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Protective effect of pai-nong-san against AOM/DSS-induced CAC in mice through inhibiting the Wnt signaling pathway

Chinese Journal of Natural Medicines 2021年第12期19卷 912-920页

作者： ZHANG Meng-Meng YIN Deng-Ke RUI Xue-Lin SHAO Fu-Ping LI Jia-Cheng XU Li YANG Ye School of Pharmacy Anhui University of Chinese MedicineHefei 230031China Anhui Provincial Key Laboratory for Chinese Medicinal Formula Hefei 230031China Institute of Pharmaceutics Anhui Academy of Chinese MedicineHefei 230021China Anhui Provincial Key Laboratory of Research&Development of Chinese Medicine Hefei 230021China

pai-nong-san(PNS), a prescription of traditional Chinese medicine, has been used for years to treat abscessation-induced diseases including colitis and colorectal cancer. This study was aimed to investigate the preventive effects and possible protective mechanism of PNS on a colitis-associated colorectal cancer(CAC) mouse model induced by azoxymethane(AOM)/dextran sodium sulfate(DSS). The macroscopic and histopathologic examinations of colon injury and DAI score were observed. The inflammatory indicators of intestinal immunity were determined by immunohistochemistry and immunofluorescence. The high throughput 16S rRNA sequence of gut microbiota in the feces of mice was performed. Western blot was used to investigate the protein expression of the Wnt signaling pathway in colon tissues. PNS improved colon injury, as manifested by the alleviation of hematochezia, decreased DAI score, increased colon length, and reversal of pathological changes. PNS treatment protected against AOM/DSS-induced colon inflammation by regulating the expression of CD4;and CD8;T cells, inhibiting the production of HIF-α, IL-6, and TNF-α, and promoting the expression of IL-4 and IFN-γ in colon tissues. Meanwhile, PNS improved the components of gut microbiota, as measured by the adjusted levels of Firmicutes, Bacteroidetes, Proteobacteria, and Lactobacillus. PNS down-regulated the protein expression of pGSK-3β, β-catenin, and c-Myc, while up-regulating the GSK-3β and p-β-catenin in colon tissues of CAC mice. In conclusion, our results suggested that PNS exhibits protective effect on AOM/DSS-induced colon injury and alleviates the development of CAC through suppressing inflammation, improving gut microbiota, and inhibiting the Wnt signaling pathway.

关键词： pai-nong-san CAC AOM-DSS Gut microbiota Wnt signaling pathway

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