The Effect of Salidroside on Liver Cytochrome P450

Název česky Vliv salidrosidu na jaterní cytochromy P450


Rok publikování 2022
Druh Konferenční abstrakty
Fakulta / Pracoviště MU

Lékařská fakulta

Popis Salidroside is the main active ingredient of Rhodiola rosea (RR), an herb with clinically documented antidepressant, antistress, anxiolytic, and antifatigue central effects. A variety of over-the-counter herbal products containing RR can be purchased in Czechia. Cytochrome P450 (CYP) is an enzyme with an essential role in the metabolism of many drugs. Various CYP–herb interactions were described, and some of them are potentially dangerous for patients. The effect of RR or salidroside on CYP remains unclear: Our project aimed to evaluate it. Wistar albino rats (n = 40) were administered with salidroside intragastrically at doses of 5, 15, and 45 mg/kg/day or with a vehicle (water) for 7 consecutive days. Liver samples were collected 24 hr after the last dose. Liver microsomes were isolated by differential ultracentrifugation. To evaluate the metabolic activity (MA) of liver microsomes, the incubations with CYP-specific substrates (diclofenac—CYP2C6, testosterone—CYP2A, CYP3A, CYP2C, CYP2B, phenacetine—CYP1A2, and dextromethorphan—CYP2D1/2) were performed. Based on the alterations of MA observed, the quantity of CYP2C6 and CYP1A2 proteins in the liver microsomes was evaluated by western blot. To assess the effect of salidroside on nuclear receptor PXR, HepG2 cells were transfected with a luciferase reporter construct and either rat or human expression vector for PXR. After the subchronic administration of a dose of 5 mg/kg/day, salidroside increased the MA of CYP2C6 and CYP1A2. Western blot analysis did not reveal a significant change in the amount of protein except the reduction in CYP2C6 after the administration of 45 mg/kg/day. Salidroside inhibited the activation of rat and human PXR in luciferase reporter assays. Our results indicate that salidroside, the main active ingredient of the RR, has a low interaction potential with CYP. However, further research is needed to confirm the safety of salidroside in clinical practise.
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