title: 6-Gingerol alleviates exaggerated vasoconstriction in diabetic rat aorta through direct vasodilation and nitric oxide generation.
abstract: The aim of the present study is to investigate the effect and potential mechanism of action of 6-gingerol on alterations of vascular reactivity in the isolated aorta from diabetic rats. Male Wistar rats were divided into two experimental groups, control and diabetics. Diabetes was induced by a single intraperitoneal injection of streptozotocin (50 mg kg(-1)), and the rats were left for 10 weeks to develop vascular complications. The effect of in vitro incubation with 6-gingerol (0.3-3 μM) on the vasoconstrictor response of the isolated diabetic aortae to phenylephrine and the vasodilator response to acetylcholine was examined. Effect of 6-gingerol was also examined on aortae incubated with methylglyoxal as an advanced glycation end product (AGE). To investigate the mechanism of action of 6-gingerol, the nitric oxide synthase inhibitor Nω-nitro-l-arginine methyl ester hydrochloride (100 μM), guanylate cyclase inhibitor methylene blue (5 μM), calcium-activated potassium channel blocker tetraethylammonium chloride (10 mM), and cyclooxygenase inhibitor indomethacin (5 μM) were added 30 minutes before assessing the direct vasorelaxant effect of 6-gingerol. Moreover, in vitro effects of 6-gingerol on NO release and the effect of 6-gingerol on AGE production were examined. Results showed that incubation of aortae with 6-gingerol (0.3-10 μM) alleviated the exaggerated vasoconstriction of diabetic aortae to phenylephrine in a concentration-dependent manner with no significant effect on the impaired relaxatory response to acetylcholine. Similar results were seen in the aortae exposed to methylglyoxal. In addition, 6-gingerol induced a direct vasodilation effect that was significantly inhibited by Nω-nitro-l-arginine methyl ester hydrochloride and methylene blue. Furthermore, 6-gingerol stimulated aortic NO generation but had no effect on AGE formation. In conclusion, 6-gingerol ameliorates enhanced vascular contraction in diabetic aortae, which may be partially attributed to its ability to increase the production of NO and stimulation of cyclic guanosine monophosphate.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Salah A
authors.initials: SA
authors.lastname: Ghareib
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia ; Department of Pharmacology, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.
authors.forename: Hany M
authors.initials: HM
authors.lastname: El-Bassossy
authors.affiliation: Department of Clinical Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia ; Department of Pharmacology, Faculty of Medicine, Beni Suef University, Beni Suef, Egypt.
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: Elberry
authors.affiliation: Department of Pediatric Cardiology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Azhar
authors.affiliation: Department of Pharmacy and Pharmacology, University of Bath, Bath, UK.
authors.forename: Malcolm L
authors.initials: ML
authors.lastname: Watson
authors.affiliation: Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Zainy Mohammed
authors.initials: ZM
authors.lastname: Banjar
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D002396:Catechols / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005233:Fatty Alcohols / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D002396:Catechols; D005233:Fatty Alcohols; D009569:Nitric Oxide; C007845:gingerol
keywords: 6-gingerol; advanced glycation end products; diabetes; nitric oxide; vascular complications; vasorelaxant