Antioxidant Properties of Polysaccharide Extract from Juice and Pomace of Psidium guajava (Pink Guava) and its Mitigating Effect in Early Stage of Atherogenesis

Abstract

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 i¬‚uorometric 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.