Protective effects of Ginkgo biloba extract against mercury(II)-induced cardiovascular oxidative damage in rats
Tunali-Akbay T, Sener G, Salvarli H, Sehirli O, Yarat A.
School of Dentistry, Department of Biochemistry, Marmara University, Turkey
This study was designed to determine the possible protective effect of Ginkgo biloba extract (EGb) against Hg II-induced oxidative damage and also thromboplastic activity in the aorta and heart tissues. Wistar albino rats of either sex (200-250 g) were divided into four groups. Rats were injected intraperitoneally with (1) control (C) group: 0.9% NaCl; (2) EGb group: Ginkgo biloba extract (Abdi Ibrahim Pharmaceutical Company, Istanbul, Turkey) at a dose of 50 mg/kg/day; (3) Hg group: a single dose of 5 mg/kg mercuric chloride (HgCl(2)); and (4) Hg + EGb group: First day EGb at a dose of 50 mg/kg/day, i.p., 1 hour after HgCl(2) (5 mg/kg) injection; following four days EGb at a dose 50 mg/kg/day, i.p. After decapitation of the rats, trunk blood was obtained and serum tumor necrosis factor-alpha (TNF-alpha), lactate dehydrogenase (LDH) activity, and malondialdehyde (MDA) and glutathione (GSH) levels were analysed. In the aorta and heart tissues total protein, MDA, GSH levels and thromboplastic activity were determined. The results revealed that HgCl(2) induced oxidative tissue damage, as evidenced by increases in MDA levels and decreased GSH levels both in serum and tissue samples. Thromboplastic activity was increased significantly following Hg administration, which verifies the cardiotoxic effects of HgCl(2). Serum LDH and TNF-alpha were elevated in the Hg group compared with the control group. Since EGb treatment reversed these responses, it seems likely that Ginkgo biloba extract can protect the cardiovascular tissues against HgCl(2)-induced oxidative damage.
PMID: 17072828 [PubMed - indexed for MEDLINE]
Protective effects of Ginkgo biloba extract against mercury(II)-induced cardiovascular oxidative damage in rats
Tunali-Akbay T, Sener G, Salvarli H, Sehirli O, Yarat A.
School of Dentistry, Department of Biochemistry, Marmara University, Turkey
This study was designed to determine the possible protective effect of Ginkgo biloba extract (EGb) against Hg II-induced oxidative damage and also thromboplastic activity in the aorta and heart tissues. Wistar albino rats of either sex (200-250 g) were divided into four groups. Rats were injected intraperitoneally with (1) control (C) group: 0.9% NaCl; (2) EGb group: Ginkgo biloba extract (Abdi Ibrahim Pharmaceutical Company, Istanbul, Turkey) at a dose of 50 mg/kg/day; (3) Hg group: a single dose of 5 mg/kg mercuric chloride (HgCl(2)); and (4) Hg + EGb group: First day EGb at a dose of 50 mg/kg/day, i.p., 1 hour after HgCl(2) (5 mg/kg) injection; following four days EGb at a dose 50 mg/kg/day, i.p. After decapitation of the rats, trunk blood was obtained and serum tumor necrosis factor-alpha (TNF-alpha), lactate dehydrogenase (LDH) activity, and malondialdehyde (MDA) and glutathione (GSH) levels were analysed. In the aorta and heart tissues total protein, MDA, GSH levels and thromboplastic activity were determined. The results revealed that HgCl(2) induced oxidative tissue damage, as evidenced by increases in MDA levels and decreased GSH levels both in serum and tissue samples. Thromboplastic activity was increased significantly following Hg administration, which verifies the cardiotoxic effects of HgCl(2). Serum LDH and TNF-alpha were elevated in the Hg group compared with the control group. Since EGb treatment reversed these responses, it seems likely that Ginkgo biloba extract can protect the cardiovascular tissues against HgCl(2)-induced oxidative damage.
PMID: 17072828 [PubMed - indexed for MEDLINE]
Electropharmacological actions of Ginkgo biloba extract on vascular smooth and heart muscles
Satoh H, Nishida S.
