Title:Dipsacoside B Exerts a Beneficial Effect on Brain Injury in the Ischemic
Stroke Rat through Inhibition of Mitochondrial E3 Ubiquitin Ligase 1
Volume: 21
Issue: 8
Author(s): Kai-Di Ren, Zi-Mei Peng, Jing Tian, Ya-Wei Peng, Yi-Yue Zhang, Xiao-Jie Zhang, Zhong-Yang Hu, Xiu-Ju Luo and Jun Peng*
Affiliation:
- Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha,
410078, China
- Hunan Provincial Key Laboratory of Cardiovascular Research, Xiangya School of Pharmaceutical
Sciences, Central South University, Changsha, 410078, China
Keywords:
Dipsacoside B, ischemic stroke, mitochondrial E3 ubiquitin ligase 1 (mul1), dynamin-related protein 1 (drp1), mitofusin 2 (mfn2), hypoxia.
Abstract:
Background: Upregulation of mitochondrial E3 ubiquitin ligase 1 (Mul1) contributes to
brain injury in ischemic stroke due to disturbance of mitochondrial dynamics, and bioinformatics
analysis predicts that Mul1 is a potential target of Dipsacoside B.
Objective: The aim of the study was to explore whether Dipsacoside B can exert a beneficial effect
on brain injury in the ischemic stroke rat via targeting Mul1.
Methods: The SD rat brains or PC12 cells were subjected to 2 h-ischemia or 8 h-hypoxia plus 24
h-reperfusion or 24 h-reoxygenation to establish the ischemic stroke rat model in vivo or in vitro,
which were treated with Dipsacoside B at different dosages. The brain or PC12 cell injury, relevant
protein levels and mitochondrial functions were measured by methods of biochemistry, flow cytometry
or Western blot.
Results: The neurological dysfunction and brain injury (such as infarction and apoptosis) observed
in the ischemic stroke rats were accompanied by increases in Mul1 and Dynamin-related protein 1
(Drp1) levels along with decreases in mitofusin 2 (Mfn2) level and ATP production. These effects
were attenuated by Dipsacoside B. Consistently, cell injury (necroptosis and apoptosis) occurred in
the PC12 cells exposed to hypoxia concomitant with the upregulation of Mul1 and Drp1 along with
downregulation of Mfn2 and mitochondrial functions (such as increases in reactive oxygen species
production and mitochondrial fission and decreases in mitochondrial membrane potential and ATP
production).These phenomena were reversed in the presence of Dipsacoside B.
Conclusion: Dipsacoside B can protect the rat brain against ischemic injury via inhibition of Mul1
due to the improvement of mitochondrial function.