Protocatechudehyde improves mitochondrial energy metabolism through the HIF1α/PDK1 signaling pathway to mitigate ischemic stroke-elicited internal capsule injury
| Autor: | Miaolin Zeng, Xixi Zhao, Jiehong Yang, Wentao Li, Jieqiong Zeng, Haitong Wan, Chongyu Shao, Huifen Zhou, Yu He |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Internal capsule Cell Survival Catechols Ischemia Apoptosis Pharmacology Mitochondrion PC12 Cells Neuroprotection Brain Ischemia Rats Sprague-Dawley Lesion 03 medical and health sciences 0302 clinical medicine Internal Capsule Drug Discovery Animals Medicine Ischemic Stroke 030304 developmental biology Membrane Potential Mitochondrial 0303 health sciences Dose-Response Relationship Drug business.industry Cerebral infarction Pyruvate Dehydrogenase Acetyl-Transferring Kinase Hypoxia-Inducible Factor 1 alpha Subunit medicine.disease Rats Disease Models Animal Neuroprotective Agents Benzaldehydes Reperfusion Injury 030220 oncology & carcinogenesis Signal transduction medicine.symptom Energy Metabolism business Signal Transduction |
| Zdroj: | Journal of Ethnopharmacology. 277:114232 |
| ISSN: | 0378-8741 |
| DOI: | 10.1016/j.jep.2021.114232 |
| Popis: | Ethnopharmacological relevance The internal capsule is vulnerable to ischemia, and mild ischemic stroke often results in lesion of the internal capsule, manifested as contralateral hemiplegia. Protocatechudehyde (PCA), a potential neuroprotective agent, has shown therapeutic effects in the study of a variety of nervous system diseases, including ischemic stroke. Aim of the study The aim of this study was to evaluate the effects of PCA on cerebral ischemia reperfusion (CI/R)-elicited internal capsule injury and to elucidate the role of mitochondrial energy metabolism in the underlying mechanism of neuroprotective effects on ischemic stroke. Materials and methods A rat tMCAO model was established to investigate the therapeutic effects of intravenous PCA (20, 40, and 80 mg/kg, once per day, continued for 7 days) on CI/R-induced internal capsule injury and the regulation of PCA on molecules related to mitochondrial energy metabolism. In vitro, an OGD/R model of PC12 cells was established to further verify the therapeutic mechanism of PCA. Results Results showed that PCA dose-dependently attenuated neurological deficit, reduced cerebral infarction, alleviated histopathological damage, and improved mitochondrial ultrastructure of the internal capsule after CI/R. Moreover, PCA reversed the upregulation of HIF1α, PDK1 and pPDHA1 expression induced by CI/R and significantly increased the content of acetyl-CoA, ATP, and the activity of ATP synthase. In vitro, PCA treatment promoted cell survival, inhibited apoptosis, attenuated the dissipation of mitochondrial membrane potential in OGD/R-treated PC12 cells, and these therapeutic effects were reversed by the combination of cobalt chloride (CoCl2), a specific pharmacological inducer of HIF1a expression. Conclusions These results indicate that PCA exerts a protective effect against CI/R-induced internal capsule injury and improves mitochondrial energy metabolism in the internal capsule, and the mechanism is associated with the inhibition of HIF1α/PDK1 signaling pathway. |
| Databáze: | OpenAIRE |
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