Severe acute inflammatory conditions may cause tissue damage, sepsis, and death. As a critical component of the extracellular matrix, hyaluronic acid (HA) has been reported to possess pro- and anti-inflammatory properties via Toll-like receptors (TLRs). In this study, we prepared different sizes and structures of HA oligosaccharides and derivatives and investigated the effects on inflammation in vitro and in vivo. Our results showed that HA tetra-saccharide was the minimum fragment to enhance inflammation, whereas HA disaccharide competitively blocked TLR4-dependent inflammation. The enzymatic HA disaccharide (ΔHA2) inhibited lipopolysaccharide (LPS)-induced inflammation. Based on structure-activity relationship analysis, we observed that anti-inflammatory activity depended on HAs polymerization degree, acetyl group, and configuration. In addition, we demonstrated that ΔHA2 reduced LPS-induced pro-inflammatory cytokines production in vivo. ΔHA2, a native metabolite of HA polysaccharides, may have a potential role against LPS-mediated inflammatory diseases.

严重的急性炎症可能导致组织损伤、败血症和死亡。作为细胞外基质的关键成分，透明质酸 (HA) 据报道通过Toll 样受体 (TLR)具有促炎和抗炎特性。在这项研究中，我们制备了不同大小和结构的 HA 寡糖及其衍生物，并研究了其在体外和体内对炎症的影响。. 我们的研究结果表明，HA 四糖是增强炎症的最小片段，而 HA 二糖竞争性地阻断了 TLR4 依赖性炎症。酶促 HA 二糖 (ΔHA2) 抑制脂多糖 (LPS) 诱导的炎症。基于构效关系分析，我们观察到抗炎活性取决于HA的聚合度、乙酰基和构型。此外，我们证明了 ΔHA2在体内减少了 LPS 诱导的促炎细胞因子的产生。ΔHA2 是 HA 多糖的天然代谢物，可能对 LPS 介导的炎症性疾病具有潜在作用。