Dalbergia odorifera extract promotes angiogenesis through upregulation of VEGFRs and PI3K/MAPK signaling pathways

Ethnopharmacological relevance: The heart wood of Dalbergia odorifera is a Chinese herbal medicine commonly used for the treatment of various ischemic diseases in Chinese medicine practice. Aim of the study: In this study, therapeutic angiogenesis effects of the Dalbergia odorifera extract (DOE) were investigated on transgenic zebrafish in vivo and human umbilical vein endothelial cells (HUVECs) in vitro. Materials and methods: The pro-angiogenic effects of DOE on zebrafish were examined by subintestinal vessels (SIVs) sprouting assay and intersegmental vessels (ISVs) injury assay. And the pro-angiogenic effects of DOE on HUVECs were examined by MTT, scratch assay, protein chip and western blot. Results: In the in vivo studies, we found that DOE was able to dose-dependently promote angiogenesis in zebrafish SIVs area. In addition, DOE could also restore the injury in zebrafish ISVs area and upregulate the reduced mRNA expression of VEGFRs including kdr, kdrl and flt-1 induced by VEGF receptor kinase inhibitor II (VRI). In the in vitro studies, we observed that DOE promoted the proliferation, migration of HUVECs and also restored the injury induced by VRI. Moreover, protein chip and western blot experiments showed the PI3K/ MAPK cell proliferation/migration pathway were activated by DOE. Conclusions: DOE has a therapeutic effects on angiogenesis, and its mechanism may be related to adjusting the VEGFRs mRNA and activation of PI3K/MAPK signaling pathway. These results suggest a strong potential for Dalbergia odorifera to be developed as an angiogenesis-promoting therapeutic.