Harmane reduces the activity of CYP2D1/2, CYP2B1, CYP2C11 and
CYP3A1 after subchronic administration in rats

a 2021

Harmane reduces the activity of CYP2D1/2, CYP2B1, CYP2C11 and CYP3A1 after subchronic administration in rats

VOHLÍDALOVÁ, Eva, Markéta STRAKOŠOVÁ, Jan JUŘICA a Ondřej ZENDULKA

Základní údaje

Originální název

Harmane reduces the activity of CYP2D1/2, CYP2B1, CYP2C11 and CYP3A1 after subchronic administration in rats

Autoři

VOHLÍDALOVÁ, Eva, Markéta STRAKOŠOVÁ, Jan JUŘICA a Ondřej ZENDULKA

Vydání

Studentská vědecká konference MUNI PHARM 2021, 2021

Další údaje

Jazyk

angličtina

Typ výsledku

Konferenční abstrakt

Obor

30104 Pharmacology and pharmacy

Stát vydavatele

Česká republika

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Organizační jednotka

Lékařská fakulta

ISBN

978-80-210-9870-1

ISSN

Klíčová slova anglicky

Cytochrome P450, harmane, metabolic activity, drug-drug interactions

Změněno: 11. 6. 2021 07:53, PharmDr. Eva Klásková

Anotace

V originále

Aims Harmane is a secondary metabolite of Passiflora incarnata with both in vitro and in vivo inhibitory effect on MAO A. The antidepressant-like effect of harmane in the preclinical model was proved by several investigators. Our study focused on the impact of harmane on the metabolic activity of selected rat liver cytochrome P450 (CYP) enzymes in vivo after subchronic administration. Methods Harmane was administered to Wistar Albino rats intragastrically at the doses of 25, 40 and 64 mg/kg/day for eight consecutive days. A vehicle (66% propylene glycol) was administered to the control group. Liver samples were drawn, and rat liver microsomes (RLM) were isolated by ultracentrifugation. In vitro incubations of RLM with CYP-specific substrates: diclofenac (CYP2C6), dextromethorphan (CYP2D1/2), phenacetin (CYP1A2), testosterone (CYP2A, CYP3A, CYP2C) were undertaken. The concentration of metabolites in samples was measured with HPLC coupled with a DAD detector. In accordance with the results of incubations, the expression of CYP2D1, CYP3A1, CYP3A2, CYP2C11 and CYP2B was further investigated with a semiquantitative western blot method. Results The dose-dependent inhibitory effect of harmane on the metabolic activity of four CYP isoforms was proved. The metabolic activity of CYP2D2 was significantly reduced after the administration of all three doses of harmane (25, 40 and 64 mg/kg). CYP2B1, CYP2C11 and CYP3A1 were significantly inhibited at the doses of 40 and 64 mg/kg. Neither inhibitory nor inducing effect of harmane on the metabolic activity was observed in CYP1A2, CYP2C6 and CYP2A1 enzymes. Conclusion Passiflora incarnata is a widely used over-the-counter herbal anxiolytic and tranquillizer supplement. Our data show the potential of harmane to influence metabolic activity in vivo. These results suggest that interaction of harmane and CYP enzymes may be of clinical importance. However, further clinical studies are needed.

Návaznosti

MUNI/A/1249/2020, interní kód MU

Název: Základní výzkum v oblasti farmakokinetiky, neurobiologie závislostí a aplikovaný výzkum v oblasti personalizované farmakoterapie v onkologii (Akronym: SV_Farmakologie2021)

Investor: Masarykova univerzita, Základní výzkum v oblasti farmakokinetiky, neurobiologie závislostí a aplikovaný výzkum v oblasti personalizované farmakoterapie v onkologii

Citovat

VOHLÍDALOVÁ, Eva, Markéta STRAKOŠOVÁ, Jan JUŘICA a Ondřej ZENDULKA. Harmane reduces the activity of CYP2D1/2, CYP2B1, CYP2C11 and CYP3A1 after subchronic administration in rats. In Studentská vědecká konference MUNI PHARM 2021. 2021. ISBN 978-80-210-9870-1.

@proceedings{1775317,
   author = {Vohlídalová, Eva and Strakošová, Markéta and Juřica, Jan and Zendulka, Ondřej},
   booktitle = {Studentská vědecká konference MUNI PHARM 2021},
   keywords = {Cytochrome P450, harmane, metabolic activity, drug-drug interactions},
   language = {eng},
   isbn = {978-80-210-9870-1},
   title = {Harmane reduces the activity of CYP2D1/2, CYP2B1, CYP2C11 and CYP3A1 after subchronic administration in rats},
   url = {https://www.pharm.muni.cz/veda-a-vyzkum/svk/2021/sbornik-abstrakt},
   year = {2021}
}

TY  - CONF
ID  - 1775317
AU  - Vohlídalová, Eva - Strakošová, Markéta - Juřica, Jan - Zendulka, Ondřej
PY  - 2021
TI  - Harmane reduces the activity of CYP2D1/2, CYP2B1, CYP2C11 and CYP3A1 after subchronic administration in rats
SN  - 9788021098701
KW  - Cytochrome P450, harmane, metabolic activity, drug-drug interactions
UR  - https://www.pharm.muni.cz/veda-a-vyzkum/svk/2021/sbornik-abstrakt
N2  - Aims Harmane is a secondary metabolite of Passiflora incarnata with both in vitro and in vivo inhibitory effect on MAO A. The antidepressant-like effect of harmane in the preclinical model was proved by several investigators. Our study focused on the impact of harmane on the metabolic activity of selected rat liver cytochrome P450 (CYP) enzymes in vivo after subchronic administration. Methods Harmane was administered to Wistar Albino rats intragastrically at the doses of 25, 40 and 64 mg/kg/day for eight consecutive days. A vehicle (66% propylene glycol) was administered to the control group. Liver samples were drawn, and rat liver microsomes (RLM) were isolated by ultracentrifugation. In vitro incubations of RLM with CYP-specific substrates: diclofenac (CYP2C6), dextromethorphan (CYP2D1/2), phenacetin (CYP1A2), testosterone (CYP2A, CYP3A, CYP2C) were undertaken. The concentration of metabolites in samples was measured with HPLC coupled with a DAD detector. In accordance with the results of incubations, the expression of CYP2D1, CYP3A1, CYP3A2, CYP2C11 and CYP2B was further investigated with a semiquantitative western blot method. Results The dose-dependent inhibitory effect of harmane on the metabolic activity of four CYP isoforms was proved. The metabolic activity of CYP2D2 was significantly reduced after the administration of all three doses of harmane (25, 40 and 64 mg/kg). CYP2B1, CYP2C11 and CYP3A1 were significantly inhibited at the doses of 40 and 64 mg/kg. Neither inhibitory nor inducing effect of harmane on the metabolic activity was observed in CYP1A2, CYP2C6 and CYP2A1 enzymes. Conclusion Passiflora incarnata is a widely used over-the-counter herbal anxiolytic and tranquillizer supplement. Our data show the potential of harmane to influence metabolic activity in vivo. These results suggest that interaction of harmane and CYP enzymes may be of clinical importance. However, further clinical studies are needed.
ER  -

VOHLÍDALOVÁ, Eva, Markéta STRAKOŠOVÁ, Jan JUŘICA a Ondřej ZENDULKA. Harmane reduces the activity of CYP2D1/2, CYP2B1, CYP2C11 and CYP3A1 after subchronic administration in rats. In \textit{Studentská vědecká konference MUNI PHARM 2021}. 2021. ISBN~978-80-210-9870-1.

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