HOMEPRODUCTSSERVICESCOMPANYCONTACTFAQResearchDictionaryPharmaMobileSign Up FREE or Login

Sofalcone, a gastric mucosa protective agent, increases vascular endothelial growth factor via the Nrf2-heme-oxygenase-1 dependent pathway in gastric epithelial cells.

Abstract
Sofalcone, 2'-carboxymethoxy-4,4-bis(3-methyl-2-butenyloxy)chalcone, is an anti-ulcer agent that is classified as a gastric mucosa protective agent. Recent studies indicate heat shock proteins such as HSP32, also known as heme-oxygenase-1(HO-1), play important roles in protecting gastrointestinal tissues from several stresses. We have previously reported that sofalcone increases the expression of HO-1 in adipocytes and pre-adipocytes, although the effect of sofalcone on HO-1 induction in gastrointestinal tissues is not clear. In the current study, we investigated the effects of sofalcone on the expression of HO-1 and its functional role in rat gastric epithelial (RGM-1) cells. We found that sofalcone increased HO-1 expression in RGM-1 cells in both time- and concentration-dependent manners. The HO-1 induction was associated with the nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in RGM-1 cells. We also observed that sofalcone increased vascular endothelial growth factor (VEGF) production in the culture medium. Treatment of RGM-1 cells with an HO-1 inhibitor (tin-protoporphyrin), or HO-1 siRNA inhibited sofalcone-induced VEGF production, suggesting that the effect of sofalcone on VEGF expression is mediated by the HO-1 pathway. These results suggest that the gastroprotective effects of sofalcone are partly exerted via Nrf2-HO-1 activation followed by VEGF production.
AuthorsAkiko Shibuya, Kenji Onda, Hirofumi Kawahara, Yuka Uchiyama, Hiroko Nakayama, Takamasa Omi, Masayoshi Nagaoka, Hirofumi Matsui, Toshihiko Hirano
JournalBiochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 398 Issue 3 Pg. 581-4 (Jul 30 2010) ISSN: 1090-2104 [Electronic] United States
PMID20599750 (Publication Type: Journal Article)
CopyrightCopyright 2010. Published by Elsevier Inc.
Chemical References
  • Anti-Ulcer Agents
  • Chalcones
  • NF-E2-Related Factor 2
  • RNA, Small Interfering
  • Vascular Endothelial Growth Factor A
  • sofalcone
  • Heme Oxygenase-1
Topics
  • Animals
  • Anti-Ulcer Agents (pharmacology)
  • Cell Line
  • Chalcones (pharmacology)
  • Cytoprotection
  • Gastric Mucosa (blood supply, drug effects, metabolism)
  • Gene Knockdown Techniques
  • Heme Oxygenase-1 (genetics, metabolism)
  • NF-E2-Related Factor 2 (metabolism)
  • Neovascularization, Physiologic (drug effects)
  • RNA, Small Interfering (genetics)
  • Rats
  • Vascular Endothelial Growth Factor A (biosynthesis)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!


Choose Username:
Email:
Password:
Verify Password: