4.5 Article

The neuroprotective effect of schisandrol A on 6-OHDA-induced PD mice may be related to PI3K/AKT and IKK/IκBα/NF-κB pathway

Journal

EXPERIMENTAL GERONTOLOGY
Volume 128, Issue -, Pages -

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.exger.2019.110743

Keywords

Parkinson's disease; Schisandrol A; 6-OHDA; Neuroprotective; Motor symptoms; Nonmotor symptoms

Funding

  1. National Natural Science Foundation of China [81573580]
  2. Key Laboratory of polysaccharide bioactivity evaluation of TCM of Liaoning Province
  3. Key techniques study of consistency evaluation of drug quality and therapeutic effect [18-400-4-08]
  4. Liaoning Distinguished Professor Project for Ying Jia (2017)
  5. Doctoral Scientific Research Foundation of Liaoning Province [2019-BS-233]

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Parkinson's disease is the second most common neurodegenerative disease. Its main pathological feature is the substantial nigra-striatum dopaminergic neuronal dysfunction, which causes insufficient release of DA, induces motor symptoms, and is accompanied by nonmotor symptoms. Schisandrol A belongs to lignan components and has anti-inflammatory, antioxidant and neuroprotective effects. In this experiment, we injected 6-OHDA into medial forebrain bundle of C57BL/6J male mice to establish the model. The motor function of mice was examined by open field test and pole test, the depression-like behavior of mice was examined by sucrose preference test and the memory function was examined by Y maze. We found that schisandrol A (20 mg/kg/d) could significantly improve the motor symptoms, and alleviate the depression-like symptoms and memory dysfunction of PD mice induced by 6-OHDA. Then we studied the neuroprotective mechanism of schisandrol A by H.E., ELISA assay kits and Western blot. Results showed that schisandrol A may enhance the PI3K/AKT pathway, inhibit the IKK/I kappa B alpha/NF-kappa B pathway, reduce neuronal inflammation and oxidative stress, and enhance the survival of DA neurons in the brain of mice. These results indicate that schisandrol A is expected to be a potential drug for improving Parkinson's disease.

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