Inhibitory Potency of Selected Therapeutic Bioactive Molecules of Standardized Terminalia arjuna (Roxb.) Extract on CYP3A4 and CYP2D6: Exploring Possible Herb-Drug Interactions
- *Corresponding Author:
- Dr. TM Vijayakumar
Assistant Professor, Department of Pharmacy Practice, SRM University
Kattankulathur-603 203, Kancheepuram District, Tamil Nadu, India
E-mail: [email protected]
Received Date: April 10, 2017; Accepted Date: May 23, 2017; Published Date: May 29, 2017
Citation: Vijayakumar TM, Ilango K, Vasanth K, Kasthuri Bai N, Mohan Kumar R, et al. (2017) Inhibitory Potency of Selected Therapeutic Bioactive Molecules of Standardized Terminalia arjuna (Roxb.) Extract on CYP3A4 and CYP2D6: Exploring Possible Herb-Drug Interactions. Nat Prod Chem Res 5:272. doi: 10.4172/2329-6836.1000272
Copyright: © 2017 Vijayakumar TM, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
A number of significant herbal drug interactions have their origins in the alteration of cytochrome P450 (CYP) activity by various phytochemicals. In the present study, inhibition potential of Terminalia arjuna extracts and its constituent gallic acid (GA) and ellagic acid (EA) to cause herb-drug interactions through rat liver cytochrome enzymes, CYP3A4, and CYP2D6 was evaluated, a rapid RP-HPLC method was developed for quantitative estimation of GA and EA in the extract. In vitro safety of the extract and active components were evaluated through CYP450 inhibition method using pooled rat microsomes and high throughput fluorometric assay with CYP3A4 and CYP2D6. The binding mode and the molecular interaction of GA and EA within the CYP3A4 and CYP2D6 active site were demonstrated using an in-silico docking studies. From CYP450-CO Complex assay, the inhibitory potential of T. arjuna standardized extract (31.02 ± 2.24%), was found to be less than positive control. In high throughput Ã¯Â¬Âuorometric assay, T. arjuna extracts exhibited higher IC50 values (48.06 ± 1.14-57.89 ± 2.15 μg/mL) compared to positive inhibitors and lower than GA (66.54 ± 1.04-83.84 ± 1.06 μg/mL), EA (69.47 ± 1.18-102.69 ± 2.87 μg/mL) on CYP3A4 and CYP2D6. Based on the inhibitory potential of test samples, it can be concluded that T. arjuna and its standardized bioactive molecules could produce weak interaction potential when co-administered with conventional medicines.