Yi-Li Wang1, Kwok-Keung Lam2, Pao-Yun Cheng3, Yen-Mei Lee4. 1. Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan. 2. Department of Pharmacology, Taipei Medical University, Taipei, Taiwan; Department of Anesthesiology, Catholic Mercy Hospital, Hsinchu, Taiwan. 3. Department of Physiology & Biophysics, Taipei, Taiwan. 4. Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan; Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan. Electronic address: ymlee@mail.ndmctsgh.edu.tw.
Abstract
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) 8h after LPS challenge. The plasma levels of ALT, LDH, TNF-α, and nitric oxide metabolites increased markedly during sepsis, which significantly reduced after celastrol treatments. Celastrol attenuated iNOS, TNF-α, NF-κB 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 8h 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.
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) 8h after LPS challenge. The plasma levels of ALT, LDH, TNF-α, and nitric oxide metabolites increased markedly during sepsis, which significantly reduced after celastrol treatments. Celastrol attenuated iNOS, TNF-α, NF-κB 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 8h 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.
Authors: Anderson Vulczak; Carlos Henrique Rocha Catalão; Luiz Alexandre Pedro de Freitas; Maria José Alves Rocha Journal: Int J Mol Sci Date: 2019-08-30 Impact factor: 5.923
Authors: Kiflai Bein; Koustav Ganguly; Timothy M Martin; Vincent J Concel; Kelly A Brant; Y P Peter Di; Swapna Upadhyay; James P Fabisiak; Louis J Vuga; Naftali Kaminski; Emrah Kostem; Eleazar Eskin; Daniel R Prows; Ann-Soo Jang; George D Leikauf Journal: Am J Physiol Lung Cell Mol Physiol Date: 2020-10-14 Impact factor: 5.464