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

• Published in: Drug design, development and therapy Vol. 10; no. Issue 1; pp. 885 - 896
• Main Authors: Chang, Kuo-Hsuan, Chen, I-Cheng, Lin, Hsuan-Yuan, Chen, Hsuan-Chiang, Lin, Chih-Hsin, Lin, Te-Hsien, Weng, Yu-Ting, Chao, Chih-Ying, Wu, Yih-Ru, Lin, Jung-Yaw, Lee-Chen, Guey-Jen, Chen, Chiung-Mei
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2016; Taylor & Francis Ltd; Dove Medical Press
• Subjects: Advertising executives; Agglomeration; Alzheimer Disease - drug therapy; Alzheimer Disease - pathology; Alzheimer's disease; Amino acids; Animal models; Apoptosis; Axonogenesis; Cell culture; Cell Line, Tumor; Cell Proliferation - drug effects; Chaperones; Chinese medicine; Chromatography; Cloning; Cytotoxicity; Dementia; Dose-Response Relationship, Drug; Drugs, Chinese Herbal - chemistry; Drugs, Chinese Herbal - pharmacology; Endoplasmic reticulum; Fusion protein; G. inflata; Ginseng; Glycyrrhiza; Glycyrrhiza - chemistry; Glycyrrhiza inflata; HEK293 Cells; Herbal medicine; Homeostasis; Humans; Medical treatment; Medicine, Chinese; Medicine, Chinese Traditional; Models, Biological; Molecular Chaperones - metabolism; Mutagenesis; Neuroblastoma; Neurodegeneration; Neurodegenerative diseases; Neurological diseases; Neurons - drug effects; Neurons - metabolism; Neuroprotection; Original Research; Panax ginseng; Plant Extracts - chemistry; Plant Extracts - pharmacology; Protein folding; Protein Unfolding - drug effects; Proteins; Quality control; Structure-Activity Relationship; tau misfolding; Tau protein; tau Proteins - chemistry; tau Proteins - metabolism; tauopathy; TCM extracts; Toxicity; Traditional Chinese medicine; Unfolded Protein Response - drug effects; Unfolded Protein Response - physiology; Up-Regulation - drug effects; UPR-mediated chaperone; Water - chemistry; United States > US; China; Taiwan; G. inflata; tau misfolding; tauopathy; Alzheimer’s disease; TCM extracts; UPR-mediated chaperones
• ISSN: 1177-8881; 1177-8881
• DOI: 10.2147/DDDT.S96454

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. 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. 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. 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.