Biomolecules & Therapeutics
Neuroprotective Effect of Astersaponin I against Parkinson’s Disease through Autophagy Induction
Lijun Zhang1,2,3, Jeoung Yun Park1, Dong Zhao1,2, Hak Cheol Kwon4 and Hyun Ok Yang1,2,5,*
1Natural Product Research Center, Korea Institute of Science and Technology, Gangneung 25451,
2Division of Bio-medical Science and Technology, KIST School, Korea University of Science and Technology, Seoul 02792, Republic of Korea
3State Key Laboratory for Chemistry and Molecular Engineering of Medical Resources, Guangxi Normal University, Guilin 541004, China
4Natural Product Informatics Research Center, Korea Institute of Science and Technology, Gangneung 25451,
5Department of Integrative Biological Sciences and Industry, Sejong University, Seoul 05006, Republic of Korea
Tel: +82-2-3408-1959, Fax: +82-2-3408-4336
Received: January 6, 2021; Revised: May 17, 2021; Accepted: June 7, 2021; Published online: July 2, 2021.
© The Korean Society of Applied Pharmacology. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
An active compound, triterpene saponin, astersaponin I (AKNS-2) was isolated from Aster koraiensis Nakai (AKNS) and the autophagy activation and neuroprotective effect was investigated on in vitro and in vivo Parkinson’s disease (PD) models. The autophagy-regulating effect of AKNS-2 was monitored by analyzing the expression of autophagy-related protein markers in SHSY5Y cells using Western blot and fluorescent protein quenching assays. The neuroprotection of AKNS-2 was tested by using a 1-methyl-4-phenyl-2,3-dihydropyridium ion (MPP+)-induced in vitro PD model in SH-SY5Y cells and an MPTP-induced in vivo PD model in mice. The compound-treated SH-SY5Y cells not only showed enhanced microtubule-associated protein 1A/1B-light chain 3-II (LC3-II) and decreased sequestosome 1 (p62) expression but also showed increased phosphorylated extracellular signal–regulated kinases (p-Erk), phosphorylated AMP-activated protein kinase (p-AMPK) and phosphorylated unc-51-like kinase (p-ULK) and decreased phosphorylated mammalian target of rapamycin (p-mTOR) expression. AKNS-2-activated autophagy could be inhibited by the Erk inhibitor U0126 and by AMPK siRNA. In the MPP+-induced in vitro PD model, AKNS-2 reversed the reduced cell viability and tyrosine hydroxylase (TH) levels and reduced the induced α-synuclein level. In an MPTP-induced in vivo PD model, AKNS-2 improved mice behavioral performance, and it restored dopamine synthesis and TH and α-synuclein expression in mouse brain tissues. Consistently, AKNS-2 also modulated the expressions of autophagy related markers in mouse brain tissue. Thus, AKNS-2 upregulates autophagy by activating the Erk/mTOR and AMPK/mTOR pathways. AKNS-2 exerts its neuroprotective effect through autophagy activation and may serve as a potential candidate for PD therapy.
Keywords: Autophagy, Parkinson’s disease, Neuroprotection, Tyrosine hydroxylase, Motor symptoms

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