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


METHODS
The 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.


RESULTS
Bioassay-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.


CONCLUSIONS
The phenolic compounds 2, 4, and 5 ameliorated the exaggerated vasoconstriction in MetS aortae through vasodilatation-NO generation mechanism.
Department of Natural Products, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Saudi Arabia.|Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt.
Hossam M
HM
Abdallah
Department of Pharmacology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Saudi Arabia.|Department of Pharmacology, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.
Hany M
HM
El-Bassossy
Department of Natural Products, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Saudi Arabia. gamals2001@yahoo.com.|Department of Pharmacognosy, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut, 71524, Egypt. gamals2001@yahoo.com.
Gamal A
GA
Mohamed
Department of Natural Products, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Saudi Arabia.|Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt.
Ali M
AM
El-Halawany
Department of Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, 21589, Saudi Arabia.
Khalid Z
KZ
Alshali
Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah, 21589, Saudi Arabia.
Zainy M
ZM
Banjar
D000818:Animals; D001011:Aorta / Q000187:drug effects; D029762:Garcinia mangostana / Q000737:chemistry*; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D020011:Protective Agents / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects
D010636:Phenols; D010936:Plant Extracts; D020011:Protective Agents; D009569:Nitric Oxide
Benzophenone; Flavonoids; Garcinia mangostana; Metabolic syndrome; Relaxation