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CHEN Jianping, REN Xinsheng, SUN Zhonghua, GUO Zaiyu. Protective effects and mechanisms of breviscapine on endothelial cells[J]. Journal of China Pharmaceutical University, 2015, 46(5): 610-616. DOI: 10.11665/j.issn.1000-5048.20150516
Citation: CHEN Jianping, REN Xinsheng, SUN Zhonghua, GUO Zaiyu. Protective effects and mechanisms of breviscapine on endothelial cells[J]. Journal of China Pharmaceutical University, 2015, 46(5): 610-616. DOI: 10.11665/j.issn.1000-5048.20150516
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Protective effects and mechanisms of breviscapine on endothelial cells

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  • This study was to investigate the protective effects and mechanisms of breviscapine on endothelial cells. ox-LDL was used to induce oxidative damage on human umbilical vein endothelial cells(HUVEC)for 20 h with or without 4 h pretreatment of various concentrations of breviscapine(10, 20, 40 μmol/L), then observe the protective effect and mechanism of breviscapine on endothelial cells insulted by ox-LDL. MTT method was used to detect cell viability, flow cytometry was used to detect cell apoptosis and reactive oxygen species, and Western blot and RT-PCR was used to detect cell signaling pathways. The results showed that breviscapine recovered HUVEC cell viability in a dose-dependent manner which inhibited by ox-LDL, and it also protected cell from apoptosis induced by ox-LDL. To explore the mechanisms of breviscapine, reactive oxygen species(ROS)was determined after pretreatment of various concentrations of breviscapine or different durations(2, 4, 6 h)of breviscapine. Results showed that breviscapine decreased ROS production in a dose- and time-dependent manner. Furthermore, cell signaling pathway analysis showed that breviscapine increased the expression of BCL-2, decreased the expression of BAX and the release of Cytochrome C and cleavage of caspase-3. Breviscapine decreased Keap1 and activated the nuclear import of Nrf2, and subsequently increased the mRNA and protein expression of downstream antioxidant enzyme as NAD(P)H: quinone oxidoreductase 1(NQO1)and glutathione transferase-S-Mu 1(GSTM1), and increasing the activity of NQO1. Besides, breviscapine decreased IKK and IKB, and inhibited nuclear translocation of NF-κB, while increasing the expression of eNOS. This study demonstrated that breviscapine has a protective role on ox-LDL-induced endothelial cell injury, which may be related to its antioxidant effects and inhibition of NF-κB activation.
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    • References (20)
  • [1]
    Lin LL,Liu AJ,Liu JG,et al.Protective effects of scutellarin and breviscapine on brain and heart ischemia in rats[J].J Cardiovasc Pharmacol,2007,50(3):327-332.
    [2]
    Qi XM,Wu GZ,Wu YG,et al.Renoprotective effect of breviscapine through suppression of renal macrophage recruitment in streptozotocin-induced diabetic rats[J].Nephron Exp Nephrol,2006,104(4):e147-157.
    [3]
    Yan L,Huang H,Tang QZ,et al.Breviscapine protects against cardiac hypertrophy through blocking PKC-alpha-dependent signaling[J].J Cell Biochem,2010,109(6):1158-1171.
    [4]
    Wang M, Zhang WB, Zhu JH, et al. Breviscapine ameliorates hypertrophy of cardiomyocytes induced by high glucose in diabetic rats via the PKC signaling pathway[J].Acta Pharmacol Sin,2009,30(8):1081-1091.
    [5]
    Li Q,Wu JH,Guo DJ,et al.Suppression of diet-induced hypercholesterolemia by scutellarin in rats[J].Planta Med,2009,75(11):1203-1208.
    [6]
    He M,Xue ZM,Li J,et al.Breviscapine inhibits high glucose-induced proliferation and migration of cultured vascular smooth muscle cells of rats via suppressing the ERK1/2 MAPK signaling pathway[J].Acta Pharmacol Sin,2012,33(5):606-614.
    [7]
    Moldovan L,Mythreye K,Goldschmidt-Clermont PJ,et al.Reactive oxygen species in vascular endothelial cell motility.Roles of NAD(P)H oxidase and Rac1[J].Cardiovasc Res,2006,71(2):236-246.
    [8]
    Hsieh HJ,Cheng CC,Wu ST,et al.Increase of reactive oxygen species(ROS)in endothelial cells by shear flow and involvement of ROS in shear-induced c-fos expression[J].J Cell Physiol,1998,175(2):156-162.
    [9]
    Steinberg D,Witztum JL.Oxidized low-density lipoprotein and atherosclerosis[J].Arterioscler Thromb Vasc Biol,2010,30:2311-2316.
    [10]
    Wiesner P,Choi SH,Almazan F,et al. Low doses of lipopolysaccharide and minimally oxidized low-density lipoprotein cooperatively activate macrophages via nuclear factor kappa B and activator protein-1:possible mechanism for acceleration of atherosclerosis by subclinical endotoxemia[J].Circ Res,2010,107(1):56-65.
    [11]
    Wagner AE,Ernst I,Iori R,et al.Sulforaphane but not ascorbigen,indole-3-carbinole and ascorbic acid activates the transcription factor Nrf2 and induces phase-2 and antioxidant enzymes in human keratinocytes in culture[J].Exp Dermatol,2010,19(2):137-144.
    [12]
    Chavakis E,Dernbach E,Hermann C,et al.Oxidized LDL inhibits vascular endothelial growth factor-induced endothelial cell migration by an inhibitory effect on the Akt/endothelial nitric oxide synthase pathway[J].Circulation,2001,103(16):2102-2107.
    [13]
    Kotamraju S,Hogg N,Joseph J,et al.Inhibition of oxidized low-density lipoprotein-induced apoptosis in endothelial cells by nitric oxide.Peroxyl radical scavenging as an antiapoptotic mechanism[J].J Biol Chem,2001,276(20):17316-17323.
    [14]
    Wang Y, Ji M, Chen L, et al. Breviscapine reduces acute lung injury induced by left heart ischemic reperfusion in rats by inhi-biting the expression of ICAM-1 and IL-18[J].Exp Ther Med,2013,6(5):1322-1326.
    [15]
    Zhang H,Cai CZ,Zhang XQ,et al.Breviscapine attenuates acute pancreatitis by inhibiting expression of PKCα and NF-κB in pancreas[J].World J Gastroenterol,2011,17(14):1825-1830.
    [16]
    Zhang DD,Hannink M.Distinct cysteine residues in Keap1 are required for Keap1-dependent ubiquitination of Nrf2 and for stabilization of Nrf2 by chemopreventive agents and oxidative stress[J].Mol Cell Biol,2003,23(22):8137-8151.
    [17]
    Kobayashi A1,Kang MI,Okawa H,et al.Oxidative stress sensor Keap1 functions as an adaptor for Cul3-based E3 ligase to regulate proteasomal degradation of Nrf2[J].Mol Cell Biol,2004,24(16):7130-7139.
    [18]
    Jain AK,Bloom DA,Jaiswal AK.Nuclear import and export signals in control of Nrf2[J].J Biol Chem,2005,280(32):29158-29168.
    [19]
    Dhakshinamoorthy S,Jaiswal AK.Functional characterization and role of INrf2 in antioxidant response element-mediated expression and antioxidant induction of NAD(P)H:quinone oxidoreductase1 gene[J].Oncogene,2001,20(29):3906-3917.
    [20]
    Hayes JD,Chanas SA,Henderson CJ,et al.The Nrf2 transcription factor contributes both to the basal expression of glutathione S-transferases in mouse liver and to their induction by the chemopreventive synthetic antioxidants,butylated hydroxyanisole and ethoxyquin[J].Biochem Soc Trans,2000,28(2):33-41.
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