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The TLR4/NF-κB/NLRP3 and Nrf2/HO-1 pathways mediate the neuroprotective effects of alkaloids extracted from Uncaria rhynchophylla in Parkinson's disease.

التفاصيل البيبلوغرافية
العنوان: The TLR4/NF-κB/NLRP3 and Nrf2/HO-1 pathways mediate the neuroprotective effects of alkaloids extracted from Uncaria rhynchophylla in Parkinson's disease.
المؤلفون: Zhang C; Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, 210009, China; Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Ministry of Education, Nanjing, 210009, China., Zhou J; Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, 210009, China; Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Ministry of Education, Nanjing, 210009, China., Zhuo L; Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, 210009, China; Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Ministry of Education, Nanjing, 210009, China., Zhang W; Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, 210009, China; Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Ministry of Education, Nanjing, 210009, China., Lv L; Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, 210009, China; Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Ministry of Education, Nanjing, 210009, China., Zhu L; Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, 210009, China; Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Ministry of Education, Nanjing, 210009, China., Zhang J; Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, 210009, China; Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Ministry of Education, Nanjing, 210009, China., Feng F; Nanjing Medical University, Nanjing, 211166, China., Liu W; Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, 210009, China; Zhejiang Center for safety study of drug substances (Industrial Technology Innovation Platform), Hangzhou, 310018, China., Han L; Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, 210009, China; Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Ministry of Education, Nanjing, 210009, China. Electronic address: hanlingfei@cpu.edu.cn., Liao W; Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, 210009, China; Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Ministry of Education, Nanjing, 210009, China. Electronic address: lwting84@163.com.
المصدر: Journal of ethnopharmacology [J Ethnopharmacol] 2024 Oct 28; Vol. 333, pp. 118391. Date of Electronic Publication: 2024 May 24.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Sequoia Country of Publication: Ireland NLM ID: 7903310 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7573 (Electronic) Linking ISSN: 03788741 NLM ISO Abbreviation: J Ethnopharmacol Subsets: MEDLINE
أسماء مطبوعة: Publication: Limerick : Elsevier Sequoia
Original Publication: Lausanne, Elsevier Sequoia.
مواضيع طبية MeSH: Alkaloids*/pharmacology , Alkaloids*/isolation & purification , Neuroprotective Agents*/pharmacology , Neuroprotective Agents*/isolation & purification , NF-E2-Related Factor 2*/metabolism , NF-kappa B*/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein*/metabolism , Toll-Like Receptor 4*/metabolism , Uncaria*/chemistry, Animals ; Male ; Mice ; Heme Oxygenase (Decyclizing)/metabolism ; Heme Oxygenase-1/metabolism ; Membrane Proteins/metabolism ; Mice, Inbred C57BL ; Oxidative Stress/drug effects ; Signal Transduction/drug effects
مستخلص: Ethnopharmacological Relevance: Parkinson's disease (PD) is the second most common neurodegenerative disorder with limited therapeutic options available. Neuroinflammation plays an important role in the occurrence and development of PD. Alkaloids extracted from Uncaria rhynchophylla (URA), have emerged as a potential neuroprotective agent because of its anti-inflammatory and anti-oxidant properties. Nevertheless, the underlying mechanism by which URA exerts neuroprotective effects in PD remains obscure.
Aim of the Study: The main aim of this study was to investigate the neuroprotective effects and underlying mechanism of URA in the treatment of PD through in vivo and in vitro models, focusing on the neuroinflammation and oxidative stress pathways.
Materials and Methods: The protective effects of URA against PD were evaluated by neurobehavioral tests, immunohistochemistry, serum biochemical assays, and real-time quantitative polymerase chain reaction in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice. The role of the TLR4/NF-κB/NLRP3 pathway and the Nrf2/HO-1 pathway in URA-mediated effects was examined in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells and a microglia-neuron coculture system.
Results: URA significantly alleviated motor deficits and dopaminergic neurotoxicity, and reversed the abnormal secretion of inflammatory and oxidative stress factors in the serum of MPTP-induced mice. URA suppressed the gene expression of Toll-like receptor 4 (TLR4), NOD-like receptor protein 3, and cyclooxygenase 2 (COX2) in the striatum of PD mice. Further studies indicated that URA inhibited activation of the TLR4/NF-κB/NLRP3 pathway and enhanced activation of the Nrf2/HO-1 pathway, reduced reactive oxygen species (ROS) production, and reversed the secretion of inflammatory mediators in LPS-stimulated BV-2 microglial cells, thereby alleviating neuroinflammatory damage to SH-SY5Y neuronal cells.
Conclusion: URA exerted neuroprotective effects against PD mainly by the inhibition of the TLR4/NF-κB/NLRP3 pathway and activation of the Nrf2/HO-1 antioxidant pathway, highlighting URA as a promising candidate for PD treatment.
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 Elsevier B.V. All rights reserved.)
فهرسة مساهمة: Keywords: Alkaloids extracted from Uncaria rhynchophylla; Neuroinflammation; Nrf2/HO-1; Parkinson's disease; TLR4/NF-κB/NLRP3 pathway
المشرفين على المادة: 0 (Alkaloids)
EC 1.14.14.18 (Heme Oxygenase (Decyclizing))
EC 1.14.14.18 (Heme Oxygenase-1)
EC 1.14.14.18 (Hmox1 protein, mouse)
0 (Membrane Proteins)
0 (Neuroprotective Agents)
0 (NF-E2-Related Factor 2)
0 (NF-kappa B)
0 (Nfe2l2 protein, mouse)
0 (NLR Family, Pyrin Domain-Containing 3 Protein)
0 (Nlrp3 protein, mouse)
0 (Tlr4 protein, mouse)
0 (Toll-Like Receptor 4)
تواريخ الأحداث: Date Created: 20240526 Date Completed: 20240713 Latest Revision: 20240715
رمز التحديث: 20240716
DOI: 10.1016/j.jep.2024.118391
PMID: 38797377
قاعدة البيانات: MEDLINE
الوصف
تدمد:1872-7573
DOI:10.1016/j.jep.2024.118391