دورية أكاديمية
Gastrodin relieves Parkinson's disease-related motor deficits by facilitating the MEK-dependent VMAT2 to maintain dopamine homeostasis.
| العنوان: | Gastrodin relieves Parkinson's disease-related motor deficits by facilitating the MEK-dependent VMAT2 to maintain dopamine homeostasis. |
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| المؤلفون: | Zhao M; State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, 611137, PR China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, PR China; Institute of Material Medica Integration and Transformation for Brain Disorders, Chengdu University traditional Chinese medicine, Chengdu, 611137, PR China., Zhou Y; State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, 611137, PR China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, PR China; Institute of Material Medica Integration and Transformation for Brain Disorders, Chengdu University traditional Chinese medicine, Chengdu, 611137, PR China., Sheng R; State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, 611137, PR China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, PR China; Institute of Material Medica Integration and Transformation for Brain Disorders, Chengdu University traditional Chinese medicine, Chengdu, 611137, PR China., Zhang H; State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, 611137, PR China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, PR China; Institute of Material Medica Integration and Transformation for Brain Disorders, Chengdu University traditional Chinese medicine, Chengdu, 611137, PR China., Xiang J; State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, 611137, PR China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, PR China; Institute of Material Medica Integration and Transformation for Brain Disorders, Chengdu University traditional Chinese medicine, Chengdu, 611137, PR China., Wang J; State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, 611137, PR China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, PR China; Institute of Material Medica Integration and Transformation for Brain Disorders, Chengdu University traditional Chinese medicine, Chengdu, 611137, PR China., Li P; State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, 611137, PR China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, PR China; Institute of Material Medica Integration and Transformation for Brain Disorders, Chengdu University traditional Chinese medicine, Chengdu, 611137, PR China., Ma T; State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, 611137, PR China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, PR China; Institute of Material Medica Integration and Transformation for Brain Disorders, Chengdu University traditional Chinese medicine, Chengdu, 611137, PR China., Liu P; State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, 611137, PR China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, PR China; Institute of Material Medica Integration and Transformation for Brain Disorders, Chengdu University traditional Chinese medicine, Chengdu, 611137, PR China., Chen Q; State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, 611137, PR China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, PR China; Institute of Material Medica Integration and Transformation for Brain Disorders, Chengdu University traditional Chinese medicine, Chengdu, 611137, PR China., Wen W; State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, 611137, PR China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, PR China; Institute of Material Medica Integration and Transformation for Brain Disorders, Chengdu University traditional Chinese medicine, Chengdu, 611137, PR China. Electronic address: wen_cdu@163.com., Xu S; State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, 611137, PR China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, PR China; Institute of Material Medica Integration and Transformation for Brain Disorders, Chengdu University traditional Chinese medicine, Chengdu, 611137, PR China. Electronic address: xushijun@cdutcm.edu.cn. |
| المصدر: | Phytomedicine : international journal of phytotherapy and phytopharmacology [Phytomedicine] 2024 Sep; Vol. 132, pp. 155819. Date of Electronic Publication: 2024 Jun 11. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Urban & Fischer Verlag Country of Publication: Germany NLM ID: 9438794 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1618-095X (Electronic) Linking ISSN: 09447113 NLM ISO Abbreviation: Phytomedicine Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Stuttgart : Urban & Fischer Verlag Original Publication: Stuttgart ; New York : G. Fischer, c1994- |
| مواضيع طبية MeSH: | Benzyl Alcohols*/pharmacology , Vesicular Monoamine Transport Proteins*/metabolism , Glucosides*/pharmacology , Dopamine*/metabolism , Mice, Inbred C57BL* , Homeostasis*/drug effects, Animals ; PC12 Cells ; Male ; Mice ; Rats ; Parkinson Disease/drug therapy ; Neuroprotective Agents/pharmacology ; 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; Disease Models, Animal ; Molecular Docking Simulation ; Gastrodia/chemistry |
| مستخلص: | Background: Dysfunction of dopamine homeostasis (DAH), which is regulated by vesicular monoamine transporter 2 (VMAT2), is a vital cause of dopamine (DA) neurotoxicity and motor deficits in Parkinson's disease (PD). Gastrodin (4-hydroxybenzyl alcohol 4-O-β-D-glucoside; GTD), a natural active compound derived from Gastrodia elata Blume, can be used to treat multiple neurological disorders, including PD. However, whether GTD regulates VMAT2-mediated DAH dysfunction in PD models remains unclear. Purpose: To explore whether GTD confers dopaminergic neuroprotection by facilitating DA vesicle storage and maintaining DAH in PD models. Methods: Mice were treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and PC12 cells with 1-methyl-4-phenyl-pyridinium (MPP + ) to induce PD characteristics. Multiple behavioural tests were performed to evaluate the motor functions of the mice. HPLC was used to measure DA and 3,4-dihydroxyphenylacetic acid (DOPAC) levels. Transmission electron microscopy was used to observe synaptic vesicles. Molecular docking and molecular dynamics were used to determine the binding affinity of GTD to the target protein. Reserpine (Res, a VMAT2 inhibitor) and PD0325901 (901, a MEK inhibitor) were employed to investigate the mechanism of GTD. Western blotting and immunohistochemistry were used to assess the expression of the target proteins. Results: GTD attenuated motor deficits and dopaminergic neuronal injury, reversed the imbalance of DAH, and increased VMAT2 levels and vesicle volume in MPTP-induced mice. GTD ameliorated cell damage, ROS release, and dysfunction of DAH in MPP + -induced PC12 cells. Moreover, the neuroprotective effects of GTD were reversed by Res in vitro and in vivo. Furthermore, GTD can activate the MEK/ERK/CREB pathway to upregulate VMAT2 in vitro and in vivo. Interestingly, 901 reversed the effects of GTD on VMAT2 and dopaminergic neuronal impairment. Conclusion: GTD relieved PD-related motor deficits and dopaminergic neuronal impairment by facilitating MEK-depended VMAT2 to regulate DAH, which offers new insights into its therapeutic potential. Competing Interests: Declaration of competing interest All authors declared no conflicts of interest to this work. (Copyright © 2024 Elsevier GmbH. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Dopamine homeostasis; Gastrodin; MEK/ERK/CREB pathway; Parkinson's disease; VMAT2 |
| المشرفين على المادة: | 5YS9U2W3RQ (gastrodin) 0 (Benzyl Alcohols) 0 (Vesicular Monoamine Transport Proteins) 0 (Glucosides) VTD58H1Z2X (Dopamine) 0 (Slc18a2 protein, mouse) 0 (Neuroprotective Agents) 9P21XSP91P (1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine) |
| تواريخ الأحداث: | Date Created: 20240617 Date Completed: 20240820 Latest Revision: 20240820 |
| رمز التحديث: | 20240820 |
| DOI: | 10.1016/j.phymed.2024.155819 |
| PMID: | 38885579 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1618-095X |
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| DOI: | 10.1016/j.phymed.2024.155819 |