Neural Regeneration Research ›› 2020, Vol. 15 ›› Issue (2): 361-368.doi: 10.4103/1673-5374.265557

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Ethanol extract from Gynostemma pentaphyllum ameliorates dopaminergic neuronal cell death in transgenic mice expressing mutant A53T human alpha-synuclein

Hyun Jin Park1, 2, Ting Ting Zhao1, Seung Hwan Kim3, Chong Kil Lee1, 2, Bang Yeon Hwang1, Kyung Eun Lee1, Myung Koo Lee1, 2   

  1. 1 Department of Pharmacy, College of Pharmacy, Chungbuk National University, Cheongju, Republic of Korea
    2 Research Center for Bioresource and Health, College of Pharmacy, Chungbuk National University, Cheongju, Republic of Korea
    3 Department of Social Physical Education, Songwon University, Gwangju, Republic of Korea
  • Online:2020-02-15 Published:2020-05-25
  • Contact: Myung Koo Lee, PhD,myklee@chungbuk.ac.kr.
  • Supported by:
    This study was supported by the National Research Foundation of Korea, grant No. 2016R1D1A3B03930722 (to MKL), Republic of Korea.

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Abstract: Gynostemma (G.) pentaphyllum (Cucurbitaceae) contains various bioactive gypenosides. Ethanol extract from G. pentaphyllum (GP-EX) has been shown to have ameliorative effects on the death of dopaminergic neurons in animal models of Parkinson’s disease (PD) induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- and 6-hydroxydopamine. PD patients exhibit multiple symptoms, so PD-related research should combine neurotoxin models with genetic models. In the present study, we investigated the ameliorative effects of GP-EX, including gypenosides, on the cell death of dopaminergic neurons in the midbrain of A53T α-synuclein transgenic mouse models of PD (A53T). Both GP-EX and gypenosides at 50 mg/kg per day were orally administered to the A53T mice for 20 weeks. α-Synuclein-immunopositive cells and α-synuclein phosphorylation were increased in the midbrain of A53T mice, which was reduced following treatment with GP-EX. Treatment with GP-EX modulated the reduced phosphorylation of tyrosine hydroxylase, extracellular signal-regulated kinase (ERK1/2), Bcl-2-associated death promoter (Bad) at Ser112, and c-Jun N-terminal kinase (JNK1/2) due to α-synuclein overexpression. In the A53T group, GP-EX treatment prolonged the latency of the step-through passive avoidance test and shortened the transfer latency of the elevated plus maze test. Gypenosides treatment exhibited the effects and efficacy similar to those of GP-EX. Taken together, GP-EX, including gypenosides, has ameliorative effects on dopaminergic neuronal cell death due to the overexpression of α-synuclein by modulating ERK1/2, Bad at Ser112, and JNK1/2 signaling in the midbrain of A53T mouse model of PD. Further studies are needed to investigate GP-EX as a treatment for neurodegenerative synucleinopathies, including PD. This study was approved by the Animal Ethics Committee of Chungbuk National University (approval No. CBNUA-956-16-01) on September 21, 2016.

Key words: A53T α-synuclein genetic mice, ERK1/2, gynostemma pentaphyllum, gypenosides, Parkinson’s disease, retention transfer latency time