Department of Pharmacology, Division of Crude and Herbal Medicine, Nara Medical University, Kashihara, Nara 634-8521, Japan
Ginkgo biloba extract (GBE) is composed mostly of two constituents: One is terpenoids (such as bilobalide, ginkgolides A, B and C), and the other is flavonoids (such as quercetin and rutin). After oral administration of GBE (160 mg) to healthy volunteers, the plasma concentrations of ginkgolides A and B and bilobalide are 41.8, 5.6 and 37.6 ng/ml, respectively. GBE and bilobalide cause a potent concentration-dependent relaxation. NG-Monomethyl-l-arginine acetate (l-NMMA), an NO synthesis inhibitor, reduces the vasodilation induced by GBE. Furthermore, the vasorelaxation of GBE is attenuated in Ca2+-free medium. Bilobalide possesses similar mechanisms. The other constituents also produce vasorelaxation. On the other hand, all the compounds markedly modify the action potential configuration in guinea pig ventricular cardiomyocytes. GBE prolongs the action potential duration (APD), whereas bilobalide shortens the APD. In patch-clamp experiments, GBE markedly inhibits the Ca2+ current (ICa), the delayed rectifier K+ current (IK) and the inwardly rectifying K+ current (IK1). On the contrary bilobalide enhances the ICa and IK currents concentration-dependently. The other constituents do not cause their actions in a uniform direction. In the rat sino-atrial (SA) node, GBE causes a negative chronotropic effect. These results indicate that GBE and the constituents produce effective electropharmacological actions in the cardiomyocytes and cause vasodilation, mainly due to the inhibitions of Ca2+ influx through the Ca2+ channel and the activation of NO release in the endothelium and aortic vascular muscles.
PMID: 15026263 [PubMed - indexed for MEDLINE
Complexation of Ginkgo biloba extract with phosphatidylcholine improves cardioprotective activity and increases the plasma antioxidant capacity in the rat
Carini M, Aldini G, Rossoni G, Morazzoni P, Facino RM.
Istituto Chimico Farmaceutico Tossicologico, University of Milan, Milan, Italy
The aim of this work was to compare in the rat the cardioprotective efficacy and the total plasma antioxidant activity of a standardised Ginkgo biloba L. extract (GB) as such (300 mg/kg/day) or complexed with phosphatidylcholine (GB-PC; 1:2 w/w), after a 5 days oral administration. At the end of the treatment, the total plasma antioxidant defence was determined by the TRAP and FRAP assays, and the hearts from all groups of animals subjected to moderate ischemia (flow reduction to 1 ml/min for 20 min) and reperfusion (15 ml/min for 30 min). The recovery of left ventricular developed pressure (LVDP) at the end of reperfusion was 35-40% of the preischemic values in both control and vehicle rats, 50.2% in the GB group and 72.5% in the GB-PC pre-treated animals. Creatine kinase (CK) outflow in the perfusate from the hearts of GB and GB-PC treated animals were restrained to a different extent vs. controls (by 71% GB-PC; by 22% GB); the rate of prostacyclin (6-keto-PGF1 alpha) release was far greater in GB-PC than in GB hearts. In parallel, the GB extract significantly increased the total antioxidant plasma capacity (by 24.5% TRAP; 27.9% FRAP) only when complexed with phospholipids. This indicates an increased bioavailability of phenolic antioxidants when suitably embedded within a lipophilic carrier. The results of this study demonstrate that complexation of Ginkgo biloba with phospholipids induces in the rat, even after a short treatment a greater resistance of the heart to ischemia/reperfusion damage in respect to the native extract, due to an increased plasma antioxidant activity.
PMID: 11458448 [PubMed - indexed for MEDLINE]
Mechanisms for the vasodilations induced by Ginkgo biloba extract and its main constituent, bilobalide, in rat aorta
Nishida S, Satoh H.
Department of Pharmacology, Division of Crude and Herbal Medicine, Nara Medical University, Kashihara, Nara 634-8521, Japan.
