Role of NO/cGMP/kATP pathway on diosgenin induced antinociceptive activity by formalin and hotplate induced model in rats

Abstract

Diosgenin is a natural steroid sourced from plants and exhibits good analgesic and anti-inflammatory activity. However, mechanism of action associated with the analgesic activity of diosgenin is not yet delineated. Hence, in the present study, we explored the mechanism of analgesic activity of diosgenin on the nitric oxide/cyclic guanosine monophosphate/adenosine monophosphate sensitive potassium channels (NO/cGMP/kATP). The role of (NO/cGMP/kATP) in the Wistar rat was studied using formalin-induced models and hot plate models with various antagonists, such as N-nitro-L-arginine methyl ester hydrochloride (L NAME), glibenclamide, 1H-(1,2,4) oxadiazole (4,3-A) quinoxaline-1-one (ODQ) and 7-nitroindazole. Two doses of diosgenin were used in the study (25 and 50 mg/kg). Diosgenin reached its maximal effect (P ˂0.001) at (50 mg/kg po) in formalin as well as a hot plate induced nociception. This study has demonstrated that prior administration of the selective neuronal nitric oxide synthase inhibitor 7-nitroindazole (0.1-1 mg/kg i.p.), glibenclamide, an ATP K+ channel inhibitor, L-NAME (10 mg/kg i.p.) and ODQ (2 mg/kg i.p.) significantly prevents the antinociceptive effect of diosgenin in formalin and hot plate induced nociception (50 mg/kg i.p administered 10 min after). It suggests that NO/cGMP/kATP has a significant role in the antinociceptive activity of diosgenin.