國家衛生研究院 NHRI:Item 3990099045/10769
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    题名: Neferine ameliorates cardiomyoblast apoptosis induced by doxorubicin: possible role in modulating NADPH oxidase/ROS-mediated NFkappaB redox signaling cascade
    作者: Priya, LB;Baskaran, R;Huang, CY;Padma, VV
    贡献者: National Institute of Cancer Research
    摘要: Doxorubicin (DOX) mediated cardiomyopathy is a major challenge in cancer chemotherapy. Redox-cycling of doxorubicin by flavoenzymes makes the heart more vulnerable to oxidative stress leading to cardiac dysfunction. The present study evaluates the role of neferine, a bisbenzylisoquinoline alkaloid, in curbing the molecular consequences of DOX-exposure in H9c2 cardiomyoblasts. Neferine pre-treatment increased cell viability upon DOX-exposure. DOX activates NADPH oxidase subunits, (p22phox, p47phox, gp91phox) as the primary event followed by peak in [Ca2+]i accumulation by 2 h, ROS by 3 h and activated ERK1/2 and p38 MAPKinases, time dependently along with the activation and translocation of NFkappaB and up-regulated COX2 and TNF-alpha expressions. Neferine pre-treatment modulated NADPH oxidase/ROS system, inhibited MAPKinases and NFkappaB activation, reduced sub G1 cell population and concomitantly increased cyclin D1 expression reducing DOX-mediated apoptosis. The study demonstrates for the first time, the molecular sequential events behind DOX toxicity and the mechanism of protection offered by neferine with specific relevance to NADPH oxidase system, MAPKinases, inflammation and apoptosis in H9c2 cells. Our data suggests the use of neferine as a new approach in pharmacological interventions against cardiovascular disorders as secondary complications.
    日期: 2017-09-25
    關聯: Scientific Reports. 2017 Sep 25;7:Article number 12283.
    Link to: http://dx.doi.org/10.1038/s41598-017-12060-9
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2045-2322&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000411648500057
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85029901008
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