Acute lung injury(ALI)is a severe disease caused by viral infection that triggers an uncontrolled inflammatory response.This study investigated the capacity of jasurolignoside(JO),a natural compound,to bind to Toll-li...Acute lung injury(ALI)is a severe disease caused by viral infection that triggers an uncontrolled inflammatory response.This study investigated the capacity of jasurolignoside(JO),a natural compound,to bind to Toll-like receptor 4(TLR4)and treat ALI.The anti-inflammatory properties of JO were evaluated in vitro through Western blotting,enzyme-linked immunosorbent assay(ELISA),immunofluorescence staining,and co-immunoprecipitation.The investigation utilized a lipopolysaccharide(LPS)-induced ALI animal model to examine the therapeutic efficacy and mechanism of JO in vivo.JO attenuated inflammatory symptoms in infected cells and tissues by modulating the NOD-like receptor family pyrin domain containing protein 3(NLRP3)inflammasome and the nuclear factorκB(NF-κB)/mitogen-activated protein kinase(MAPK)pathway.Molecular docking simulations revealed JO binding to TLR4 active sites,confirmed by cellular thermal shift assay.Surface plasmon resonance(SPR)demonstrated direct interaction between JO and TLR4 with a Kd value of 35.1μmol·L^(-1).Moreover,JO inhibited tumor necrosis factorα(TNF-α),interleukin-1β(IL-1β),and IL-6 secretion and reduced leukocyte,neutrophil,lymphocyte,and macrophage infiltration in ALI-affected mice.JO also enhanced lung function and reduced ALI-related mortality.Immunohistochemical staining demonstrated JO's ability to suppress TLR4 expression in ALI-affected mouse lung tissue.This study establishes that JO can bind to TLR4 and effectively treat ALI,indicating its potential as a therapeutic agent for clinical applications.展开更多
基金supported by the National Natural Science Foundation of China(No.82260799)Guangxi Science and Technology Base and Talent Project(No.AA23026010)+3 种基金Undergraduate Innovation and Entrepreneurship Training Program(No.S202110600120)Guangxi Overseas“100 Persons’Plan”Highlevel Expert,University of Chinese Medicine(No.2022BS008)Guangxi University Young and Middle-aged Teachers Research Basic Ability Improvement Project(No.2023KY0303)Jiangxi Province 2022 Annual Graduate Student Innovation Special Fund Project(No.YC2022-B189)。
文摘Acute lung injury(ALI)is a severe disease caused by viral infection that triggers an uncontrolled inflammatory response.This study investigated the capacity of jasurolignoside(JO),a natural compound,to bind to Toll-like receptor 4(TLR4)and treat ALI.The anti-inflammatory properties of JO were evaluated in vitro through Western blotting,enzyme-linked immunosorbent assay(ELISA),immunofluorescence staining,and co-immunoprecipitation.The investigation utilized a lipopolysaccharide(LPS)-induced ALI animal model to examine the therapeutic efficacy and mechanism of JO in vivo.JO attenuated inflammatory symptoms in infected cells and tissues by modulating the NOD-like receptor family pyrin domain containing protein 3(NLRP3)inflammasome and the nuclear factorκB(NF-κB)/mitogen-activated protein kinase(MAPK)pathway.Molecular docking simulations revealed JO binding to TLR4 active sites,confirmed by cellular thermal shift assay.Surface plasmon resonance(SPR)demonstrated direct interaction between JO and TLR4 with a Kd value of 35.1μmol·L^(-1).Moreover,JO inhibited tumor necrosis factorα(TNF-α),interleukin-1β(IL-1β),and IL-6 secretion and reduced leukocyte,neutrophil,lymphocyte,and macrophage infiltration in ALI-affected mice.JO also enhanced lung function and reduced ALI-related mortality.Immunohistochemical staining demonstrated JO's ability to suppress TLR4 expression in ALI-affected mouse lung tissue.This study establishes that JO can bind to TLR4 and effectively treat ALI,indicating its potential as a therapeutic agent for clinical applications.
