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The extract of Ginkgo biloba EGb 761 reactivates a juvenile profile in the skeletal muscle of sarcopenic rats by transcriptional reprogramming.

ABSTRACT: Sarcopenia is a major public health problem in industrialized nations, placing an increasing burden on public healthcare systems because the loss of skeletal muscle mass and strength that characterizes this affection increases the dependence and the risk of injury caused by sudden falls in elderly people. Albeit exercise and caloric restriction improve sarcopenia-associated decline of the muscular performances, a more suitable and focused pharmacological treatment is still lacking.In order to evaluate such a possible treatment, we investigated the effects of EGb 761, a Ginkgo biloba extract used in chronic age-dependent neurological disorders, on the function of the soleus muscle in aged rats. EGb 761 induced a gain in muscular mass that was associated with an improvement of the muscular performances as assessed by biochemical and electrophysiological tests. DNA microarray analysis shows that these modifications are accompanied by the transcriptional reprogramming of genes related to myogenesis through the TGFbeta signaling pathway and to energy production via fatty acids and glucose oxidation. EGb 761 restored a more juvenile gene expression pattern by regenerating the aged muscle and reversing the age-related metabolic shift from lipids to glucose utilization.Thus, EGb 761 may represent a novel treatment for sarcopenia both more manageable and less cumbersome than exercise and caloric restriction.

SUBMITTER: Bidon C

PROVIDER: S-EPMC2778626 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

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The extract of Ginkgo biloba EGb 761 reactivates a juvenile profile in the skeletal muscle of sarcopenic rats by transcriptional reprogramming.

Bidon Caroline C Lachuer Joël J Molgó Jordi J Wierinckx Anne A de la Porte Sabine S Pignol Bernadette B Christen Yves Y Meloni Rolando R Koenig Herbert H Biguet Nicole Faucon NF Mallet Jacques J

PloS one 20091124 11

<h4>Background</h4>Sarcopenia is a major public health problem in industrialized nations, placing an increasing burden on public healthcare systems because the loss of skeletal muscle mass and strength that characterizes this affection increases the dependence and the risk of injury caused by sudden falls in elderly people. Albeit exercise and caloric restriction improve sarcopenia-associated decline of the muscular performances, a more suitable and focused pharmacological treatment is still lac ...[more]

PMID: 19956636

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Project description:Unilateral inner ear damage is followed by behavioral recovery due to central vestibular compensation. The dose-dependent therapeutic effect of Ginkgo biloba extract EGb 761 on vestibular compensation was investigated by behavioral testing and serial cerebral [18F]-Fluoro-desoxyglucose ([18F]-FDG)-μPET in a rat model of unilateral labyrinthectomy (UL). Five groups of 8 animals each were treated with EGb 761-supplemented food at doses of 75, 37.5 or 18.75 mg/kg body weight 6 weeks prior and 15 days post UL (groups A,B,C), control food prior and EGb 761-supplemented food (75 mg/kg) for 15 days post UL (group D), or control food throughout (group E). Plasma levels of EGb 761 components bilobalide, ginkgolide A and B were analyzed prior and 15 days post UL. Behavioral testing included clinical scoring of nystagmus, postural asymmetry, head roll tilt, body rotation during sensory perturbation and instrumental registration of mobility in an open field before and 1, 2, 3, 5, 7, 15 days after UL. Whole-brain [18F]-FDG-μPET was recorded before and 1, 3, 7, 15 days after UL. The EGb 761 group A (75 mg/kg prior/post UL) showed a significant reduction of nystagmus scores (day 3 post UL), of postural asymmetry (1, 3, 7 days post UL), and an increased mobility in the open field (day 7 post UL) as compared to controls (group E). Application of EGb 761 at doses of 37.5 and 18.75 mg/kg prior/post UL (groups B,C) resulted in faster recovery of postural asymmetry, but did not influence mobility relative to controls. Locomotor velocity increased with higher plasma levels of ginkgolide A and B. [18F]-FDG-μPET revealed a significant decrease of the regional cerebral glucose metabolism (rCGM) in the vestibular nuclei and cerebellum and an increase in the hippocampal formation with higher plasma levels of ginkgolides and bilobalide 1 and 3 days post UL. Decrease of rCGM in the vestibular nucleus area and increase in the hippocampal formation with higher plasma levels persisted until day 15 post UL. In conclusion, Ginkgo biloba extract EGb 761 improves vestibulo-ocular motor, vestibulo-spinal compensation, and mobility after UL. This rat study supports the translational approach to investigate EGb 761 at higher dosages for acceleration of vestibular compensation in acute vestibular loss.

