Abstract
Withaferin-A dose-dependently (10 tob40 mg/kg) displayed anxiolytic activity, as measured by an increase in open arm exploration time in the elevated plus-maze (EPM), following intraperitoneal (i.p.) administration in rats. Acute administration of withaferin-A at 40.0 mg/kg significantly (P<0.05) increased open arm exploration time by 176% as compared to vehicle control, which is similar to the benzodiazepine diazepam at 1.0 and 3.0 mg/kg (191 and 200%, respectively). However, 24 h following sub chronic 5-day administration of diazepam twice daily (bid) at 3.0 mg/kg, diazepam was devoid of anxiolytic activity at 1.0 mg/kg, as measured by no difference in open arm exploration time when compared with vehicle control, while the 3.0 mg/kg dose still produced a significant (P<0.05) 175% increase in open arm exploration time. In contrast, following sub chronic administration of withaferin-A (40.0 mg/kg), a significant (P<0.01) enhancement in open arm exploration time was observed at 40.0 mg/kg (665% as compared to control). Therefore, withaferin-A resulted in anxiolysis which is similar to diazepam following acute administration in the EPM. However, following sub chronic administration unlike diazepam which showed an attenuation of anxiolytic activity, withaferin-A displayed enhanced anxiolytic efficacy and was devoid of tolerance. Key words: Withaferin-A, anxiety, benzodiazepines, nitric oxide, elevated plus-maze.
Highlights
Withania somnifera Dunal (WS), known as Ashwagandha or Indian ginseng has been commonly used in Indian traditional medicines for over 3,000 years
Acute administration of withaferin-A at 40 mg/kg produced significant (P
Withaferin-A showed enhanced anxiolytic efficacy following sub chronic administration when compared to its effects following acute administration
Summary
Withania somnifera Dunal (WS), known as Ashwagandha or Indian ginseng has been commonly used in Indian traditional medicines for over 3,000 years. WS has been categorized as Rasayana in Ayurveda, which is known to augment defense against diseases, arrest aging, revitalize the body in debilitated condition, increase the capability of the individual to resist adverse environmental. It has been used to treat stress, insomnia, arthritis and age related disorders including neurodegeneration (Gupta et al, 2003; Mishra et al, 2000). The biologically active constituents in WS are alkaloids (ashwagandhin, cuscohygrine, anahygrine, topine, etc.), steroidal compounds including ergostane type teroidallactones, withaferin-A, withanolides A–Y, with asomniferin A, withasomnidienone, withasomnierose A–C, withanone, etc. Other constituents include saponins containing an additional acyl group (sitoindoside VII and VIII), and withanolides with a glucose at carbon 27 (sitoindoside IX and X) (Elsakka et al, 1990; Ganzera et al, 2003).
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