Abstract:
:(±)-Sodium5-bromo-2-(α-hydroxypentyl) benzoate (brand name: brozopine, BZP, 1a), derived from L-3-n-butylphthalide (L-NBP), has been reported to protect the brain from stoke and has been approved by CFDA in Phase I-II clinical trials. However, it remains to be investigated whether 1a may exhibit any cardioprotective effect on ischemia-reperfusion (I/R) injury. In the current study, C57BL/6 and ICR mice were pretreated with 1a, and myocardium I/R were then performed. We found that 1a not only significantly reduced the infarct size and improved cardiac contractile function after acute MI/R in both species, but also protected hearts from chronic MI-related cardiac injury. Mechanically, we found that 1a physically binds to 12/15-LOX-2 using molecular docking. The shRNA-mediated 12/15-LOX-2 knockdown almost completely blocked the protective effect of 1a. Our findings, for the first time, strongly indicate that 1a may serve as a potent and promising cardioprotective agent in treatment of I/R related injury, at least partially through targeting 12/15-LOX-2.
journal_name
J Mol Cell Cardioljournal_title
Journal of molecular and cellular cardiologyauthors
Xiao Y,Song C,Lin Q,Shi X,Yu W,Huang X,Wang H,Chen Y,Wang R,Geng X,Qin M,Hu K,Fan Y,Qiao Y,Gao E,Zhao W,Chang Jdoi
10.1016/j.yjmcc.2019.07.014subject
Has Abstractpub_date
2019-10-01 00:00:00pages
52-66eissn
0022-2828issn
1095-8584pii
S0022-2828(18)31083-6journal_volume
135pub_type
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