Berberine Ameliorates MCAO Induced Cerebral Ischemia/Reperfusion Injury via Activation of the BDNF–TrkB–PI3K/Akt Signaling Pathway

Abstract

Cerebral ischemic injury remains associated with high mortality rates and lacks effective therapeutic intervention. Berberine (BBR) possesses anti-oxidant, anti-inflammatory, and anti-tumor activities, as well as potent neuroprotective effects. Although recent studies have examined the neuroprotective effects of berberine, little is known regarding its usefulness in treating cerebral ischemia. Thus, the aim of this study is to investigate the possible effect and the mechanism of berberine against cerebral ischemic injury using the middle cerebral artery occlusion (MCAO) model. Rats were randomly divided into three groups: control group, MCAO group, and MCAO + BBR group. Modified neurological severity score tests (mNSS) and infarct volumes were measured to determine the neuroprotective effects of berberine. Neuronal survival in striatum was examined by TUNEL staining and immunohistochemistry. Western blotting measured the expression of BDNF, TrkB, p-Akt and cleaved caspase-3. The results demonstrated that BBR could significantly protect against MCAO. Berberine also increased the expression of BDNF, TrkB, and p-Akt, which were reduced after MCAO. Furthermore, treatment with BBR declined the apoptosis-related proteins induced by MCAO. However, treatment with LY294002 (PI3K inhibitor) reversed the BBR-induced increases in BDNF and p-Akt proteins and decreased cleaved caspase-3 protein expression in focal cerebral ischemic rats. In summary, our results demonstrated that BBR could exert neuroprotective effects through reduction of striatum apoptosis via the BDNF–TrkB–PI3K/Akt signaling pathway.

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Abbreviations

MCAO:

Middle cerebral artery occlusion

BBR:

Berberine

BDNF:

Brain-derived neurotrophic factor

TrkB:

Tropomyosin receptor kinase B

mNSS:

Modified neurological severity score test

ECA:

External carotid artery

ICA:

Internal carotid artery

TTC:

2,3,5-Triphenyltetrazolium chloride

TUNEL:

Terminal deoxynucleotidyl transferase dUTP nick end labeling

DAPI:

4,6-Diamidino-2-phenylindole

BCA:

Bicinchoninic acid

PVDF:

Polyvinylidenedifluoride

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Correspondence to Min Zhang.

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Yang, J., Yan, H., Li, S. et al. Berberine Ameliorates MCAO Induced Cerebral Ischemia/Reperfusion Injury via Activation of the BDNF–TrkB–PI3K/Akt Signaling Pathway. Neurochem Res 43, 702–710 (2018). https://doi.org/10.1007/s11064-018-2472-4

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Keywords

  • Berberine
  • MCAO
  • BDNF
  • TrkB
  • PI3K/Akt
  • Apoptosis