Förster resonance energy transfer reveals phillygenin and swertiamarin concurrently target AKT on different binding domains to increase the anti-inflammatory effect
作者机构:State Key Laboratory of Medicinal Chemical BiologyCollege of Pharmacy and Tianjin Key Laboratory of Molecular Drug ResearchNankai UniversityTianjin 300000China College of Life HealthDalian UniversityDalian 116622China Dalian Fusheng Pharmaceutical Co.Ltd.Dalian 116000China
出 版 物:《Chinese Chemical Letters》 (中国化学快报(英文版))
年 卷 期:2024年第35卷第5期
页 面:207-212页
核心收录:
学科分类:1007[医学-药学(可授医学、理学学位)] 0703[理学-化学] 10[医学]
基 金:supported by the National Natural Science Foundation of China(No.81973449)
主 题:FRET Swertiamarin Phillygenin AKT Anti-inflammation Combinatorial drug
摘 要:The clinical benefit of combination therapy is significant,but it is not easy to define the mechanism of complexity and *** studies illustrate that phillygenin(Phi)binds in the allosteric inhibit pocket of protein kinase B(AKT),and swertiamarin(Swe)acts on the pleckstrin homology(PH)domain of ***,the combined synergistic effect of relieving the inflammatory response has yet to be *** on high sensitivity,specificity and fast-responsibility fluorescent sensors,the Förster resonance energy transfer(FRET)technique offers a route to provide clear insights into physiological and pathological *** the study,molecular docking,the fluorescent probes of Phi and Swe for FRET were designed and *** analysis shown that Swe and Phi concurrently acted on the PH domain and allosterically inhibited pocket of AKT,*** combination of Swe and Phi significantly increased the heat stability of AKT and decreased protease-induced *** lipopolysaccharides(LPS)-induced mice and cells,the combination arrested AKT activation,nuclear factor kappa-B(NF-κB)phosphorylation,and the expression of tumor necrosis factor-α(TNF-α),interleukin(IL)-6 and *** conclusion,FRET revealed Phi and Swe concurrently targeted AKT on different domains and the combination of Phi and Swe enhanced the anti-inflammatory effect.