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The aqueous extract of Glycyrrhiza inflata can upregulate unfolded protein response-mediated chaperones to reduce tau misfolding in cell models of Alzheimer’s disease

Authors Chang K, Chen I, Lin H, Chen H, Lin C, Lin T, Weng Y, Chao C, Wu Y, Lin J, Lee-Chen G, Chen C

Received 15 September 2015

Accepted for publication 16 December 2015

Published 29 February 2016 Volume 2016:10 Pages 885—896

DOI https://doi.org/10.2147/DDDT.S96454

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Arun Kapoor

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Wei Duan


Kuo-Hsuan Chang,1,* I-Cheng Chen,1,* Hsuan-Yuan Lin,2 Hsuan-Chiang Chen,2 Chih-Hsin Lin,1 Te-Hsien Lin,2 Yu-Ting Weng,1 Chih-Ying Chao,1 Yih-Ru Wu,1 Jung-Yaw Lin,2 Guey-Jen Lee-Chen,2 Chiung-Mei Chen1

1Department of Neurology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 2Department of Life Science, National Taiwan Normal University, Taipei, Taiwan, Republic of China

*These authors contributed equally to this work

Background:
Alzheimer’s disease (AD) and several neurodegenerative disorders known as tauopathies are characterized by misfolding and aggregation of tau protein. Although several studies have suggested the potential of traditional Chinese medicine (TCM) as treatment for neurodegenerative diseases, the role of TCM in treating AD and tauopathies have not been well explored.
Materials and methods: Tau protein was coupled to the DsRed fluorophore by fusing a pro-aggregation mutant of repeat domain of tau (ΔK280 tauRD) with DsRed. The ΔK280 tauRD-DsRed fusion gene was then used to generate Tet-On 293 and SH-SY5Y cell clones as platforms to test the efficacy of 39 aqueous extracts of TCM in reducing tau misfolding and in neuroprotection.
Results: Seven TCM extracts demonstrated a significant reduction in tau misfolding and reactive oxidative species with low cytotoxicity in the ΔK280 tauRD-DsRed 293 cell model. Glycyrrhiza inflata and Panax ginseng also demonstrated the potential to improve neurite outgrowth in the ΔK280 tauRD-DsRed SH-SY5Y neuronal cell model. G. inflata further rescued the upregulation of ERN2 (pro-apoptotic) and downregulation of unfolded-protein-response-mediated chaperones ERP44, DNAJC3, and SERP1 in ΔK280 tauRD-DsRed 293 cells.
Conclusion: This in vitro study provides evidence that G. inflata may be a novel therapeutic for AD and tauopathies. Future applications of G. inflata on animal models of AD and tauopathies are warranted to corroborate its effect of reducing misfolding and potential disease modification.

Keywords: Alzheimer’s disease, tauopathy, tau misfolding, TCM extracts, G. inflata, UPR-mediated chaperones

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