Bhawana Gupta (TCGLS Member), Sabyasachi Chakraborty (TCGLS Member), Soumya Saha (TCGLS Member), Sunita Chandel (TCGLS Member), Gulab Singh (TCGLS Member), Atul Kumar Baranwal (TCGLS Member), Manish Banerjee (TCGLS Member), Mousumi Chatterjee (TCGLS Member), Ashok Chaudhury.
Canadian Journal of Physiology and Pharmacology Volume 94 Issue 7 Pages 788-796, 1996
Shikonin possess a diverse spectrum of Pharmacol. properties in multiple therapeutic areas. However, the nociceptive effect of shikonin is not largely known. To investigate the antinociceptive potential of shikonin, panel of GPCRs, ion channels, and enzymes involved in pain pathogenesis were studied. To evaluate the translation of shikonin efficacy in vivo, it was tested in 3 established rat pain models. Our study reveals that shikonin has significant inhibitory effect on pan sodium channel/N1E115 and NaV1.7 channel with half maximal inhibitory concn. (IC50) value of 7.6 μmol/L and 6.4 μmol/L, resp., in a cell-based assay. Shikonin exerted significant dose dependent antinociceptive activity at doses of 0.08%, 0.05%, and 0.02% w/v in pinch pain model. In mech. hyperalgesia model, dose of 10 and 3 mg/kg (i.p.) produced dose-dependent analgesia and showed 67% and 35% reversal of hyperalgesia resp. at 0.5 h. Following oral administration, it showed 39% reversal at 30 mg/kg dose. When tested in first phase of formalin induced pain, shikonin at 10 mg/kg dose inhibited paw flinching by ∼71%. In all studied preclin. models, analgesic effect was similar or better than std. analgesic drugs. The present study unveils the mechanistic role of shikonin on pain modulation, predominantly via sodium channel modulation, suggesting that shikonin could be developed as a potential pain blocker