Protection of lethal toxicity of endotoxin by Salvia miltiorrhiza BUNGE is via reduction in tumor necrosis factor alpha release and liver injury

Protection of lethal toxicity of endotoxin by Salvia miltiorrhiza BUNGE is via reduction in tumor necrosis factor alpha release and liver injury
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DOI:
10.1016/j.intimp.2005.11.008
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发表时间:
2006-05-01
影响因子:
5.6
通讯作者:
Chan, DKO
Chan, DKO
中科院分区:
医学2区
文献类型:
--
作者:
Wan, JMF;Sit, WH;Chan, DKO

文献摘要

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革兰氏阴性菌引起的脓毒症是重症监护病房患者发生的危及生命的综合征,脂多糖(LPS)是其主要原因之一。许多药用植物的天然产物通过调节多种促炎细胞因子而对内毒素血症诱导的脓毒症具有治疗价值。在本研究中,我们表明,丹参(SM)BUNGE或丹参,在中国医院用于治疗各种全身和外科感染,能够通过抑制TNF-α释放和保护肝损伤来阻断LPS在小鼠中的致死毒性。SM抑制LPS诱导的TNF-α释放的能力通过对人外周血白细胞(PBL)和RAW 264.7巨噬细胞系进行的体外实验进一步证实。通过流式细胞术进行的免疫表型分析显示,SM处理的PBL和LPS攻击小鼠的脾细胞中的T辅助细胞(CD 4)和T抑制细胞(CD 8)的比例得到改善。LPS诱导的血浆谷丙转氨酶(GPT)的下降提供了SM对肝损伤具有保护作用的证据。本研究解释了SM的一些已知生物学活性,并支持SM在预防革兰阴性菌引起的炎性疾病中的临床应用。(c)2005 Elsevier B. V.保留所有权利。
Lipopolysaccharide (LPS) has been implicated as one of the major cause of Gram-negative bacteria-induced sepsis that are life-threatening syndromes occurring in intensive care unit patients. Many natural products derived from medicinal plants may contain therapeutic values on protecting endotoxemia-induced sepsis by virtue their ability to modulate multiple pro-inflammatory cytokines. In the present study, we show that Salvia miltiorrhiza (SM) BUNGE or Danshen, used in treatment of various systemic and surgical infections in the hospitals of China, was able to block the lethal toxicity of LPS in mice via suppression of TNF-alpha release and protection on liver injury. The ability of SM to suppress LPS-induced TNF-alpha release is further confirmed by in vitro experiments conducted on human peripheral blood leukocytes (PBL) and the RAW 264.7 macrophage cell line. Immunophenotyping by flow cytometry shows improved T-helper cell (CD4) and T-suppressor cells (CD8) ratio in SM-treated PBL and splenocytes of LPS-challenged mice. The drop in plasma glutamate-pyruvate transaminase (GPT) induced by LPS provides evidence that SM can protect hepatic damage. The present study explains some known biological activities of SM, and supports the clinical application of SM in the prevention of inflammatory diseases induced by Gram-negative bacteria. (c) 2005 Elsevier B.V. All rights reserved.