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[Effects of Ginaton on the markers of myocardial injury during cardiopulmonary bypass].

OBJECTIVE: To evaluate the effects of Ginaton (Ginkgo biloba leaf extract) on the myocardial injury markers (MIMs) during cardiopulmonary bypass (CPB). METHODS: Forty patients with congenital heart diseases, scheduled to take atrial septum or ventricular septum repairing operation, were randomly divided into the Ginaton group and the control group, 20 cases in each group. Patients in both groups received St. Thomas' cardioplegic perfusion via radix aortae, while Ginaton (0.5 mg/kg) was added into the perfusion for the Ginton group. Cardiac surgery were started after complete heart arrest. Central venous blood was obtained before and at 0, 6th, 12th, 24th and 48th hour after operation for detection of serum C reaction protein (CRP) by immunoturbidimetry, as well as creation kinase-MB isoenzyme (CK-MB), cardiac troponin T (cTnT) and cardiac troponin I (cTnI) with enzyme-linked immunosorbent assay (ELISA). RESULTS: There was no difference in serum concentration of CRP, CK-MB, cTnT and cTnI between the two groups before operation (P > 0.05). These indexes increased immediately after operation in both groups ( P < 0.05). They reached the peak value 12 hrs after CPB and reduced to normal level 48 hrs post-operation in the control group, with the value significantly higher than that in the Ginaton group at all the corresponding time points (P < 0.05, or P < 0.01). CONCLUSION: Perfusion with Ginaton during CPB could significantly decrease the release of MIMs and improve post-CPB cardiac function recovery, exerting favorable myocardium-protective effects.

Biomarkers↗

New experimental model for the evaluation of adaptogenic products.

A new animal model for evaluating improvement in physical work performance and endurance in an adverse environment is described. In this model, rats in restraint were exposed to 5 degrees C at 480 mmHg atmospheric pressure. Results were compared to an animal forced to swim in water at 23 degrees C. In both the models, colonic temperature (Tr) of the rats was continually monitored during exposure to adverse environment and during recovery at 32 degrees C and normal atmospheric pressure. The time and pattern for Tr fall to 23 degrees C and its recovery to 37 degrees C were used as measures of endurance. The cold-hypoxia-restraint model was found to provide more precise results compared with the cold-swimming model. Panax ginseng root and Ginkgo biloba leaf extracts were compared for their positive endurance-promoting properties using both models.

Adaptation, Physiological↗

Transcriptional suppression of the adrenal cortical peripheral-type benzodiazepine receptor gene and inhibition of steroid synthesis by ginkgolide B.

Treatment of rats and adrenocortical cells with ginkgolide B (GKB), a purified component of Ginkgo biloba leaf extracts, reduces the mRNA, protein, and ligand-binding levels of the adrenal peripheral-type benzodiazepine receptor (PBR), a mitochondrial cholesterol-binding protein, leading to decreased corticosteroid synthesis. In the Y1 adrenocortical cell line, GKB reduced both PBR levels and cyclic AMP-induced steroid formation. In these cells, GKB, but not various steroids and vitamins, reduced the expression of a reporter gene driven by the DNA sequence -624/-513 relative to the transcription start site of the PBR encoding gene. GKB treatment did not affect the SV40 promoter and increased the cytochrome P450 17alpha-hydroxylase gene promoter driven expression of the reporter gene. Electrophoretic mobility shift assays (EMSAs) indicated the presence of a functional transcriptional element bound to the -624/-513 DNA fragment. This GKB-induced inhibition of PBR was mediated by an interaction with a transcription factor that binds to the -636/-616 PBR-promoter region. Deletion or mutation of this sequence eliminated the DNA-protein interaction and the inhibitory effect of GKB on PBR gene transcription. This DNA-binding protein could be detected in nuclear extracts of rat brain, liver, and testis, but not kidney. It is also present in the human adrenal glands. However, the inhibitory effect following GKB treatment could be seen only in the adrenal glands. These results demonstrate that the GKB-activated inhibition of glucocorticoid production is due to a specific transcriptional suppression of the adrenal PBR gene and suggest that GKB might serve as a pharmacological tool to control excess glucocorticoid formation.

Adrenal Cortex↗

A double-blind placebo-controlled study of ArginMax, a nutritional supplement for enhancement of female sexual function.

