Ginkgolide B increases hydrogen sulfide and protects against endothelial dysfunction in diabetic rats

Abstract

AimTo evaluate the effect of ginkgolide B treatment on vascular endothelial function in diabetic rats.MethodsThe study included four groups with 15 male Sprague-Dawley rats: control group; control group treated with ginkgolide B; diabetic group; and diabetic treated with ginkgolide B. The activity of superoxide dismutase (SOD), malondialdehyde content, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits, and glutathione peroxidase 1 (GPX1) protein expression were determined in aortic tissues. Vasoconstriction to phenylephrine (PHE) and vasorelaxation to acetylcholine (Ach) and sodium nitroprusside (SNP) were assessed in aortic rings. Nitric oxide (NO) and hydrogen sulfide (H2S) were measured, as well as cystathionine γ lyase (CSE) and cystathionine β synthetase (CBS) protein expression, and endothelial nitric oxide synthase (eNOS) activity.ResultsDiabetes significantly impaired PHE-induced vasoconstriction and Ach-induced vasorelaxation (P < 0.001), reduced NO bioavailability and H2S production (P < 0.001), SOD activity, and GPX1 protein expression (P < 0.001), and increased malondialdehyde content and NADPH oxidase subunits, and CSE and CBS protein expression (P < 0.001). Ginkgolide B treatment improved PHE vasoconstriction and Ach vasorelaxation (P < 0.001), restored SOD (P = 0.005) and eNOS (P < 0.001) activities, H2S production (P = 0.044) and decreased malondialdehyde content (P = 0.014). Vasorelaxation to SNP was not significantly different in control and diabetic rats with or without ginkgolide B treatment. Besides, ginkgolide B increased GPX1 protein expression and reduced NADPH oxidase subunits, CBS and CSE protein expression.ConclusionGinkgolide B alleviates endothelial dysfunction by reducing oxidative stress and elevating NO bioavailability and H2S production in diabetic rats.

Role of Endothelial Dysfunction in Cardiovascular Diseases: The Link Between Inflammation and Hydrogen Sulfide

“…The novel mitochondria-targeted H 2 S donors AP123 and AP39 are proven to prevent hyperglycemiatriggered oxidative stress and metabolic abnormalities in microvascular endothelial cells, suggesting that these compounds could be useful for the treatment of diabetic vascular complications (Gero et al, 2016). Induction of H 2 S by Ginkgolide B alleviates endothelial dysfunction via inhibiting oxidative stress and increasing NO bioavailability in diabetic rats (Wang et al, 2015a). It is likely that the cardiovascular protective effects of H 2 S in diabetes may be mediated by inhibition of oxidative stress.…”

Ginkgolide B protects human umbilical vein endothelial cells against xenobiotic injuries via PXR activation

“…Ginkgolide B is a major terpene lactone and an active component of Ginkgo biloba [9] . Previous studies indicated that ginkgolide B exhibits many pharmacological properties, including anti-oxidant [10] , anti-inflammatory [11,12,13] , anti-tumor [14] , and anti-apoptotic activity [12,15,16] . Due to the widespread use of Ginkgo biloba extract as a supplement, its effects on drug metabolizing enzymes are of interest.…”

Effects of hydrogen sulphide donor, sodium hydrosulphide treatment on the erectile dysfunction in L‐NAME‐induced hypertensive rats

“…Huang, Xia, and Jiang () showed a reduced concentration of H 2 S and decreased the protein expression of CBS and CSE in the CC from diabetic rats. Conversely, Wang, Chen, Li, Lu, and Zhao () demonstrated that H 2 S levels in diabetic rats were reduced, but the protein expression of CBS and CSE was upregulated in diabetic rat aorta. NaHS treatment prevented the reduction of plasma (Ahmad et al, ) and renal (Tain et al, ) H 2 S levels in spontaneously hypertensive rats.…”