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P2Y1 receptor is a G-protein-coupled receptor that plays a critical role in the immune response of inflammatory bowel diseases. However, its regulatory effects on CD4+ T cell response have not been fully elucidated. The study aimed to characterize the role of P2Y1R in Th17 cell differentiation and colonic inflammation. Our results demonstrated that P2Y1R was significantly increased in the splenocytes of colitic mice, which was positively associated with the expression of RORγt and IL-17A. P2Y1R deficiency significantly ameliorated DSS-induced colitis and its Th17 responses. In parallel, P2Y1R deficiency greatly impaired the differentiation of Th17 cell, down-regulated the mRNA expression of IL-17A and RORγt, and protein expression of RORγt in vitro. More importantly, it was found that P2Y1R deficiency markedly increased AMPK phosphorylation of Th17 polarized CD4+ T cells, and antagonist of AMPK significantly reversed the inhibitory effect of P2Y1R deficiency on Th17 cell generation in vivo and in vitro. Overall, these findings demonstrated that P2Y1R deficiency could suppress Th17 cell differentiation in an AMPK-dependent manner to ameliorate colitis, and P2Y1R can act as an important regulator of Th17 cell differentiation to control colonic inflammation.

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Scope: The dysbiosis of intestinal microecology plays an important pathogenic role in the development of inflammatory bowel disease. Methods and Results: A polysaccharide named Fuc-S, with a molecular weight of 156 kDa, was prepared by the ultrasonic degradation of fucoidan. Monosaccharide composition, FTIR, methylation, and NMR spectral analysis indicated that Fuc-S may have a backbone consisting of →3)-α-L-Fucp-(1→, →4)-α-L-Fucp-(1→ and →3, 4)-α-D-Glcp-(1→. Moreover, male C57BL/6 mice were fed three cycles of 1.8% dextran sulfate sodium (DSS) for 5 days and then water for 7 days to induce colitis. The longitudinal microbiome alterations were evaluated using 16S amplicon sequencing. In vivo assays showed that Fuc-S significantly improved clinical manifestations, colon shortening, colon injury, and colonic inflammatory cell infiltration associated with DSS-induced chronic colitis in mice. Further studies revealed that these beneficial effects were associated with the inhibition of Akt, p-38, ERK, and JNK phosphorylation in the colon tissues, regulating the structure and abundance of the gut microbiota, and modulating the host–microbe tryptophan metabolism of the mice with chronic colitis. Conclusion: Our data confirmed the presence of glucose in the backbone of fucoidan and provided useful information that Fuc-S can be applied as an effective functional food and pharmaceutical candidate for IBD treatment.

Type 2 diabetes mellitus (T2DM) has become a universal and chronic global public health concern and causes multiple complex complications. In order to meet the rapidly growing demand for T2DM treatment, increased research has been focused on hypoglycemic drugs. Cyclocarya paliurus (Batal.) Iljinsk is the only living species of the genus Cyclocarya Iljinskaja, whose leaves have been extensively used as a functional tea to treat obesity and diabetes in China. An enormous amount of very recent pharmacological research on the leaves of C. paliurus has demonstrated that they carry out numerous biological activities, such as hypoglycemic, anti-inflammatory, and intestinal microbiota regulation. Multiple in vitro and in vivo studies have also shown that the extracts of C. paliurus leaves are innocuous and safe. This study aims to provide an up-to-date review of the botany, traditional uses, phytochemistry, pharmacological effects against diabetes, toxicology, and clinical studies of C. paliurus leaves, in hopes of promoting a better understanding of their role in the prevention and treatment of T2DM.