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6-Gingerol alleviates exaggerated vasoconstriction in diabetic rat aorta through direct vasodilation and nitric oxide generation.

Ghareib SA, El-Bassossy HM, Elberry AA, Azhar A, Watson ML, Banjar ZM - Drug Des Devel Ther (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.

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.

No MeSH data available.


Related in: MedlinePlus

Effect of 6-gingerol (10−6 to 10−3 M) on the generation of advanced glycation end products (AGEs).Notes: Bars show mean ± SEM of n=3. ***Significantly (P<0.001) different from BSA group. ###Significantly (P<0.001) different from BSA-ribose group.Abbreviation: SEM, standard error of the mean.
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f5-dddt-9-6019: Effect of 6-gingerol (10−6 to 10−3 M) on the generation of advanced glycation end products (AGEs).Notes: Bars show mean ± SEM of n=3. ***Significantly (P<0.001) different from BSA group. ###Significantly (P<0.001) different from BSA-ribose group.Abbreviation: SEM, standard error of the mean.

Mentions: Incubation of BSA with ribose increased AGE significantly (P<0.001), as assessed by fluorimetry. This increased level of AGE was significantly (P<0.001) ameliorated when incubated with AG (1 mM, as positive control), while there was no effect when incubated with different concentrations of 6-gingerol (Figure 5).


6-Gingerol alleviates exaggerated vasoconstriction in diabetic rat aorta through direct vasodilation and nitric oxide generation.

Ghareib SA, El-Bassossy HM, Elberry AA, Azhar A, Watson ML, Banjar ZM - Drug Des Devel Ther (2015)

Effect of 6-gingerol (10−6 to 10−3 M) on the generation of advanced glycation end products (AGEs).Notes: Bars show mean ± SEM of n=3. ***Significantly (P<0.001) different from BSA group. ###Significantly (P<0.001) different from BSA-ribose group.Abbreviation: SEM, standard error of the mean.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4644177&req=5

f5-dddt-9-6019: Effect of 6-gingerol (10−6 to 10−3 M) on the generation of advanced glycation end products (AGEs).Notes: Bars show mean ± SEM of n=3. ***Significantly (P<0.001) different from BSA group. ###Significantly (P<0.001) different from BSA-ribose group.Abbreviation: SEM, standard error of the mean.
Mentions: Incubation of BSA with ribose increased AGE significantly (P<0.001), as assessed by fluorimetry. This increased level of AGE was significantly (P<0.001) ameliorated when incubated with AG (1 mM, as positive control), while there was no effect when incubated with different concentrations of 6-gingerol (Figure 5).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.

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.

No MeSH data available.


Related in: MedlinePlus