Antihypertensive activity and vascular reactivity mechanisms of Vitex pubescens leaf extracts in spontaneously hypertensive rats

Abstract

Background Vitex pubescens has been used traditionally in hypertension treatment but not yet scientifically assessed. The objective of the study is to investigate the antihypertensive and vasorelaxant activities of V. pubescens , study its underlying pharmacological mechanisms, and identify the relevant vasoactive compounds. Methods Successive extractions of V. pubescens leaf were carried out to produce petroleum ether (VPPE), chloroform (VPCE), methanol (VPME), and water (VPWE) extracts. Spontaneously hypertensive rats (SHRs) received a daily oral administration of the extracts (500 mg/kg/day; n = 6) or verapamil (15 mg/kg/day; n = 6) for 2 weeks, while the systolic and diastolic blood pressures were measured using non-invasive tail-cuff method. Vasorelaxation assays of the extracts were later conducted using phenylephrine (PE, 1 μM) pre-contracted aortic ring preparation. Mechanisms of vasorelaxation by the most potent fraction were studied using vasorelaxation assays with selected blockers/inhibitors. GC-MS was conducted to determine the active compounds. Results VPPE elicited the most significant diminution in systolic and diastolic blood pressure of treated SHRs and produced the most significant vasorelaxation in the aortic rings. Vasorelaxant effects of F2-VPPE were significantly reduced in endothelium-denuded aortic rings by glibenclamide (1 μM), whereas calcium chloride and PE-induced contractions were significantly suppressed. Endothelium removal of the aortic rings or incubation with indomethacin (10 μM), atropine (1 μM), methylene blue (10 μM), propranolol (1μM) and L-NAME (10 μM) did not significantly alter F2-VPPE-induced vasorelaxation. Seven compounds were identified using GC-MS, including spathulenol. Conclusion F2-VPPE exerted its endothelium-independent vasorelaxation by inhibition of vascular smooth muscle contraction induced by extracellular Ca +2 influx through trans-membrane Ca +2 channels and/or Ca +2 release from intracellular stores, and by activation of K ATP channels. The vasorelaxation effects of V. pubescens could be mediated by the compound, spathulenol.

Vasorelaxant Effects of the Vitex Agnus-Castus Extract

“…These results are consistent with our previous study reporting a tracheorelaxant function of VACE [ 17 ]. This VACE relaxant function may partly be endothelium-independent, potentially through the inhibition of calcium receptors, either extracellular and/or intracellular, and by activation of K ATP channels [ 21 ]. This does not exclude the involvement of other potential mechanisms, such as inhibition of β -adrenergic receptors in ASM cells [ 33 ].…”

“…However, these functions are mainly not scientifically assessed. Recently, the leaf extracts of Vitex pubescens have been reported to have antihypertensive and vasorelaxant action in the aorta [ 21 ]. Therefore, this study was aimed to investigate the vascular effects of Vitex agnus-castus extract on rabbit aorta rings under various experimental conditions.…”

Plants With Antihypertensive Activities: A Review

“…Spathulenol is the main compound of Vitex pubescens which acts as a smooth muscle vasorelaxant, anti-inflammatory and antioxidant 36 . The leaves of Vitex pubescens were shown to have antihypertensive activity tested on Rats 9 . Vitex pubescens was extracted with petroleum ether, chloroform, methanol, and water, wherein petroleum ether extract was considered the strongest extract and was selected for fractionation.…”

Novel Blood Pressure-Lowering Effect of Spathulenol in Rats

“…In recent years, there has been an increasing demand for using natural compounds from plant sources as an alternative for treatment and prevention of various diseases including cardiovascular diseases (Al-Akwaa et al 2020). Demands for new antihypertensives are primarily due to safety issues as synthetic substances record new side effects every year.…”