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Celastrol prevents circulatory failure via induction of heme oxygenase-1 and heat shock protein 70 in endotoxemic rats

作者 Wang, Yi-Li; Lam, Kwok-Keung; Cheng, Pao-Yun; Lee, Yen-Mei

期刊 JOURNAL OF ETHNOPHARMACOLOGY , MAR 13 2015,:162

DOI 10.1016/j.jep.2014.12.062 PubMed 25571843

摘要 Ethnopharmacological relevance: Celastrol, a quinone methide extracted from the root of Tripterygium wilfordii Hook, possesses anti-oxidant and anti-inflammatory effects. Tripterygium wilfordii Hook is officially listed in the Chinese Pharmacopoeia and is used traditionally against rheumatoid arthritis, ankylosing spondylitis, and cancer. Furthermore, the circulatory protective effect of celastrol on an in vivo animal model of sepsis was investigated.Aim of the study: Sepsis is a systemic inflammatory disorder that increases tissue oxidative stress and leads to multiple organ injury. We evaluated the beneficial effects of celastrol on multiple organ failure induced by lipopolysaccharide (LPS) in rats.Materials and methods: Celastrol (0.5 and 1.0 mg/kg, i.v.) was administered to anaesthetized rats 2 h before and 30 min after LPS challenge (10 mg/kg, i.v.). Eight hours later, cardiac and aortic protein expressions related to inflammatory responses, superoxide anion production, and reduced glutathione (GSH) level were measured.Results: Treatment with celastrol prevented circulatory failure (bradycardia and hypotension) 8 h after LPS challenge. The plasma levels of ALT, LDH, TNE-alpha, and nitric oxide metabolites increased markedly during sepsis, which significantly reduced after celastrol treatments. Celastrol attenuated iNOS, TNF-alpha, NF-kappa B phospho-p65 expression, superoxide anion production, and caspase 3 activity in the cardiovascular system, all of which were markedly elevated after LPS challenge. Furthermore, celastrol induced HO-1 and HSP70 expressions increase in nuclear levels of Nrf2 and HSF-1, respectively, and increase cardiac GSH level 8 h after LPS challenge.Conclusion: Anti-inflammatory and anti-oxidant effects of celastrol contribute to prevent circulatory failure in sepsis. Induction of HO-1 and HSP70 by celastrol participates in these beneficial effects. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

涉及物种 雷公藤 Tripterygium wilfordii