Polar components of Phaleria macrocarpa Fruit Exert Antihypertensive and Vasorelaxant Effects by Inhibiting Arterial Tone and Extracellular Calcium Influx

Background: Phaleria macrocarpa (PM) has been used conventionally to cure hypertension. Objective: The objective of the study is to determine the active fraction and its chemical composition responsible for antihypertensive activity of PM fruit using a bioactivity‑guided investigation on different extracts of the fruit. Materials and Methods: Among the extracts of PM, water extract (WE) showed prominent effect in screening test by inhibiting noninvasive blood pressure (BP) in spontaneously hypertensive rats (SHRs). WE was investigated further using hypertensive and normotensive experimental models. Results: WE caused dose‑dependent hypotensive effect in normotensive rats with adrenergic and cholinergic effects by inhibiting the elevated levels of norepinephrine hydrochloride and acetylcholine hydrochloride induced mean arterial pressure (MAP) and heart rate (HR). In addition, WE enhanced the activity of nonselective β‑agonist isoprenaline on MAP and inhibited the increased HR. Similarly, WE demonstrated significant inhibition on pulse wave velocity (PWV), MAP, and HR in SHRs. Fractions of WE were tested for vasorelaxation effect on rat aortic explant. Among the fractions, water fraction-4 (PF-4) showed pronounced effects. Column chromatography of PF‑4 yielded two subfractions; among them, sub-fraction-2 (SF-2) displayed significant vasorelaxation effect in endothelium‑denuded and endothelium‑intact aortas. Further, SF‑2 revealed significant inhibition in calcium influx and mobilization from intracellular stores. Gas chromatography‑mass spectroscopy analysis of SF‑2 revealed abundance of kaempferol 3‑O‑β glucuronide, mangiferin, gallic acid, and rutin. Conclusions: This study demonstrates that polar phytochemical fraction of PM fruit has a promising potential of reducing PWV, BP, and HR. This antihypertensive effect is probably due to the inhibition of arterial tone and extracellular calcium influx.