GABA-A Receptor Modulation and Anticonvulsant, Anxiolytic, and Antidepressant Activities of Constituents from Artemisia indica Linn.

Imran Khan,Waqar Ahmad,Abeer Abdelhalim,Nasiara Karim,Mary Chebib

doi:10.1155/2016/1215393

Abstract

Artemisia indica, also known as “Mugwort,” has been widely used in traditional medicines. However, few studies have investigated the effects of nonvolatile components of Artemisia indica on central nervous system's function. Fractionation of Artemisia indica led to the isolation of carnosol, ursolic acid, and oleanolic acid which were evaluated for their effects on GABA-A receptors in electrophysiological studies in Xenopus oocytes and were subsequently investigated in mouse models of acute toxicity, convulsions (pentylenetetrazole induced seizures), depression (tail suspension and forced swim tests), and anxiety (elevated plus maze and light/dark box paradigms). Carnosol, ursolic acid, and oleanolic acid were found to be positive modulators of α1β2γ2L GABA-A receptors and the modulation was antagonized by flumazenil. Carnosol, ursolic acid, and oleanolic acid were found to be devoid of any signs of acute toxicity (50–200 mg/kg) but elicited anticonvulsant, antidepressant, and anxiolytic activities. Thus carnosol, ursolic acid, and oleanolic acid demonstrated CNS activity in mouse models of anticonvulsant, antidepressant, and anxiolysis. The anxiolytic activity of all three compounds was ameliorated by flumazenil suggesting a mode of action via the benzodiazepine binding site of GABA-A receptors.

Highlights

Artemisia indica is known as “Mugwort” in the local community in South Asia and belongs to the family “Asteraceae.” The plant is perennial shrub with height of 2–8 meters tall, found in Northern area of Pakistan as well as in Asia and Europe at high altitude of cold temperate zone [1]
Ursolic acid, and oleanolic acid enhanced the response to 5 μM GABA at α1β2γ2L GABA-A receptors (Figure 2)
We studied the ability of neutralizing benzodiazepine antagonist flumazenil to block the potentiation of carnosol, ursolic

Summary

Introduction

Artemisia indica is known as “Mugwort” in the local community in South Asia and belongs to the family “Asteraceae.” The plant is perennial shrub with height of 2–8 meters tall, found in Northern area of Pakistan as well as in Asia and Europe at high altitude of cold temperate zone [1]. Artemisia species possesses antiplasmodial [2], antispasmodic and bronchodilator [3], antihypertensive [4], antiallergic [5], hepatoprotective [3], and antibacterial activities [6]. Various species of this plant have been reported to possess antihyperglycemic effects as well [1]. Several species of Artemisia have been reported to possess CNS activities. Artemisia absinthium has been shown to possess antidepressant activity in mouse models of tail suspension and forced swimming tests [7]. Artemisia dracunculus has been reported to possess central antinociceptive effect [8]

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