Curcumin Diglutaric Acid, a Prodrug of Curcumin Reduces Pain Hypersensitivity in Chronic Constriction Injury of Sciatic Nerve Induced-Neuropathy in Mice

Pharmaceuticals

Pornchai Rojsitthisak¹  Chawanphat Muangnoi²  Thanchanok Limcharoen³  Pasarapa Towiwat⁴  Hasriadi⁵  PeththaWadu Dasuni Wasana⁵  Opa Vajragupta⁶ 

[1] Department of Food and Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand;Institute of Nutrition, Mahidol University, Salaya 73170, Thailand;Inter-Department Program of Pharmacology, Graduate School, Chulalongkorn University, Bangkok 10330, Thailand;Natural Products for Ageing and Chronic Diseases Research Unit, Chulalongkorn University, Bangkok 10330, Thailand;Pharmaceutical Sciences and Technology Program, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand;Research Affairs, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand;

关键词: neuropathic pain;    chronic constriction injury;    curcumin diglutaric acid;    mechanical allodynia;    thermal hyperalgesia;   

DOI  :  10.3390/ph13090212

来源: DOAJ

【 摘 要 】

The drug treatment for neuropathic pain remains a challenge due to poor efficacy and patient satisfaction. Curcumin has been reported to alleviate neuropathic pain, but its clinical application is hindered by its low solubility and poor oral bioavailability. Curcumin diglutaric acid (CurDG) is a curcumin prodrug with improved water solubility and in vivo antinociceptive effects. In this study, we investigated the anti-inflammatory mechanisms underlying the analgesic effect of CurDG in the chronic constriction injury (CCI)-induced neuropathy mouse model. Repeated oral administration of CurDG at a low dose equivalent to 25 mg/kg/day produced a significant analgesic effect in this model, both anti-allodynic activity and anti-hyperalgesic activity appearing at day 3 and persisting until day 14 post-CCI surgery (p < 0.001) while having no significant effect on the motor performance. Moreover, the repeated administration of CurDG diminished the increased levels of the pro-inflammatory cytokines: TNF-α and IL-6 in the sciatic nerve and the spinal cord at the lowest tested dose (equimolar to 25 mg/kg curcumin). This study provided pre-clinical evidence to substantiate the potential of pursuing the development of CurDG as an analgesic agent for the treatment of neuropathic pain.

【 授权许可】

Unknown