title: Antiangiogenesis and antioxidant activity of ethanol extracts of Pithecellobium jiringa.
abstract: BACKGROUND
  Angiogenesis plays a critical role in embryonic development and various physiological processes. However, excessive angiogenesis is associated with several pathological conditions including cancer. Pithecellobium jiringa (Jack) Prain is a traditional medicinal plant from the family Leguminosae. It is native to the Southeast Asia, where it has been used traditionally for treatment of various ailments such as hypertension and diabetes. The present work is aimed to study antioxidant and antiangiogenesis activities of P. jiringa ethanol extracts.
  
  
  METHODS
  P. jiringa fruit rinds were extracted with ethanol and 50% ethanol. The antioxidant property was analysed using, 1,1-diphenyl-2-picryl-hydrazyl free radical scavenging assay. Phytochemical analysis was performed using thin layer chromatography and colorimetric methods. Then, cell growth inhibition was studied against a panel of human cell lines by MTT test. In vitro inhibition of angiogenesis was studied by the following assays: isolated rat aortic rings cell viability, colony formation, endothelial cell migration, endothelial tube formation on matrigel, and expression of vascular endothelial growth factor by endothelial cells. In vivo antiangiogenesis effect was studied by utilising fertilised chick embryos assay. The results were statistically analysed by analysis of variance.
  
  
  RESULTS
  Ethanolic and 50% hydro-ethanolic extracts showed relatively high concentration of total phenolics associated with potent antioxidant activity. The rat aortic rings study conducted showed potent inhibition of the microvessels outgrowth with IC50s 5.27 ± 0.81 μg/ml (ethanolic) and 4.45 ± 0.63 μg/ml (50% hydro-ethanolic). Both extracts arrested the growth of human endothelial cells via down-regulation of VEGF expression, leading to inhibition of other angiogenesis cascades including migration of endothelial cells, and formation of capillary network on matrigel matrix. The extracts also inhibited the neovascularisation of chick embryo chorioallantoic membrane.
  
  
  CONCLUSIONS
  P. jiringa extracts inhibit angiogenesis by blocking the VEGF expression thus inhibiting endothelial cells proliferation, migration and differentiation most likely due to presence of the antioxidant phenolics.
authors.affiliation: EMAN Testing & Research Laboratory, Department of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, Penang 11800, Malaysia.
authors.forename: Nahdzatul Syima
authors.initials: NS
authors.lastname: Muslim
authors.forename: Zeyad D
authors.initials: ZD
authors.lastname: Nassar
authors.forename: Abdalrahim F A
authors.initials: AF
authors.lastname: Aisha
authors.forename: Armaghan
authors.initials: A
authors.lastname: Shafaei
authors.forename: Norshirin
authors.initials: N
authors.lastname: Idris
authors.forename: Amin Malik Shah Abdul
authors.initials: AM
authors.lastname: Majid
authors.forename: Zhari
authors.initials: Z
authors.lastname: Ismail
mesh_terms: D020533:Angiogenesis Inhibitors / Q000032:analysis / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000032:analysis / Q000494:pharmacology*; D001011:Aorta; D002196:Capillaries / Q000187:drug effects*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000187:drug effects; D015536:Down-Regulation; D042783:Endothelial Cells / Q000187:drug effects; D007887:Fabaceae / Q000737:chemistry*; D005638:Fruit; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism; D010636:Phenols / Q000032:analysis / Q000494:pharmacology*; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D000975:Antioxidants; D010636:Phenols; D010936:Plant Extracts; D042461:Vascular Endothelial Growth Factor A