This study was open to women over the age of 21 years with an interest in improving their sexual function. Of the 77 participants, 34 received ArginMax and 43 received a placebo. ArginMax for Women is a proprietary nutritional supplement consisting of extracts of ginseng, ginkgo, and damiana, L-arginine, multivitamins, and minerals. After 4 weeks, 73.5% of the ArginMax group improved in satisfaction with their overall sex life, compared with 37.2% of the placebo group (p < 0.01). Notable improvements were also observed in sexual desire, reduction of vaginal dryness, frequency of sexual intercourse and orgasm, and clitoral sensation. No significant side effects were noted.

Adult↗

[Determination of 4-O-methylpyridoxine (MPN) by HPLC with diode-array detector].

We have developed a simple and rapid method for measuring 4-O-methylpyridoxine (MPN) in the serum of an acute poisoning patient by high-performance liquid chromatograph (HPLC) with a diode-array detector. MPN, a poisonous ingredient of ginkgo seeds was extracted using an Isolute C18 solid-phase extraction column. Equal volumes of the extract were injected into a C18 HPLC column using acetonitrile-10 mM phosphate buffer (pH 3) as the mobile phase. Excellent linearity was obtained over the range of 1-1000 ng at a wavelength of 290 nm, and its detection limit of approximately 0.5 ng was considered to be satisfactory. The mean recovery of MPN in the serum was 92.9 +/- 6.1%. The method was used successfully in a case of acute poisoning.

Chromatography, High Pressure Liquid↗

Chemistry and biology of terpene trilactones from Ginkgo biloba.

Ginkgo biloba, the ginkgo tree, is the oldest living tree, with a long history of use in traditional Chinese medicine. In recent years, the leaf extracts have been widely sold as phytomedicine in Europe and as a dietary supplement worldwide. Effects of Ginkgo biloba extracts have been postulated to include improvement of memory, increased blood circulation, as well as beneficial effects to sufferers of Alzheimer's disease. The most unique components of the extracts are the terpene trilactones, that is, ginkgolides and bilobalide. These structurally complex molecules have been attractive targets for total synthesis. Terpene trilactones are believed to be partly responsible for the neuromodulatory properties of Ginkgo biloba extracts, and several biological effects of the terpene trilactones have been discovered in recent years, making them attractive pharmacological tools that could provide insight into the effects of Ginkgo biloba extracts.

Biology↗

Involvement of Ca2+, CaMK II and PKA in EGb 761-induced insulin secretion in INS-1 cells.

EGb 761, a standardized form of Ginkgo biloba L. (Ginkgoaceae) leaf extract, was recently reported to increase pancreatic beta-cell function. To determine whether EGb 761 elicits insulin secretion directly, we treated INS-1 rat beta cells with EGb 761 and then measured insulin release. Treatment of EGb 761 (50 microg/ml) significantly stimulated insulin secretion in INS-1 cells, compared with untreated control (p<0.05) and the stimulatory effect of EGb 761 on insulin secretion was dose-dependent. To elucidate the mechanism of EGb 761-induced insulin secretion, we investigated the involvement of calcium. The treatment with nifedipine, an L-type calcium channel blocker, prevented EGb 761-induced insulin secretion and furthermore, EGb 761 itself elevated [Ca(2+)](i), suggesting the involvement of calcium in this process. To identity the protein kinases involved in EGb 761-induced insulin secretion, INS-1 cells were treated with different kinase inhibitors and their effects on EGb 761-induced secretion were investigated. KN62 and H89, calium/calmodulin kinase (CaMK) II and protein kinase A (PKA) inhibitor, respectively, significantly reduced EGb 761-induced insulin secretion. Immunoblotting studies showed an increase in the phosphorylated-forms of CaMK II and of PKA substrates after EGb 761 treatment. Our data suggest that EGb 761-induced insulin secretion is mediated by [Ca(2+)](i) elevation and subsequent activation of CaMK II and PKA.

Animals↗

The effect of EGb 761 on retinal lipid peroxidation and glutathione peroxidase level in experimental lens induced uveitis.

An acute lens-induced necrotizing intraocular inflammation was produced in pigmented guinea pigs. Treatment of these animals by 100 mg/kg/day EGb 761 a free oxygen radical scavenger for 10 days, reduced retinal lipid peroxidation (p > 0.05) and increased the retinal glutathione peroxidase level (p > 0.05). Although not significantly, these findings suggest that EGb 761 could be combined with other antiinflammatory drugs and may be beneficial in the treatment of uveitis.

Administration, Oral↗

EGb761 pretreatment reduces monoamine oxidase activity in mouse corpus striatum during 1-methyl-4-phenylpyridinium neurotoxicity.

