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Mechanism of Shaoyaotang in Regulating Water Metabolism and Intestinal Epithelial Permeability in Ulcerative Colitis Through cAMP/PKA/CREB Signaling Pathway / 中国实验方剂学杂志
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 53-60, 2023.
Article in Chinese | WPRIM | ID: wpr-965648
ABSTRACT
ObjectiveTo investigate the role of cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/cAMP-response element binding protein (CREB) signaling pathway in water metabolism and intestinal epithelial permeability in ulcerative colitis (UC) and the intervention mechanism of Shaoyaotang based on the theory of large intestine governing fluids. MethodSixty male SD rats were divided into blank group, model group, mesalazine group (0.42 g·kg-1), Shaoyaotang low-dose group (11.1 g·kg-1), Shaoyaotang medium-dose group (22.2 g·kg-1) and Shaoyaotang high-dose group (44.4 g·kg-1), with 10 in each group. The UC rat model of internal retention of dampness-heat was established by compound factors. The blank group and the model group were given normal saline (ig). The mesalazine group was given mesalazine (ig), and Shaoyaotang low-, medium- and high-dose groups were administrated with corresponding doses of Shaoyaotang (ig). The treatment lasted for 14 days. The diarrhea score and fecal moisture content of rats in each group were observed. The contents of diamine oxidase (DAO) and D-lactic acid in plasma were detected by enzyme-linked immunosorbent assayELISA). The protein expressions of aquaporin (AQP)8, AQP4, ZO-1 and Occludin in colon tissues were detected by immunohistochemistry, while those of cAMP, PKA and CREB in colon tissues were determined by Western blot. ResultCompared with the normal group, the model group had elevated diarrhea score and fecal moisten content (P<0.01), increased contents of DAO and D-lactic acid in plasma (P<0.01) and decreased protein expressions of ZO-1, Occludin, AQP8, AQP4, cAMP, PKA and CREB in colon (P<0.01). Compared with the conditions in the model group, the contents of DAO and D-lactic acid in plasma in each administration groups were lower (P<0.01), while the protein expressions of ZO-1, Occludin, AQP8, AQP4, cAMP, PKA and CREB in colon were higher (P<0.01). ConclusionShaoyaotang alleviates the diarrhea in UC, probably through activating cAMP/PKA/CREB signaling pathway, up-regulating expressions of AQPs, enhancing tight junctions in intestinal epithelium and thus improving the water metabolism in colon and the intestinal mucosal permeability.

Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Chinese Journal of Experimental Traditional Medical Formulae Year: 2023 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Chinese Journal of Experimental Traditional Medical Formulae Year: 2023 Type: Article