Abstract
ischaemic stroke accounts for almost 11% of all deaths worldwide and has a high incidence of permanent disability among patients. Baicalein has many beneficial pharmacological properties, including anti-inflammatory and anti-oxidant effects. However, the neuroprotective effect of baicalein is still unclear. The current study scrutinizes the neuroprotective effect of baicalein against the ischaemic/reperfusion (I/R) injury via alteration of the nuclear factor kappa B (NF-kB) and AMP-activated protein kinase/nuclear factor erythroid 2-related factor 2 AMPK/Nrf2 signaling pathway. Wistar rats were used for the current study. In rats, I/R injury was caused by transient occlusion of the middle cerebral artery for 1 h accompanied by reperfusion for 24 h. The rats were divided into different groups and treated with the different doses of baicalein (2.5, 5 and 10 mg/kg). The effects of baicalein on the murine neurological function were determined via infarct volume, neurological defect scores, and brain water content. The -inflammatory cytokines and oxidative stress were estimated in the region of the cortical along with the expression of apoptosis markers, such as B-cell lymphoma 2, Bax, and caspase-3. Quantitative reverse transcription polymerase chain reaction was used for the estimation of the NF-kB, cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2) and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) expression. Baicalein significantly (p < 0.001) ameliorated the infarction volume, brain water content, and neurological outcome, and the malondialdehyde level, and reduced the level of interleukin-1β, interleukin-6, tumor necrosis factor-α, superoxide dismutase, glutathione, and catalase in a dose-dependent manner. Baicalein significantly (p < 0.001) altered the expression of COX-2, PGE2, LOX-1 and NF-kB as compared to I/R control group rats. Baicalein significantly reduced the Nrf2 and AMPK levels, and protected the rat brain against the I/R injury, suggesting a neuroprotective effect via down-regulation of NF-kB and LOX-1 expression and the AMPK/Nrf2 pathway.
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Abbreviations
- I/R:
-
ischaemia/reperfusion
- tMCAO:
-
Transient occlusion of the middle cerebral artery
- NF-kB:
-
Nuclear factor kappa B
- AMPK:
-
AMP-activated protein kinase
- Nrf2:
-
Nuclear factor erythroid 2-related factor 2
- Bcl-2:
-
B-cell lymphoma 2
- COX-2:
-
Cyclooxygenase-2
- PGE2:
-
Prostaglandin E2
- LOX-1:
-
Lectin-like oxidized low-density lipoprotein receptor-1
- IL-1β:
-
Interleukin-1β
- IL-6:
-
Interleukin-6
- TNF-α:
-
Tumor necrosis factor-α
- SOD:
-
Superoxide dismutase
- GSH:
-
Glutathione
- CAT:
-
Catalase
- CIR:
-
Cerebral ischaemic stroke
- MMPs:
-
Metalloproteinases
- ROS:
-
Reactive oxygen species
- DMEM:
-
Dulbecco's modified Eagle's medium
- OGD:
-
Oxygen–glucose deprivation
- LDH:
-
Lactate dehydrogenase
- PBS:
-
Phosphate buffer saline
- GSH-Px:
-
Glutathione peroxidase
- 8-OHdG:
-
8-Hydroxy-2′-deoxyguanosine
- ATP:
-
Adenosine triphosphate
- NOS:
-
Nitric oxide
- MAPKs:
-
Mitogen-activated protein kinases
- AMPK:
-
Adenosine monophosphate-activated protein kinase
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Hebei University's Affiliated Hospital, China, sponsored this research.
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YY, WM, HZ and CL organized the experiments; WM performed the experiments; HZ analyzed the data. All the authors equally wrote the paper.
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Yuan, Y., Men, W., Shan, X. et al. Baicalein exerts neuroprotective effect against ischaemic/reperfusion injury via alteration of NF-kB and LOX and AMPK/Nrf2 pathway. Inflammopharmacol 28, 1327–1341 (2020). https://doi.org/10.1007/s10787-020-00714-6
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DOI: https://doi.org/10.1007/s10787-020-00714-6