Potential herb-drug interaction risk of Sedum sarmentosum Bunge extract and cyclosporine A

Sedum sarmentosum Bunge extract (SSBE) is widely used in clinical practice to treat various liver diseases. Cyclosporine A (CsA) is a potent immunosuppressant known to cause hepatotoxicity. However, it is unclear whether combining SSBE and CsA is effective or increases the risk of adverse reactions. This study explored the potential herb-drug interaction between SSBE and CsA. Male rats were given an oral dose of CsA (2.5 mg/kg) 1 hour after a single dose of SSBE (600 mg/kg) or vehicle. Blood CsA concentrations measured by ultrahigh-performance liquid chromatography-tandem mass spectrometry revealed that SSBE dramatically increased the CsA exposure; the C_max and area under the curve from 0 to 48 hours (AUC_0→48h) values were significantly increased by 150% and 220% (from 222.89 to 567.06 ng/mL and from 2089.37 to 6615.08 ng/mL·h), respectively. In parallel, the exposure of the CsA metabolite AM1 was significantly reduced, with C_max and AUC_0→48h decreased by 68% and 70%, respectively. In vitro study demonstrated that SSBE and its active constituents inhibited CYP3A activity and suppressed CsA metabolism to AM1. In conclusion, SSBE significantly increased the systemic exposure of CsA, and the effect might be related to inhibition of CYP3A activity. Additional caution should be exercised when treating CsA and SSBE together, as it may cause unexpected potential herb-drug interaction. SIGNIFICANCE STATEMENT: Sedum sarmentosum Bunge extract significantly increased cyclosporine A blood levels, and the effect might be related to inhibition of CYP3A activity. Therefore, coadministration of Sedumsarmentosum Bunge extract and cyclosporine A requires additional caution due to the risk of herb-drug interaction.