Shatavari and anxiety-like behaviours check study.
Garabadu D., Krishnamurthy S. 2014. Asparagus racemosus attenuates anxiety-like behaviour in experimental animal models. Cel Mol Neurobiol 34:511-521.
From its traditional use in Ayurvedic medicine as a rasayana drug, Asparagus racemosus (AR) (shatavari) is now used worldwide as a medicinal plant, with reported pharmacological activities including adaptogenic, anti-stress, gastroduodenal ulcer protective, anticancer, immunomodulatory and diabetic-induced anti nephropathic effects. Saponins are thought to be the major active constituents of shatavari, with methanolic extract of AR (MAR) being shown to possess the highest amount of saponins. In previous studies, standardised MAR has demonstrated anti-depressant, nootropic and anti-amnesic effects as well as modulating stress-related pathways including the hypothalamus-pituitary-adrenal (HPA)-axis and brain monoaminergic systems. Within these studies, however, the anxiolytic activity of MAR in animals has not been reported.
Anxiety disorders include different forms of abnormal and pathological fear, which may be associated with other mental disorders. Dysregulation of neurotransmitter systems including the serotonergic, noradrenergic, and GABAergic systems, are implicated in the pathogenesis of anxiety disorders and may be a potential target for anxiolytic treatment. The current study was designed to explore the anxiolytic activity of standardised MAR compared to diazepam (DZ) in male adult rats, as well as establish the minimum effective dose for the GABAergic-mediated response of MAR and assess the sedative effective of MAR.
A set of three experiments formed the study. In the first, 24 male rats were equally divided into five groups: Control, DZ-1.0, MAR-50, MAR-100 and MAR-200. The control group received the vehicle only and the DZ-1.0 received diazepam 1.0mg/kg orally. The MAR groups received 50, 100 and 200mg/kg per oral respectively of a standardised methanolic extract of root of AR with total saponin content at 62.2%. All groups received treatment for seven consecutive days with behavioural performances observed and quantified. After being sacrificed, the amygdala tissue was collected through micro-dissection for analysis. Both MAR100 and MAR-200 demonstrated anxiolytic effects comparable to the DZ-1.0 group in the tested behavioural performances. MAR (100 and 200 mg/kg) enhanced the level of amygdalar serotonin and norepinephrine and also increased the expression of 5-HT2A receptors in the amygdala. No statistically significant differences in behaviours were observed in the MAR-50 group compared to the control group.
The second experiment was to elicit the GABAmediated mechanism with the minimum effective anxiolytic dose of MAR. Five groups of five rats: vehicle only (control group), 1.0mg/kg of diazepam (two groups) or 100mg/kg of MAR (two groups) for seven days. On the seventh day, 10.0mg/kg flumazenil was administered to one of the MAR and one of the DZ groups 30 minutes before the oral administration of the studied drugs, with behaviour performances monitored and analysed. Flumazenil, a GABAA antagonist, was found to attenuate the anxiolytic effect of MAR (100mg/kg) and DZ (1.0mg/kg) in all tested environments, indicating a GABAA mediated mechanism of MAR.
In the third experiment, the sedative effect of the minimum anxiolytic dose of MAR was investigated. Fifteen male rats were divided into three groups to receive control, DZ 6.0mg/kg (the sedative dose of DZ) and MAR (100mg/kg) for seven days with behavioural performances observed and quantified. Whilst the DZ group demonstrated a sedative-like effect compared to the control rats, the MAR group did not display any sedative-like effect. Hence in this experiment, MAR demonstrated an anxiolytic effect without any sedative effects.
This study is the first to report the GABA-mediated anxiolytic effect of MAR. Additionally, the authors proposed that, based on the findings, methanolic extract of Asparagus racemosus probably attenuates anxiety behaviour through modulation of the amygdalar serotonergic and norepinephrinergic systems. With no additional effects seen at the higher dose, the authors propose that 100mg/kg MAR to be the optimal dose for anxiolytic effect. The study demonstrates in a good quality, well-designed trial, a novel mechanism of action of Asparagus racemosus and in vivo efficacy comparable to diazepam. Further studies in humans to confirm efficacy and safety should be the focus of future research.
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|Publication:||Australian Journal of Herbal Medicine|
|Date:||Mar 1, 2015|
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