CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Center for Ocean Mega-Science, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China.
Laboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology (Qingdao), No. 1 Wenhai Road, Qingdao 266237, China.
Int J Mol Sci. 2022 Jul 26;23(15):8205. doi: 10.3390/ijms23158205.
Endotoxemia is mainly caused by a massive burst of inflammatory cytokines as a result of lipopolysaccharide (LPS) invasion. Chitooligosaccharides (COS) is expected to be a potential drug for relieving endotoxemia due to its anti-inflammatory properties. However, the structural parameters of COS are often ambiguous, and the effect of degree of acetylation (DA) of COS on its anti-inflammatory remains unknown. In this study, four COSs with different DAs (0%, 12%, 50% and 85%) and the same oligomers distribution were successfully obtained. Their structures were confirmed by H NMR and MS analysis. Then, the effect of DA on the anti-inflammatory activity and relieving endotoxemia potential of COS was researched. The results revealed that COS with a DA of 12% had better anti-inflammatory activity than COSs with other DAs, mainly in inhibiting LPS-induced inflammatory cytokines burst, down-regulating its mRNA expression and reducing phosphorylation of IκBα. Furthermore, this COS showed an obviously protective effect on endotoxemia mice, such as inhibiting the increase in inflammatory cytokines and transaminases, alleviating the injury of liver and intestinal tissue. This study explored the effect of DA on the anti-inflammatory activity of COS for the first time and lays the foundation for the development of COS as an anti-inflammatory drug against endotoxemia.
内毒素血症主要是由于脂多糖 (LPS) 入侵导致炎症细胞因子大量爆发而引起的。壳寡糖 (COS) 因其具有抗炎特性,有望成为缓解内毒素血症的潜在药物。然而,COS 的结构参数通常不明确,并且 COS 的乙酰化程度 (DA) 对其抗炎作用的影响尚不清楚。在这项研究中,成功获得了具有不同 DA(0%、12%、50%和 85%)但具有相同低聚物分布的四种 COS。它们的结构通过 H NMR 和 MS 分析得到确认。然后,研究了 DA 对 COS 抗炎活性和缓解内毒素血症潜力的影响。结果表明,DA 为 12%的 COS 具有比其他 DA 更好的抗炎活性,主要表现在抑制 LPS 诱导的炎症细胞因子爆发、下调其 mRNA 表达和减少 IκBα 的磷酸化。此外,这种 COS 对内毒素血症小鼠表现出明显的保护作用,例如抑制炎症细胞因子和转氨酶的增加,减轻肝和肠组织的损伤。本研究首次探讨了 DA 对 COS 抗炎活性的影响,为开发 COS 作为治疗内毒素血症的抗炎药物奠定了基础。