title: Chlorogenic acid and luteolin synergistically inhibit the proliferation of interleukin-1β-induced fibroblast-like synoviocytes through regulating the activation of NF-κB and JAK/STAT-signaling pathways.
abstract: BACKGROUND
  Chlorogenic acid (CGA) and luteolin (Lut) are the predominant constituents of Caulis Lonicerae, which is usually used in the treatment for rheumatoid arthritis (RA).
  
  
  OBJECTIVE
  In this study, we investigated whether CGA and Lut could synergistically inhibit the proliferation of fibroblast-like synoviocytes (FLSs) in RA synovial tissues.
  
  
  METHODS
  Rat FLS cells (RSC-364) induced by interleukin (IL)-1β were treated by CGA, Lut or both of them. The apoptosis rates were detected by flow cytometer. Protein expression of key molecules of NF-κB and JAK/STAT signaling pathways were detected by Western blot.
  
  
  CONCLUSIONS
  Treatment with CGA and Lut inhibited the proliferation of RSC-364 cells stimulated by IL-1β significantly and induced cell apoptosis notably. The ratio of apoptosis in RSC-364 cells induced with IL-1β accompanied by both CGA and Lut increased approximately 7-fold compared with those incubated with IL-1β alone. The results of immunoblot analysis revealed that the key molecules involved in the NF-κB and JAK/STAT-signaling pathways, including NF-κB p50, p100, IKKα/β, gp103, JAK1 and STAT3, were decreased significantly in RSC-364 cells treated by IL-1β plus CAG and Lut compared with those incubated with IL-1β alone. Additionally, the amounts of phospho-IKKα/β and phospho-STAT3 were also decreased significantly in cells treated with CGA and Lut. Furthermore, the synergistic effect of CGA and Lut was superior to the effect of one of these two ingredients.
  
  
  CONCLUSIONS
  Our finding suggested that the combination of CGA and Lut may be a potential therapeutic treatment for the inflammatory proliferation of synoviocytes in patients with RA.
authors.affiliation: a Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing , Dongzhimen Hospital, Beijing University of Chinese Medicine , Beijing , China .
authors.forename: Lixia
authors.initials: L
authors.lastname: Lou
authors.affiliation: b Department of Rheumatology , Putuo District Center Hospital , Shanghai , China , and.
authors.forename: Yujun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: a Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing , Dongzhimen Hospital, Beijing University of Chinese Medicine , Beijing , China .
authors.forename: Jingwei
authors.initials: J
authors.lastname: Zhou
authors.affiliation: a Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing , Dongzhimen Hospital, Beijing University of Chinese Medicine , Beijing , China .
authors.forename: Yi
authors.initials: Y
authors.lastname: Wei
authors.affiliation: c College of Pharmacy, Guangxi University of Chinese Medicine , Nanning , China.
authors.forename: Jiagang
authors.initials: J
authors.lastname: Deng
authors.affiliation: a Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing , Dongzhimen Hospital, Beijing University of Chinese Medicine , Beijing , China .
authors.forename: Bin
authors.initials: B
authors.lastname: Dong
authors.affiliation: a Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing , Dongzhimen Hospital, Beijing University of Chinese Medicine , Beijing , China .
authors.forename: Limin
authors.initials: L
authors.lastname: Chai
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002726:Chlorogenic Acid / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D053613:Janus Kinase 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047311:Luteolin / Q000494:pharmacology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D016328:NF-kappa B; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D002726:Chlorogenic Acid; C507906:Jak1 protein, rat; D053613:Janus Kinase 1; D047311:Luteolin
keywords: Chlorogenic acid; Janus-activated kinase/signal transducer and activator of transcription 3; fibroblast-like synoviocytes; interleukin-1β; luteolin; nuclear factor kappa B