Curcumin Diethyl γ-Aminobutyrate, a Prodrug of Curcumin, for Enhanced Treatment of Inflammatory Pain.
ACS Pharmacol Transl Sci
; 5(9): 774-790, 2022 Sep 09.
Article
in En
| MEDLINE
| ID: mdl-36110378
ABSTRACT
Curcumin is a naturally occurring polyphenol compound with potential analgesic effects. It has been shown to improve pain-like behaviors in numerous models of pain. Despite its potential, curcumin exhibits poor physicochemical and pharmacokinetic properties, which hinder its oral therapeutic efficacy. Curcumin diethyl γ-aminobutyrate (CUR-2GE), a carbamate prodrug of curcumin, was designed to overcome these limitations and demonstrated greater anti-neuroinflammatory effects compared to curcumin in vitro. Thus, this study evaluated the effect of CUR-2GE and its parent compound on pain-like behaviors in carrageenan- and LPS-induced mouse models. The possible side effects of CUR-2GE were also assessed by exploring its effects on motor coordination and spontaneous locomotor activity after acute and chronic treatments. The results showed that CUR-2GE improved mechanical and thermal hyperalgesia and locomotor activity to a greater extent than curcumin in carrageenan-induced mice. These results are in line with the ability of CUR-2GE to suppress peripheral inflammation in the paw tissue of carrageenan-induced mice, indicated by a significant decrease in TNF-α and IL-6 expression levels. Similarly, in LPS-induced mice, CUR-2GE improved sickness and pain-like behaviors (exploratory behaviors and long-term locomotor activity) to a greater extent than curcumin. Furthermore, CUR-2GE significantly reduced the level of proinflammatory cytokines in both the plasma and spinal cord tissue of LPS-induced mice, exhibiting significantly higher inhibition than curcumin. Moreover, the motor coordination, and locomotive behaviors of mice were not affected by both acute and chronic administration of CUR-2GE, indicating no potential CNS side effects. Thus, CUR-2GE demonstrated enhanced therapeutic efficacy in mouse models of inflammatory pain without any possible CNS side effects, suggesting its potential to be developed as an analgesic agent against inflammatory pain.
Full text:
1
Database:
MEDLINE
Therapeutic Methods and Therapies TCIM:
Terapias_biologicas
/
Plantas_medicinales
Language:
En
Journal:
ACS Pharmacol Transl Sci
Year:
2022
Type:
Article
Affiliation country:
Thailand