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Protostemonine effectively attenuates lipopolysaccharide-induced acute lung injury in mice

  
@article{APS9706,
	author = {Ya-xian WU and Hui-qiong HE and Yun-juan NIE and Yun-he DING and Lei SUN and Feng QIAN},
	title = {Protostemonine effectively attenuates lipopolysaccharide-induced acute lung injury in mice},
	journal = {Acta Pharmacologica Sinica},
	volume = {39},
	number = {1},
	year = {2017},
	keywords = {},
	abstract = {Abstract
Protostemonine (PSN) is the main anti-inflammatory alkaloid extracted from the roots of Stemona sessilifolia (known as “Baibu” in traditional Chinese medicine). Here, we reported the inhibitory effects of PSN on lipopolysaccharide (LPS)-induced macrophage activation in vitro and LPS-induced acute lung injury in mice. Macrophage cell line RAW264.7 cells and mouse bone marrow-derived macrophages (BMDMs) were treated with PSN (1, 3, 10, 30 and 100 μmol/L) for 0.5 h and then challenged with LPS (0.1 μg/mL) for 24 h. Pretreatment with PSN significantly inhibited LPS-induced phosphorylation of MAPKs and AKT, iNOS expression and NO production in the macrophages. C57BL/6 mice were intratracheally injected with LPS (5 mg/kg) to induce acute lung injury (ALI). The mice were subsequently treated with PSN (10 mg/kg, ip) at 4 and 24 h after LPS challenge. PSN administration significantly attenuated LPS-induced inflammatory cell infiltration, reduced pro-inflammatory cytokine (TNF-α, IL-1β and IL-6) production and eliminated LPS-mediated lung edema. Furthermore, PSN administration significantly inhibited LPS-induced pulmonary MPO activity. Meanwhile, LPS-induced phosphorylation of p38 MAPK, iNOS expression and NO production in the lungs were also suppressed. The results demonstrate that PSN effectively attenuates LPS-induced inflammatory responses in vitro and in vivo; the beneficial effects are associated with the decreased phosphorylation of MAPK and AKT and the reduced expression of pro-inflammatory mediators, such as iNOS, NO and cytokines. These data suggest that PSN may be a potential therapeutic agent in the treatment of ALI.},
	issn = {1745-7254},	url = {http://www.chinaphar.com/article/view/9706}
}