دورية أكاديمية
Epimedium flavonoids improve cerebral white matter lesions by inhibiting neuroinflammation and activating neurotrophic factor signal pathways in spontaneously hypertensive rats.
| العنوان: | Epimedium flavonoids improve cerebral white matter lesions by inhibiting neuroinflammation and activating neurotrophic factor signal pathways in spontaneously hypertensive rats. |
|---|---|
| المؤلفون: | Wei W; Department of Pharmacy, Xuanwu Hospital of Capital Medical University, Beijing, China; Beijing Geriatric Medical Research Center, Beijing Engineering Research Center for Nervous System Drugs, National Center for Neurological Disorders, National Clinical Research Center for Geriatric Diseases, Beijing, China., Ma D; Department of Pharmacy, Xuanwu Hospital of Capital Medical University, Beijing, China; Beijing Geriatric Medical Research Center, Beijing Engineering Research Center for Nervous System Drugs, National Center for Neurological Disorders, National Clinical Research Center for Geriatric Diseases, Beijing, China. Electronic address: ma_denglei@126.com., Gu L; Department of Pharmacy, Xuanwu Hospital of Capital Medical University, Beijing, China; Department of Pharmacy, Wuxi TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Wuxi, China., Li Y; Department of Pharmacy, Xuanwu Hospital of Capital Medical University, Beijing, China; Beijing Geriatric Medical Research Center, Beijing Engineering Research Center for Nervous System Drugs, National Center for Neurological Disorders, National Clinical Research Center for Geriatric Diseases, Beijing, China., Zhang L; Department of Pharmacy, Xuanwu Hospital of Capital Medical University, Beijing, China; Beijing Geriatric Medical Research Center, Beijing Engineering Research Center for Nervous System Drugs, National Center for Neurological Disorders, National Clinical Research Center for Geriatric Diseases, Beijing, China., Li L; Department of Pharmacy, Xuanwu Hospital of Capital Medical University, Beijing, China; Beijing Geriatric Medical Research Center, Beijing Engineering Research Center for Nervous System Drugs, National Center for Neurological Disorders, National Clinical Research Center for Geriatric Diseases, Beijing, China., Zhang L; Department of Pharmacy, Xuanwu Hospital of Capital Medical University, Beijing, China; Beijing Geriatric Medical Research Center, Beijing Engineering Research Center for Nervous System Drugs, National Center for Neurological Disorders, National Clinical Research Center for Geriatric Diseases, Beijing, China. Electronic address: xwzhanglan@126.com. |
| المصدر: | International immunopharmacology [Int Immunopharmacol] 2024 Sep 30; Vol. 139, pp. 112683. Date of Electronic Publication: 2024 Jul 16. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 100965259 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-1705 (Electronic) Linking ISSN: 15675769 NLM ISO Abbreviation: Int Immunopharmacol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Amsterdam ; New York : Elsevier Science, c2001- |
| مواضيع طبية MeSH: | Rats, Inbred SHR* , Signal Transduction*/drug effects , Flavonoids*/pharmacology , Flavonoids*/therapeutic use , Epimedium* , White Matter*/drug effects , White Matter*/pathology , White Matter*/metabolism , Neuroinflammatory Diseases*/drug therapy, Animals ; Male ; Rats ; Cerebral Small Vessel Diseases/drug therapy ; Nerve Growth Factors/metabolism ; Nerve Growth Factors/genetics ; Disease Models, Animal ; Microglia/drug effects ; Hypertension/drug therapy ; Astrocytes/drug effects |
| مستخلص: | Cerebral small vessel disease (CSVD) is one of the most common nervous system diseases. Hypertension and neuroinflammation are considered important risk factors for the development of CSVD and white matter (WM) lesions. We used the spontaneously hypertensive rat (SHR) as a model of early-onset CSVD and administered epimedium flavonoids (EF) for three months. The learning and memorization abilities were tested by new object recognition test. The pathological changes of WM were assessed using magnetic resonance imaging, transmission electron microscopy (TEM), Luxol fast blue and Black Gold staining. Oligodendrocytes (OLs) and myelin basic protein were detected by immunohistochemistry. The ultrastructure of the tight junctions was examined using TEM. Microglia and astrocytes were detected by immunofluorescence. RNA-seq was performed on the corpus callosum of rats. The results revealed that EF could significantly improve the learning and memory impairments in SHR, alleviate the injury and demyelination of WM nerve fibers, promote the differentiation of oligodendrocyte precursor cells (OPCs) into mature OLs, inhibit the activation of microglia and astrocytes, inhibit the expression of p38 MAPK/NF-κB p65/NLRP3 and inflammatory cytokines, and increase the expression of tight-junction related proteins ZO-1, occludin, and claudin-5. RNA-seq analysis showed that the neurotrophin signaling pathway played an important role in the disease. RT-qPCR and WB results showed that EF could regulate the expression of nerve growth factor and brain-derived neurotrophic factor and their downstream related proteins in the neurotrophin signaling pathway, which might explain the potential mechanism of EF's effects on the cognitive impairment and WM damage caused by hypertension. Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2024. Published by Elsevier B.V.) |
| فهرسة مساهمة: | Keywords: Cerebral small vessel disease; Cognitive impairment; Epimedium flavonoids; Neuroinflammation; Spontaneously hypertensive rats; White matter lesions |
| المشرفين على المادة: | 0 (Flavonoids) 0 (Nerve Growth Factors) |
| تواريخ الأحداث: | Date Created: 20240717 Date Completed: 20240813 Latest Revision: 20240813 |
| رمز التحديث: | 20240813 |
| DOI: | 10.1016/j.intimp.2024.112683 |
| PMID: | 39018691 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1878-1705 |
|---|---|
| DOI: | 10.1016/j.intimp.2024.112683 |