title: Anti-inflammatory activity of ethanol extract derived from Phaseolus angularis beans.
abstract: BACKGROUND
  Phaseolus angularis Wight (adzuki bean) is an ethnopharmacologically well-known folk medicine that is prescribed for infection, edema, and inflammation of the joints, appendix, kidney and bladder in Korea, China and Japan.
  
  
  OBJECTIVE
  The anti-inflammatory effect of this plant and its associated molecular mechanisms will be investigated.
  
  
  METHODS
  The immunomodulatory activity of Phaseolus angularis ethanol extract (Pa-EE) in toll like receptor (TLR)-activated macrophages induced by ligands such as lipopolysaccharide (LPS), Poly (I:C), and pam3CSK was investigated by assessing nitric oxide (NO) and prostaglandin (PG)E(2) levels. To identify which transcription factors such as nuclear factor (NF)-κB and their signaling enzymes can be targeted to Pa-EE, biochemical approaches including reporter gene assays, immunoprecipitation, kinase assays, and immunoblot analyses were also employed. Finally, whether Pa-EE was orally available, ethanol (EtOH)/hydrochloric acid (HCl)-induced gastritis model in mice was used.
  
  
  RESULTS
  Pa-EE dose-dependently suppressed the release of PGE(2) and NO in LPS-, Poly(I:C)-, and pam3CSK-activated macrophages. Pa-EE strongly down-regulated LPS-induced mRNA expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2. Interestingly, Pa-EE markedly inhibited NF-κB, activator protein (AP)-1, and cAMP response element binding protein (CREB) activation; further, according to direct kinase assays and immunoblot analyses, Pa-EE blocked the activation of the upstream signaling molecules spleen tyrosine kinase (Syk), p38, and transforming growth factor β-activated kinase 1 (TAK1). Finally, orally administered Pa-EE clearly ameliorated EtOH/HCl-induced gastritis in mice.
  
  
  CONCLUSIONS
  Our results suggest that Pa-EE can be further developed as a promising anti-inflammatory remedy because it targets multiple inflammatory signaling enzymes and transcription factors.
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Tao
authors.initials: T
authors.lastname: Yu
authors.forename: Hyo Min
authors.initials: HM
authors.lastname: Ahn
authors.forename: Ting
authors.initials: T
authors.lastname: Shen
authors.forename: Keejung
authors.initials: K
authors.lastname: Yoon
authors.forename: Hyun-Jae
authors.initials: HJ
authors.lastname: Jang
authors.forename: Yong Jin
authors.initials: YJ
authors.lastname: Lee
authors.forename: Hyun Mo
authors.initials: HM
authors.lastname: Yang
authors.forename: Jae Hun
authors.initials: JH
authors.lastname: Kim
authors.forename: Changhyuk
authors.initials: C
authors.lastname: Kim
authors.forename: Moon Hi
authors.initials: MH
authors.lastname: Han
authors.forename: Sang-Hun
authors.initials: SH
authors.lastname: Cha
authors.forename: Tae Wong
authors.initials: TW
authors.lastname: Kim
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Jaehwi
authors.initials: J
authors.lastname: Lee
authors.forename: Jae Youl
authors.initials: JY
authors.lastname: Cho
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000737:chemistry*; D005756:Gastritis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D057809:HEK293 Cells; D006801:Humans; D006851:Hydrochloric Acid; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D027805:Phaseolus / Q000737:chemistry; D010936:Plant Extracts / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012997:Solvents / Q000737:chemistry*; D000072377:Syk Kinase; D051193:Toll-Like Receptors / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D000893:Anti-Inflammatory Agents; D017362:Cyclic AMP Response Element-Binding Protein; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D000431:Ethanol; D006851:Hydrochloric Acid; D047908:Intracellular Signaling Peptides and Proteins; D020930:MAP Kinase Kinase Kinases; D016328:NF-kappa B; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D010936:Plant Extracts; D011505:Protein-Tyrosine Kinases; D012997:Solvents; D000072377:Syk Kinase; D051193:Toll-Like Receptors; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; D019061:src-Family Kinases; D000099151:MAP Kinase Kinase Kinase 7; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; C000606896:SYK protein, human; C000606897:Syk protein, mouse