姜黄素通过瞬时感受器电位辣椒素1受体发挥抑制肠道伤害感受和逆转内脏痛觉过敏的作用

Department of Physiology, Shanghai Jiaotong University, School of Medicine, Shanghai, China

Background: 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. Methods: 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 ex vivo 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. Key Results: In the anesthetized rat, curcumin (4 mg kg-1 min-1 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-1), 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-1) 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. Conclusions & Inferences: 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. © 2013 John Wiley & Sons Ltd.

Rong, W.; Department of Physiology, Shanghai Jiaotong University, School of Medicine, 280 South Chongqing Road, Shanghai 200025, China; email:weifangrong@shsmu.edu.cn