title: Aloe-emodin from rhubarb (Rheum rhabarbarum) inhibits lipopolysaccharide-induced inflammatory responses in RAW264.7 macrophages.
abstract: BACKGROUND
  Rheum rhabarbarum (rhubarb) has long been used for the treatment of inflammation in China and other Asian countries. However, the mechanism underlying the anti-inflammatory activity of this medicinal plant is not fully understood. The present study was designed to investigate the anti-inflammatory effects of anthraquinones, the major constituents in rhubarb, and the molecular mechanism involved in their anti-inflammatory effects.
  
  
  METHODS
  RAW264.7 cells were stimulated by lipopolysaccharide (LPS) in the presence or absence of the compounds examined. The proliferation of RAW264.7 cells was assayed by the Alamar-Blue method. The quantity of nitric oxide (NO) was determined by Griess assay. The expression of pro-inflammatory cytokines was determined by enzyme-linked immunosorbent assay (ELISA) and quantitative real-time PCR. Inducible nitric oxide synthase (iNOS), inhibitor of nuclear factor κBα (IκBα), extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (MAPK), c-Jun NH2-terminal kinase (JNK), and Akt/phosphoinositide 3-kinase (PI3K) protein expression levels were determined by Western blotting.
  
  
  RESULTS
  Aloe-emodin markedly suppressed the production of NO, interleukin-6 (IL-6), and interleukin-1β (IL-1β) in LPS-stimulated RAW264.7 cells with no apparent cytotoxicity. The mRNA expression levels of iNOS, IL-6, and IL-1β genes were also significantly inhibited by aloe-emodin. Western blot analysis showed that aloe-emodin suppressed LPS-induced iNOS protein expression, IκBα degradation, and the phosphorylation of ERK, p38, JNK, and Akt.
  
  
  CONCLUSIONS
  These results demonstrate that aloe-emodin is the bioactive component of rhubarb that confers an anti-inflammatory effect through a likely mechanism involving a decrease in pro-inflammatory cytokine production in LPS-induced RAW264.7 macrophages via inhibition of NF-κB, MAPK, and PI3K pathways.
authors.affiliation: Chengdu University of Traditional Chinese Medicine, Chengdu 610075, PR China.
authors.forename: Boyang
authors.initials: B
authors.lastname: Hu
authors.affiliation: Chengdu University of Traditional Chinese Medicine, Chengdu 610075, PR China.
authors.forename: Hai
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Chengdu University of Traditional Chinese Medicine, Chengdu 610075, PR China.
authors.forename: Xianli
authors.initials: X
authors.lastname: Meng
authors.affiliation: Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, PR China. Electronic address: wangfei@cib.ac.cn.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.affiliation: Chengdu University of Traditional Chinese Medicine, Chengdu 610075, PR China. Electronic address: areticlemxl@gmail.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
mesh_terms: D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D020672:I-kappa B Proteins / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012250:Rheum
chemical_list: D000880:Anthraquinones; D000893:Anti-Inflammatory Agents; D020672:I-kappa B Proteins; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; C000606205:Nfkbia protein, mouse; D012333:RNA, Messenger; D000072000:NF-KappaB Inhibitor alpha; D009569:Nitric Oxide; C518327:aloe emodin; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases
keywords: Aloe-emodin; Aloe-emodin (PubChem CID: 10207); Anthraquinone; Chrysophanol (PubChem CID: 10208); Emodin (PubChem CID: 3220); Inflammation; Macrophage; Physcion (PubChem CID: 10639); Rhein (PubChem CID: 10168); Rhubarb