Phenolics from Garcinia mangostana alleviate exaggerated vasoconstriction in metabolic syndrome through direct vasodilatation and nitric oxide generation.

Hossam M Abdallah,Zainy M Banjar,Ali M El-Halawany,Khalid Z Alshali,Hany M El-Bassossy,Gamal A Mohamed

doi:10.1186/s12906-016-1340-5

Abstract

BackgroundExaggerated vasoconstriction plays a very important role in the hypertension, a major component of metabolic syndrome (MetS). In the current work, the potential protective effect of methanol extract of fruit hulls of Garcinia mangostana L. on the exaggerated vasoconstriction in MetS has been investigated. In addition, the bioactive fraction and compounds as well as the possible mechanism of action have been illustrated.MethodsThe effect of methanol extract of G. mangostana (GMT) fruit hulls on the vascular reactivity of aorta isolated from animals with MetS was investigated through bioassay-guided fractionation procedures. GMT was partitioned with chloroform (I) and the remaining mother liquor was fractionated on a Diaion HP-20 with H2O, 50 and 100 % methanol to give fractions II, III, and IV, respectively. The effect of total extract (GMT), bioactive fraction and the bioactive compounds on the vasoconstriction were examined in aortae isolated from animals with MetS by incubation for 30 min before exposing aortae to cumulative concentrations of phenylephrine (PE). The direct relaxant effect was also examined by adding cumulative concentrations of the bioactive fraction and its bioactive compounds to PE precontracted vessels. In addition, aortic nitric oxide (NO) and reactive oxygen species (ROS) production was investigated.ResultsBioassay-guided fractionation of GMT revealed isolation of garcimangosone D (1), aromadendrin-8-C-β-D-glucopyranoside (2), 2,4,3′-trihydroxy benzophenone-6-O-β-D-glucopyranoside (3), maclurin-6-O-β-D-glucopyranoside (rhodanthenone) (4), epicatechin (5), and 2,3′,4,5′,6-pentahydroxy benzophenone (6). Only compounds 2, 4, and 5 significantly alleviated the exaggerated vasoconstriction of MetS aortae and in the same time showed significant vasodilation of PE pre-contracted aortae. To further illustrate the mechanism of action, the observed vasodilation was completely blocked by the nitric oxide (NO) synthase inhibitor, Nω-nitro-L-arginine methyl ester hydrochloride and inhibited by guanylate cyclase inhibitor, methylene blue. However, vasodilation was not affected by the potassium channel blocker, tetraethylammonium or the cyclooxygenase inhibitor, indomethacin. In addition, compounds 2, 4, and 5 stimulated NO generation from isolated aortae to levels comparable with acetylcholine. Furthermore, 4 and 5 inhibited reactive oxygen species generation in MetS aortae.ConclusionThe phenolic compounds 2, 4, and 5 ameliorated the exaggerated vasoconstriction in MetS aortae through vasodilatation-NO generation mechanism.Electronic supplementary materialThe online version of this article (doi:10.1186/s12906-016-1340-5) contains supplementary material, which is available to authorized users.

Highlights

Exaggerated vasoconstriction plays a very important role in the hypertension, a major component of metabolic syndrome (MetS)
Metabolic syndrome characteristics Addition of fructose (10 %) to every day drinking water and salt (3 %) to the diet for 12 weeks led to a significant increase in body weight, fasting blood glucose, insulin and mean arterial blood pressure compared with control rats (Table 1)
Effect of G. mangostana (GMT) and fractions Effect on exaggerated vasoconstriction Aortae isolated from MetS animals showed exaggerated vasoconstriction responses to PE compared to control group (Fig. 1a)

Summary

Introduction

Exaggerated vasoconstriction plays a very important role in the hypertension, a major component of metabolic syndrome (MetS). Metabolic syndrome (MetS) is considered as a major worldwide problem that is characterized by hypertension, hyperinsulinemia and obesity. This syndrome is affecting more than quarter of the world population, due to lack of physical activity and high calorie nutrition [1]. People affected by metabolic syndrome are in high risk of developing cardiovascular complications [2]. This is attributed to the effect of hyperglycaemia and oxidative stress on vascular biology [3]. Searching for drugs that have the ability to overcome endothelial dysfunction will help in the treatment of diabetic complications

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Conclusion