title: GABA-A Receptor Modulation and Anticonvulsant, Anxiolytic, and Antidepressant Activities of Constituents from Artemisia indica Linn.
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.
authors.affiliation: Department of Pharmacy, University of Swabi, Khyber Pakhtunkhwa 23340, Pakistan.
authors.forename: Imran
authors.initials: I
authors.lastname: Khan
authors.affiliation: Department of Pharmacy, University of Malakand, Khyber Pakhtunkhwa 18800, Pakistan.
authors.forename: Nasiara
authors.initials: N
authors.lastname: Karim
authors.affiliation: Department of Pharmacy, University of Malakand, Khyber Pakhtunkhwa 18800, Pakistan.
authors.forename: Waqar
authors.initials: W
authors.lastname: Ahmad
authors.affiliation: Faculty of Science, Taibah University, Medina 30001, Saudi Arabia.
authors.forename: Abeer
authors.initials: A
authors.lastname: Abdelhalim
authors.affiliation: Faculty of Pharmacy, University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: Mary
authors.initials: M
authors.lastname: Chebib