UM  > 中華醫藥研究院
Diethyl blechnic, a novel natural product isolated from salvia miltiorrhiza bunge, inhibits doxorubicin-induced apoptosis by inhibiting ROS and activating JNK1/2
Yu J.2; Gao H.2; Wu C.2; Xu Q.-M.1; Lu J.-J.2; Chen X.2
2018-06-19
Source PublicationInternational Journal of Molecular Sciences
ISSN14220067 16616596
Volume19Issue:6
Abstract

Doxorubicin (DOX) is a widely used antineoplastic agent in clinics. However, its clinical application is largely limited by its cardiotoxicity. Diethyl blechnic (DB) is a novel compound isolated from Salvia miltiorrhiza Bunge. Here, we study the effect of DB on DOX-induced cardiotoxicity and its underlying mechanisms. Cellular viability was tested by 3-[-4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and protein level was evaluated by Western blotting. 5,5’,6,6’-tetrachloro-1,1’,3,3’-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) staining was performed to determine the mitochondrial membrane potential (MMP). Hoechst 33342 staining and TUNEL staining was performed to test the apoptosis. Reactive oxygen species (ROS) generation was investigated by using flow cytometry. DB significantly inhibited DOX-induced apoptosis in H9c2 cells and primary cultured cardiomyocytes. Moreover, DB decreased cell apoptotic morphological changes and reversed the mitochondrial membrane potential induced by DOX. Meanwhile, pre-treatment with DB increased the expression levels of B-cell lymphoma 2 (Bcl-2), B-cell lymphoma-extra-large (Bcl-xl), and survivin and reduced the expression levels of Bcl-2-associated X protein (Bax), p-p53, cytochrome c (cyt c), and cleaved-caspase 3, 7, 8, 9 in the protein levels in DOX-treated H9c2 cells. Furthermore, DB suppressed ROS generation. The DB-mediated protective effects were accompanied by increased c-Jun N-terminal kinase1/2 (JNK1/2) expression. In addition, SP600125, the inhibitor of JNK1/2, abolished the protective effect of DB. We concluded that DB protected cardiomyocytes against DOX-induced cytotoxicity by inhibiting ROS and activating the JNK1/2 pathway. Therefore, DB is a promising candidate as a cardioprotective agent against DOX-induced cardiotoxicity.

KeywordCardiotoxicity Diethyl Blechnic Dox Jnk1/2 Ros
DOI10.3390/ijms19061809
URLView the original
Indexed BySCI
WOS Research AreaBiochemistry & Molecular Biology ; Chemistry
WOS SubjectBiochemistry & Molecular Biology ; Chemistry, Multidisciplinary
WOS IDWOS:000436506600264
Fulltext Access
Citation statistics
Cited Times [WOS]:3   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.Soochow University
2.Universidade de Macau
Recommended Citation
GB/T 7714
Yu J.,Gao H.,Wu C.,et al. Diethyl blechnic, a novel natural product isolated from salvia miltiorrhiza bunge, inhibits doxorubicin-induced apoptosis by inhibiting ROS and activating JNK1/2[J]. International Journal of Molecular Sciences,2018,19(6).
APA Yu J.,Gao H.,Wu C.,Xu Q.-M.,Lu J.-J.,&Chen X..(2018).Diethyl blechnic, a novel natural product isolated from salvia miltiorrhiza bunge, inhibits doxorubicin-induced apoptosis by inhibiting ROS and activating JNK1/2.International Journal of Molecular Sciences,19(6).
MLA Yu J.,et al."Diethyl blechnic, a novel natural product isolated from salvia miltiorrhiza bunge, inhibits doxorubicin-induced apoptosis by inhibiting ROS and activating JNK1/2".International Journal of Molecular Sciences 19.6(2018).
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Yu J.]'s Articles
[Gao H.]'s Articles
[Wu C.]'s Articles
Baidu academic
Similar articles in Baidu academic
[Yu J.]'s Articles
[Gao H.]'s Articles
[Wu C.]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Yu J.]'s Articles
[Gao H.]'s Articles
[Wu C.]'s Articles
Terms of Use
No data!
Social Bookmark/Share
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.