Alchornea glandulosa Ethyl Acetate Fraction Exhibits Antiangiogenic Activity: Preliminary Findings from In Vitro Assays Using Human Umbilical Vein Endothelial Cells

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Processo FAPESP: 03/02176-7

Alchornea glandulosa has traditionally been used in Brazilian folk medicine for the treatment of immune-inflammatory diseases and as an antiulcer agent to heal gastric ulcer and gastritis. Angiogenesis is a complex multistep process that consists of proliferation, migration, and anastomosis of endothelial cells and has a major role in the development of pathologic conditions, such as inflammatory diseases. To investigate a possible link between the anti-inflammatory activities and antiangiogenic effects of A. glandulosa ethyl acetate fraction (AGF), this study examined which features of the angiogenic process could be disturbed by this fraction. The antiangiogenic activity of AGF was determined in vitro by using human umbilical vein endothelial cells (HUVEC), and cell viability, proliferation, apoptosis, invasion, and capillary-like structures formation were addressed. To elucidate the mechanism of action, nuclear factor kappa B (NF kappa B), a transcription factor implicated in these processes, was also evaluated in HUVEC incubated with AGF. A significant decrease in proliferation, a relevant increase in apoptosis, and a strong reduction in invasion capacity (as assessed by bromodeoxyuridine, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling, and double-chamber assays, respectively) were observed. AGF also led to a drastic reduction in the number of capillary-like structures formed when HUVEC were cultured on growth factor-reduced Matrigel-coated plates. In addition, incubation of HUVEC with AGF resulted in reduced NF kappa B activity. These findings emphasize the antiangiogenic potential of AGF and support its therapeutic use for disorders that involve excessive angiogenesis, such as chronic inflammation and tumor growth.