Protection of lethal toxicity of endotoxin by Salvia miltiorrhiza BUNGE is via reduction in tumor necrosis factor alpha release and liver injury.
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.
Wan
Jennifer Man-Fan
JM
Food and Nutritional Science Division, Department of Zoology, The University of Hong Kong, Kadoorie Biological Sciences Building, Pokfulam Road, Hong Kong, SAR, China. jmfwan@hkusua.hku.hk
Sit
Wai-Hung
WH
Lee
Cheuk-Lun
CL
Fu
Kelvin Hoi-Man
KH
Chan
Daniel Kwong-On
DK
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D016516:CD4-CD8 Ratio; D002460:Cell Line; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008070:Lipopolysaccharides; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D028321:Plant Preparations / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D027561:Salvia miltiorrhiza / Q000737:chemistry*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D017855:Transferases (Other Substituted Phosphate Groups) / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D004365:Drugs, Chinese Herbal; D008070:Lipopolysaccharides; D028321:Plant Preparations; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D017855:Transferases (Other Substituted Phosphate Groups); C106504:UDP-GlcNAc-undecaprenyl phosphate N-acetylglucosaminyl 1-phosphate transferase