Angiogenesis, in which a vascular network is established from pre-existing vessels, is a complex multistep process. Mechanisms underlying angiogenesis can be investigated using a variety of in vitro, ex vivo and in vivo approaches. Evaluation of several promising plants and plant metabolites, including terpenoids, revealed promising anti-angiogenic activity. Since the maesasaponins displayed anti-angiogenic activity in the chick chorioallantoic membrane (CAM) assay, their activity was further investigated in several test systems. The rat aorta ring assay was compared with the placental vein assay and then selected for the ex vivo investigation of the saponins. Besides their effect on the viability of HUVEC, the anti-angiogenic capacity of the compounds was also investigated in an in vivo zebrafish assay. The activity of the saponins in the viability assay was more pronounced than in the rat aorta ring assay and similar to the effect observed in the CAM assay. The use of different test systems, however, implies different results in the case of saponins.
SchultzGS, WysockiA. (2009) Interactions between extracellular matrix and growth factors in wound healing. Wound Repair and Regeneration, 17, 153–162.
4.
SatoY. (2003) Molecular diagnosis of tumor angiogenesis and anti-angiogenic cancer therapy. International Journal of Clinical Oncology, 8, 200–206.
5.
StatonCA, StribblingSM, TazzymanS, HughesR, BrownNJ, LewisCE. (2004) Current methods for assaying angiogenesis in vitro and in vivo. International Journal of Experimental Pathology, 85, 233–248.
6.
SindambiweJB, BaldéAM, De BruyneT, PietersL, Van den HeuvelH, ClaeysM, Van den BergheDA, VlietinckAJ. (1996) Triterpenoid saponins from Maesa lanceolata. Phytochemistry, 41, 269–277.
7.
ApersS, ForiersA, SindambiweJB, VlietinckA, PietersL. (1998) Separation of a triterpenoid saponin mixture from Maesa lanceolata: semipreparative reversed-phase wide pore high performance liquid chromatography with temperature control. Journal of Pharmaceutical and Biomedical analysis, 18, 737–743.
8.
ApersS, De BruyneT, ClaeysM, VlietinckAJ, PietersLAC. (1999) New acylated triterpenoid saponins from Maesa lanceolata. Phytochemistry, 52, 1121–1131.
9.
ApersS, BürgermeisterJ, BaronikovaS, VermeulenP, PaperD, Van MarckE, VlietinckAJ, PietersLAC. (2002) Anti-angiogenic activity of natural products: in vivo and in vitro test models. Journal de Pharmacie de Belgique, 57, 47–49.
10.
HosangM. (1985) Suramin binds to platelet-derived growth factor and inhibits its biological activity. Journal of Cellular Biochemistry, 29, 265–273.
11.
OlanderJV, ConnollyDT, DelarcoJE. (1991) Specific binding of vascular permeability factor to endothelial cells. Biochemical and Biophysical Research Communications, 175, 67–76.
12.
PesentiE, SolaF, MongelliN, GrandiM, SpreaficoF. (1992) Suramin prevents neovascularisation and tumour growth blocking of basic fibroblast growth factor activity. British Journal of Cancer, 66, 367–372.
13.
BrownKJ, MaynesSF, BezosA, MaguireDJ, FordMD, ParishCR. (1996) A novel in vitro assay for human angiogenesis. Laboratory Investigation, 75, 539–555.
14.
HornickCA, MyersA, Sadowska-KrowickaH, AnthonyCT, WolteringEA. (2003) Inhibition of angiogenic initiation and disruption of newly established vascular networks by juice from Morinda citrifolia (noni). Angiogenesis, 6, 143–149.
15.
ZhaoBZ, YangXR, GuoW, CuiJR. (2007) [Anti-angiogenic effect and possible mechanism of sodium aescinate]. Chinese Journal of New Drugs, 16, 1357-1360 [In Chinese].
16.
WangX-H, XuB, LiuJ-T, CuiJ-R. (2008) Effect of β-escin sodium on endothelial cells proliferation, migration and apoptosis. Vascular Pharmacology, 49, 158–165.
17.
SenguptaS, TohS-A, SellersLA, SkepperJN, KoolwijkP, LeungHW, YeungH-W, WongRNS, SasisekharanR, FanT-PD. (2004) Modulating angiogenesis: The yin and the yang in Ginseng. Circulation, 110, 1219–1225.
18.
LuengKW, CheungLWT, PonYL, WongRNS, MakNK, FanT-PD, AuSCL, Tombran-TinkJ, WongAST. (2007) Ginsenoside Rb1 inhibits tube-like structure formation of endothelial cells by regulating pigment epithelium-derived factor through the oestrogen β receptor. British Journal of Pharmacology, 152, 207-215.
19.
GoRS, RitmanEL, OwenWG. (2003) Angiogenesis in rat aortic rings stimulated by very low concentrations of serum and plasma. Angiogenesis, 6, 25–29.
20.
BarónikováS, ApersS, Vanden BergheD, CosP, VermeulenP, Van DaeleA, PietersL, Van MarckE, VlietinckA. (2004) An ex-vivo aniogenesis assay as a screening method for natural compounds and herbal drug preparations. Planta Medica, 70, 887–892.
21.
LawsonND, WeinsteinBM. (2002) In vivo imaging of embryonic vascular development using transgenic zebrafish. Developmental Biology, 248, 307–318.
22.
SoomroS, KonkimallaVB, LangenbergT, MahringerA, HorwedelC, HolenyaP, BrandA, CatinC, FrickerG, DewerchinM, CarmelietP, ConwayEM, JansenH, EfferthT. (2011) Design of novel artemisinin-like derivatives with cytotoxic and anti-angiogenic properties. Journal of Cellular and Molecular Medicine, 5, 1122–1135.
23.
ParngC, SengWL, SeminoC, McGrathP. (2002) Zebrafish: a preclinical model for drug screening. Assay and Drug Development Technologies, 248, 307–318.
