Ethanol extracts of Cinnamomum migao H.W. Li attenuates neuroinflammation in cerebral ischemia-reperfusion injury via regulating TLR4-PI3K-Akt-NF-κB pathways.
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引用次数: 0
Abstract
Ethnopharmacological relevance: Cinnamomum migao H.W. Li, commonly known as migao (MG), is used in the Miao region of China for treating cardiovascular and cerebrovascular diseases, attributed to its detoxifying (Jiedu in Chinese), blood-activating (Huoxue in Chinese), and Qi-promoting (Tongqi in Chinese) effects. However, the therapeutic potential of MG for ischemic stroke (IS) has yet to be explored. Therefore, this study was to explore the protective effect of MG against cerebral ischemia-reperfusion injury caused by IS.
Aim of the study: The aim of this study was to investigate whether ethanol extract of MG (EEMG) attenuates cerebral ischemia-reperfusion injury, and explored the underlying mechanisms.
Materials and methods: Middle cerebral artery occlusion and reperfusion (MCAO/R) was established, and the efficacy of EEMG was evaluated using triphenyltetrazolium chloride (TTC), immunofluorescence, hematoxylin-eosin staining (HE) staining, and real-time quantitative PCR (qRT-PCR). Qualitative analysis of EEMG was analyzed for chemical composition by liquid chromatography-mass spectrometry (LC-MS). The molecular mechanism of EEMG was explored by metabolomics, network pharmacology, immunoblotting, immunofluorescence staining, gene knockdown, and agonist treatment.
Results: The results showed that EEMG can alleviate ischemic injury in MCAO/R-operated rats and neuronal damage of OGD/R-treated SH-SY5Y cells. Specifically, EEHGT inhibited the release of inflammatory factors and reversed serum metabolic profile disorders of MCAO/R rats. Network pharmacology analysis showed that the PI3K-Akt and NF-κB signaling pathways maybe involved in EEMG-mediated neuroprotective effects on ischemic injury and inhibition of inflammatory response. As we expected, EEMG can activate PI3K-AKT and suppress NF-kB signaling pathways both in MCAO/R-operated rats and OGD/R-treated BV2 cells. The results showed that knockdown of TLR4 abolished the EEMG-mediated inhibition on neuroinflammation in OGD/R-treated BV2 cells. After treating BV2 cells with the TLR4 agonist neoseptin 3, EEMG showed a trend toward inhibiting neuroinflammation but with no significant difference. Additionally, EEMG was found to improve liver injury caused by cerebral ischemia-reperfusion and associated with NF-κB signaling pathway in this study.
Conclusions: Collectively, this study demonstrated that EEMG attenuates neuroinflammation in cerebral ischemia-reperfusion injury via regulating TLR4-PI3K-Akt-NF-κB pathways.
期刊介绍：
The Journal of Ethnopharmacology is dedicated to the exchange of information and understandings about people''s use of plants, fungi, animals, microorganisms and minerals and their biological and pharmacological effects based on the principles established through international conventions. Early people confronted with illness and disease, discovered a wealth of useful therapeutic agents in the plant and animal kingdoms. The empirical knowledge of these medicinal substances and their toxic potential was passed on by oral tradition and sometimes recorded in herbals and other texts on materia medica. Many valuable drugs of today (e.g., atropine, ephedrine, tubocurarine, digoxin, reserpine) came into use through the study of indigenous remedies. Chemists continue to use plant-derived drugs (e.g., morphine, taxol, physostigmine, quinidine, emetine) as prototypes in their attempts to develop more effective and less toxic medicinals.
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