Synergistic Effects of Danshen (Salvia Miltiorrhizae Radix et Rhizoma) and Sanqi (Notoginseng Radix et Rhizoma) Combination in Angiogenesis Behavior in EAhy 926 Cells

Background: This study investigated the combination effects of the Danshen and Sanqi herb pair on angiogenesis in vitro. Methods: Nine combination ratios of Danshen-Sanqi extracts (DS-SQ) were screened for their angiogenic effects in the human vascular endothelial EAhy 926 cell line via cell proliferation, cell migration and tube formation activities against the damage to the cells exerted by DL-homocysteine (Hcy) and adenosine (Ado). The type of interaction (synergistic, antagonistic, additive) between Danshen and Sanqi was analyzed using combination index (CI) and isobologram models. The angiogenic activities of key bioactive compounds from Danshen and Sanqi were tested in the same models. Results: DS-SQ ratios of 2:8 and 3:7 (50-300 µg/mL) potentiated angiogenic synergistic effects (CI < 1) in all three assays. The observed wound healing effects of DS-SQ 2:8 was significantly attenuated by phosphatidylinositol-3 kinases (PI3K), mitogen-activated protein kinase (MEK) and extracellular signal-regulated kinases (ERK) inhibitors which inferred the potential mechanistic pathways. Out of all the tested compounds, Notoginsenoside R1 from Sanqi exhibited the most potent bioactivity in cell proliferation assay. Conclusions: This study provides scientific evidence to support the traditional use of the Danshen-Sanqi combination for vascular disease, in particular through their synergistic interactions on previously unexamined angiogenic pathways.