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Novel flavonoid 1,3,4-oxadiazole derivatives ameliorate MPTP-induced Parkinson's disease via Nrf2/NF-κB signaling pathway.
Meng, Hua-Wen; Shen, Zhen-Bao; Meng, Xian-She; Yin, Ze-Qun; Wang, Xue-Rui; Zou, Ting-Feng; Liu, Zhi-Gang; Wang, Tian-Xiang; Zhang, Shuang; Chen, Yuan-Li; Yang, Xiao-Xiao; Li, Qing-Shan; Duan, Ya-Jun.
Affiliation
  • Meng HW; Key Laboratory of Metabolism and Regulation for Major Diseases of Anhui Higher Education Institutes, College of Food and Biological Engineering, Hefei University of Technology, Hefei, China.
  • Shen ZB; Key Laboratory of Metabolism and Regulation for Major Diseases of Anhui Higher Education Institutes, College of Food and Biological Engineering, Hefei University of Technology, Hefei, China.
  • Meng XS; Key Laboratory of Metabolism and Regulation for Major Diseases of Anhui Higher Education Institutes, College of Food and Biological Engineering, Hefei University of Technology, Hefei, China.
  • Leng-Wei; Key Laboratory of Metabolism and Regulation for Major Diseases of Anhui Higher Education Institutes, College of Food and Biological Engineering, Hefei University of Technology, Hefei, China.
  • Yin ZQ; Department of Cardiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
  • Wang XR; Key Laboratory of Metabolism and Regulation for Major Diseases of Anhui Higher Education Institutes, College of Food and Biological Engineering, Hefei University of Technology, Hefei, China.
  • Zou TF; Key Laboratory of Metabolism and Regulation for Major Diseases of Anhui Higher Education Institutes, College of Food and Biological Engineering, Hefei University of Technology, Hefei, China.
  • Liu ZG; Key Laboratory of Metabolism and Regulation for Major Diseases of Anhui Higher Education Institutes, College of Food and Biological Engineering, Hefei University of Technology, Hefei, China.
  • Wang TX; Key Laboratory of Metabolism and Regulation for Major Diseases of Anhui Higher Education Institutes, College of Food and Biological Engineering, Hefei University of Technology, Hefei, China.
  • Zhang S; Key Laboratory of Metabolism and Regulation for Major Diseases of Anhui Higher Education Institutes, College of Food and Biological Engineering, Hefei University of Technology, Hefei, China.
  • Chen YL; Key Laboratory of Metabolism and Regulation for Major Diseases of Anhui Higher Education Institutes, College of Food and Biological Engineering, Hefei University of Technology, Hefei, China.
  • Yang XX; Key Laboratory of Metabolism and Regulation for Major Diseases of Anhui Higher Education Institutes, College of Food and Biological Engineering, Hefei University of Technology, Hefei, China.
  • Li QS; Key Laboratory of Metabolism and Regulation for Major Diseases of Anhui Higher Education Institutes, College of Food and Biological Engineering, Hefei University of Technology, Hefei, China. Electronic address: liqs@hfut.edu.cn.
  • Duan YJ; Key Laboratory of Metabolism and Regulation for Major Diseases of Anhui Higher Education Institutes, College of Food and Biological Engineering, Hefei University of Technology, Hefei, China; Department of Cardiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Univ
Bioorg Chem ; 138: 106654, 2023 09.
Article de En | MEDLINE | ID: mdl-37300959
Parkinson's disease (PD) is a progressive neurodegenerative disorder with a complex etiology. Neuroinflammation and oxidative stress are important factors driving the progression of PD. It has been reported that 1,3,4-oxadiazole and flavone derivatives have numerous biological functions, especially in the aspect of anti-inflammatory and antioxidant. Based on the strategy of pharmacodynamic combination, we introduced 1,3,4-oxadiazole moiety into the flavonoid backbone, designed and synthesized a series of novel flavonoid 1,3,4-oxadiazole derivatives. Further, we evaluated their toxicity, anti-inflammatory and antioxidant activities using BV2 microglia. Following a comprehensive analysis, compound F12 showed the best pharmacological activity. In vivo, we induced the classical PD animal model by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into C57/BL6J mice. Our results showed that compound F12 ameliorated MPTP-induced dysfunction in mice. Further, compound F12 reduced oxidative stress by promoting the nucleation of nuclear factor erythroid 2-related factor 2 (Nrf2) and decreased the inflammatory response by inhibiting the nuclear translocation of nuclear factor-κB (NF-κB) in vivo and in vitro. Meanwhile, compound F12 inhibited the mitochondrial apoptotic pathway to rescue microglia inflammation-mediated loss of dopaminergic neurons. In conclusion, compound F12 reduced oxidative stress and inflammation and could be as a potential agent for PD treatment.
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Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Maladie de Parkinson / Neuroprotecteurs Type d'étude: Prognostic_studies Limites: Animals Langue: En Journal: Bioorg Chem Année: 2023 Type de document: Article Pays d'affiliation: Chine Pays de publication: États-Unis d'Amérique

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Maladie de Parkinson / Neuroprotecteurs Type d'étude: Prognostic_studies Limites: Animals Langue: En Journal: Bioorg Chem Année: 2023 Type de document: Article Pays d'affiliation: Chine Pays de publication: États-Unis d'Amérique