Adjudin attenuates lipopolysaccharide (LPS)- and ischemia-induced microglial activation.
Neuroinflammation caused by microglial activation plays a key role in ischemia, neurodegeneration and many other CNS diseases. In this study, we found that Adjudin, a potential non-hormonal male contraceptive, exhibits additional function to reduce the production of proinflammatory mediators. Adjudin significantly inhibited LPS-induced IL-6 release and IL-6, IL-1β, TNF-α expression in BV2 microglial cells. Furthermore, Adjudin exhibited anti-inflammatory properties by suppression of NF-κB p65 nuclear translocation and DNA binding activity as well as ERK MAPK phosphorylation. To determine the in vivo effect of Adjudin, we used a permanent middle cerebral artery occlusion (pMCAO) mouse model and found that Adjudin could reduce ischemia-induced CD11b expression, a marker of microglial activation. Furthermore, Adjudin treatment attenuated brain edema and neurological deficits after ischemia but did not reduce infarct volume. Thus, our data suggest that Adjudin may be useful for mitigating neuroinflammation.
School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, People's Republic of China.
Jiaxiang
J
Shao
Tengyuan
T
Liu
Qian Reuben
QR
Xie
Tingting
T
Zhang
Hemei
H
Yu
Boshi
B
Wang
Weihai
W
Ying
Dolores D
DD
Mruk
Bruno
B
Silvestrini
C Yan
CY
Cheng
Weiliang
W
Xia
D000704:Analysis of Variance; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001929:Brain Edema / Q000209:etiology / Q000517:prevention & control; D020520:Brain Infarction / Q000209:etiology / Q000517:prevention & control; D039481:CD11b Antigen / Q000378:metabolism; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006834:Hydrazines / Q000627:therapeutic use*; D007191:Indazoles / Q000627:therapeutic use*; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy* / Q000473:pathology*; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D017628:Microglia / Q000187:drug effects*; D016328:NF-kappa B / Q000378:metabolism; D009422:Nervous System Diseases / Q000188:drug therapy / Q000209:etiology; D011597:Psychomotor Performance / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
C432482:1-(2,4-dichlorobenzyl)indazole-3-carbohydrazide; D000893:Anti-Inflammatory Agents; D039481:CD11b Antigen; D006834:Hydrazines; D007191:Indazoles; D008070:Lipopolysaccharides; D016328:NF-kappa B