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Concept: Ginkgo biloba

175

Numerous studies have looked at the potential benefits of various nootropic drugs such as Ginkgo biloba extract (EGb761®; Tanakan®) and piracetam (Nootropyl®) on age-related cognitive decline often leading to inconclusive results due to small sample sizes or insufficient follow-up duration. The present study assesses the association between intake of EGb761® and cognitive function of elderly adults over a 20-year period.

Concepts: Time, Sample size, Cognition, Ginkgo biloba, Association of Ideas, Ginkgo, Nootropic, Piracetam

174

Laboratory evidence suggests that certain specialty dietary supplements have antiinflammatory properties, though evidence in humans remains limited. Data on a nationally representative sample of 9,947 adults from the 1999-2004 cycles of the National Health and Nutrition Examination Survey were used to assess the associations between specialty supplement use and inflammation, as measured by serum high-sensitivity C-reactive protein (hs-CRP) concentration. Using survey-weighted multivariate linear regression, significant reductions in hs-CRP concentrations were associated with regular use of glucosamine (17%, 95% confidence interval (CI): 7, 26), chondroitin (22%, 95% CI: 8, 33), and fish oil (16%, 95% CI: 0.3, 29). No associations were observed between hs-CRP concentration and regular use of supplements containing methylsulfonylmethane, garlic, ginkgo biloba, saw palmetto, or pycnogenol. These results suggest that glucosamine and chondroitin supplements are associated with reduced inflammation in humans and provide further evidence to support an inverse association between use of fish oil supplements and inflammation. It is important to further investigate the potential antiinflammatory role of these supplements, as there is a need to identify safe and effective ways to reduce inflammation and the burden of inflammation-related diseases such as cancer and cardiovascular disease.

Concepts: Inflammation, Chondroitin sulfate, Nutrition, Cardiovascular disease, Anti-inflammatory, C-reactive protein, Ginkgo biloba, Ginkgo

35

Ginkgo biloba L. (Ginkgoaceae) is one of the most distinctive plants. It possesses a suite of fascinating characteristics including a large genome, outstanding resistance/tolerance to abiotic and biotic stresses, and dioecious reproduction, making it an ideal model species for biological studies. However, the lack of a high-quality genome sequence has been an impediment to our understanding of its biology and evolution.

Concepts: DNA, Gene, Biology, Organism, Life, Drosophila melanogaster, Ginkgo biloba, Ginkgo

27

Flavonols and terpene lactones are putatively responsible for the properties of Ginkgo biloba leaf extracts that relate to prevention and treatment of cardiovascular disease and cerebral insufficiency. Here, we characterized rat systemic and cerebral exposure to these ginkgo compounds after dosing, as well as the compounds' pharmacokinetics.

Concepts: Cardiovascular disease, Rat, Leaf, Ginkgo biloba, Ginkgo

23

Several drugs, including aminoglycosides and platinum-based chemotherapy agents, are well known for their ototoxic properties. However, FDA-approved drugs are not routinely tested for ototoxicity, so their potential to affect hearing often goes unrecognized. This issue is further compounded for natural products, where there is a lack of FDA oversight and the manufacturer is solely responsible for ensuring the safety of their products. Natural products such as herbal supplements are easily accessible and commonly used in the practice of traditional eastern and alternative medicine. Using the zebrafish lateral line, we screened a natural products library to identify potential ototoxins. We found that the flavonoids quercetin and kaempferol, both from the Gingko biloba plant, demonstrated significant ototoxicity, killing up to 30 % of lateral line hair cells. We then examined a third Ginkgo flavonoid, isorhamnetin, and found similar levels of ototoxicity. After flavonoid treatment, surviving hair cells demonstrated reduced uptake of the vital dye FM 1-43FX, suggesting that the health of the remaining hair cells was compromised. We then asked if these flavonoids enter hair cells through the mechanotransduction channel, which is the site of entry for many known ototoxins. High extracellular calcium or the quinoline derivative E6 berbamine significantly protected hair cells from flavonoid damage, implicating the transduction channel as a site of flavonoid uptake. Since known ototoxins activate cellular stress responses, we asked if reactive oxygen species were necessary for flavonoid ototoxicity. Co-treatment with the antioxidant D-methionine significantly protected hair cells from each flavonoid, suggesting that antioxidant therapy could prevent hair cell loss. How these products affect mammalian hair cells is still an open question and will be the target of future experiments. However, this research demonstrates the potential for ototoxic damage caused by unregulated herbal supplements and suggests that further supplement characterization is warranted.

Concepts: Antioxidant, Chemotherapy, Flavonoid, Cisplatin, Ginkgo biloba, Flavonols, Ginkgo, Living fossil

3

Molecular phylogenetic studies have not yet reached a consensus on the placement of Ginkgoales, which is represented by the only living species, Ginkgo biloba (common name: ginkgo). At least six discrepant placements of ginkgo have been proposed. This study aimed to use the chloroplast phylogenomic approach to examine possible factors that lead to such disagreeing placements. We found the sequence types used in the analyses as the most critical factor in the conflicting placements of ginkgo. In addition, the placement of ginkgo varied in the trees inferred from nucleotide sequences, which notably depended on breadth of taxon sampling, tree-building methods, codon positions, positions of Gnetopsida (common name: gnetophytes), and including or excluding gnetophytes in datasets. In contrast, the trees inferred from amino acid sequences congruently supported the monophyly of Cycadales (common name: cycads) and ginkgo, regardless of which factors were examined. Our site-stripping analysis further revealed that the high substitution saturation of nucleotide sequences mainly derived from the third codon positions and contributed to the variable placements of ginkgo. In summary, the possible misleading factors we surveyed did not affect results inferred from analyses of amino acid sequences. Congruent topologies in our amino acid trees give more confidence in supporting the ginkgo-cycad sister-group hypothesis.

Concepts: DNA, Gene, Amino acid, Plant, Phylogenetics, Ginkgo biloba, Ginkgo, Ginkgoaceae

2

In patients with mild cognitive impairment (MCI), gait instability, particularly in dual-task situations, has been associated with impaired executive function and an increased fall risk. Ginkgo biloba extract (GBE) could be an effective mean to improve gait stability.

Concepts: Ginkgo biloba, Ginkgo

2

It is difficult to determine if certain dietary supplements are safe for human consumption. Extracts of leaves of Ginkgo biloba trees are dietary supplements used for various purported therapeutic benefits. However, recent studies reported they increased risk of liver cancer in rodents. Therefore, this study assessed the association between ginkgo consumption and liver function using NHANES 2001-2012 data (N = 29,684). Since alcohol is known to adversely affect liver function, association of its consumption with liver function was also assessed. Alcohol and ginkgo extract intake of adult consumers and clinical markers of liver function (alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, lactate dehydrogenase, bilirubin) were examined. Moderate consumers of alcohol (0.80 ± 0.02 drinks/day) had higher levels of aspartate aminotransferase and gamma glutamyl transferase than non-consumers (P < 0.001). There was no difference (P > 0.01) in levels of markers of liver function in 616 ginkgo consumers (65.1 ± 4.4 mg/day intake) compared to non-consumers. While moderate alcohol consumption was associated with changes in markers of liver function, ginkgo intake as typically consumed by U.S. adults was not associated with these markers. Biomarkers measured by NHANES may be useful to examine potential adverse effects of dietary supplements for which insufficient human adverse event and toxicity data are available.

Concepts: Cirrhosis, Liver function tests, Aspartate transaminase, Alanine transaminase, Hepatology, Ginkgo biloba, Chemical pathology, Ginkgo

2

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.

Concepts: Auditory system, Hearing impairment, Tinnitus, Ginkgo biloba, Startle reaction, Gerbil, Meriones unguiculatus, Meriones

2

This is an update of a Cochrane review first published in The Cochrane Library in Issue 2, 2004 and previously updated in 2007 and 2009.Tinnitus can be described as the perception of sound in the absence of external acoustic stimulation. At present no specific therapy for tinnitus is acknowledged to be satisfactory in all patients. There are a number of reports in the literature suggesting that Ginkgo biloba may be effective in the management of tinnitus. However, there also appears to be a strong placebo effect in tinnitus management.

Concepts: Clinical trial, Evidence-based medicine, Cochrane Collaboration, Cochrane Library, MEDLINE, Ginkgo biloba, Ginkgo, Centre for Reviews and Dissemination