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Protective Effect of 20(S)-Protopanaxadiol on D-Gal-Induced Cognitively Impaired Mice Based on Its Target Protein Brain-type Creatine Kinase.
Zhang, Hantao; Chen, Feiyan; Xu, Shuyi; Zhang, Wenjing; Li, Rimei; Yao, Qi; Zhao, Yunan; Zhu, Zhu; Chen, Lin.
Afiliación
  • Zhang H; Department of Physiology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
  • Chen F; Research and Innovation Center, College of Traditional Chinese Medicine Integrated Chinese and Western Medicine College, Nanjing University of Chinese Medicine, Nanjing 210023, China.
  • Xu S; Department of Physiology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
  • Zhang W; Department of Physiology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
  • Li R; Department of Physiology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
  • Yao Q; Kunshan Huaqiao Senior High School, Suzhou 215332, China.
  • Zhao Y; Department of Pathology and Pathophysiology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
  • Zhu Z; Department of Pathology and Pathophysiology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
  • Chen L; Department of Pathology and Pathophysiology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
J Agric Food Chem ; 2023 Feb 08.
Article en En | MEDLINE | ID: mdl-36752334
Ginseng is an important medicinal herb consumed as dietary supplements. Ginsenosides and their metabolites have been reported to enhance cognitive performance, but their underlying mechanisms remain unclear. Brain-type creatine kinase (CK-BB) was previously screened out as one of the potential targets in brain tissues. In vitro, the strongest direct interaction between 20(S)-protopanaxadiol (PPD), a ginsenoside metabolite, and CK-BB was detected using biolayer interferometry (BLI). Drug affinity responsive target stability, cellular thermal shift assay, BLI, and isothermal titration calorimetry were subsequently used, and the binding of PPD to CK-BB was verified. The binding sites of the CK-BB/PPD complex were clarified by molecular docking and site-directed mutagenesis. Enzyme activity assay showed that the binding of PPD to CK-BB in vitro enhanced its activity. In vivo, PPD increased CK-BB activity in D-gal-induced mice. PPD also improved the D-gal-induced cognitive deficits and ameliorated alterations in oxidative stress and hippocampal synaptic plasticity. Therefore, the integration of PPD with its target protein CK-BB may promote CK-BB activity, thereby ameliorating hippocampal synaptic plasticity and cognitive deficits in D-gal-treated mice.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: J Agric Food Chem Año: 2023 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: J Agric Food Chem Año: 2023 Tipo del documento: Article País de afiliación: China
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