title: Apigenin inhibits pancreatic stellate cell activity in pancreatitis.
abstract: BACKGROUND
  Chronic pancreatitis (CP) is characterized by recurrent pancreatic injury, resulting in inflammation, necrosis, and fibrosis. There are currently no drugs limiting pancreatic fibrosis associated with CP, and there is a definite need to fill this void in patient care.
  
  
  METHODS
  Pancreatitis was induced in C57/BL6 mice using supraphysiologic doses of cerulein, and apigenin treatment (once daily, 50 μg per mouse by oral gavage) was initiated 1 wk into the recurrent acute pancreatitis (RAP) protocol. Pancreata were harvested after 4 wk of RAP. Immunostaining with fibronectin antibody was used to quantify the extent of pancreatic fibrosis. To assess how apigenin may decrease organ fibrosis, we evaluated the effect of apigenin on the proliferation and apoptosis of human pancreatic stellate cells (PSCs) in vitro. Finally, we assessed apigenin's effect on the gene expression in PSCs stimulated with parathyroid hormone-related protein, a profibrotic and proinflammatory mediator of pancreatitis, using reverse transcription-polymerase chain reaction.
  
  
  RESULTS
  After 4 wk of RAP, apigenin significantly reduced the fibrotic response to injury while preserving acinar units. Apigenin inhibited viability and induced apoptosis of PSCs in a time- and dose-dependent manner. Finally, apigenin reduced parathyroid hormone-related protein-stimulated increases in the PSC messenger RNA expression levels of extracellular matrix proteins collagen 1A1 and fibronectin, proliferating cell nuclear antigen, transforming growth factor-beta, and interleukin-6.
  
  
  CONCLUSIONS
  These in vivo and in vitro studies provide novel insights regarding apigenin's mechanism(s) of action in reducing the severity of RAP. Additional preclinical testing of apigenin analogs is warranted to develop a therapeutic agent for patients at risk for CP.
authors: Department of Surgery, University of Texas Medical Branch, Galveston, Texas.
authors: Amy A
authors: AA
authors: Mrazek
authors: Department of Surgery, University of Texas Medical Branch, Galveston, Texas.
authors: Laura J
authors: LJ
authors: Porro
authors: Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, Texas.
authors: Vandanajay
authors: V
authors: Bhatia
authors: Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, Texas; Sealy Center for Cancer Cell Biology, University of Texas Medical Branch, Galveston, Texas.
authors: Miriam
authors: M
authors: Falzon
authors: Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston, Texas.
authors: Heidi
authors: H
authors: Spratt
authors: Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, Texas.
authors: Jia
authors: J
authors: Zhou
authors: Department of Surgery, University of Texas Medical Branch, Galveston, Texas; Sealy Center for Cancer Cell Biology, University of Texas Medical Branch, Galveston, Texas. Electronic address: cechao@utmb.edu.
authors: Celia
authors: C
authors: Chao
authors: Department of Surgery, University of Texas Medical Branch, Galveston, Texas; Sealy Center for Cancer Cell Biology, University of Texas Medical Branch, Galveston, Texas.
authors: Mark R
authors: MR
authors: Hellmich
mesh_terms: D000818:Animals; D047310:Apigenin / Q000494:pharmacology / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D058954:Pancreatic Stellate Cells / Q000187:drug effects* / Q000473:pathology; D050500:Pancreatitis, Chronic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D044162:Parathyroid Hormone-Related Protein / Q000494:pharmacology
chemical_list: D044162:Parathyroid Hormone-Related Protein; D047310:Apigenin
keywords: Apigenin; Chronic pancreatitis; Pancreatic stellate cells; Parathyroid hormone–related protein