1.Bibenzyl from Dendrobium inhibits angiogenesis and its underlying mechanism.
Chenyuan GONG ; Bin LU ; Li YANG ; Lei WANG ; Lili JI
Acta Pharmaceutica Sinica 2013;48(3):337-42
Bibenzyl is a type of active compounds abundant in Dendrobium. In the present study, we investigated the inhibitory effects of six bibenzyls isolated from Dendrobium species on vascular endothelial growth factor (VEGF)-induced tube formation in human umbilical vascular endothelial cells (HUVECs). All those bibenzyls inhibited VEGF-induced tube formation at 10 micromol x L(-1) except tristin, and of which moscatilin was found to have the strongest activity at the same concentration. The lowest effective concentration of moscatilin was 1 micromol x L(-1). Further results showed that moscatilin inhibited VEGF-induced capillary-like tube formation on HUVECs in a concentration-dependent manner. Western blotting results showed that moscatilin also inhibited VEGF-induced phosphorylation of VEGFR2 (Flk-1/KDR) and extracellular signal-regulated kinase 1/2 (ERK1/2). Further results showed that moscatilin inhibited VEGF-induced activation of c-Raf and MEK1/2, which are both upstream signals of ERK1/2. Taken together, results presented here demonstrated that moscatilin inhibited angiogenesis via blocking the activation of VEGFR2 (Flk-1/KDR) and c-Raf-MEK1/2-ERK1/2 signals.
2.Altered expression of genes related with angiogenesis and oxidative stress during the development of oxygen-induced retinopathy in newborn mice
Zengyang YU ; Chenyuan GONG ; Guoqing ZHANG ; Lili JI
Chinese Pharmacological Bulletin 2014;(10):1397-1401
Aim To observe the retinal angiogenesis and detect the altered expression of genes related with angiogenesis and oxidative stress during the develop-ment of oxygen-induced retinopathy ( OIR) in newborn mice. Methods OIR was established in newborn mice according to the protocol of Smith et al. Newborn mice at 7 days old were placed into 75 . 5% oxygen for up to 5 days, and then they were put in room air for another 5 days. Retinal neovascularization was ob-served by immunofluorescence staining with cluster of differentiation 31 ( CD31 ) . Gene expression was de-tected using Real-time PCR analysis. Retinal CD31 immunofluorescence staining assay showed that relative hypoxia induced retinal neovascularization in OIR mice after hyperoxia-induced subside of retinal microvascu-lar. Results Real-time PCR analysis showed that vas-cular endothelial growth factor ( VEGF) and its recep-tor ( VEGFR) such as VEGFA, VEGFD, VEGFR1, VEGFR2 gene expression were increased in OIR mouse as compared to control. Platelet-derived growth factor ( PDGF) and its receptor ( PDGFR) such as PDGFA, PDGFB, PDGFRa, PDGFRb gene expression was also increased in OIR mouse as compared to control. Matrix metalloproteinases ( MMPs ) such as MMP2 gene ex-pression were increased in OIR mouse as compared to control. Gene expressions of nuclear factor-related fac-tor ( Nrf2 ) and its downstream genes such as the two subunits of glutamate-cysteine ligase ( GCL):the cata-lytic subunit ( GCLC) and regulatory subunit ( GCLM) were both decreased in OIR mouse as compared to con-trol. Conclusion Our research demonstrates that the expression of genes related with angiogenesis is in-creased in retinas in the development of OIR in mice, whereas the expression of Nrf2 and its downstream genes is all decreased.