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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Aging Neurosci. | doi: 10.3389/fnagi.2019.00230

Gami-Chunggan Formula prevents motor dysfunction in MPTP/p-induced and A53T α-synuclein overexpressed Parkinson’s disease mouse model though DJ-1 and BDNF expression

Sora Ahn1, Quan Feng Liu2,  Jae-Hwan Jang3, Ha Jin Jeong4, Youngman Kim5, Dong-hee Kim5, Guwon Jeong5,  Seung Tack Oh5, Seong-Uk Park6,  Seung-Yeon Cho6,  Hi-Joon Park1 and  Songhee Jeon4, 7*
  • 1College of Korean Medicine, Kyung Hee University, South Korea
  • 2Dongguk University Gyeongju, South Korea
  • 3College of Medicine, Kyung Hee University, South Korea
  • 4Chonnam National University, South Korea
  • 5Dongkwang Pharm Co., Ltd., South Korea
  • 6Kyung Hee University Hospital at Gangdong, Kyung Hee University, South Korea
  • 7Chonnam National University Medical School, South Korea

The Gami-Chunggan formula (GCF) is a modification of the Chunggan (CG) decoction, which has been used to treat movement disorders such as Parkinson’s disease (PD) in Traditional East Asian Medicine. To evaluate the neuroprotective effects of GCF in chronic PD animal models, we used either a 5-week treatment of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine with probenecid (MPTP/p) or the α-synuclein A53T overexpressed PD mouse model. C57BL/6 mice were treated with MPTP, in combination with probenecid, for 5 weeks. GCF was administered simultaneously with MPTP injection for 38 days. The A53T α-synuclein overexpressed mice were also fed with GCF for 60 days. Using behavioral readouts and western blot analyses, it was observed that GCF prevents motor dysfunction in the MPTP/p-induced and A53T α-synuclein overexpressed mice. Moreover, GCF inhibited the reduction of dopaminergic neurons in the substantia nigra (SN) and fibers in the striatum (ST) against MPTP/p challenge. The expression of DJ-1 was increased but that of α-synuclein was decreased in the SN of PD-like brains by GCF administration. In vitro experiments also showed that GCF inhibited 6-OHDA-induced neurotoxicity in SH-SY5Y neuroblastoma cell lines and that it did so to a greater degree than CG. Furthermore, GCF induced BDNF expression through phosphorylation of Akt, ERK, CREB, and AMPK in the SN of PD-like brains. Therefore, use of the herbal medicine GCF offers a potential remedy for neurodegenerative disorders, including Parkinson’s disease.

Keywords: Gami-Chunggan , A53T alpha-synuclein, DJ-1, Probenecid, BDNF, MPTP (1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine), Parkinson ' s disease

Received: 29 Nov 2018; Accepted: 13 Aug 2019.

Copyright: © 2019 Ahn, Liu, Jang, Jeong, Kim, Kim, Jeong, Oh, Park, Cho, Park and Jeon. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Songhee Jeon, Chonnam National University Medical School, Gwangju, South Korea, jsong0304@chonnam.ac.kr