title: Anti-fibrotic effects of phenolic compounds on pancreatic stellate cells.
abstract: BACKGROUND
  Pancreatic fibrosis is a prominent histopathological characteristic of chronic pancreatitis and plausibly a dynamic process of transition to the development of pancreatic ductal adenocarcinoma. Conversely, the activation of pancreatic stellate cells (PSCs) has been recently suggested as the key initiating step in pancreatic fibrosis. As natural polyphenols had been largely applied in complementary therapies in the past decade, in this study, we aimed to investigate which groups of phenolic compounds exert promising inhibitory actions on fibrogenesis as there are few effective strategies for the treatment of pancreatic fibrosis to date.
  
  
  METHODS
  We examined the anti-fibrotic effects of a variety of herbal constituents using a cellular platform, the LTC-14 cells, which retained essential characteristics and morphologies of primary PSCs, by means of various biochemical assays including cell viability test, real-time polymerase chain reaction and Western blotting analysis.
  
  
  RESULTS
  Among a number of commonly used herbal constituents, we found that the application of rhein, emodin, curcumin and resveratrol significantly suppressed the mRNA and protein levels of several fibrotic mediators namely alpha-smooth muscle actin, type I collagen and fibronectin in LTC-14 cells against transforming growth factor-beta stimulation. Though the values of cytotoxicity varied, the mechanism of the anti-fibrotic action of these four phenolic compounds was principally associated with a decrease in the activation of the nuclear factor-kappaB signaling pathway.
  
  
  CONCLUSIONS
  Our findings suggest that the mentioned phenolic compounds may serve as anti-fibrotic agents in PSC-relating disorders and pathologies, particularly pancreatic fibrosis.
authors.affiliation: School of Fundamental Medical Science, Guangzhou University of Chinese Medicine, Guangzhou, China.
authors.forename: Zesi
authors.initials: Z
authors.lastname: Lin
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, 3/F, SCM Building, 7 Baptist University Road, Kowloon, Hong Kong, SAR, China.
authors.forename: Lu-Cong
authors.initials: LC
authors.lastname: Zheng
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, 3/F, SCM Building, 7 Baptist University Road, Kowloon, Hong Kong, SAR, China.
authors.forename: Hong-Jie
authors.initials: HJ
authors.lastname: Zhang
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, 3/F, SCM Building, 7 Baptist University Road, Kowloon, Hong Kong, SAR, China. tsang@hkbu.edu.hk.
authors.forename: Siu Wai
authors.initials: SW
authors.lastname: Tsang
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, 3/F, SCM Building, 7 Baptist University Road, Kowloon, Hong Kong, SAR, China. bzxiang@hkbu.edu.hk.
authors.forename: Zhao-Xiang
authors.initials: ZX
authors.lastname: Bian
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D005355:Fibrosis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D058954:Pancreatic Stellate Cells / Q000187:drug effects* / Q000378:metabolism; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D024042:Collagen Type I; D005353:Fibronectins; D010636:Phenols; D016212:Transforming Growth Factor beta