Advertisement

Archives of Pharmacal Research

, Volume 42, Issue 11, pp 1012–1020 | Cite as

Schisandrin A ameliorates MPTP-induced Parkinson’s disease in a mouse model via regulation of brain autophagy

  • Yinghao ZhiEmail author
  • Yongxi Jin
  • Lulu Pan
  • Aiguo Zhang
  • Feiwen Liu
Research Article

Abstract

Schisandrin A (Sch A) is one of the principal bioactive lignans isolated from Fructus schisandrae. In this study, we demonstrated its protective effect and biochemical mechanism of action in a 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-induced mouse model of Parkinson’s disease. Sch A significantly ameliorated behavioural abnormalities and increased the number of nigral dopaminergic neurons detected by tyrosine hydroxylase immunohistochemistry. Pre-treatment with Sch A significantly decreased the levels of the inflammatory mediators IL-6, IL-1β, and TNF-α and markedly improved antioxidant defences by inhibiting the activity of MDA and increasing that of SOD. Furthermore, Sch A activated expression of the autophagy-related proteins LC3-II, beclin1, parkin, and PINK1 and increased mTOR expression. Taken together, these findings indicate that Sch A has neuroprotective effects against the development of Parkinson’s disease via regulation of brain autophagy.

Keywords

Schizandrin A Parkinson’s disease Autophagy LC3-II 

Notes

Acknowledgements

This study was funded by Chinese Medicine Science and Technology Project of Zhejiang Province (Grant No. 20162097009594).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Supplementary material

12272_2019_1186_MOESM1_ESM.jpg (432 kb)
Supplementary material 1 (JPEG 432 kb)

