Khaleghi Fatemeh, Jantan Ibrahim, Din Laily Bin, Yaacob Wan A, Khalilzadeh Mohammad A, Bukhari Syed Nasir Abbas
Pharmaceutical Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
J Nat Med. 2014 Apr;68(2):351-7. doi: 10.1007/s11418-013-0805-9. Epub 2013 Oct 24.
1-(6-Hydroxy-2-isopropenyl-1-benzofuran-5-yl)-1-ethanone (1), isolated from the roots of Petasites hybridus L., and a series of synthetic benzoxazepine derivatives of compound 1 (2-6) were evaluated for their immunomodulatory effects. The compounds were evaluated for their effects on the respiratory burst of human whole blood and isolated human polymorphonuclear leukocytes (PMNs) using luminol- and lucigenin-based chemiluminescence (CL) assays, and their effect on chemotactic migration of PMNs was assessed using the Boyden chamber technique. Compound 1 exhibited stronger inhibition than acetylsalicylic acid (ASA) on luminol-enhanced CL of PMNs. It also inhibited PMN chemotaxis with an IC50 value comparable to that of ibuprofen. Of the compounds tested, 5 was the most effective in inhibiting luminol-enhanced CL and also strongly inhibited lucigenin-enhanced CL with IC50 values lower than that of ASA. Compound 2 was the most active in inhibiting migration of PMNs and was five times stronger than ibuprofen. The results suggest that compound 1 and its synthesized benzoxazepine derivatives, especially compounds 2 and 5, were able to modulate the innate immune response of phagocytes at different steps, emphasizing their potential as leads for the development of new immunomodulatory agents.
从蜂斗菜（Petasites hybridus L.）根部分离得到的1-(6-羟基-2-异丙烯基-1-苯并呋喃-5-基)-1-乙酮（1）以及化合物1的一系列合成苯并恶唑嗪衍生物（2 - 6）进行了免疫调节作用评估。使用基于鲁米诺和光泽精的化学发光（CL）测定法评估了这些化合物对人全血呼吸爆发和分离的人多形核白细胞（PMN）的影响，并使用博伊登室技术评估了它们对PMN趋化迁移的影响。化合物1对PMN的鲁米诺增强CL的抑制作用比乙酰水杨酸（ASA）更强。它还抑制PMN趋化性，其IC50值与布洛芬相当。在所测试的化合物中，5在抑制鲁米诺增强CL方面最有效，并且还强烈抑制光泽精增强CL，其IC50值低于ASA。化合物2在抑制PMN迁移方面最具活性，比布洛芬强五倍。结果表明，化合物1及其合成的苯并恶唑嗪衍生物，尤其是化合物2和5，能够在不同步骤调节吞噬细胞的先天免疫反应，强调了它们作为新型免疫调节剂开发先导物的潜力。
