title: Betulin inhibits pro-inflammatory cytokines expression through activation STAT3 signaling pathway in human cardiac cells.
abstract: OBJECTIVE
  Signal transducer and activator of transcription 3 (STAT3) is an important regulator of cardiac survival pathways. Decreased expression or activity of STAT3 in patients with end-stage heart failure demonstrated a clinical relevance of STAT3 in cardiac diseases. Betulin, a pentacyclic triterpene, has drawn extensive attention towards its beneficial effects. However, little is known about its roles in cardiac cells.
  
  
  METHODS
  We investigated the effects of betulin on the pro-inflammatory processes in human cardiac AC16 cells. Genes expression of pro-inflammatory cytokines and activation of NF-κB signaling were analyzed. Besides, levels of phosphorylated STAT3 and its down-stream target genes were measured to evaluate the activation of STAT3. Finally, STAT3 inhibitor and small interfering RNA (siRNA) oligos were used to determine the roles of STAT3 in AC16 cells treated with betulin.
  
  
  RESULTS
  Our results revealed that betulin inhibited pro-inflammatory cytokines expression and NF-κB signaling activation through STAT3 signaling. Besides, betulin treatment also induced the expression of Bcl-xL, an anti-apoptotic downstream effector of STAT3.
  
  
  CONCLUSIONS
  Our results, for the first time, uncovered the cardioprotective roles of betulin, which may be useful to reduce the occurrence of adverse cardiovascular events.
authors.affiliation: Department of Anesthesiology, Qilu Hospital, Shandong University, Jinan, P.R. China. yjingui1323@126.com  
authors.forename: S-Y
authors.initials: SY
authors.lastname: Zhang
authors.forename: Q-F
authors.initials: QF
authors.lastname: Zhao
authors.forename: N-N
authors.initials: NN
authors.lastname: Fang
authors.forename: J-G
authors.initials: JG
authors.lastname: Yu
mesh_terms: D002460:Cell Line; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D005786:Gene Expression Regulation; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014315:Triterpenes / Q000494:pharmacology*; D000094062:Betulinic Acid
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D050796:STAT3 Transcription Factor; D014315:Triterpenes; C494086:STAT3 protein, human; C002503:betulin; D000094062:Betulinic Acid