ASHWAGHANDHA (WITHANIA SOMNIFERA):

Environmental Health Perspectives * Volume 107, Number 10, October 1999

Ancient-Modern Concordance in Ayurvedic Plants: Some Examples

Sukh Dev

Source
University of Delhi, B.R.A. Centre for Biomedical Research, Delhi, India

Extract from Full Text
Ashwagandha (root) is another important anti-aging plant. We have investigated this plant in some detail because its extract showed high affinity for both GABAA and GABAB receptors. Receptor-binding assay-guided fractionation of the crude methanol extract resulted in a butanol fraction with retention of GABAB receptor activity [concentration that inhibits 50% (IC50) – 47 pg/mL] and an aqueous fraction that retained both GABAA (IC50 – 0.37 pg/mL) and GABAB (IC50 – 15.8 pg/mL) affinities.

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Phytother Res. 2010 Aug;24(8):1147-50.

The methanolic extract of Withania somnifera ACTS on GABAA receptors in gonadotropin releasing hormone (GnRH) neurons in mice.

Bhattarai JP, Ah Park S, Han SK.

Source
Department of Oral Physiology and BK21 program, School of Dentistry and Institute of Oral Bioscience, Chonbuk National University, Jeonju, 561-756, Republic of Korea.

Abstract
The effect of the methanol extract of Withania somnifera (mWS) on the gonadotropin releasing hormone (GnRH) neuron was examined in juvenile mice using the whole cell patch clamp technique. GnRH neurons are the fundamental regulators of the pulsatile release of GnRH needed for puberty and fertility. GnRH neurons were depolarized by bath application of the mWS (400 ng/microl) under the condition of a high Cl(-) pipette solution in current clamp mode. In voltage clamp mode, mWS induced reproducible inward currents (31.7 +/- 5.51 pA, n = 14). The mWS-induced inward currents persisted in the presence of tetrodotoxin (TTX, 0.5 microM), but were suppressed by bicuculline methiodide (BMI, 20 microM), a GABA(A) receptor antagonist. These results show that mWS affects the neuronal activities by mediating the GABA(A) receptor, which suggests that WS contains an ingredient with possible GABAmimetic activity.

PMID: 20044800

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Indian J Exp Biol. 2008 Jun;46(6):465-9.

Effect of Withania somnifera Dunal root extract against pentylenetetrazol seizure threshold in mice: possible involvement of GABAergic system.

Kulkarni SK, Akula KK, Dhir A.

Source
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160 014, India. [email protected]

Abstract
Withania somnifera (ashwagandha) is a widely used herb in the Ayurvedic system of medicine. The objective of the present study was to elucidate the effect of W. somnifera root extract (Ws) alone or in combination with exogenous gamma-amino butyric acid (GABA), a GABA receptor agonist or with diazepam, a GABA receptor modulator against pentylenetetrazol (PTZ, iv) seizure threshold in mice. Minimal dose of PTZ (iv, mg/kg) needed to induce different phases (myoclonic jerks, generalized clonus and tonic extension) of convulsions were recorded as an index of seizure threshold. Ws (100 or 200 mg/kg, po) increased the PTZ seizure threshold for the onset of tonic extension phase whereas a lower dose (50 mg/kg, po) did not show any effect on the seizure threshold. Co-administration of a sub-effective dose of Ws (50 mg/kg, po) with a sub-protective dose of either GABA (25 mg/kg, ip) or diazepam (0.5 mg/kg, ip) increased the seizure threshold. The results suggested that the anticonvulsant effect of W. somnifera against PTZ seizure threshold paradigm involved the GABAAergic modulation.

PMID: 18697606

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Indian J Med Res. 1991 Aug;94:312-5.

Pharmacological effects of Withania somnifera root extract on GABAA receptor complex.

Mehta AK, Binkley P, Gandhi SS, Ticku MK

Source
Department of Pharmacology, University of Texas Health Science Center.

Abstract
A methanolic extract of W. somnifera root inhibited the specific binding of [3H]GABA and [35S]TBPS, and enhanced the binding of [3H]flunitrazepam to their putative receptor sites. The extract (5 micrograms) inhibited [3H]GABA binding by 20 +/- 6 per cent whereas a concentration of 1 mg of the extract produced 100 per cent inhibition. The extract (5-100 micrograms) produced 20 +/- 4 to 91 +/- 16 per cent enhancement of [3H]flunitrazepam binding. In functional studies using 36Cl-influx assay in mammalian spinal cord neurons, W. somnifera root extract increased 36Cl-influx in the absence of GABA. This effect on 36Cl-influx was blocked by bicuculline and picrotoxin; and enhanced by diazepam. These results suggest that the W. somnifera extract contains an ingredient which has a GABA-mimetic activity.

PMID: 1660034