| Summary: | <i>Echinacea purpurea</i> is popularly used as a food supplement or nutritional supplement for its immune regulatory function against various threats. As one of its promising components, <i>Echinacea purpurea</i> (L.) Moench polysaccharide (EPP) has a wide range of biological activities. To evaluate the effect of EPP as a dietary supplement on ulcerative colitis (UC), this study used sodium dextran sulfate (DSS) to induce a UC model, extracted EPP using the ethanol subsiding method, and then supplemented with EPP by gavage for 7 days. Then, we evaluated the efficacy of EPP on DSS rats in terms of immunity, anti-inflammation, and intestinal flora. The result showed that EPP could alleviate colonic shortening and intestinal injury in rats with DSS-induced colitis, decrease the disease activity index (DAI) score, downregulate serum levels of inflammatory cytokines, and contribute to the restoration of the balance between the T helper cells 17 (Th17) and the regulatory T cells (Treg) in the spleen and mesenteric lymph nodes (MLNs). Meanwhile, EPP could downregulate the expression of Toll-like receptors 4 (TLR4), myeloid differentiation factor 88 (MyD88), and nuclear factor kappa-B (NF-κB) in colon tissue. In addition, the results of 16SrRNA sequencing showed that EPP also had a regulatory effect on intestinal flora of UC rats. These results indicate that EPP might achieve a beneficial effect on UC rats as a dietary supplement through restoring Th17/Treg balance, inhibiting the TLR4 signaling pathway and regulating intestinal flora, suggesting its possible application as a potential functional food ingredient alleviating UC.
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