title: Baicalein attenuates hypertrophic scar formation via inhibition of the transforming growth factor-β/Smad2/3 signalling pathway.
abstract: BACKGROUND
  Hypertrophic scars (HPSs) are characterized by excessive fibrosis associated with aberrant function of fibroblasts. Currently no satisfactory treatment has been developed.
  
  
  OBJECTIVE
  To investigate the effect of baicalein on HPSs and its underlying mechanisms.
  
  
  METHODS
  Baicalein was administered intradermally (10 μmol L(-1) in 100 μL sterile saline plus 10% dimethylsulfoxide) to mechanical-load-induced scars in mice once a day for 14 or 28 days. Histological and immunohistochemical studies were performed to evaluate scar hypertrophy and the function of fibroblasts. Human HPS-derived fibroblasts (HSFs) were determined by immunofluorescence study, collagen gel contraction assay and wound-healing assay. Also, protein expression of the transforming growth factor (TGF)-β signalling pathway was detected using Western blotting. Lastly, a molecular docking study and kinase binding assay were conducted in search of the potential interaction between baicalein and activin receptor-like kinase (ALK)5.
  
  
  RESULTS
  Baicalein treatment significantly attenuated HPS formation and collagen deposition in a mechanical-load-induced mouse model. Baicalein also inhibited the proliferation and activation of fibroblasts in vitro and in vivo. Furthermore, baicalein impaired the contractile and migration ability of HSFs. Protein expression investigation revealed that baicalein had an inhibitory effect on TGF-β/Smad2/3 signalling. Such bioactivity of baicalein may result from its selective binding to the ATP-binding pocket of ALK5, as suggested by the molecular docking study and kinase binding assay.
  
  
  CONCLUSIONS
  Baicalein could serve as a promising agent for treatment of HPSs and a selective ALK5 inhibitor.
authors: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, Shanghai, 200011, China.
authors: Y F
authors: YF
authors: Zhang
authors: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, Shanghai, 200011, China.
authors: S Z
authors: SZ
authors: Zhou
authors: Department of Anesthesiology, Renji Hospital; School of Medicine, Shanghai Jiao Tong University, Shanghai, 200011, China.
authors: X Y
authors: XY
authors: Cheng
authors: Clinical College of the General Hospital of Beijing Military Region, Anhui Medical University, Hefei, China.
authors: B
authors: B
authors: Yi
authors: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, Shanghai, 200011, China.
authors: S Z
authors: SZ
authors: Shan
authors: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, Shanghai, 200011, China.
authors: J
authors: J
authors: Wang
authors: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, Shanghai, 200011, China.
authors: Q F
authors: QF
authors: Li
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002648:Child; D017439:Cicatrix, Hypertrophic / Q000188:drug therapy* / Q000378:metabolism; D003879:Dermatologic Agents / Q000494:pharmacology*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects; D044950:Flavanones / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008807:Mice, Inbred BALB C; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D051899:Smad2 Protein / Q000037:antagonists & inhibitors*; D051900:Smad3 Protein / Q000037:antagonists & inhibitors*; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors*; D055815:Young Adult
chemical_list: D000975:Antioxidants; D003879:Dermatologic Agents; D044950:Flavanones; D018125:Receptors, Transforming Growth Factor beta; C497782:SMAD2 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1; C006680:baicalein; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625841:TGFBR1 protein, human; C000625842:Tgfbr1 protein, mouse