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

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 cur...

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Autores principales: Limcharoen, Thanchanok, Dasuni Wasana, Peththa Wadu, , Hasriadi, Muangnoi, Chawanphat, Vajragupta, Opa, Rojsitthisak, Pornchai, Towiwat, Pasarapa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7558758/
https://www.ncbi.nlm.nih.gov/pubmed/32867013
http://dx.doi.org/10.3390/ph13090212
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author Limcharoen, Thanchanok
Dasuni Wasana, Peththa Wadu
, Hasriadi
Muangnoi, Chawanphat
Vajragupta, Opa
Rojsitthisak, Pornchai
Towiwat, Pasarapa
author_facet Limcharoen, Thanchanok
Dasuni Wasana, Peththa Wadu
, Hasriadi
Muangnoi, Chawanphat
Vajragupta, Opa
Rojsitthisak, Pornchai
Towiwat, Pasarapa
author_sort Limcharoen, Thanchanok
collection PubMed
description 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.
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spelling pubmed-75587582020-10-26 Curcumin Diglutaric Acid, a Prodrug of Curcumin Reduces Pain Hypersensitivity in Chronic Constriction Injury of Sciatic Nerve Induced-Neuropathy in Mice Limcharoen, Thanchanok Dasuni Wasana, Peththa Wadu , Hasriadi Muangnoi, Chawanphat Vajragupta, Opa Rojsitthisak, Pornchai Towiwat, Pasarapa Pharmaceuticals (Basel) Article 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. MDPI 2020-08-27 /pmc/articles/PMC7558758/ /pubmed/32867013 http://dx.doi.org/10.3390/ph13090212 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Limcharoen, Thanchanok
Dasuni Wasana, Peththa Wadu
, Hasriadi
Muangnoi, Chawanphat
Vajragupta, Opa
Rojsitthisak, Pornchai
Towiwat, Pasarapa
Curcumin Diglutaric Acid, a Prodrug of Curcumin Reduces Pain Hypersensitivity in Chronic Constriction Injury of Sciatic Nerve Induced-Neuropathy in Mice
title Curcumin Diglutaric Acid, a Prodrug of Curcumin Reduces Pain Hypersensitivity in Chronic Constriction Injury of Sciatic Nerve Induced-Neuropathy in Mice
title_full Curcumin Diglutaric Acid, a Prodrug of Curcumin Reduces Pain Hypersensitivity in Chronic Constriction Injury of Sciatic Nerve Induced-Neuropathy in Mice
title_fullStr Curcumin Diglutaric Acid, a Prodrug of Curcumin Reduces Pain Hypersensitivity in Chronic Constriction Injury of Sciatic Nerve Induced-Neuropathy in Mice
title_full_unstemmed Curcumin Diglutaric Acid, a Prodrug of Curcumin Reduces Pain Hypersensitivity in Chronic Constriction Injury of Sciatic Nerve Induced-Neuropathy in Mice
title_short Curcumin Diglutaric Acid, a Prodrug of Curcumin Reduces Pain Hypersensitivity in Chronic Constriction Injury of Sciatic Nerve Induced-Neuropathy in Mice
title_sort curcumin diglutaric acid, a prodrug of curcumin reduces pain hypersensitivity in chronic constriction injury of sciatic nerve induced-neuropathy in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7558758/
https://www.ncbi.nlm.nih.gov/pubmed/32867013
http://dx.doi.org/10.3390/ph13090212
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