Key Laboratory of Marine Drugs of Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China; Center for Innovation Marine Drug Screening & Evaluation and Laboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao 266237, China; Key Laboratory of Marine Chemistry Theory and Technology, Ministry of Education, Qingdao 266100, China.
Key Laboratory of Marine Drugs of Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China; Marine Biomedical Research Institute of Qingdao, Qingdao 266071, China.
Carbohydr Polym. 2022 Jan 15;276:118699. doi: 10.1016/j.carbpol.2021.118699. Epub 2021 Sep 24.
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.
严重的急性炎症反应可能导致组织损伤、脓毒症和死亡。作为细胞外基质的重要组成部分，透明质酸（HA）已被报道通过 Toll 样受体（TLR）发挥促炎和抗炎作用。在本研究中，我们制备了不同大小和结构的 HA 寡糖及其衍生物，并研究了它们在体外和体内的炎症作用。结果表明，HA 四糖是增强炎症的最小片段，而 HA 二糖则竞争性地阻断 TLR4 依赖性炎症。酶解的 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，我们还证明了 ΔHA2 可减少 LPS 诱导的体内促炎细胞因子的产生。ΔHA2 是 HA 多糖的天然代谢物，可能在对抗 LPS 介导的炎症性疾病方面具有潜在作用。