Project description:Noise induced hearing loss (NIHL) is a common disease in modern societies and may lead to maladaptations within the auditory system that finally result in subjective tinnitus. Available therapies may only alleviate the symptoms rather than restore normal hearing. In a previous study we demonstrated that the prophylactic application of Ginkgo biloba extract EGb 761® significantly reduces NIHL and tinnitus development in our Mongolian gerbil (Meriones unguiculatus) animal model. Here, we tested whether the application of EGb 761® has beneficial effects after the formation of permanent NIHL and tinnitus. To this end we monitored the therapeutic effects of EGb 761® on noise trauma-induced changes in signal processing within the auditory system of our animal model by behavioral (acoustic startle response, ASR) and electrophysiological approaches (auditory brainstem responses, ABR). We found that-in contrast to vehicle-three weeks of daily oral EGb 761® treatment (100 mg/kg body weight) led to a restoration of hearing thresholds back to pre-trauma conditions. In addition, all 9 animals that displayed behavioral signs of subjective tinnitus showed improvement, with 7 of them showing complete relief of tinnitus symptoms during the time of EGb 761® treatment. After discontinuation of EGb 761® treatment, tinnitus related behavior reappeared in all but one of these animals while auditory thresholds remained restored. A detailed analysis of ABR waves revealed that EGb 761® treatment did not simply change auditory processing back to pre-trauma conditions, but led to subtle changes of ABR wave amplitude and latency at different levels of the auditory pathway, with an overall increase of response to low stimulus intensities and a decrease at high intensities. The functional relevance of these changes may be the observed improvement of hearing thresholds while at the same time suppression of responses to high stimulus intensities may point to a global inhibitory mechanism that counteracts tinnitus.

Project description:Background: Patients who experienced an ischemic stroke are at risk for cognitive impairment. Quantified Ginkgo biloba extract EGb 761® has been used to treat cognitive dysfunction, functional impairment and neuropsychiatric symptoms in mild cognitive impairment and dementia. Objectives: To assess the cognitive-related effects of EGb 761® treatment in patients after acute ischemic stroke, as well as the feasibility of patient selection and outcome measures. Methods: We conducted a randomized, multicentric, open-label trial at 7 centers in China. Patients scoring 20 or lower on the National Institutes of Health Stroke Scale were enrolled between 7 and 14 days after stroke onset and randomly assigned to receive 240 mg per day of EGb 761® or no additional therapy for 24 weeks in a 1:1 ratio. Both groups received standard treatments for the prevention of recurrent stroke during the trial. General cognitive function and a battery of cognitive tests for sub-domains were evaluated at 24 weeks. All patients were monitored for adverse events. Results: 201 patients ≥50 years old were included, with 100 assigned to the EGb 761® group and 101 to the reference group. The mean change from baseline on the global cognitive function as assessed by the Montreal Cognitive Assessment score was 2.92 in the EGb 761® group and 1.33 in the reference group (between-group difference: 1.59 points; 95% confidence interval [CI], 0.51 to 2.67; p < 0.005). For cognitive domains, EGb 761® showed greater effects on the Hopkins Verbal Learning Test Total Recall (EGb 761® change 1.40 vs. reference -0.49) and Form 1 of the Shape Trail Test (EGb 761® change -38.2 vs. reference -15.6). Potentially EGb 761®-related adverse events occurred in no more than 3% of patients. Conclusion: Over the 24-week period, EGb 761® treatment improved overall cognitive performance among patients with mild to moderate ischemic stroke. Our findings provide valuable recommendations for the design of future trials, including the criteria for patient selection. Clinical Trial Registration: www.isrctn.com, identifier ISRCTN11815543.

Dataset Information

The extract of Ginkgo biloba EGb 761 reactivates a juvenile profile in the skeletal muscle of sarcopenic rats by transcriptional reprogramming.

Publications

The extract of Ginkgo biloba EGb 761 reactivates a juvenile profile in the skeletal muscle of sarcopenic rats by transcriptional reprogramming.

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