Vasodilating actions of Ginkgo biloba extract (GBE) and bilobalide, a main constituent, were examined using rat aorta ring strips. GBE at the concentration ranges from 0.03 to 3 mg/ml had a potent concentration-dependent relaxation, reaching 70 +/- 4.5% (n = 6, P < 0.001) at 3 mg/ml. Bilobalide at 0.1 to 100 microM also caused the relaxation in a concentration-dependent manner. At 100 microM, bilobalide caused dilation by 17.6 +/- 3.9% (n = 7, P < 0.05). NG-monomethyl-L-arginine acetate (L-NMMA)(100 microM), an NO synthesis inhibitor, reduced the vasodilation of GBE (3 mg/ml) to 57.6 +/- 2.5% (n = 6, P < 0.05), and was accompanied with a decrease in the rate of relaxation. Tetraethylammonium (TEA)(100 microM), a Ca(2+)-activated K(+) channel inhibitor, also decreased the GBE (3 mg/ml)-induced relaxation to 63.1 +/- 4.6% (n = 6), but not significantly. Indomethacin tended to reduce the GBE (3 mg/ml)-induced vasorelaxation to 67.3 +/- 4.1% (n = 6). In contrast, the vasorelaxation of GBE (3 mg/ml) was strongly attenuated to 53 +/- 6.1% (n = 7, P < 0.05) in Ca(2+)-free medium. Similarly, the vasorelaxation induced by bilobalide significantly decreased both by pretreatment with NO inhibitor (L-NMMA) and in Ca(2+)-free solution. These results indicate that the relaxation induced by GBE would be due to the inhibition of Ca(2+) influx through the Ca(2+) channel and the activation of NO release, and might be in part due to the inhibitions of Ca(2+)-activated K(+) current and PGI(2) release, in the endothelium and aortic vascular muscles. Bilobalide possesses the similar mechanisms for the vasodilation.
PMID: 12672511 [PubMed - indexed for MEDLINE]
The use of Ginkgo biloba in Raynaud's disease: a double-blind placebo-controlled trial
Muir AH, Robb R, McLaren M, Daly F, Belch JJ
Peripheral Vascular Diseases Research Unit, University Department of Medicine, Ninewells Hospital & Medical School, Dundee, UK
Raynaud's phenomenon (RP) is a common and painful condition characterized by episodic digital ischaemia produced by emotion and cold. Treatment of RP is notoriously difficult because of the high incidence of side effects. The aim of our study was to investigate the clinical efficacy of a standardized Ginkgo biloba extract (Seredrin) in the treatment of RP in patients with no apparent, associated condition such as systemic sclerosis. A two-week assessment period was done during which patients were asked to record frequency, severity and duration of attacks in diaries. Subjects were then randomized independently of the study centre to receive either active or placebo treatment for 10 weeks, during which time the same data were recorded in their diaries. Patients were seen after two and four weeks of treatment and at the end of the 10-week treatment phase. Blood samples pre- and post-treatment were taken for haemorrheology. Only in the number of attacks per day was there a significant effect of treatment over placebo. The number of attacks per week prior to treatment with Seredrin was 13.2 +/- 16.5 reducing to 5.8 +/- 8.3, a reduction of 56%, whereas placebo reduced the number by only 27% (p < or = 0.00001). There were no significant differences in haamorrheology between the two groups. Ginkgo biloba phytosome may be effective in reducing the number of Raynaud's attacks per week in patients suffering from Raynaud's disease.
Publication Types:
· Clinical Trial
· Randomized Controlled Trial
PMID: 12710841 [PubMed - indexed for MEDLINE]
Valuation of nitric oxide scavenging activity of certain spices in vitro: a preliminary study
Baliga MS, Jagetia GC, Rao SK, Babu K.
Department of Radiobiology Kasturba Medical College, Manipal-576 119, Karnataka, India
The plant extracts of some commonly used spices were examined for their possible regulatory effect on nitric oxide (NO) levels using sodium nitroprusside as a NO donor in vitro. Most of the extracts tested demonstrated direct scavenging of NO and exhibited significant activity and the potency of scavenging activity was in the following order: Foeniculum vulgare (aqueous) > Citrus limettiodes > Murraya koenigii (seed, aqueous) > Murraya koenigii (leaf, aqueous) > Curcuma aromatica (aqueous) > Murraya koenigii (leaf, dichloromethane:methanol) > Mentha arvensis (chloroform) > Mentha arvensis (aqueous) > Curcuma longa > Gingko biloba > Foeniculum vulgare (dichloromethane:methanol) > Zingiber officinale (aqueous) > Curcuma aromatica (ethanolic) > Murraya koenigii (seed, dichloromethane:methanol). All the evaluated extracts exhibited a dose-dependent NO scavenging activity. The aqueous extract of Foeniculum vulgare showed a greatest NO scavenging effect of 79.75% at 62.5 microg/mL as compared to the positive control, Gingko biloba where 36.22% scavenging was observed at similar concentration. The present results suggest that these spices might be potent and novel therapeutic agents for scavenging of NO and the regulation of pathological conditions caused by excessive generation of NO and its oxidation product, peroxynitrite.
Publication Types:
· Evaluation Studies
PMID: 13678266 [PubMed - indexed for MEDLINE]