title: In vivo and in vitro anti-inflammatory activities of Persicaria chinensis methanolic extract targeting Src/Syk/NF-κB.
abstract: BACKGROUND
  Persicaria chinensis L. (Polygonaceae) [also synonym as Polygonum chimnense L.] has been used as Chinese traditional medicine to treat ulcer, eczema, stomach ache, and various inflammatory skin diseases. Due to no molecular pharmacological evidence of this anti-inflammatory herbal plant, we investigated the inhibitory mechanisms and target proteins contributing to the anti-inflammatory responses of the plant by using its methanolic extract (Pc-ME).
  
  
  METHODS
  We used lipopolysaccharide (LPS)-treated macrophages and a murine HCl/EtOH-induced gastritis model to evaluate the anti-inflammatory activity of Pc-ME. HPLC analysis was employed to identify potential active components of this extract. Molecular approaches including kinase assays, reporter gene assays, immunoprecipitation analysis, and overexpression of target enzymes were used to confirm target enzymes.
  
  
  RESULTS
  Pc-ME inhibited LPS-induced nitric oxide and prostaglandin E2 release by RAW264.7 macrophages and ameliorated HCl/EtOH-induced gastric ulcers in mice. The nuclear translocation of NF-κB (p65 and p50) was suppressed by Pc-ME. Phosphorylation of Src and Syk, their kinase activities, and formation of the signaling complex of these proteins were repressed by Pc-ME. Phosphorylation of p85 and Akt induced by Src or Syk overexpression was blocked by Pc-ME. In the mouse gastritis model, orally administered Pc-ME suppressed the increased phosphorylation of IκBα, Αkt, Src, and Syk. Caffeic acid, kaempferol, and quercetin, identified as major anti-inflammatory components of Pc-ME by HPLC, displayed strong nitric oxide inhibitory activity in LPS-treated macrophages.
  
  
  CONCLUSIONS
  Pc-ME might play a pivotal ethnopharmacologic role as an anti-inflammatory herbal medicine by targeting Syk and Src kinases and their downstream transcription factor NF-κB.
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea; Department of Animal Science, Patuakhali Science and Technology University, Bangladesh.
authors.forename: Muhammad Jahangir
authors.initials: MJ
authors.lastname: Hossen
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Kwang-Soo
authors.initials: KS
authors.lastname: Baek
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Eunji
authors.initials: E
authors.lastname: Kim
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Woo Seok
authors.initials: WS
authors.lastname: Yang
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Deok
authors.initials: D
authors.lastname: Jeong
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Jun Ho
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Dae-Hyuk
authors.initials: DH
authors.lastname: Kweon
authors.affiliation: Department of Biochemistry, Kangwon National University, Chucheon 220-700, Republic of Korea.
authors.forename: Deok Hyo
authors.initials: DH
authors.lastname: Yoon
authors.affiliation: Department of Biochemistry, Kangwon National University, Chucheon 220-700, Republic of Korea.
authors.forename: Tae Woong
authors.initials: TW
authors.lastname: Kim
authors.affiliation: Department of Veterinary Physiology, College of Veterinary Medicine, Biosafety Research Institute, Chonbuk National University, Jeonju 561-756, Republic of Korea. Electronic address: jhkim1@chonbuk.ac.kr.
authors.forename: Jong-Hoon
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea. Electronic address: jaecho@skku.edu.
authors.forename: Jae Youl
authors.initials: JY
authors.lastname: Cho
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D000431:Ethanol; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D005756:Gastritis / Q000139:chemically induced / Q000188:drug therapy; D057809:HEK293 Cells; D006801:Humans; D006851:Hydrochloric Acid; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D008070:Lipopolysaccharides; D008264:Macrophages; D008297:Male; D000432:Methanol / Q000737:chemistry; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D028502:Polygonum; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D012997:Solvents / Q000737:chemistry; D000072377:Syk Kinase; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D005419:Flavonoids; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010936:Plant Extracts; D047428:Protein Kinase Inhibitors; D012997:Solvents; D000431:Ethanol; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D019061:src-Family Kinases; D006851:Hydrochloric Acid; D000432:Methanol
keywords: Anti-inflammatory effect; NF-κB.; Nitric oxide; Persicaria chinensis (Polygonaceae); Prostaglandin E(2); Quercetin