Protective effects and mechanisms of breviscapine on endothelial cells

CHEN Jianping; REN Xinsheng; SUN Zhonghua; GUO Zaiyu

doi:10.11665/j.issn.1000-5048.20150516

Journal of China Pharmaceutical University > 2015 > 46(5): 610-616. > DOI: 10.11665/j.issn.1000-5048.20150516

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.
- breviscapine,
- reactive oxygen species,
- endothelial cells,
- cell apoptosis

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