Therapeutic potential of curcumin and dimethyl chalcone in chronic constriction injury-induced neuropathic pain: Behavioural and histological insights
Year: 2026
Type: article
Abstract: Introduction TRPA1, a key molecule in the pathogenesis of neuropathic pain, oxidative stress, and neurogenic inflammation, few mechanism-based drug therapies are available, and the current study explores the anti-neuropathic activities of curcumin and chalcone derivatives using integrated in-silico and in-vivo strategies. Methods In this study, Molecular Docking and Molecular Dynamics simulations were used to examine the interaction of curcumin, demethoxy curcumin and dimethyl Chalcone derivative with the TRPA1 and their in-vivo analgesic and neuroprotective potential in neuropathic pain Wistar rats was assessed by behavioural and histopathological analysis. Results Curcumin, dimethoxy curcumin, dimethyl chalcone, and HC-030031 were found to have stable binding with TRPA1 by molecular docking and dynamics simulation. In the CCI-induced neuropathic pain model, curcumin and dimethyl chalcone were able to produce analgesic activity similar to HC-030031 and pregabalin (***P < 0.0001) and significantly improve the histopathology of the sciatic nerve, indicating their potential as TRPA1-targeted therapeutics for neuropathic pain. Conclusion The TRPA1 binding of curcumin and dimethyl chalcone was stable and they exhibited a significant analgesic and neuroprotective effect in neuropathic pain models. In particular, the work identified dimethyl chalcone as a new scaffold for the targeting of TRPA1, unlike the other reported mechanism of action of curcumin and chalcone derivatives. Although chalcone analogues have been mostly tested in synthetic libraries and in vitro systems, this study offers mechanistic in vivo proof of the therapeutic potential of the natural compounds targeting the TRPA1 channel for neuropathic pain.
Language: English
Subfield: Physiology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,550
OpenAlex ID: W7165645461