Acute lung injury(ALI)is a sudden onset systemic inflammatory response.ALI causes severe morbidity and death and currently no effective pharmacological therapies exist.Natural products represent an excellent resource for discovering new drugs.Screening anti-inflammatory compounds from the natural product bank may offer viable candidates for molecular-based therapies for ALI.In this study,165 natural compounds were screened for anti-inflammatory activity in lipopolysaccharide(LPS)-challenged macrophages.Among the screened compounds,flavokawain B(FKB)significantly reduced LPS-induced pro-inflammatory IL-6 secretion in macrophages.FKB also reduced the formation of LPS/TLR4/MD2 complex by competitively binding to MD2,suppressing downstream MAPK and NF-KB signaling activation.Finally,FKB treatment of mice reduced LPS-induced lung injury,systemic and local inflammatory cytokine production,and macrophage infiltration in lungs.These protective activities manifested as increased survival in the ALI model,and reduced mortality upon bacterial infection.In summary,we demonstrate that the natural product FKB protects against LPS-induced lung injury and sepsis by interacting with MD2 and inhibiting inflammatory responses.FKB may potentially serve as a therapeutic option for the treatment of ALI.

Wu Luo;Li-bin Yang;Chen-chen Qian;Bao Ma;Gloria M.Manjengwa;Xiao-min Miao;Jie Wang;Cheng-hong Hu;Bo Jin;Ling-xi Zhang;Chao Zheng;Guang Liang;Yi Wang

Chemical Biology Research Center,School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou 325035,China;MedicalResearch Center,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou 325000,China;Department of Endocrinology,the Second Affiliated Hospital of Zhejiang University,Hangzhou 310009,China;School of Pharmaceutical Sciences,Hangzhou Medical College,Hangzhou 311399,China;Wenzhou Institute,University of Chinese Academy of Sciences,Wenzhou 325001,China

中国药理学报（英文版）

[1]Wu Luo;Li-bin Yang;Chen-chen Qian;Bao Ma;Gloria M.Manjengwa;Xiao-min Miao;Jie Wang;Cheng-hong Hu;Bo Jin;Ling-xi Zhang;Chao Zheng;Guang Liang;Yi Wang-.Flavokawain B alleviates LPS-induced acute lung injury via targeting myeloid differentiation factor 2)[J].中国药理学报（英文版）,2022(07):1758-1768

Flavokawain,flavokawain

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