References

  1. Aksoy D, Solmaz V, Cavusoglu T, Meral A, Ates U, Erbas O (2017) Neuroprotective effects of exenatide in a Rotenone-Induced rat model of Parkinson’s disease. Am J Med Sci 354:319–324CrossRefGoogle Scholar
  2. Burchell VS, Nelson DE, Sanchez-Martinez A, Delgado-Camprubi M, Ivatt RM, Pogson JH, Randle SJ, Wray S, Lewis PA, Houlden H, Abramov AY, Hardy J, Wood NW, Whitworth AJ, Laman H, Plun-Favreau H (2013) The Parkinson’s disease-linked proteins Fbxo7 and Parkin interact to mediate mitophagy. Nat Neurosci 16:1257–1265CrossRefGoogle Scholar
  3. Cheng M, Liu L, Lao Y, Liao W, Liao M, Luo X, Wu J, Xie W, Zhang Y, Xu N (2016) MicroRNA-181a suppresses parkin-mediated mitophagy and sensitizes neuroblastoma cells to mitochondrial uncoupler-induced apoptosis. Oncotarget 7:42274–42287PubMedPubMedCentralGoogle Scholar
  4. De Vries RL, Przedborski S (2013) Mitophagy and Parkinson’s disease: be eaten to stay healthy. Mol Cell Neurosci 55:37CrossRefGoogle Scholar
  5. Di H, Cao Y, He R, Na H, Liu Z, Miao L, Yin J (2012) Schizandrin, an antioxidant Lignan from Schisandra chinensis, ameliorates Aβ1-42-induced memory impairment in mice. Oxid Med Cell Longev 2012:721721Google Scholar
  6. Exner N, Lutz AK, Haass C, Winklhofer KF (2012) Mitochondrial dysfunction in Parkinson’s disease: molecular mechanisms and pathophysiological consequences. EMBO J 31:3038–3062CrossRefGoogle Scholar
  7. Hu D, Li C, Han N, Miao L, Wang D, Liu Z, Wang H, Yin J (2012) Deoxyschizandrin isolated from the fruits of Schisandra chinensis ameliorates Aβ1-42-induced memory impairment in mice. Planta Med 78:1332CrossRefGoogle Scholar
  8. Kaur B, Prakash A (2017) Ceftriaxone attenuates glutamate-mediated neuro-inflammation and restores BDNF in MPTP model of Parkinson’s disease in rats. Pathophysiology 24:71–79CrossRefGoogle Scholar
  9. Koo KA (2004) Dibenzocyclooctadiene lignans from Schisandra chinensis protect primary cultures of rat cortical cells from glutamate-induced toxicity. J Neurosci Res 76:397–405CrossRefGoogle Scholar
  10. Kwon DH, Cha HJ, Choi EO, Leem SH, Kim GY, Moon SK, Chang YC, Yun SJ, Hwang HJ, Kim BW (2018) Schisandrin A suppresses lipopolysaccharide-induced inflammation and oxidative stress in RAW 264.7 macrophages by suppressing the NF-κB, MAPKs and PI3 K/Akt pathways and activating Nrf2/HO-1 signaling. Int J Mol Med 41:264–274PubMedGoogle Scholar
  11. Luchtman DW, Shao D, Song C (2009) Behavior, neurotransmitters and inflammation in three regimens of the MPTP mouse model of Parkinson’s disease. Physiol Behav 98:130CrossRefGoogle Scholar
  12. Qin XQ, Liang YG, Gao HZ, Qu HY, Dong RH, Wu XW, Li HY, Liu ZY (2011) Reversing mechanism of schizandrin A on multi-drug resistance of K562/ADR, HL60/ADR, MCF-7/ADR cell lines. Chin Pharmacol Bull 27:329–334Google Scholar
  13. Schapira AHV (1994) Evidence for mitochondrial dysfunction in Parkinson’s disease—a critical appraisal. Mov Disord Off J Mov Disord Soc 9:125–138CrossRefGoogle Scholar
  14. Song F, Zeng K, Liao L, Yu Q, Tu P, Wang X (2016) Schizandrin A inhibits microglia-mediated neuroninflammation through inhibiting TRAF6-NF-κB and Jak2-Stat3 signaling pathways. PLoS ONE 11:e0149991CrossRefGoogle Scholar
  15. Sowndhararajan K, Deepa P, Kim M, Park SJ, Kim S (2017) An overview of neuroprotective and cognitive enhancement properties of lignans from Schisandra chinensis. Biomed Pharmacother 97:958–968CrossRefGoogle Scholar
  16. Steinkellner T, Zell V, Farino ZJ, Sonders MS, Villeneuve M, Freyberg RJ, Przedborski S, Lu W, Freyberg Z, Hnasko TS (2018) Role for VGLUT2 in selective vulnerability of midbrain dopamine neurons. J Clin Invest 128:774–788CrossRefGoogle Scholar
  17. Su X, Gao C, Shi F, Feng X, Liu L, Qu D, Wang C (2017) A microemulsion co-loaded with Schizandrin A-docetaxel enhances esophageal carcinoma treatment through overcoming multidrug resistance. Drug Deliv 24:10CrossRefGoogle Scholar
  18. Tiong YL, Ng KY, Koh RY, Ponnudurai G, Chye SM (2019) Melatonin prevents oxidative stress-induced mitochondrial dysfunction and apoptosis in high glucose-treated schwann cells via upregulation of Bcl2, NF-kappaB, mTOR, Wnt signalling pathways. Antioxidants (Basel) 8:198CrossRefGoogle Scholar
  19. Wang CP, Li GC, Shi YW, Zhang XC, Li JL, Wang ZW, Ding F, Liang XM (2014) Neuroprotective effect of schizandrin A on oxygen and glucose deprivation/reperfusion-induced cell injury in primary culture of rat cortical neurons. J Physiol Biochem 70:735–747CrossRefGoogle Scholar
  20. Wu W, Xu H, Wang Z, Mao Y, Yuan L, Luo W, Cui Z, Cui T, Wang XL, Shen YH (2015) PINK1-Parkin-mediated mitophagy protects mitochondrial integrity and prevents metabolic stress-induced endothelial injury. PLoS ONE 10:e0132499CrossRefGoogle Scholar
  21. Zhou Y, Xie JX (1999) Parkinson’s disease and oxidative stress. Sheng li ke xue jin zhan [Progress in physiology] 30:169Google Scholar
  22. Zhou F, Wang M, Ju J, Wang Y, Liu Z, Zhao X, Yan Y, Yan S, Luo X, Fang Y (2019) Schizandrin A protects against cerebral ischemia-reperfusion injury by suppressing inflammation and oxidative stress and regulating the AMPK/Nrf2 pathway regulation. Am J Transl Res 11:199–209PubMedPubMedCentralGoogle Scholar

Copyright information

© The Pharmaceutical Society of Korea 2019

Authors and Affiliations

  • Yinghao Zhi
    • 1
    Email author
  • Yongxi Jin
    • 1
  • Lulu Pan
    • 1
  • Aiguo Zhang
    • 1
  • Feiwen Liu
    • 1
  1. 1.Department of RehabilitationWenzhou Hospital of Traditional Chinese MedicineWenzhouChina

Personalised recommendations