Polyphenol Extracts from Ziziphus jujuba Mill. "Junzao" Attenuates Ulcerative Colitis by Inhibiting the NLRP3 and MAPKs Signaling Pathways and Regulating Gut Microbiota Homeostasis in Mice.

ABSTRACT

SCOPE Polyphenols are the major active substances in red jujube fruit, and their anti-inflammatory and antioxidant activities suggest their potential utility in the prevention of ulcerative colitis (UC). METHODS AND RESULTS: In this study, the effect of polyphenol extracts from red jujube (Ziziphus jujuba Mill. "Junzao") (PERJ) on the dextron sulfate sodium (DSS)-induced UC mice is investigated. The result shows that PERJ effectively improves clinical symptoms, including food and water intake, the disease activity insex (DAI) and spleen index, and routine blood levels, and alleviates the shortening of the colon, in mice with DSS-induced UC. Meanwhile, PERJ remarkably decreases the expression of proinflammatory factors. Moreover, PERJ repairs intestinal barrier damage by increasing the expression level of mucin 2 and mucin 3, and the result is also confirmed in the histological assessment. Besides, the expression levels of Nod-like receptor family pyrin domain-containing 3 (NLRP3) and mitogen-activated protein kinase cascade (MAPKs) signaling pathway-related proteins are inhibited by the PERJ administration. Finally, 16S rRNA sequencing analyses reveal that PERJ reverses intestinal microbiota dysbiosis by enhancing the abundance of Firmicutes and decreasing that of Proteobacteria and Bacteroidetes. CONCLUSION: PERJ probably inhibits the development of UC by suppressing the NLRP3 and MAPKs signaling pathways and regulating gut microbiota homeostasis, and can be considered as a potential resource for preventing UC.