Planta Med 2015; 81 - PW_122
DOI: 10.1055/s-0035-1565746

Withanolides and alkaloids from Withania somnifera roots with binding affinity to opioid, cannabinoids and GABAergic receptors

VP Sonar 1, F Cottiglia 1, S Ruiu 2, A Orrù 2, N Anzani 1, C Floris 3
  • 1Department of Life and Environmental Sciences, Drug Sciences Section, University of Cagliari, via Ospedale 72, Cagliari 09124, Cagliari, Italy
  • 2CNR- Institute of Translational Pharmacology, U.O.S. of Cagliari, Science and Technology Park of Sardinia Polaris., Pula, Italy
  • 3Department of Scienze Chimiche e Geologiche, University of Cagliari, Cittadella Universitaria di Monserrato, Monserrato 09042, Monserrato, Italy

Withania somnifera Dunal (Solanaceae) is a plant commonly used in Ayurvedic medicine to treat several diseases [1]. Interestingly, Kulkarni and Ninan [2] demonstrated that, in mice chronically treated with morphine, a methanol extract of W. somnifera roots prevented the development of tolerance to the antinociceptive effect of morphine. These studies suggested a possible anti-nociceptive effect of W. somnifera. Using behavioral approaches we demonstrated for the first time the ability of a W. somnifera methanol extract (WSE) pre-treatment to prolong analgesia and to prevent the development of rebound hyperalgesia in mice treated with morphine [3]. Consequently, we examined the affinity of WSE and a soluble ethyl acetate fraction obtained from WSE towards opioid, cannabinoid, GABAergic and glutamatergic receptors using radioligand receptor binding assays. WSE exhibited the highest affinity for the GABAA receptors (Kì= 13 µg/mL) while the ethyl acetate fraction showed good binding affinity for the opioid and cannabinoid receptors (Kì= 12 – 44 µg/mL). From the active extracts four withanolides (withanolide A, withanone, 12-deoxywithastramonolide and withaferin A), four alkaloids (anaferine, (+)-sedridine, tropine, choline) along ferulic acid methyl ester have been isolated. Some compounds exhibited moderate binding affinity (Kì= 15 – 40 µM) for opioid and cannabinoids receptors.

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