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Puerarin attenuates intracerebral hemorrhage-induced early brain injury possibly by PI3K/Akt signal activation-mediated suppression of NF-κB pathway |
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| Authors: | Jun Zeng Shizhong Zheng Yizhao Chen Yaoming Qu Jiayu Xie Enhui Hong Hongzhu Lv Rui Ding Liang Feng Zhichong Xie |
| Institution: | 1. Department of Neurosurgery, Zhujiang Hospital, The Engineering Technology Research Center of Education Ministry of China, The National Key Clinical Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Southern Medical University, Guangzhou, China
Department of Neurosurgery, Huashan Hospital, Institute of Neurosurgery, Shanghai Medical College, Fudan University, Shanghai, China Contribution: Conceptualization (equal), Data curation (equal), Formal analysis (equal), Investigation (equal), Methodology (equal), Software (equal), Validation (equal), Visualization (equal), Writing - original draft (equal);2. Department of Neurosurgery, Zhujiang Hospital, The Engineering Technology Research Center of Education Ministry of China, The National Key Clinical Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Southern Medical University, Guangzhou, China Department of Neurosurgery, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, China Contribution: Conceptualization (equal), Data curation (equal), Formal analysis (equal), Investigation (equal), Methodology (equal), Software (equal), Validation (equal), Visualization (equal), Writing - original draft (equal);3. Department of Neurosurgery, Zhujiang Hospital, The Engineering Technology Research Center of Education Ministry of China, The National Key Clinical Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Southern Medical University, Guangzhou, China;4. Department of Radiology, Zhujiang Hospital, Southern Medical University, Guangzhou, China Contribution: Formal analysis (supporting), Investigation (supporting), Methodology (supporting), Software (supporting), Visualization (supporting), Writing - review & editing (supporting);5. Department of Neurosurgery, Zhujiang Hospital, The Engineering Technology Research Center of Education Ministry of China, The National Key Clinical Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Southern Medical University, Guangzhou, China Contribution: Formal analysis (supporting), Investigation (supporting), Methodology (supporting), Software (supporting), Visualization (supporting), Writing - review & editing (supporting);6. Department of Neurosurgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China Contribution: Formal analysis (supporting), Investigation (supporting), Methodology (supporting), Software (supporting), Visualization (supporting), Writing - review & editing (supporting);7. Department of Neurosurgery, Chenzhou No. 1 People's Hospital, Chenzhou, China Contribution: Formal analysis (supporting), Investigation (supporting), Methodology (supporting), Software (supporting), Visualization (supporting), Writing - review & editing (supporting) |
| Abstract: | Intracerebral hemorrhage (ICH) can induce intensively oxidative stress, neuroinflammation, and brain cell apoptosis. However, currently, there is no highly effective treatment available. Puerarin (PUE) possesses excellent neuroprotective effects by suppressing the NF-κB pathway and activating the PI3K/Akt signal, but its role and related mechanisms in ICH-induced early brain injury (EBI) remain unclear. In this study, we intended to observe the effects of PUE and molecular mechanisms on ICH-induced EBI. ICH was induced in rats by collagenase IV injection. PUE was intraperitoneally administrated alone or with simultaneously intracerebroventricular injection of LY294002 (a specific inhibitor of the PI3K/Akt signal). Neurological deficiency, histological impairment, brain edema, hematoma volume, blood–brain barrier destruction, and brain cell apoptosis were evaluated. Western blot, immunohistochemistry staining, reactive oxygen species (ROS) measurement, and enzyme-linked immunosorbent assay were performed. PUE administration at 50 mg/kg and 100 mg/kg could significantly reduce ICH-induced neurological deficits and EBI. Moreover, PUE could notably restrain ICH-induced upregulation of the NF-κB pathway, pro-inflammatory cytokines, ROS level, and apoptotic pathway and activate the PI3K/Akt signal. However, LY294002 delivery could efficaciously weaken these neuroprotective effects of PUE. Overall, PUE could attenuate ICH-induced behavioral defects and EBI possibly by PI3K/Akt signal stimulation-mediated inhibition of the NF-κB pathway, and this made PUE a potential candidate as a promising therapeutic option for ICH-induced EBI. |
| Keywords: | ICH EBI puerarin NF-κB PI3K |