EGb761 produces reversible inhibition of both monoamine oxidase (MAO) isoforms in the central nervous system. 1-Methyl-4-phenylpyridinium (MPP+) neurotoxicity is prevented by treatment with the MAO inhibitor pargyline. We investigated EGb761's effect on striatal MAO activity during MPP+ neurotoxicity. C-57 black mice were pretreated with EGb761 (10 mg/kg) daily for 17 days followed by administration of MPP+ (0.72 mg/kg). MPP+ enhanced striatal MAO (30%) activity at 6 h, and EGb761 prevented this effect. MAO-B activity in striatum was enhanced (70%) 6 h after MPP+ administration and was reduced to almost normal levels in EGb761 + MPP+ group compared to MPP+ group. Pretreatment with EGb761 partially prevented (32%) the striatal dopamine-depleting effect of MPP+ and prevented the reduction in striatal tyrosine hydroxylase activity (100%). Results suggest that EGb761 supplements may be effective in reducing MAO activity as well as enhancement in dopamine metabolism, thereby preventing MPP+-neurotoxicity.

1-Methyl-4-phenylpyridinium↗

[Gingko biloba extract EGb 761 and pentoxifylline in intermittent claudication. Secondary analysis of the clinical effectiveness].

Clinical trials on the efficacy of EGb 761 and pentoxifylline are summarized in the context of their methods and results and compared with each other. All placebo-controlled, randomized and double-blind studies with the major target objective of "pain-free walking distance" were selected. The pentoxifylline studies were adopted from a survey of the existing literature in the English language, which has been brought up to date via DIMDI research. The studies on both active substances are fraught with similar difficulties as to method, and are not different as regards their quality. The increase in walking distance is highly variable, especially in the pentoxifylline studies. On average through each and all of the studies on both preparations, an increase of 45% (EGb 761) or 57% (pentoxifylline) in relation to initial values is here found. No differences in the documentation of efficacy and the clinical efficacy were discovered between the two substances, both of which are registered as effective substances in the treatment of peripheral arterial occlusion (pAO) in accordance with the Federal German Drugs Law (Arzneimittelgesetz, AMG) of 1976.

Dose-Response Relationship, Drug↗

Anxiolytic activity of ginkgolic acid conjugates from Indian Ginkgo biloba.

Ginkgolic acid conjugates (GAC) (6-alkylsalicylates, namely n-tridecyl-, n-pentadecyl-, n-heptadecyl-, n-pentadecenyl- and n-heptadecenylsalicylates) isolated from the leaves of Indian Ginkgo biloba Linn., (IGb) were tested for their putative role in anxiety in rats. Elevated plus maze, open-field behaviour, novelty-induced feeding latency and social interaction were the rodent behavioural models used in this study. GAC (0.3 and 0.6 mg/kg, each, p.o.) on single acute administration, showed dose-related changes in the behaviour. GAC (0.6 mg/kg) and DZ augmented open arm entries, the open arm/closed arm entries ratio and increased time spent in the open arm on the elevated plus maze. In the open field, GAC (0.6 mg/kg) and DZ significantly increased ambulation and reduced the immobility time. EGb 761 showed a similar profile. GAC (0.6 mg/kg) and DZ significantly attenuated the increased latency to feed in novel environment. By contrast, EGb 761 and Ginkocer further augmented feeding latency. None of the drugs tested showed any significant effect in the social interaction test. GAC showed consistent and significant anxiolytic activity in all the variables investigated. By contrast, EGb 761 and Ginkocer, which are devoid of GAC, did not evoke significant activity. However, increased rearing and decreased immobility time only in open field behaviour shown by EGb 761 may be due to some antianxiety activity of a lesser degree. Our observations suggest that GAC may be the active constituents of Ginkgo biloba responsible for the anxiolytic activity.

Animals↗

[The correction of the increased blood viscosity syndrome in brain ischemia in rats with a combination of dikvertin and ascorbic acid].

In experiments in vitro on a model of the syndrome of increased blood viscosity dikvertin reduced blood viscosity, weakened aggregation of red cells and raised their property of becoming distorted. A mixture of dikvertin and ascorbic acid improved the hemorrheologic parameters better than do dikvertin and tanakan. On a model of chronic ischemia of the brain of rats attended with deterioration of blood rheologic parameters, it was demonstrated that a course of treatment with a dikvertin and ascorbic acid complex decreases the manifestations of the syndrome of increased blood viscosity.

Animals↗