Research Paper|Volume 11, Issue 3|pp 986—1007

Shaoyao Gancao Tang (SG-Tang), a formulated Chinese medicine, reduces aggregation and exerts neuroprotection in spinocerebellar ataxia type 17 (SCA17) cell and mouse models

Chiung-Mei Chen¹, Wan-Ling Chen¹, Chen-Ting Hung², Te-Hsien Lin², Ming-Chung Lee³, I-Cheng Chen¹, Chih-Hsin Lin¹, Chih-Ying Chao¹, Yih-Ru Wu¹, Kuo-Hsuan Chang¹, Hsiu Mei Hsieh-Li², Guey-Jen Lee-Chen²

¹Department of Neurology, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan 33305, Taiwan
²Department of Life Science, National Taiwan Normal University, Taipei 11677, Taiwan
³Brion Research Institute, New Taipei City 23143, Taiwan

Received: November 3, 2018Accepted: January 24, 2019Published: February 13, 2019

https://doi.org/10.18632/aging.101804

Copyright: © 2019 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Spinocerebellar ataxia (SCA) type 17 is an autosomal dominant ataxia caused by expanded polyglutamine (polyQ) tract in the TATA-box binding protein (TBP). Substantial studies have shown involvement of compromised mitochondria biogenesis regulator peroxisome proliferator-activated receptor gamma-coactivator 1 alpha (PGC-1α), nuclear factor erythroid 2-related factor 2 (NRF2), nuclear factor-Y subunit A (NFYA), and their downstream target genes in the pathogenesis of polyQ-expansion diseases. The extracts of Paeonia lactiflora (P. lactiflora) and Glycyrrhiza uralensis (G. uralensis) have long been used as a Chinese herbal medicine (CHM). Shaoyao Gancao Tang (SG-Tang) is a formulated CHM made of P. lactiflora and G. uralensis at a 1:1 ratio. In the present study, we demonstrated the aggregate-inhibitory and anti-oxidative effect of SG-Tang in 293 TBP/Q₇₉ cells. We then showed that SG-Tang reduced the aggregates and ameliorated the neurite outgrowth deficits in TBP/Q₇₉ SH-SY5Y cells. SG-Tang upregulated expression levels of NFYA, PGC-1α, NRF2, and their downstream target genes in TBP/Q₇₉ SH-SY5Y cells. Knock down of NFYA, PGC-1α, and NRF2 attenuated the neurite outgrowth promoting effect of SG-Tang on TBP/Q₇₉ SH-SY5Y cells. Furthermore, SG-Tang inhibited aggregation and rescued motor-deficits in SCA17 mouse model. The study results suggest the potential of SG-Tang in treating SCA17 and probable other polyQ diseases.