Antidesmone, a unique tetrahydroquinoline alkaloid, prevents acute lung injury via regulating MAPK and NF-κB activities.
Acute lung injury, characterized by inflammation, is a main cause of respiratory failure that affects patients worldwide. Antidesmone is one compound mainly isolated from Ajugade cumbens Thunb (Labiatae), an herb agent of Labiatae family. In this research, we investigated the anti-inflammation effect of antidesmone in vitro and in vivo. Antidesmone exerted none apparently cytotoxicity in vitro and toxic in vivo. In vitro results demonstrated that antidesmone suppressed the excess inflammatory cytokines production, including tumor necrosis factor-α, interleukin-6 and interleukin-1β in lipopolysaccharide (LPS)-exposed RAW264.7 cells. In vivo results suggested that antidesmone inhibited inflammatory cytokines in the bronchoalveolar lavage fluid and lung tissue after LPS stimulation. Moreover, antidesmone attenuated the nuclear translocation of p65. Mechanism study revealed that mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways play important roles in antidesmone's action. Taken together, our data uncover a relative toxic anti-inflammatory drug, antidesmone, can inhibit inflammation on stimulated macrophages and thereby prevents acute lung injury by regulating MAPK and NF-κB signaling pathways.
Department of Traditional Chinese Medicine, HuaDong Hospital, FuDan University, Shanghai 200040, PR China.
XinGang
X
Lu
Department of Anesthesiology, Obstetrics and Gynecology Hospital, FuDan University, Shanghai 200040, PR China.
YingXiu
Y
Pu
Department of Gastroenterology, Inner Mongolia Autonomous Region Hospital of Traditional Chinese Medicine, Hohhot, Inner Mongolia 010020, PR China.
WeiGuang
W
Kong
Department of Pulmonary, HuaDong Hospital, FuDan University, Shanghai 200040, PR China.
XiaoDan
X
Tang
Department of Pulmonary, HuaDong Hospital, FuDan University, Shanghai 200040, PR China.
JiAn
J
Zhou
Department of Traditional Chinese Medicine, HuaDong Hospital, FuDan University, Shanghai 200040, PR China.
HaiXin
H
Gou
Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University, Shanghai 200433, PR China.
Xiao
X
Song
Department of Pharmacy, HuaDong Hospital, FuDan University, Shanghai 200040, PR China.
HaiFeng
H
Zhou
Department of Pharmacy, HuaDong Hospital, FuDan University, Shanghai 200040, PR China.
NingZhou
N
Gao
Department of Pharmacy, HuaDong Hospital, FuDan University, Shanghai 200040, PR China. Electronic address: shj421@126.com.
Jie
J
Shen
D055371:Acute Lung Injury / Q000188:drug therapy*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001372:Aza Compounds / Q000627:therapeutic use*; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D018836:Inflammation Mediators / Q000378:metabolism; D019686:Lamiaceae / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D000067996:RAW 264.7 Cells; D015398:Signal Transduction / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D001372:Aza Compounds; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; C471325:antidesmone; D020928:Mitogen-Activated Protein Kinases
Acute lung injury; Antidesmone; MAPK; NF-κB; RAW264.7 cell