Abdallah Hossam M, El-Bassossy Hany M, Mohamed Gamal A, El-Halawany Ali M, Alshali Khalid Z, Banjar Zainy M
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.
BMC Complement Altern Med. 2016 Sep 13;16(1):359. doi: 10.1186/s12906-016-1340-5.
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.
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.
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.
The phenolic compounds 2, 4, and 5 ameliorated the exaggerated vasoconstriction in MetS aortae through vasodilatation-NO generation mechanism.
血管过度收缩在高血压（代谢综合征的主要组成部分）中起着非常重要的作用。在当前研究中，对山竹果皮甲醇提取物对代谢综合征中血管过度收缩的潜在保护作用进行了研究。此外，还阐明了生物活性成分和化合物以及可能的作用机制。
通过生物测定引导的分级分离程序，研究了山竹甲醇提取物（GMT）对从患有代谢综合征的动物分离的主动脉血管反应性的影响。GMT用氯仿（I）进行分配，剩余母液在Diaion HP-20上用H2O、50%和100%甲醇分级分离，分别得到级分II、III和IV。在将主动脉暴露于累积浓度的去氧肾上腺素（PE）之前，通过孵育30分钟，研究了总提取物（GMT）、生物活性级分和生物活性化合物对从患有代谢综合征的动物分离的主动脉血管收缩的影响。还通过向PE预收缩的血管中添加累积浓度的生物活性级分及其生物活性化合物来研究直接舒张作用。此外，还研究了主动脉一氧化氮（NO）和活性氧（ROS）的产生。
GMT的生物测定引导分级分离显示分离出了山竹酮D（1）、芳樟醇-8-C-β-D-葡萄糖苷（2）、2,4,3'-三羟基二苯甲酮-6-O-β-D-葡萄糖苷（3）、麦卢因-6-O-β-D-葡萄糖苷（红丹酮）（4）、表儿茶素（5）和2,3',4,5',6-五羟基二苯甲酮（6）。只有化合物2、4和5能显著减轻代谢综合征主动脉的过度血管收缩，同时对PE预收缩的主动脉有显著的血管舒张作用。为了进一步阐明作用机制，观察到的血管舒张被一氧化氮（NO）合酶抑制剂Nω-硝基-L-精氨酸甲酯盐酸盐完全阻断，并被鸟苷酸环化酶抑制剂亚甲蓝抑制。然而，血管舒张不受钾通道阻滞剂四乙铵或环氧化酶抑制剂吲哚美辛的影响。此外，化合物2、4和5刺激分离的主动脉产生NO，使其水平与乙酰胆碱相当。此外，4和5抑制代谢综合征主动脉中活性氧的产生。
酚类化合物2、4和5通过血管舒张-NO生成机制改善了代谢综合征主动脉的过度血管收缩。
