Direct evidence for GABAergic activity of Withania somnifera on mammalian ionotropic GABAA and GABAρ receptors.

ETHNOPHARMACOLOGICAL RELEVANCE: Withania somnifera (WS) has been traditionally used in Ayurvedic medicine as a remedy for debility, stress, nervous exhaustion, insomnia, loss of memory, and to enhance cognitive function. This study provides an empirical evidence to support the traditional use of WS to aid in mental process engaging GABAergic signaling. AIM OF THE STUDY: We evaluated the effect of aqueous WS root extract (aqWS), and its two main components, withaferin A and withanolide A, on the main inhibitory receptors in the central nervous system: ionotropic GABAA receptors. MATERIALS AND METHODS: The pharmacological activity of aqWS, withaferin A and withanolide A, was tested on native rat brain GABAA channels microtransplanted into Xenopus oocytes and GABAρ1 receptors heterologously expressed in oocytes. The GABAergic activity of aqWS compounds was evaluated by the two-electrode voltage-clamp method and the fingerprint of the extract was done by LC-MS. RESULTS: Concentration-dependent inward ion currents were elicited by aqWS in microtransplanted oocytes with an EC50 equivalent to 4.7 mg/mL and a Hill coefficient (nH) of 1.6. The GABAA receptor antagonist bicuculline blocked these currents. Our results show that aqWS activated inotropic GABAA channels but with lower efficacy compared to the endogenous agonist GABA. We also demonstrate for first time that aqWS is a potent agonist of GABAρ1 receptors. GABAρ1 receptors were 27 fold more sensitive to aqWS than GABAA receptors. Furthermore, aqWS activated GABAρ1 receptors eliciting maximum currents that were no significantly different to those produced by GABA (paired t-test; p=0.533). The differential activity on GABAA and GABA ρ1 receptors and the reported lack of significant GABA presence in WS root extract indicates that the GABAergic activity of aqWS is not mediated by GABA. WS main active components, witaferin A and withanolide A, were tested to determine if they were responsible for the activation of the GABA receptors. Neither compound activated GABAA nor GABAρ1 receptors, suggesting that other constituent/s in WS are responsible for GABAA receptor mediated responses. CONCLUSIONS: Our results provide evidence indicating that key constituents in WS may have an important role in the development of pharmacological treatments for neurological disorders associated with GABAergic signaling dysfunction such as general anxiety disorders, sleep disturbances, muscle spasms, and seizures. In addition, the differential activation of GABA receptor subtypes elucidates a potential mechanism by which WS accomplishes its reported adaptogenic properties.

Structure and diversity of phyllostomid bat assemblages on riparian corridors in a human-dominated tropical landscape.

Tropical forests around the world have been lost, mainly because of agricultural activities. Linear elements like riparian vegetation in fragmented tropical landscapes help maintain the native flora and fauna. Information about the role of riparian corridors as a reservoir of bat species, however, is scanty. We assessed the value of riparian corridors on the conservation of phyllostomid bat assemblage in an agricultural landscape of southern Mexico. For 2 years (2011-2013), mist-netting at ground level was carried out twice during the dry season (December to May) and twice during the wet season (June to November) in different habitats: (1) riparian corridors in mature forest, (2) riparian corridors in pasture, (3) continuous forest away from riparian vegetation, and (4) open pastures. Each habitat was replicated three times. To determine the influence of vegetation structure on bat assemblages, all trees (≥10 cm dbh) were sampled in all habitats. Overall, 1752 individuals belonging to 28 species of Phyllostomidae were captured with Sternodermatinae being the most rich and abundant subfamily. Riparian corridors in mature forest and pastures had the greatest species richness and shared 65% of all species. Open pastures had the lowest richness and abundance of bats with no Phyllostominae species recorded. Six of the 18 species recorded could be considered as habitat indicators. There was a positive relationship between bat species composition and tree basal area. Our findings suggest that contrary to our expectations, bats with generalist habits and naturally abundant could be useful detector taxa of habitat modification, rather than bats strongly associated with undisturbed forest. Also in human-dominated landscapes, the maintenance of habitat elements such as large trees in riparian corridors can serve as reservoirs for bat species, especially for those that are strongly associated with undisturbed forest.