Angiogenic effect of saponin extract from Panax notoginseng on HUVECs in vitro and zebrafish in vivo

Abstract

Angiogenesis plays an important role in a wide range of physiological processes such as wound healing and fetal development. In fact, many diseases are associated with imbalance in the regulation of angiogenesis in which there is either excessive or insufficient blood vessel formation. Panax notoginseng, a blood circulation invigorating herb, is commonly used in traditional Chinese medicine to treat circulation-related diseases. However, the biological effects of saponin extract from Panax notoginseng (PNS) on angiogenesis and the underlying mechanisms are yet to be fully elucidated. This investigation describes the angiogenic effects of PNS on human umbilical vein endothelial cells (HUVECs) in vitro and zebrafish in vivo. The 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)5[(phenylamino)carbonyl]2H-tetrazolium hydroxide (XTT) assay and microscopic cell counting demonstrated that the extract was able to stimulate the proliferation of HUVECs. Meanwhile, the numbers of invaded cells and tube branches were significantly increased in PNS treatment groups. PNS was also shown to promote changes in the subintestinal vessels, a feature of angiogenesis, in zebrafish. In addition, by using real-time polymerase chain reaction (PCR), PNS was found to enhance vascular endothelial growth factor (VEGF) and kinase-domain region/fetal liver kinase-1 in mice (KDR/Flk-1) mRNA expression, and the PNS-induced HUVECs proliferation could be abolished by a KDR/Flk-1 inhibitor. Furthermore, the proliferation of HUVECs induced by PNS was significantly attenuated by inhibitors of PI3K-Akt-eNOS. All the results suggest that PNS can promote angiogenesis, and that the proangiogenic effects involve the VEGF-KDR/Flk-1 and PI3K-Akt-eNOS signaling pathways.

Pro-angiogenic activity of astragaloside IV in HUVECs in vitro and zebrafish in vivo

“…4D). However, contrary to our previous reports that pro-angiogenic chemicals stimulate vessel spike formation in SIVs of healthy zebrafish (16,17), AS-IV did not produce the pro-angiogenic effect under the same conditions (Fig. 4E).…”

Whole extracts of Radix Achyranthis Bidentatae and Radix Cyathulae promote angiogenesis in human umbilical vein endothelial cells in vitro and in zebrafish in vivo

“…There are several regulatory sites by exogenous compounds for stimulating angiogenesis. For example, TCM can activate multiple pathways for promoting angiogenesis (15)(16)(17)(18). However, in the present study, the whole extracts of RAB and RC promoted angiogenesis mainly via stimulating migration of ECs in HUVECs in vitro, but not through cell proliferation or tube formation.…”

Anti-angiogenic Activity of Erxian Decoction, a Traditional Chinese Herbal Formula, in Zebrafish

“…[19][20][21][22][23][24][25][26][27][28][29] Different varieties of drugs tested in zebrafish elicit similar responses to those observed in mammalian models, [30][31][32] considering the remarkable homology in the molecular and signaling pathways involved in vessel formations between zebrafish and mammals. [33][34][35] Compared with other drug screening systems, the dominant advantages of the zebrafishbased assay include: (1) it is suitable for high-throughput drug screening; (2) it offers more relevant information to humans compared to other invertebrate models and in vitro cell lines, while it costs much less than mammalian systems.…”