In-vitro assessment of CYP3A4 and CYPC29 inhibition potential of Lupeol using human liver microsomes

  • LAXMAN DATTU KHATAL Bharati Vidyapeeth College of Pharmacy, Kolhapur, Near Chitranagri, Kolhapur-416013, Maharashtra, India
  • Harinath More


Background: Lupeol is a dietary triterpene, possesses numerous biological activities. Lupeol is currently under development for chemotherapy and chemoprevention. The aim of present study was to determine the potential inhibitory effect of Lupeol on cytochrome P450 (CYP3A4 and CYP2C9 isozymes) activities in human liver microsomes (HLM).

Methods:  The inhibition studies were conducted using testosterone 6β-hydroxylase (CYP3A4), and diclofenac 4’-Hydroxylase (CYP2C9) activity assay using positive control Ketoconazole and Sulphaphenazole, respectively. Inhibition study was performed by incubating lupeol (0 to 20 μM) with human liver microsomes, and the metabolite formation was analyzed by liquid chromatography-Tandem Mass Spectrometry (LC-MS/MS).

Results: Luepol did not inhibit CYP3A4 and CYP2C9 isozymes mediated activities in human liver microsomes up to a maximum tested concentration of 20µM based on solubility under tested invitro conditions.

Conclusions: Lupeol is not an inhibitor of the CYP3A4 and CYP2C9 isozymes. IC50 is greater than highest tested concentration as well as physiological concentration, where effect was measured with confidence. Therefore, clinically relevant pharmacokinetic herb-drug interactions are unlikely to occur between Lupeol and co-administered substrates of these CYP isozymes. Looking at the spectrum of biological activities and CYP inhibition potential of Lupeol; Lupeol can be used as adjuvant/ chemotherapy agent/ chemopreventive agent in therapy.

Keywords: Lupeol, HLM, CYP3A4 and CYP2C9, Inhibition, herb–drug interactions


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KHATAL L, More H. In-vitro assessment of CYP3A4 and CYPC29 inhibition potential of Lupeol using human liver microsomes. JDDT [Internet]. 15Mar.2019 [cited 24Oct.2021];9(2):231-6. Available from: