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Ginkgo biloba special extract EGb 761 in generalized anxiety disorder and adjustment disorder with anxious mood: a randomized, double-blind, placebo-controlled trial.
Ginkgo biloba special extract EGb 761, an anti-dementia drug, enhances cognitive functioning and stabilizes mood in cognitively impaired elderly subjects. Moreover, EGb 761 had been found to alleviate symptoms of anxiety in people with mental decline, therefore it was now tested for clinical efficacy in younger patients suffering from anxiety. One hundred and seven patients with generalized anxiety disorder (GAD, n=82) or adjustment disorder with anxious mood (ADWAM, n=25) according to the diagnostic and statistical manual of mental disorders, third edition - revised (DSM-III-R) were randomized to daily doses of 480 mg EGb 761, 240 mg EGb 761 or placebo for 4 weeks. Intention-to-treat (ITT) analyses were performed on the primary outcome measure, the Hamilton rating scale for anxiety (HAMA), and the secondary variables, the clinical global impression of change (CGI-C), the Erlangen anxiety tension and aggression scale (EAAS), the list of complaints (B-L'), and the patient's global rating of change. The HAMA total scores decreased by -14.3 (+/-8.1), -12.1 (+/-9.0) and -7.8 (+/-9.2) in the high-dose EGb 761, the low-dose EGb 761 and the placebo group, respectively. Changes were significantly different from placebo for both treatment groups with p=0.0003 (high-dose group) and p=0.01 (low-dose). Regression analyses revealed a dose-response trend (p=0.003). EGb 761 was significantly superior to placebo on all secondary outcome measures. It was safe and well tolerated and may thus be of particular value in elderly patients with anxiety related to cognitive decline.
Ginkgo biloba special extract EGb 761, an anti-dementia drug, enhances cognitive functioning and stabilizes mood in cognitively impaired elderly subjects. Moreover, EGb 761 had been found to alleviate symptoms of anxiety in people with mental decline, therefore it was now tested for clinical efficacy in younger patients suffering from anxiety. One hundred and seven patients with generalized anxiety disorder (GAD, n=82) or adjustment disorder with anxious mood (ADWAM, n=25) according to the diagnostic and statistical manual of mental disorders, third edition - revised (DSM-III-R) were randomized to daily doses of 480 mg EGb 761, 240 mg EGb 761 or placebo for 4 weeks. Intention-to-treat (ITT) analyses were performed on the primary outcome measure, the Hamilton rating scale for anxiety (HAMA), and the secondary variables, the clinical global impression of change (CGI-C), the Erlangen anxiety tension and aggression scale (EAAS), the list of complaints (B-L'), and the patient's global rating of change. The HAMA total scores decreased by -14.3 (+/-8.1), -12.1 (+/-9.0) and -7.8 (+/-9.2) in the high-dose EGb 761, the low-dose EGb 761 and the placebo group, respectively. Changes were significantly different from placebo for both treatment groups with p=0.0003 (high-dose group) and p=0.01 (low-dose). Regression analyses revealed a dose-response trend (p=0.003). EGb 761 was significantly superior to placebo on all secondary outcome measures. It was safe and well tolerated and may thus be of particular value in elderly patients with anxiety related to cognitive decline.
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The discriminative stimulus properties of EGb 761, an extract of Ginkgo biloba.
Stimulus control was established in a group of nine rats using a dose of EGb 761 of 10 mg/kg, administered i.p., 15 min before training. A two-lever operant task using a fixed-ratio 10 schedule of sweetened milk reinforcement was used. Based upon a criterion for the presence of stimulus control of five consecutive sessions during which 83% or more of all responses were on the appropriate lever, a mean of 24 sessions was required to reach criterion performance. Subsequently, it was observed that EGb 761-induced stimulus control is significantly antagonized by the selective 5-HT1A antagonist WAY-100635, but is unaffected by the 5-HT2 antagonist pirenperone. Furthermore, EGb 761 generalized to the selective 5-HT1A agonist, 8-hydroxy-dipropylaminotetralin [8-OH-DPAT], and this generalization was blocked by WAY-100635. The present results indicate that EGb 761 is able to induce stimulus control when administered via the intraperitoneal route, and that its stimulus effects are mediated in part by activity at the 5-HT1A receptor.
Stimulus control was established in a group of nine rats using a dose of EGb 761 of 10 mg/kg, administered i.p., 15 min before training. A two-lever operant task using a fixed-ratio 10 schedule of sweetened milk reinforcement was used. Based upon a criterion for the presence of stimulus control of five consecutive sessions during which 83% or more of all responses were on the appropriate lever, a mean of 24 sessions was required to reach criterion performance. Subsequently, it was observed that EGb 761-induced stimulus control is significantly antagonized by the selective 5-HT1A antagonist WAY-100635, but is unaffected by the 5-HT2 antagonist pirenperone. Furthermore, EGb 761 generalized to the selective 5-HT1A agonist, 8-hydroxy-dipropylaminotetralin [8-OH-DPAT], and this generalization was blocked by WAY-100635. The present results indicate that EGb 761 is able to induce stimulus control when administered via the intraperitoneal route, and that its stimulus effects are mediated in part by activity at the 5-HT1A receptor.
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Anxiolytic activity of ginkgolic acid conjugates from Indian Ginkgo biloba.
Satyan KS, Jaiswal AK, Ghosal S, Bhattacharya SK.
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.
Satyan KS, Jaiswal AK, Ghosal S, Bhattacharya SK.
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.
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Decreased cerebral 5-HT1A receptors during ageing: reversal by Ginkgo biloba extract (EGb 761).
Huguet F, Drieu K, Piriou A.
Investigation of [3H]8-hydroxy-2(di-n-propylamino)tetralin binding to 5-HT1A receptors in cerebral cortex membranes of Wistar rats showed that the maximal number of binding sites (Bmax) was reduced significantly (22%) in aged (24-month-old) as compared with young (4-month-old) animals. Chronic treatment with Ginkgo biloba extract did not alter binding in young rats but increased binding density significantly (33%) in aged rats. These results confirm previously described age-related 5-hydroxytryptaminergic alterations. Together with data in the literature, they also suggest a restorative effect in aged rats, associated with decreased receptor density resulting from the protective action of Ginkgo biloba extract treatment on neuronal membrane.
Huguet F, Drieu K, Piriou A.
Investigation of [3H]8-hydroxy-2(di-n-propylamino)tetralin binding to 5-HT1A receptors in cerebral cortex membranes of Wistar rats showed that the maximal number of binding sites (Bmax) was reduced significantly (22%) in aged (24-month-old) as compared with young (4-month-old) animals. Chronic treatment with Ginkgo biloba extract did not alter binding in young rats but increased binding density significantly (33%) in aged rats. These results confirm previously described age-related 5-hydroxytryptaminergic alterations. Together with data in the literature, they also suggest a restorative effect in aged rats, associated with decreased receptor density resulting from the protective action of Ginkgo biloba extract treatment on neuronal membrane.
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Extract of Ginkgo biloba EGb 761 facilitates fear conditioning measured by fear-potentiated startle.
Yang YL, Su YW, Ng MC, Chang CL, Lu KT.
Extract of Ginkgo biloba EGb 761 has been used in the treatment of various common geriatric complaints including vertigo, short-term memory loss, hearing loss, lack of attention, vigilance and cerebral vascular disorder. Recent results suggest that it can serve as a cognitive enhancer and anti-stress buffer. It raises a possibility that EGb 761 may be involved in the fear conditioning. In this study, we used fear-potentiated startle (FPS) to evaluate the possible effects of EGb 761 on the acquisition stage of fear conditioning. Our results showed that administration of EGb 761 30 min prior to the conditioning facilitated acquisition of conditioned fear in a dose dependent manner. No significant differences had been observed in either basal startle response or shock activity. These results indicated that the facilitation effect of EGb 761 was not the result of impaired basal startle response or enhanced pain perception. Subsequent control experiment results indicated that the facilitation effect of EGb 761 on the acquisition was not due to anxiogenic effect or non-specific effect. Our data present the first evidence that EGb 761 can enhance fear memory formation rather than serve as an anti-stress buffer.
Yang YL, Su YW, Ng MC, Chang CL, Lu KT.
Extract of Ginkgo biloba EGb 761 has been used in the treatment of various common geriatric complaints including vertigo, short-term memory loss, hearing loss, lack of attention, vigilance and cerebral vascular disorder. Recent results suggest that it can serve as a cognitive enhancer and anti-stress buffer. It raises a possibility that EGb 761 may be involved in the fear conditioning. In this study, we used fear-potentiated startle (FPS) to evaluate the possible effects of EGb 761 on the acquisition stage of fear conditioning. Our results showed that administration of EGb 761 30 min prior to the conditioning facilitated acquisition of conditioned fear in a dose dependent manner. No significant differences had been observed in either basal startle response or shock activity. These results indicated that the facilitation effect of EGb 761 was not the result of impaired basal startle response or enhanced pain perception. Subsequent control experiment results indicated that the facilitation effect of EGb 761 on the acquisition was not due to anxiogenic effect or non-specific effect. Our data present the first evidence that EGb 761 can enhance fear memory formation rather than serve as an anti-stress buffer.