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...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-08-01
|
| Series: | Pharmaceuticals |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1424-8247/13/9/212 |
| _version_ | 1797555418617085952 |
|---|---|
| author | Thanchanok Limcharoen Peththa Wadu Dasuni Wasana Hasriadi Chawanphat Muangnoi Opa Vajragupta Pornchai Rojsitthisak Pasarapa Towiwat |
| author_facet | Thanchanok Limcharoen Peththa Wadu Dasuni Wasana Hasriadi Chawanphat Muangnoi Opa Vajragupta Pornchai Rojsitthisak Pasarapa Towiwat |
| author_sort | Thanchanok Limcharoen |
| collection | DOAJ |
| 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 (<i>p</i> < 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. |
| first_indexed | 2024-03-10T16:47:13Z |
| format | Article |
| id | doaj.art-ceade92a27ba4e25b2d6bb244ea669b7 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T16:47:13Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-ceade92a27ba4e25b2d6bb244ea669b72023-11-20T11:30:43ZengMDPI AGPharmaceuticals1424-82472020-08-0113921210.3390/ph13090212Curcumin Diglutaric Acid, a Prodrug of Curcumin Reduces Pain Hypersensitivity in Chronic Constriction Injury of Sciatic Nerve Induced-Neuropathy in MiceThanchanok Limcharoen0Peththa Wadu Dasuni Wasana1Hasriadi2Chawanphat Muangnoi3Opa Vajragupta4Pornchai Rojsitthisak5Pasarapa Towiwat6Inter-Department Program of Pharmacology, Graduate School, Chulalongkorn University, Bangkok 10330, ThailandPharmaceutical Sciences and Technology Program, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, ThailandPharmaceutical Sciences and Technology Program, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, ThailandInstitute of Nutrition, Mahidol University, Salaya 73170, ThailandResearch Affairs, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, ThailandDepartment of Food and Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, ThailandNatural Products for Ageing and Chronic Diseases Research Unit, Chulalongkorn University, Bangkok 10330, ThailandThe 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 (<i>p</i> < 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.https://www.mdpi.com/1424-8247/13/9/212neuropathic painchronic constriction injurycurcumin diglutaric acidmechanical allodyniathermal hyperalgesia |
| spellingShingle | Thanchanok Limcharoen Peththa Wadu Dasuni Wasana Hasriadi Chawanphat Muangnoi Opa Vajragupta Pornchai Rojsitthisak Pasarapa Towiwat Curcumin Diglutaric Acid, a Prodrug of Curcumin Reduces Pain Hypersensitivity in Chronic Constriction Injury of Sciatic Nerve Induced-Neuropathy in Mice Pharmaceuticals neuropathic pain chronic constriction injury curcumin diglutaric acid mechanical allodynia thermal hyperalgesia |
| 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 | neuropathic pain chronic constriction injury curcumin diglutaric acid mechanical allodynia thermal hyperalgesia |
| url | https://www.mdpi.com/1424-8247/13/9/212 |
| work_keys_str_mv | AT thanchanoklimcharoen curcumindiglutaricacidaprodrugofcurcuminreducespainhypersensitivityinchronicconstrictioninjuryofsciaticnerveinducedneuropathyinmice AT peththawadudasuniwasana curcumindiglutaricacidaprodrugofcurcuminreducespainhypersensitivityinchronicconstrictioninjuryofsciaticnerveinducedneuropathyinmice AT hasriadi curcumindiglutaricacidaprodrugofcurcuminreducespainhypersensitivityinchronicconstrictioninjuryofsciaticnerveinducedneuropathyinmice AT chawanphatmuangnoi curcumindiglutaricacidaprodrugofcurcuminreducespainhypersensitivityinchronicconstrictioninjuryofsciaticnerveinducedneuropathyinmice AT opavajragupta curcumindiglutaricacidaprodrugofcurcuminreducespainhypersensitivityinchronicconstrictioninjuryofsciaticnerveinducedneuropathyinmice AT pornchairojsitthisak curcumindiglutaricacidaprodrugofcurcuminreducespainhypersensitivityinchronicconstrictioninjuryofsciaticnerveinducedneuropathyinmice AT pasarapatowiwat curcumindiglutaricacidaprodrugofcurcuminreducespainhypersensitivityinchronicconstrictioninjuryofsciaticnerveinducedneuropathyinmice |