Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China.
Division of Rheumatology, Department of Medicine, Queen's University, Kingston, ON K7L 4B4, Canada.
Molecules. 2022 May 19;27(10):3267. doi: 10.3390/molecules27103267.
Previously synthesized -butyrylated hyaluronic acid (BHA) provides anti-inflammatory effects in rat models of acute gouty arthritis and hyperuricemia. However, the mechanism of action remains to be elucidated. Herein, the anti-inflammatory and antioxidative activities of BHA and the targeted signaling pathways were explored with LPS-induced RAW264.7 and an adjuvant-induced inflammation in a rat model. Results indicated that BHA inhibited the generation of pro-inflammatory cytokines TNFα, IL-1β and IL-6, reduced ROS production and down-regulated JAK1-STAT1/3 signaling pathways in LPS-induced RAW264.7. In vivo, BHA alleviated paw and joint swelling, decreased inflammatory cell infiltration in paw tissues, suppressed gene expressions of p38 and p65, down-regulated the NF-κB and MAPK signaling pathways and reduced protein levels of TNFα, IL-1β and IL-6 in joint tissues of arthritis rats. This study demonstrated the pivotal role of BHA in anti-inflammation and anti-oxidation, suggesting the potential clinical value of BHA in the prevention of inflammatory arthritis and is worthy for development as a new pharmacological treatment.
先前合成的 -丁酰化透明质酸（BHA）在急性痛风性关节炎和高尿酸血症的大鼠模型中具有抗炎作用。然而，其作用机制仍有待阐明。本研究采用 LPS 诱导的 RAW264.7 细胞和佐剂诱导的大鼠炎症模型，探讨了 BHA 的抗炎和抗氧化活性及其靶向信号通路。结果表明，BHA 抑制了 LPS 诱导的 RAW264.7 细胞中促炎细胞因子 TNFα、IL-1β 和 IL-6 的产生，减少了 ROS 的产生，并下调了 JAK1-STAT1/3 信号通路。在体内，BHA 减轻了爪和关节肿胀，减少了爪组织中炎性细胞浸润，抑制了关节炎大鼠关节组织中 p38 和 p65 基因的表达，下调了 NF-κB 和 MAPK 信号通路，并降低了关节组织中 TNFα、IL-1β 和 IL-6 的蛋白水平。本研究表明 BHA 在抗炎和抗氧化中具有重要作用，提示 BHA 在预防炎症性关节炎方面具有潜在的临床价值，值得进一步开发为一种新的药理学治疗方法。
