title: Extract of Salvia miltiorrhiza (Danshen) induces Nrf2-mediated heme oxygenase-1 expression as a cytoprotective action in RAW 264.7 macrophages.
abstract: BACKGROUND
  Danshen (Salvia miltiorrhiza) is widely used in traditional herbal medicines for relief of a variety of symptoms related to complications arising from vascular diseases such as hypertension, diabetes, and atherosclerosis. Induction of heme oxygenase-1 (HO-1) expression protects against oxidative stress-induced cell damage, which plays an important role in cytoprotection in a variety of pathological models.
  
  
  METHODS
  In the present study, we investigated the effect of Danshen on the up-regulation of HO-1, an inducible and cytoprotective enzyme in RAW 264.7 macrophages. Molecular mechanisms underlying the effects, especially protective effects, was elucidated by analyzing the activation of transcription factors and their upstream signalling, and by evaluating the inhibitory effect of HO-1 on ROS production.
  
  
  RESULTS
  Danshen induced HO-1 mRNA expression and protein production, and nuclear translocation of NF-E2-related factor 2 in RAW 264.7 macrophages. Pharmacological inhibitors of PI3K/Akt and MEK1 attenuated HO-1 induction in Danshen-stimulated RAW 264.7 macrophages. Furthermore, Danshen pretreatment reduced intracellular production of reactive oxygen species after stimulation with hydrogen peroxide; this effect was reversed by the HO-1 inhibitor ZnPP.
  
  
  CONCLUSIONS
  Danshen induced HO-1 expression through PI3K/Akt-MEK1-Nrf2 pathway and reduced intracellular production of reactive oxygen species via induction of HO-1 expression. The results support a role of HO-1 in the cytoprotective effect of Danshen.
authors.affiliation: Department of Microbiology, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Seung Eun
authors.initials: SE
authors.lastname: Lee
authors.forename: Seong Il
authors.initials: SI
authors.lastname: Jeong
authors.forename: Hana
authors.initials: H
authors.lastname: Yang
authors.forename: Se Hee
authors.initials: SH
authors.lastname: Jeong
authors.forename: Young Pyo
authors.initials: YP
authors.lastname: Jang
authors.forename: Cheung-Seog
authors.initials: CS
authors.lastname: Park
authors.forename: Jinju
authors.initials: J
authors.lastname: Kim
authors.forename: Yong Seek
authors.initials: YS
authors.lastname: Park
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D000975:Antioxidants / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000494:pharmacology*; D004790:Enzyme Induction; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D048369:MAP Kinase Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology; D013058:Mass Spectrometry; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010618:Phenanthrolines / Q000302:isolation & purification / Q000494:pharmacology*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D018517:Plant Roots; D010946:Plants, Medicinal; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism; D027561:Salvia miltiorrhiza / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection
chemical_list: D000975:Antioxidants; D004365:Drugs, Chinese Herbal; D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D010618:Phenanthrolines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C028972:dan-shen root extract; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D048369:MAP Kinase Kinase 1; C482127:Map2k1 protein, mouse