The effect of salidroside, an active component of Rhodiola rosea, on the metabolic activity of rat and human cytochromes P450 in preclinical studies

Salidroside (SAL) is the active ingredient of the traditional adaptogenic herb Rhodiola rosea. Cytochromes P450 (P450), crucial enzymes in drug metabolism, are central to understanding drug–herb interactions. This study investigates the impact of SAL on the metabolic activity of selected P450 in both rat and human systems. Wistar rats were administered intragastrically with SAL 5, 15, or 45 mg/kg/day for seven days. The metabolic activity of CYP1A2, CYP2C6, CYP2D, and CYP3A was measured in rat liver microsomes (RLMs). Amounts and gene expressions of CYP1A2 and CYP2C6 were assessed in RLMs using Western blot and two-step qRT-PCR. rPXR, hPXR, and CAR3 gene reporter assays were conducted. The in vitro inhibitory studies of SAL in both drug-naïve rat and human liver microsomes were performed. Interactions between SAL and human P450 were also studied by in silico methods. SAL at the dose of 5 mg/kg/day slightly increased the specific activity of the P450 studied. However, SAL did not change either the P450 protein levels or the expression of the corresponding genes in rat liver. It also did not cause direct inhibition of rat and human P450 in liver microsomes in vitro. Molecular docking with human P450 confirmed these findings. Moreover, SAL inhibited the agonist-mediated induction of both rat and human PXR. Based on our findings, SAL is unlikely to pose a significant risk of P450-mediated drug-herb interactions and rather preserves the constitutional CYP3A metabolic activity via interaction with PXR. Not applicable.