a 2022

The Effect of Salidroside on Liver Cytochrome P450

KLÁSKOVÁ, Eva; Jan JUŘICA; Tomáš HAMMER; Rajamanikkam KAMARAJ; Petr PÁVEK et al.

Základní údaje

Originální název

The Effect of Salidroside on Liver Cytochrome P450

Název česky

Vliv salidrosidu na jaterní cytochromy P450

Autoři

KLÁSKOVÁ, Eva ORCID; Jan JUŘICA; Tomáš HAMMER; Rajamanikkam KAMARAJ; Petr PÁVEK a Ondřej ZENDULKA

Vydání

70th Czech-Slovak Pharmacological Days, 2022

Další údaje

Jazyk

angličtina

Typ výsledku

Konferenční abstrakt

Obor

30104 Pharmacology and pharmacy

Stát vydavatele

Česká republika

Utajení

není předmětem státního či obchodního tajemství

Označené pro přenos do RIV

Ne

Organizační jednotka

Lékařská fakulta

ISSN

Klíčová slova česky

cytochrome P450, jaterní mikrosomy, Rhodiola rosea, salidrosid

Klíčová slova anglicky

cytochrome P450, liver microsomes, Rhodiola rosea, salidroside
Změněno: 18. 7. 2022 09:13, PharmDr. Eva Klásková

Anotace

V originále

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.

Návaznosti

MUNI/A/1440/2021, interní kód MU
Název: Preklinický a klinický výzkum Farmakologického ústavu v oblasti farmakokinetiky, neurobiologie závislostí a personalizované farmakoterapie v onkologii (Akronym: Farm-Pre-Klin)
Investor: Masarykova univerzita, Preklinický a klinický výzkum Farmakologického ústavu v oblasti farmakokinetiky, neurobiologie závislostí a personalizované farmakoterapie v onkologii
MUNI/IGA/1261/2020, interní kód MU
Název: The influence of promising herbal antidepressant salidroside on drug metabolizing enzymes
Investor: Masarykova univerzita, The influence of promising herbal antidepressant salidroside on drug metabolizing enzymes