دورية أكاديمية
Tetrahydroxy stilbene glycoside ameliorates neuroinflammation for Alzheimer's disease via cGAS-STING.
| العنوان: | Tetrahydroxy stilbene glycoside ameliorates neuroinflammation for Alzheimer's disease via cGAS-STING. |
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| المؤلفون: | Gao D; Department of Pharmacy, Xuanwu Hospital of Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing Engineering Research Center for Nervous System Drugs, Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing, 100053, China., Hao JP; Department of Pharmacy, Xuanwu Hospital of Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing Engineering Research Center for Nervous System Drugs, Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing, 100053, China., Li BY; Department of Pharmacy, Xuanwu Hospital of Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing Engineering Research Center for Nervous System Drugs, Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing, 100053, China., Zheng CC; Department of Pharmacy, Xuanwu Hospital of Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing Engineering Research Center for Nervous System Drugs, Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing, 100053, China., Miao BB; Department of Pharmacy, Xuanwu Hospital of Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing Engineering Research Center for Nervous System Drugs, Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing, 100053, China., Zhang L; Department of Pharmacy, Xuanwu Hospital of Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing Engineering Research Center for Nervous System Drugs, Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing, 100053, China., Li YL; Department of Pharmacy, Xuanwu Hospital of Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing Engineering Research Center for Nervous System Drugs, Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing, 100053, China., Li L; Department of Pharmacy, Xuanwu Hospital of Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing Engineering Research Center for Nervous System Drugs, Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing, 100053, China., Li XJ; Senior Department of Infectious Diseases, the Fifth Medical Center of PLA General Hospital, Beijing, 100039, China., Zhang L; Department of Pharmacy, Xuanwu Hospital of Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing Engineering Research Center for Nervous System Drugs, Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing, 100053, China. Electronic address: xwzhanglan@126.com. |
| المصدر: | European journal of pharmacology [Eur J Pharmacol] 2023 Aug 15; Vol. 953, pp. 175809. Date of Electronic Publication: 2023 Jun 14. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 1254354 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0712 (Electronic) Linking ISSN: 00142999 NLM ISO Abbreviation: Eur J Pharmacol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2005- : Amsterdam : Elsevier Science Original Publication: Amsterdam, North Holland Pub. Co. |
| مواضيع طبية MeSH: | Alzheimer Disease*/drug therapy , Stilbenes*/pharmacology , Stilbenes*/therapeutic use, Mice ; Animals ; Inflammasomes/metabolism ; Glycosides ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Neuroinflammatory Diseases ; Lipopolysaccharides ; Cytokines/metabolism ; Nucleotidyltransferases/metabolism ; Mice, Transgenic |
| مستخلص: | Alzheimer's disease (AD), also known as senile dementia, is the most common degenerative disease of the central nervous system. Neuroinflammation is currently believed to be a crucial factor in the progression of AD, while its exact mechanism remains unclear. In this study, we demonstrated that AD transgenic mice exhibited cognitive deficits accompanied by the elevated serum and brain inflammation. Treating with a natural active ingredient tetrahydroxy stilbene glucoside (TSG) from the Chinese herb Polygonum multiflorum that has been well known for its unique anti-aging effect, learning-memory ability of AD mice was distinctly improved. Meanwhile, it was observed that the expressions of serum inflammatory cytokines and the activation of microglia in cerebral cortex and hippocampus were suppressed after TSG treatment, which was probably attributable to the decrease of cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) triggered immune response and NLRP3 inflammasome activation. Furthermore, cell culture experiments employing LPS combined with IFN-γ induced microglia activation showed that TSG reversed the polarization status of M1-type microglia to restore the quiescence, and cGAS-STING elevation was observed in the activated microglia and normalized by TSG incubation. In addition, TSG suppressed the production of inflammatory cytokines such as IL-1β, IL-6, TNF-α, IFN-α and IFN-β, as well as the expression of IFN regulatory proteins such as IFIT1 and IRF7 in the LPS/IFN-γ-stimulated inflammatory response in BV2 cell. Finally, it was also verified that TSG are, in part, through a cGAS-STING dependent pathway and triggered NLRP3 inflammasome activation to inhibit neuroinflammation through interfering with cGAS-STING inhibitors. Taken together, our findings highlight the health benefits of TSG and its potential application in preventing cognitive disorders by inhibiting neuroinflammation through cGAS-STING signaling pathway in AD. Competing Interests: Declaration of competing interest The authors declare that the study was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Alzheimer's disease; NLRP3 inflammasome; Neuroinflammation; Tetrahydroxy stilbene glucoside; cGAS-STING pathway |
| المشرفين على المادة: | 0 (Inflammasomes) 0 (Glycosides) 0 (NLR Family, Pyrin Domain-Containing 3 Protein) 0 (Lipopolysaccharides) 0 (2',3',4',5'-tetrahydroxystilbene-2-O-beta-D-glucoside) 0 (Cytokines) EC 2.7.7.- (Nucleotidyltransferases) 0 (Stilbenes) |
| تواريخ الأحداث: | Date Created: 20230616 Date Completed: 20230630 Latest Revision: 20230630 |
| رمز التحديث: | 20230630 |
| DOI: | 10.1016/j.ejphar.2023.175809 |
| PMID: | 37328043 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1879-0712 |
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| DOI: | 10.1016/j.ejphar.2023.175809 |