Lactic acid fermented Elaeagnus multiflora Thunb. fruit: suppressive effect of its extracts on angiogenesis

Abstract

Abstract Background Angiogenesis has been considered as one of the hallmarks of tumor progression and cancer malignancy. Meanwhile, the fruit of Elaeagnus multiflora Thunb. or cherry silverberry (CS), was found to have strong biological activities including anti-cancer and anti-angiogenesis. In this study, the influence of the extracts of E. multiflora Thunb. fruits fermented by mono- and co-culture of L. plantarum and L. casei on the new blood vessel formation in human umbilical vascular endothelial cell (HUVEC) stimulated by vascular endothelial growth factor (VEGF) as well as the underlying mechanism was elucidated. Results Sulforhodamine B, scratch wound-healing, Transwell migration, capillary-like tube formation, rat aortic ring assays, and morphological analysis were performed to determine the effect of the fermented fruit extracts on the VEGF-induced angiogenic events (motility, migration, invasion, formation of capillary-like tube, blood vessel sprouting ex vivo). The findings showed that at concentration of 25–50 µg/ml, the extracts of CS fermented by mixed cultures is the most effective in inhibiting angiogenesis in HUVECs. Moreover, analysis of the biomarker proteins related to angiogenesis through Western blot technique showed that the fermented extracts exert their anti-angiogenic activity by regulating the VEGFR2 signaling pathway and its possible downstream targets namely Erk ½ and FAK. Conclusion Taken together, the results suggest that the extracts of CS fruits fermented by co-culture of L. plantarum and L. casei has the potential to be utilized in the development of functional food and ingredient with anti-angiogenic properties. Graphical Abstract