Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Jan-Dec:23:2515690X18810001.
doi: 10.1177/2515690X18810001.

In Vivo Modulation of Rat Liver Microsomal Cytochrome P450 Activity by Antimalarial, Anti-HIV, and Antituberculosis Plant Medicines

Regina Appiah-Opong  1 , Isaac Tuffour  1 , Ebenezer Ofori-Attah  1 , Abigail Aning  1 , Philip Atchoglo  1 , Eunice Ampem Danso  1 , Believe Ahedor  1 , Samuel Adjei  1 , Alexander K Nyarko  1
Affiliations

In Vivo Modulation of Rat Liver Microsomal Cytochrome P450 Activity by Antimalarial, Anti-HIV, and Antituberculosis Plant Medicines

Regina Appiah-Opong et al. J Evid Based Integr Med. 2018 Jan-Dec.

Abstract

Drug interactions are key reasons for adverse drug reactions and attrition from market. Major infectious diseases causing morbidity/mortality in Ghana are malaria, tuberculosis, and HIV/AIDS. In this study, plant medicines commonly used to treat/manage these diseases in Ghana were investigated for their potential to modulate rat cytochrome P450 enzyme activities. Fluorescence and high-performance liquid chromatography-based assays were used to assess effects of antimalarial plant medicines, Fever (FEV), Mal-TF (MAL), and Kantinka terric (KT); anti-TB medicines, Chestico (CHES), CA + ST Pains + HWNT (TF), and Kantinka herbatic (KHB); and anti-HIV/AIDS medicines, Wabco (WAB), AD + T/AD (LIV) and Kantinka BA (KBA) on rat liver microsomal cytochrome P450 enzyme activities. Effects of medicines on rat biochemical and hematological parameters were also assessed. Generally, the medicines altered microsomal CYP1A1/1A2, CYP2B1/2B2, CYP2C9, and CYP2D6 activities. Only KBA elicited an increase (80%) in CYP1A1/1A2 activity. FEV, MAL, CHES, WAB, and LIV strongly inhibited the enzyme activity. All the medicines significantly inhibited CYP2C9 (24%-80%) activity. CYP2D6 activity increased after treatment with MAL, KBA, LIV, and TF. Also, MAL, WAB, LIV, KHB, and CHES increased CYP2B1/2B2 activity, while KT decrease the activity. Generally, the medicines altered liver function in the rats. Cholesterol levels declined after KBA treatment only. White and red blood cell counts, hemoglobin and hematocrit levels were significantly reduced in KT- and KBA-treated rats. Our results suggest that use of the medicines could have implications for drug interactions and safety, particularly if the medicines are administered over prolonged periods. Further investigations are imperative to establish clinical relevance of these results.

Keywords: cytochrome P450; herb-drug interactions; plant medicine.

PubMed Disclaimer

Conflict of interest statement

Declaration of Conflicting Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Increase in EROD (CYP1A1/1A2) activity by drugs and plant medicines used to treat/manage malaria, tuberculosis, and HIV/AIDS in Ghana. Assay conditions are described in section “Ethoxy- and Pentoxy-Resorufin O-Dealkylation.” The charts represent mean and standard deviations of triplicate experiments. The asterisk (*) indicates statistically significant difference (P < .05) from untreated control experiments as determined by the Student’s t test (refer to section Plant Medicines for names of medicines).
Figure 2.
Figure 2.
Increase in PROD (CYP2B1/2B2) activity by drugs and plant medicines used to treat/manage malaria, tuberculosis, and HIV/AIDS in Ghana. Assay conditions are described in section “Ethoxy- and Pentoxy-Resorufin O-Dealkylation.” The charts represent mean and standard deviations of triplicate experiments. The asterisk (*) indicates statistically significant difference (P < .05) from untreated control experiments as determined by the Student’s t test.
Figure 3.
Figure 3.
Increase in CYP2C9 activity by drugs and plant medicines used to treat/manage malaria, tuberculosis, and HIV/AIDS in Ghana. Assay conditions are described in section “Diclofenac Hydroxylation.” The charts represent mean and standard deviations of duplicate experiments. The asterisk (*) indicates statistically significant difference (P < .05) from untreated control experiments as determined by the Student’s t test.
Figure 4.
Figure 4.
Increase in CYP2D6 activity by drugs and plant medicines used to treat/manage malaria, tuberculosis, and HIV/AIDS in Ghana. Assay conditions are described in section Dextromethorphan O-Demethylation.” The charts represent mean and standard deviations of duplicate experiments. The asterisk (*) indicates statistically significant difference (P < .05) from untreated control experiments as determined by the Student’s t test.
See this image and copyright information in PMC

References

    1. Zlokarnik G, Grootenhuis PDJ, Watson JB. High throughput P450 inhibition screens in early drug discovery. Drug Discov Today. 2005;10:1443–1450. - PubMed
    1. Ingelman-Sundberg M. Genetic polymorphisms of cytochrome P450 2D6 (CYP2D6): clinical consequences, evolutionary aspects and functional diversity. Pharmacogenom J. 2005;5:6–13. - PubMed
    1. Ai N, Fan X, Ekins S. In silico methods for predicting drug-drug interactions with cytochrome P-450s, transporters and beyond. Adv Drug Deliv Rev. 2015;86:46–60. doi:10.1016/j.addr.2015.03.006 - PubMed
    1. Martin J, Fay M. Cytochrome P450 drug interactions: are they clinically relevant? Aust Prescr. 2001;24:10–12.
    1. Zhang ZY, Wong YN. Enzyme kinetics for clinically relevant CYP inhibition. Curr Drug Metab. 2005;6:241–257. - PubMed

Publication types

MeSH terms

LinkOut - more resources