Abstract | BACKGROUND: METHODS: C57/B6 mice, BV2 microglia and HT22 hippocampal neurons were used for in-vivo and in-vitro experiments. I/R injury models were constructed using middle cerebral artery occlusion (MCAO/R) and oxygen- glucose deprivation/reoxygenation (OGD/R), respectively. The expression of apoptosis and inflammatory proteins, and endoplasmic reticulum (ER) stress proteins were gauged by Western blotting (WB). The contents of inflammatory cytokines in OGD/R-induced BV2 microglia were testified by enzyme-linked immunosorbent assay (ELISA). Cell counting kit-8 (CCK-8), TUNEL assay and flow cytometry (FCM) were utilized to examine the viability and apoptosis of cells. The neurological, learning and memory functions were evaluated by the modified neurological severity score (mNSS) and water maze experiment. 2, 3, 5-triphenyltetrazole chloride (TTC) staining was utilized to calculate the volume of cerebral infarction and cerebral edema in the peri- infarct area. Apoptosis-related proteins, inflammation-related proteins and ER stress proteins were gauged by WB. ELISA was conducted to verify inflammatory cytokines. RESULTS: PPG treatment notably abated the expression of ER stress proteins and inflammatory factors in OGD/R-induced BV2 microglia and boosted HT22 neuron's viability and eased their apoptosis in comparison to the control group. In vivo, PPG treatment signally lessened cerebral infarct area, cerebral edema, and neurological deficit scores in MCAO/R mice. Additionally, PPG caused a dramatic decline in neuronal apoptosis and levels of ER stress proteins and inflammatory factors in the brain's peri- infarct region of MCAO/R mice. Mechanically, PPG blocked the TLR4/NF-κB pathway in OGD/R-induced BV2, HT22 neurons, and the MCAO/R mice. CONCLUSION: PPG attenuates brain I/R damage probably by suppressing ER stress and neuroinflammation via inactivation of the TLR4/NF-κB pathway, suggesting that PPG may be a candidate drug for treating cerebral I/R injury.
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Authors | Xinming Li, Zongxin Cheng, Xiaohong Chen, Dejiang Yang, Huanhuan Li, Youqing Deng |
Journal | International immunopharmacology
(Int Immunopharmacol)
Vol. 111
Pg. 109057
(Oct 2022)
ISSN: 1878-1705 [Electronic] Netherlands |
PMID | 35964408
(Publication Type: Journal Article)
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Copyright | Copyright © 2022 Elsevier B.V. All rights reserved. |
Chemical References |
- Benzocycloheptenes
- Cytokines
- Heat-Shock Proteins
- NF-kappa B
- Toll-Like Receptor 4
- purpurogallin
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Topics |
- Animals
- Apoptosis
- Benzocycloheptenes
- Brain Edema
- Brain Ischemia
(drug therapy, metabolism)
- Cytokines
(therapeutic use)
- Endoplasmic Reticulum Stress
- Heat-Shock Proteins
(metabolism)
- Infarction, Middle Cerebral Artery
(drug therapy, metabolism)
- Mice
- NF-kappa B
(metabolism)
- Neuroinflammatory Diseases
- Reperfusion
- Reperfusion Injury
(metabolism)
- Signal Transduction
- Toll-Like Receptor 4
(metabolism)
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