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Beneficial consequences of Lupeol on middle cerebral artery-induced cerebral ischemia in the rat involves Nrf2 and P38 MAPK modulation

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Abstract

Lupeol has been reported to exhibit anti-inflammatory and anti-tumor activities in many diseases, but its potential effects in cerebral ischemia injury have not been studied to date. In this work we present evidence for a beneficial effect of lupeol in a rat model of middle cerebral artery occlusion (MCAO) followed by reperfusion (MCAO/R) injury and provide some histological and biochemical evidence for its mechanism of action. A cerebral MCAO rat model was established by vascular occlusion for 2 h, followed by 24 h reperfusion period. The infarct volume, neurological deficits, and brain water content were compared with animals treated during reperfusion with different concentrations of lupeol. Macroscopic parameters, cell viability, pro-inflammatory factors generation, as well as oxidative stress parameters and associated apoptotic signaling cascades were evaluated. Treatment with lupeol significantly reduced the cerebral infarct volume and water content and recovered neuro behavioral functions in affected rats. Lupeol treatment down-regulated the expression of oxidative stress and inflammation factors. In addition, lupeol activated Nrf2, suppressed caspase-3 activity, reduced BAX/Bcl-2 ratio and inhibited phosphorylation of p38 MAPK. The data suggest that lupeol may exert protective effects against cerebral ischemia by suppressing oxidative stress and reduction of inflammation factors possible via activation of nuclear transcription factors and inhibition of cell death pathways.

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Authors and Affiliations

  1. Department of Neurosurgery, Liaocheng people’s hospital, No. 67 Dongchang West Road, Liaocheng City, Shandong Province, 252000, People’s Republic of China

    Zhiyuan Zhang, Chongfu Xu, Jiheng Hao, Meng Zhang, Zidong Wang, Tengkun Yin, Kai Lin, Weidong Liu, Qunlong Jiang, Zhongchen Li & Liyong Zhang

  2. Department of Ultrasound, No. 67 Dongchang West Road, Liaocheng City, Shandong Province, 252000, People’s Republic of China

    Dan Wang

  3. Department of Neurosurgery, Chinese PLA General Hospital, No.28 Fuxing Road, Haidian District, Beijing City, 100853, People’s Republic of China

    Zhiqi Mao & Huaiyu Tong

Authors
  1. Zhiyuan Zhang
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  2. Chongfu Xu
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  3. Jiheng Hao
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  4. Meng Zhang
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  11. Dan Wang
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  12. Zhiqi Mao
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  14. Liyong Zhang
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Contributions

ZYZ, CFX, JHH, HYT and LYZ conceived and designed research. ZYZ, GFX, MZ, ZDW, TKY, KL, WDL and QLJ conducted experiments. ZCL, DW and ZQM contributed new reagents or analytical tools. ZYZ, CFX, JHH, HYT, TKY and KL analyzed data. ZYZ, CFX, JHH, HYT and LYZ wrote the manuscript. All authors read and approved the manuscript.

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Correspondence to Liyong Zhang.

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This study was approved by the Animal Ethics Committee of Liaocheng people’s hospital. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

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Zhang, Z., Xu, C., Hao, J. et al. Beneficial consequences of Lupeol on middle cerebral artery-induced cerebral ischemia in the rat involves Nrf2 and P38 MAPK modulation. Metab Brain Dis 35, 841–848 (2020). https://doi.org/10.1007/s11011-020-00565-8

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