Title:DL-3-n-butylphthalide Attenuates Cerebral Ischemia-Reperfusion Injury
by Inhibiting Mitochondrial Omi/HtrA2-Mediated Apoptosis
Volume: 20
Issue: 1
Author(s): Shuo Huang*, Qianyan He, Xin Sun, Yang Qu, Reziya Abuduxukuer, Jiaxin Ren, Kejia Zhang, Yi Yang and Zhen-Ni Guo
Affiliation:
- Department of Neurology, Stroke Center, The First Hospital of Jilin University, Chang Chun, Jilin, China
Keywords:
Ischemia-reperfusion injury, DL-3-n-butylphthalide, mitochondria, apoptosis, neuronal injury.
Abstract:
Background: Ischemic stroke is a major cause of death and disability worldwide and
results from inadequate cerebrovascular blood supply; mitochondrial dysfunction plays an essential
role in its pathogenesis. DL-3-n-butylphthalide (NBP) is an effective medicine for ischemic stroke
that reduces cell apoptosis and improves long-term prognosis.
Objective: Whether and how NBP regulates mitochondria-associated apoptosis in cerebral ischemia-
reperfusion injury remains unclear.
Methods: Male Sprague Dawley rats were subjected to a middle cerebral artery occlusion (MCAO)
stroke and treated with low (20 mg/kg) or high (80 mg/kg) concentrations of NBP. The Omi/HtrA2
inhibitor UCF-101 was used as a positive control. Cerebral infarction, neuron injury and neuronal
apoptosis were assessed to determine the efficacy of NBP compared to UCF-101. We assessed the
expression of the Omi/HtrA2 signaling pathway by western blotting and tested the mRNA expression
of mitochondrial metabolism-related genes by PCR.
Results: Compared to the MCAO group, both low and high concentrations of NBP substantially
improved cerebral infarction, neuron injury, and neuronal apoptosis; high concentrations of NBP
were more potent than low concentrations. The expression of proteins of the mitochondrial
Omi/HtrA2 signaling pathway, including Omi/HtrA2, XIAP, PARL, OPA1, CHOP, and ClpP, was
inhibited in the NBP group.
Conclusion: Overall, early application of NBP attenuated cerebral ischemia-reperfusion injury by
inhibiting mitochondrial Omi/HtrA2-mediated apoptosis in rats. Our study supports a novel neuroprotective
mechanism of NBP, making it a promising therapeutic agent for ischemic stroke.
