Dihydroarteannuin ameliorates lupus symptom of BXSB mice by inhibiting production of TNF-alpha and blocking the signaling pathway NF-kappa B translocation.
The aim of this study was to investigate the mechanisms of action of Dihydroarteannuin (DHA), a semi-synthesized agent from the starting material artemisinin extracted from the Chinese Traditional Herbs Artemisia annua, on ameliorating the symptoms of lupus on BXSB mice. The concentration of TNF-alpha in the culture supernatant of the peritoneal macrophages and in the sera of BXSB mice was determined by the ELISA method. NF-kappaB protein expression and translocation were assayed by the EMSA method and laser confocal scanning microscopy method, respectively. IkappaB-alpha and NF-kappaB p65 protein expression were determined by the Western blot method. Renal tissue of the BXSB mice was prepared for assaying inhibitory activity of DHA on NF-kappaB, p65 and IkappaB-alpha protein expression in vivo. The peritoneal macrophages were prepared for analysis inhibitory effects of DHA on translocation of NF-kappaB into nuclear in vitro. We found that DHA strongly reduced the production of TNF-alpha in the culture supernatant of the peritoneal macrophages and in the sera of BXSB mice in vitro or in vivo. The results demonstrated that DHA decreased the expression of NF-kappaB subunit p65 protein and the activation of NF-kappaB in the renal tissue of BXSB mice in vivo. DHA effectively inhibited the nuclear translocation of NF-kappaB in peritoneal macrophages of BXSB mice in vitro. Furthermore, it was demonstrated that the degradation of IkappaB-alpha protein was significantly inhibited by DHA. These observations suggested that the inhibitory effects of DHA on TNF-alpha production may result from the block in the NF-kappaB signaling pathway upstream of IkappaB degradation.
Li
Wei-dong
WD
Department of Pharmacology, Health Science Center, Peking University, 38 Xue-yuan Road, Beijing 100083, PR China. lwdpharma@126.com
Dong
Yan-jun
YJ
Tu
You-you
YY
Lin
Zhi-bin
ZB
D000818:Animals; D037621:Artemisinins; D015153:Blotting, Western; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D007441:Intubation, Gastrointestinal; D008070:Lipopolysaccharides / Q000378:metabolism / Q000494:pharmacology; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D015394:Molecular Structure; D021381:Protein Transport / Q000187:drug effects; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D051996:Transcription Factor RelA / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D037621:Artemisinins; D008070:Lipopolysaccharides; D012717:Sesquiterpenes; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C112717:dihydroarteannuin B; C039060:artenimol