Erxian Decoction, a Traditional Chinese Herbal Formula, Inhibits Angiogenesis in Human Umbilical Vein Endothelial Cells

Abstract

Our previous study demonstrated that Erxian Decoction (EXD), a traditional Chinese herbal formula, inhibited angiogenesis in zebrafish embryos. To further investigate the anti-angiogenic activity and mechanism of EXD, we evaluated its inhibitory effect on angiogenesis in mammalian endothelial cells in vitro. Cell based assays included proliferation, apoptosis, migration, tube formation and cell cycle analysis. Real-time quantitative polymerase chain reaction (qPCR) and Western blotting were carried out to evaluate the molecular targets and signaling pathways of EXD in human umbilical vein endothelial cells (HUVECs). EXD inhibited proliferation, migration and tube formation in HUVECs. EXD also caused HUVEC apoptosis and cell increase in G 0 /G 1 phase in cell cycle analysis. Furthermore, it decreased the mRNA expressions of vascular endothelial growth factor A (VEGF-A), VEGFR-1 and VEGFR-2 in HUVECs. It also inhibited extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt activation, suggesting the involvement of these signaling pathways in the anti-angiogenic action of EXD in HUVECs. The anti-angiogenic activity of EXD provides new insights to its clinical application and may lead to potential drug development for treating various cancers, especially in menopausal period in the future.Key words angiogenesis; Erxian Decoction; human umbilical vein endothelial cell; vascular endothelial growth factor A Angiogenesis, which is the formation of new blood vessels from existing ones, plays an important role in tumor growth and metastasis.1) New blood vessels are essential for the delivery of oxygen and nutrients to the tumor microenvironment, especially when the tumor volume is 1-2 mm in diameter. 2)Furthermore, the formation of new blood vessels seems critical by providing route for metastasis and thus it is considered as the major cause of cancer mortality.3) These have led to the design of therapeutic strategies including preventing the formation of new vessels called anti-angiogenesis and damaging existing vessels called vascular targeting, toward the tumor vasculature.4) Angiogenesis has been identified as a hallmark of tumor progression, and there is extensive evidence suggesting that anti-angiogenic therapy might be a promising anticancer therapeutic strategy. 5)

Erxian Decoction Attenuates TNF-α Induced Osteoblast Apoptosis by Modulating the Akt/Nrf2/HO-1 Signaling Pathway

“…Chemical components of each herb in EXD were determined from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) (Ru et al, 2014), TCM database @taiwan (Sanderson, 2011), Herbal Ingredients Targets (HIT), Traditional Chinese Medicine Integrated Database (TCMID) (Xue et al, 2013), and previous literature (Bian et al, 2013; Yu et al, 2013). The molecular properties of the herbs, including molecular weight (MW), Moriguchi octanol-water partition coefficient (AlogP), oral bioavailability (OB), drug-likeness (DL), number of donor atoms for H-bonds (nHDon), and number of acceptor atoms for H-bonds (nHAcc) were compared in Table S1 .…”