Explaining Uncertain Hepatoprotective Effects: When Silibinin Co-Administered with Other Drugs.

Objective: This study investigated the herb-drug interaction between silibinin and carbamazepine (CBZ) and the potential risk of adverse drug reactions (ADR) when silibinin is co-administered with other drugs.

Methods: Primary fresh hepatocytes were cultured, and an methylthiazolyldiphenyl-tetrazolium bromide assay was performed after administration of different concentrations of CBZ, and silibinin. Meanwhile, a retrospective study on hepatic adverse reactions involving the combination of silibinin with other drugs was performed using the Food and Drug Administration Adverse Event Reporting System (FAERS).

Results: The protective effects of silibinin on CBZ do not appear on hepatocytes in a dose-dependent manner. When silibinin (25μM) was co-administered with CBZ (2mM), the cell viability increased from 47.8% to 75.9% (p<0.05), while increasing the silibinin concentration to 50μM with CBZ (2mM), the hepatocyte viability significantly declined from 47.8% to 38.7% (p<0.05). In the FAERS database, the risk of adverse reactions significantly increases when combined with silibinin. The silibinin co-administration was significantly associated with hepatotoxicity reports.

Conclusions: The results of the cell experiment showed that silibinin's liver protective effects were uncertain when it was combined with CBZ. FAERS database analysis revealed elevated risks of ADRs with silibinin co-administration, collectively highlighting the necessity for vigilance against unanticipated herb-drug interactions.