Antinociceptive Efficacy of Flavonoids Rich Latex Extract from Pergularia daemia involving Larg/nitric oxide/cGMP/K+ ATP channels Pathway in Experimental Animals

Abstract

Pergularia daemia is a hispid perennial herb, its latex used in traditional ayurvedic and siddha medicine for migraine, head ache, muscle sprain and swelling sores, boils. Despite of its pain relieving potential, the mechanisms of these effects have yet to be elucidated. The methanolic flavonoids rich Pergularia daemia latex (PDL) extract subjected into particular peripheral and central antinociceptive effects in laboratory animals. The present study was to determine the involvement of nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/ potassium (K+ ) channels pathway in the peripheral antinociception induced by flavonoids rich PDL. It was executed systemically for (50, 100 and 200 mg/kg p.o.) to generate dose dependent antinociception when evaluated using acetic acid induced abdominal writhing and formalin test with measured mean IC50 value of 169.9 mg/kg, 136.6 mg/kg and 174.8 mg/kg respectively. PDL at similar doses showed significant dose dependent inhibition of neurogenic pain induced by capsaicin (1.6 g/paw/ IC50 = 194.9 mg/kg) and glutamate (10 µmol/paw/ IC50 = 204.6 mg/kg) which elicits the participation of vanilloid (TRPV) receptors and glutamatergic system. Moreover, PDL displayed reversed antinociception with L-arginine (a NO precursor) (100 mg/kg, s.c.), implying the involvement of L-arginine/nitric oxide pathway besides methylene blue (10 mg/kg, s.c.) remarkably increased the antinociception and an ATP-sensitive K+ channel antagonist glibenclamide (10 mg/kg, i.p.) reversed antinociceptive activity when administered systemically induced by PDL. Conjointly, the results suggested that PDL induced antinociceptive activity was possibly related to inactivate TRPV receptor, glutamatergic system along with the activation of NO/cGMP/ATP sensitive K+ channel pathway