Possible Mechanism of Action of the Hypotensive Effect of Peperomia pellucida and Interactions between Human Cytochrome P450 Enzymes

Chukwuemeka R Nwokocha

doi:10.4172/2167-0412.1000105

Abstract

Background: Peperomia pellucida is used as a medicinal plant and as an antihypertensive remedy. We investigated the possible mechanism of this action and its impact on cytochrome P450 (CYP) enzyme activity. Methods: Mean arterial pressure and heart rate were recorded via cannulation of the carotid artery on anaesthetized, normotensive Sprague-Dawley rats following intravenous administration of Peperomia pellucida aqueous (10-30 mg/ kg) plant extract (PPAE). Recordings of the contractile activity of the aortic rings to the extract (1.9-8.6 mg/ml) were done using standard organ bath techniques. Impact on CYP3A4 and CYP2D6 enzyme activities was investigated using human liver and heterologously expressed microsomes. Results: We observed a dose-dependent reduction in systolic, diastolic, MAP and HR. Pre-treatment with atropine (2 mg/kg) and propranolol (1 mg/kg) but not mepyramine (2 mg/kg) significantly (p<0.05) reduced the hypotensive and negative chronotropic activities caused by the extract, while L-NAME (5 mg/kg) completely abolished it. PPAE significantly (p<0.05) relaxed the phenylephrine (10 -9 -10 -4 M) and KCl- induced contractions and displayed moderate inhibition of CYP3A4 enzyme activity with IC50 values of 0.466 ± 0.126 mg/mL and 0.153 ± 0.054 mg/mL, respectively using heterogenously expressed CYP3A4 and human liver microsomes (HLMs) Conclusion: Results suggest dose-dependent hypotensive, bradycardic and vasorelaxant effects of PPAE are mediated through Nitric oxide-dependent mechanisms. The impact on CYPs enzyme activities indicate unlikely adverse drug effect when Peperomia pellucida is consumed with other medications reliant on CYP3A4 metabolism.

Highlights

Peperomia pellucida is used as a medicinal plant and as an antihypertensive remedy
Effect of graded doses of Peperomia pellucida on blood pressure and heart rates Intravenous administration of increasing dose Peperomia pellucida aqueous extract caused a dose-dependent reduction in systolic blood pressure (SBP), diastolic blood pressure (DBP), Heart rate and mean arterial pressure (MAP) (Table 1)
The major findings of this study are that the aqueous extract of Peperomia pellucida produced a dose-dependent decrease in systolic blood pressure, diastolic blood pressure, MAP and heart rate in normotensive rats

Summary

Introduction

Peperomia pellucida is used as a medicinal plant and as an antihypertensive remedy. We investigated the possible mechanism of this action and its impact on cytochrome P450 (CYP) enzyme activity. Hypertension is a major cardiovascular burden that has been estimated to cause 7.1 million premature deaths and 45 % of the disease burden [1] It remains inadequately managed everywhere [2], and in spite of the large number of antihypertensive medications, most people in developing countries have poor access to modern healthcare and cannot afford these drugs due to cost. They resort to alternative herbal remedies to manage hypertension.Such alternative remeadies include the use of herbs and natural plant products, one of the plant used is Peperomia pellucid [3]. It is reported to have anti-inflammatory properties [6] analgesic activity[4,6,7,8] antipyretic [9] as well as antibacterial [5,7,10] used in the treatment of abscesses, furuncles, and conjunctivitis [6]

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