2. Academic Validation
  3. Human liver microsomes study on the inhibitory effect of plantainoside D on the activity of cytochrome P450 activity

Human liver microsomes study on the inhibitory effect of plantainoside D on the activity of cytochrome P450 activity

  • BMC Complement Med Ther. 2022 Jul 23;22(1):197. doi: 10.1186/s12906-022-03671-5.
Jin Zhou # 1,  Xian Qian # 1,  Yanqing Zhou 1,  Shili Xiong 2,  Shuxia Ji 1,  Ying Wang 3,  Ping Zhao 4
Affiliations

Affiliations

  • 1 Department of Pharmacy, Shanghai Baoshan Luodian Hospital, Shanghai, 201908, China.
  • 2 Clinical Research Center, Shanghai Baoshan Luodian Hospital, No.121 Luoxi Road, Baoshan District, Shanghai, 201908, China.
  • 3 School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, 201203, China. wnyn@163.com.
  • 4 Clinical Research Center, Shanghai Baoshan Luodian Hospital, No.121 Luoxi Road, Baoshan District, Shanghai, 201908, China. zhaopingshanghai@163.com.
  • # Contributed equally.
PMID: 35870998 DOI: 10.1186/s12906-022-03671-5
Abstract

Background: Plantainoside D is widely existed in the herbs and possesses various pharmacological activities, making it possible to co-administrate with Other herbs. Its effect on Cytochrome P450 enzymes (P450) is a risk factor for inducing adverse drug-drug interactions. To assess the effect of plantainoside D on the activity of major P450 isoenzymes in human liver microsomes.

Methods: The Cocktail method was conducted in human liver microsomes in the presence of probe substrates. The activity of P450 isoenzymes was evaluated by the production of corresponding metabolites. The concentration-dependent and time-dependent inhibition assays were performed in the presence of 0, 2.5, 5, 10, 25, 50, and 100 μM plantainoside D to characterize the inhibitory effect of plantainoside D.

Results: Significant inhibition was observed in the activity of CYP1A2, 2D6, and 3A, which was concentration-dependent with the IC50 values of 12.83, 8.39, and 14.66 μM, respectively. The non-competitive manner and competitive manner were observed in the CYP3A inhibition (Ki = 7.16 μM) and CYP1A2 (Ki = 6.26 μM) and 2D6 inhibition (Ki = 4.54 μM), respectively. Additionally, the inhibition of CYP3A was found to be time-dependent with the KI of 1.28 μM-1 and Kinact of 0.039 min-1.

Conclusions: Weak inhibitory effects of plantainoside D on the activity of CYP1A2, 2D6, and 3A were revealed in vitro, implying its potential of inducing interactions with CYP1A2-, 2D6-, and 3A-metabolized drugs. Although further in vivo validations are needed, the feasibility of the Cocktail method in evaluating P450 activity has been verified.

Keywords

CYP450 activity; Cocktail method; IC50; Microsomes; Time-dependent inhibition.

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