title: Antinociceptive properties of shikonin: in vitro and in vivo studies.
abstract: Shikonin possess a diverse spectrum of pharmacological 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 concentration (IC50) value of 7.6 μmol/L and 6.4 μmol/L, respectively, 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 mechanical hyperalgesia model, dose of 10 and 3 mg/kg (intraperitoneal) produced dose-dependent analgesia and showed 67% and 35% reversal of hyperalgesia respectively 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 preclinical models, analgesic effect was similar or better than standard 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.
authors.affiliation: a Department of Bio and Nano Technology, Bio and Nano Technology Centre, Guru Jambheshwar University of Science and Technology, Hisar 125 001 (Haryana), India.|b TCG Life Sciences Private Ltd., R&D Centre Biology, Bengal Intelligent Park Ltd., Block EP and GP, Sector V, Salt Lake, Kolkata 700091 (West Bengal), India.
authors.forename: Bhawana
authors.initials: B
authors.lastname: Gupta
authors.affiliation: b TCG Life Sciences Private Ltd., R&D Centre Biology, Bengal Intelligent Park Ltd., Block EP and GP, Sector V, Salt Lake, Kolkata 700091 (West Bengal), India.
authors.forename: Sabyasachi
authors.initials: S
authors.lastname: Chakraborty
authors.affiliation: b TCG Life Sciences Private Ltd., R&D Centre Biology, Bengal Intelligent Park Ltd., Block EP and GP, Sector V, Salt Lake, Kolkata 700091 (West Bengal), India.
authors.forename: Soumya
authors.initials: S
authors.lastname: Saha
authors.affiliation: b TCG Life Sciences Private Ltd., R&D Centre Biology, Bengal Intelligent Park Ltd., Block EP and GP, Sector V, Salt Lake, Kolkata 700091 (West Bengal), India.
authors.forename: Sunita Gulabsingh
authors.initials: SG
authors.lastname: Chandel
authors.affiliation: b TCG Life Sciences Private Ltd., R&D Centre Biology, Bengal Intelligent Park Ltd., Block EP and GP, Sector V, Salt Lake, Kolkata 700091 (West Bengal), India.
authors.forename: Atul Kumar
authors.initials: AK
authors.lastname: Baranwal
authors.affiliation: b TCG Life Sciences Private Ltd., R&D Centre Biology, Bengal Intelligent Park Ltd., Block EP and GP, Sector V, Salt Lake, Kolkata 700091 (West Bengal), India.
authors.forename: Manish
authors.initials: M
authors.lastname: Banerjee
authors.affiliation: b TCG Life Sciences Private Ltd., R&D Centre Biology, Bengal Intelligent Park Ltd., Block EP and GP, Sector V, Salt Lake, Kolkata 700091 (West Bengal), India.
authors.forename: Mousumi
authors.initials: M
authors.lastname: Chatterjee
authors.affiliation: a Department of Bio and Nano Technology, Bio and Nano Technology Centre, Guru Jambheshwar University of Science and Technology, Hisar 125 001 (Haryana), India.
authors.forename: Ashok
authors.initials: A
authors.lastname: Chaudhury
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D009285:Naphthoquinones / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000700:Analgesics; D009285:Naphthoquinones; C016101:shikonin
keywords: NaV1.7; canal ionique; canal sodique; douleur; douleur au pincement; douleur causée par la formaline; formalin induced pain; hyperalgesia; hyperalgésie; ion channel; pain; pinch pain; shikonin; shikonine; sodium channel