Curcumin acts via transient receptor potential vanilloid‐1 receptors to inhibit gut nociception and reverses visceral hyperalgesia. Issue 6 (3rd May 2013)

• Record Type: Journal Article
• Authors: Zhi, L.; Dong, L.; Kong, D.; Sun, B.; Sun, Q.; Grundy, D.; Zhang, G.; Rong, W.
• Is Part Of: Neurogastroenterology & motility. Volume 25:Issue 6(2013:Jun.)
• Page Start: e429
• Page End: e440
• Publication Date: 2013-05-03
• Subjects: Gastrointestinal system -- Motility -- Periodicals; Gastrointestinal system -- Innervation -- Periodicals; 616.33
• DOI: 10.1111/nmo.12145
• Languages: English
• ISSNs: 1350-1925

Abstract

<abstract abstract-type="main" xml:lang="en" id="nmo12145-abs-0001"> <title>Abstract</title> <sec id="nmo12145-sec-0001" sec-type="section"> <title>Background</title> <p>An antinociceptive effect has been reported for curcumin in animal models and in humans, but the molecular mechanisms of curcumin's effect remain undefined. In this study, we explored the possibility that curcumin inhibit visceral nociception via antagonizing the transient receptor potential vanilloid‐1 (TRPV1) receptor.</p> </sec> <sec id="nmo12145-sec-0002" sec-type="section"> <title>Methods</title> <p>The effects of curcumin were explored using two experimental models: viscero‐motor response (VMR) to colorectal distension (CRD) in rats and jejunal afferent firing in the <italic>ex vivo</italic> mouse jejunum preparations [TRPV1 knockout (KO) and wild‐type mice, naive and trinitrobenzene sulfonic acid (TNBS)‐treated Kunming mice]. In addition, capsaicin‐induced calcium transients and whole‐cell currents were examined in acutely dissociated dorsal root ganglia (DRG) neurons.</p> </sec> <sec id="nmo12145-sec-0003" sec-type="section"> <title>Key Results</title> <p>In the anesthetized rat, curcumin (4 mg kg<sup>−1</sup> min<sup>−1</sup> for 3 min) caused a marked and rapidly reversible inhibition of CRD‐induced VMRs. In the mouse jejunum, the mesenteric afferent nerve response to ramp distension was attenuated by curcumin (3, 10 μmol L<sup>−1</sup>), an effect that was significantly reduced in TRPV1 KO mice compared with wild‐type (WT) controls. Moreover, in WT mice, curcumin (1–30 μmol L<sup>−1</sup>) was found to inhibit the afferent responses to capsaicin in a concentration‐dependent manner. Trinitrobenzene sulfonic acid‐induced hypersensitivity of jejunal afferents was also attenuated by curcumin. Curcumin potently inhibited capsaicin‐induced rise in intracellular calcium and inward currents in mouse or rat DRG neurons.</p> </sec> <sec id="nmo12145-sec-0004" sec-type="section"> <title>Conclusions & Inferences</title> <p>Our results provide strong evidence that curcumin inhibit visceral nociception via antagonizing TRPV1 and may be a promising lead for the treatment of functional gastrointestinal diseases.</p> </sec> </abstract>