EGFR activity in breast cancer cells ⁽³³⁾. Suggested mechanisms for reduced efficacy of silibinin in liver tumor-bearing animals that were co-administered ethanol include impaired hepatic processing of silibinin ⁽¹⁰⁾.

Silybin and isosilybin were shown to strongly inhibit PXR-mediated CYP3A4 induction ⁽³⁵⁾.