Investigation of Greek flora for the development of novel angiogenesis modulators

Angiogenesis refers to the process of creation of new blood vessels, which are critical for diverse biological processes. However, an imbalance in angiogenesis contributes to the pathogenesis of numerous disorders, such as ulcers, strokes tumour growth and metastasis [1]. Plant-derived compounds have recently emerged as a novel potential class of angiogenesis modulators without causing major side effects. Greek flora, which is known for its richness and diversity, consists of at least 6300 taxa. Over 15% of Greek species and subspecies are endemic and could be an excellent source of novel active compounds. The aim of our study was to identify potential innovative compounds in the rapidly growing therapeutic field of angiogenesis related diseases. Based on a preliminary screening of 170 pure compounds as lead candidates and study of literature, a total of 200 plant species originating from the Greek flora were collected. A numerous of EtOAc (155) and MeOH (120) extracts were prepared using the Accelerated Solvent Extraction (ASE) technique and then were evaluated with endothelial cell-based functional assays [2]. The 70 most active extracts, such as Nepeta orphanideae, Glycyrrhiza glabra and Inula pseudomolinela, were selected for microfractionation with Fast Centrifugal Partition Chromatography (FCPC) using a stepwise elution/extrusion method. A representative number of the fractions were gingerly chosen for further biological evaluation and the active fractions were further purified using several chromatographic techniques in order to identify their bioactive components. As a result of this bio-guided procedure, 90 pure secondary metabolites were isolated and further evaluated by endothelial cell-based functional assays, in order to discover new natural angiogenesis modulators. Finally, the results of biological evaluation demonstrated that bioactive constituents belong to categories such as triterpenes, sesquiterpenic lactones and flavonoids.

Keywords: Angiogenesis modulators, Greek flora, Fast Centrifugal Partition Chromatography (FCPC), Bio-guided isolation endothelial cells

References:

[1] Carmeliet, P. Mechanisms of angiogenesis and arteriogenesis. Nat. Med. 2000; 4: 389 – 395

[2] Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods. 1983; 65: 55 – 63