Ginkgolide B increases hydrogen sulfide and protects against endothelial dysfunction in diabetic rats.
OBJECTIVE
To evaluate the effect of ginkgolide B treatment on vascular endothelial function in diabetic rats.


METHODS
The 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.


RESULTS
Diabetes 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.


CONCLUSIONS
Ginkgolide B alleviates endothelial dysfunction by reducing oxidative stress and elevating NO bioavailability and H2S production in diabetic rats.
Guo-guang Wang, Department of Pathophysiology, School of Basic Medicine, Wannan Medical College, 22 # West of Wenchang Road, Wuhu, China, guoguangw1226@sina.com.
Guo-Guang
GG
Wang
Qing-Ying
QY
Chen
Wei
W
Li
Xiao-Hua
XH
Lu
Xue
X
Zhao
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003542:Cystathionine gamma-Lyase / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D046934:Ginkgolides / Q000627:therapeutic use*; D005979:Glutathione Peroxidase / Q000378:metabolism; D006862:Hydrogen Sulfide / Q000378:metabolism*; D007783:Lactones / Q000627:therapeutic use*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D000094765:Glutathione Peroxidase GPX1
D005343:Fibrinolytic Agents; D046934:Ginkgolides; D007783:Lactones; D009599:Nitroprusside; D009569:Nitric Oxide; D008315:Malondialdehyde; C045856:ginkgolide B; D005979:Glutathione Peroxidase; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D013482:Superoxide Dismutase; D019255:NADPH Oxidases; D003542:Cystathionine gamma-Lyase; D000109:Acetylcholine; D006862:Hydrogen Sulfide; D000094765:Glutathione Peroxidase GPX1; C000722069:Gpx1 protein, rat