Shugan Decoction Ameliorated WAS-Induced Abnormal Colonic Motility in Rats by Inhibiting Colonic TRPV4-PGE2 Signaling

Aim: To clarify the function of transient receptor potential vanilloid 4 (TRPV4)-prostaglandin E2 (PGE₂) signaling in the colon of rats with irritable bowel syndrome (IBS) induced by water-avoidance stress (WAS). On this basis, to explore whether colonic TRPV4-PGE₂ signaling is involved in the mechanism of action of Chinese herbal formula Shugan Decoction (SGD) on IBS.

Methods: The rat model of IBS was induced by chronic WAS, and the number of fecal pellets was counted. Meanwhile, the visceral pain pressure threshold was measured using colorectal distension. Western blot or immunofluorescence was used to measure the protein expressions of TRPV4, EP1, and EP3 in the colon. ELISA was used to determine the contents of PGE₂ in colonic tissue. The contractile activities of the colonic longitudinal muscle strips were observed via an organ bath experiment.

Results: Compared with the control group, the content of PGE₂, the expressions of TRPV4, EP1, and EP3 receptors in the colon of the rats in the WAS group increased, accompanied by enhanced fecal pellet output and reduced visceral pain pressure threshold; meanwhile, the tension and the amplitude of the spontaneous contraction of the colonic longitudinal muscle were significantly enhanced. These parameter values in the SGD group were significantly restored compared with those in the WAS group. The suppression of contractile tension and amplitude by the TRPV4 inhibitor HC-067047 in the WAS group was greater than that in the control and SGD groups. The enhancement of contractile amplitude by PGE₂ in the WAS group was weaker than that in the control group but was stronger than that in the SGD group. Interestingly, the suppression of contractile tension by the EP1 antagonist ONO-8711 in the SGD group was less than that in the WAS group.

Conclusion: SGD can ameliorate dysmotility of colonic longitudinal muscle and visceral hypersensitivity caused by WAS maybe by reducing the release of PGE₂ and decreasing the expression of TRPV4 and EP1.

Shugan Decoction; irritable bowel syndrome; prostaglandin E receptor; prostaglandin E2; transient receptor potential vanilloid 4.