Lipid-soluble extracts from Salvia miltiorrhiza inhibit production of LPS-induced inflammatory mediators via NF-κB modulation in RAW 264.7 cells and perform antiinflammatory effects in vivo.
Salvia miltiorrhiza, a traditional Chinese herbal medicine, is used to treat various inflammatory diseases. In the present study, the antiinflammatory effects of S. miltiorrhiza lipid-soluble extracts (SMLE) were demonstrated in vitro and in vivo, along with its underlying mechanism of action. SMLE significantly inhibited the production of NO, TNF-α, IL-1β and IL-6 in lipopolysaccharides (LPS)-stimulated RAW 264.7 cells. SMLE also inhibited the LPS-induced degradation of IκB-α in the cytoplasm and the translocation of p65 to the nucleus in RAW 264.7 cells. In addition, SMLE inhibited the production of intracellular reactive oxygen species (ROS) and the surface expression of CD14 induced by LPS. In animal models, intraperitoneal administration of SMLE increased the survival rate of endotoxemia and sepsis in mice. The topical administration of SMLE significantly inhibited ear edema induced by PMA. It was found that SMLE inhibits the LPS-induced gene and protein expression of iNOS, TNF-α, IL-1β and IL-6 in macrophages by blocking NF-κB activation, and these effects are mediated, at least in part, through the inhibition of intracellular ROS generation and the surface expression of CD14. The results suggest a possible therapeutic application of SMLE in inflammatory diseases and provide scientific evidence in support of the traditional Chinese medical practice of treatment with S. miltiorrhiza.
Institute of Medicinal Plant Development, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100193, PR China.
Meng
M
Li
Lei
L
Zhang
Run-Lan
RL
Cai
Yuan
Y
Gao
Yun
Y
Qi
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002470:Cell Survival; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D019446:Endotoxemia / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D008055:Lipids / Q000737:chemistry; D018950:Lipopolysaccharide Receptors / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000009:adverse effects / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000276:immunology* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D008517:Phytotherapy; D017382:Reactive Oxygen Species / Q000378:metabolism; D027561:Salvia miltiorrhiza / Q000737:chemistry* / Q000276:immunology; D018805:Sepsis / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology; D012995:Solubility; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D004365:Drugs, Chinese Herbal; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D008055:Lipids; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse