Neurochemical Research

, Volume 43, Issue 10, pp 1914–1926 | Cite as

Glycyrrhizic Acid Alleviates 6-Hydroxydopamine and Corticosterone-Induced Neurotoxicity in SH-SY5Y Cells Through Modulating Autophagy

  • Guangyi Yang
  • Jing Li
  • Youli Cai
  • Zhonghua Yang
  • Rong LiEmail author
  • Wenjun FuEmail author
Original Paper


Recent researches have shown that autophagy is associated with the pathogenesis of neurodegenerative disorders, but there is no paper to investigate the effects of autophagy modulation on Parkinson’s disease depression (PDD). In addition, glycyrrhizic acid (GA), the major bioactive ingredient of Radix glycyrrhizae, can induce autophagy and ease rotenone-induced Parkinson’s disease (PD). However, there is also no paper to study the action and molecular mechanisms of GA on PDD. In this research, we built the injury model of SH-SY5Y cells through 6-hydroxydopamine (6-OHDA) and corticosterone (CORT). Then, our results showed that GA markedly increased the viability and decreased the apoptosis in SH-SY5Y cells after pre-treating with 6-OHDA and CORT. Moreover, GA notably decreased the expressions of α-Syn and p-S1292-LRRK2 proteins, and significantly increased the levels of CREB and BDNF proteins. Previous papers have suggested that CORT contributed to dopaminergic neurodegeneration via the glucocorticoid (GC)/glucocorticoid receptor (GR) interaction, and our results showed that GA reduced GC level and hypothalamic–pituitary–adrenal (HPA) activity in SH-SY5Y cells by regulating GR signaling pathway. Furthermore, mechanism investigations also showed that GA had the ability to up-regulate the conversion of LC3B II/I and the expression of Beclin-1, and induce autophagy in SH-SY5Y cells, which were reversed by the autophagy inhibitor 3-methyladenine (3-MA). Collectively, these findings proved that GA exerted efficient activity against neurotoxicity in SH-SY5Y cells induced by 6-OHDA and CORT via activation of autophagy, which should be developed as an efficient candidate for treating PDD in the future.


Autophagy Glycyrrhizic acid Neurotoxicity Parkinson’s disease depression SH-SY5Y cells 



This work was supported by National Natural Science foundation of China (No. 81573922), Hubei province technical innovation project (No. 2017ACA176), Natural Science Foundation of Guangdong Province (No. 2017ZC0135) and Elite Youth Education Program of Guangzhou University of Chinese Medicine (No. QNYC20140104).

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of PharmacyShenzhen Bao’an Traditional Chinese Medical Hospital (Group)ShenzhenChina
  2. 2.Department of CardiologyFirst Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhouChina
  3. 3.School of Basic Medical ScienceGuangzhou University of Chinese MedicineGuangzhouChina
  4. 4.South China Research Center for Acupuncture and Moxibustion, School of Basic Medical ScienceGuangzhou University of Chinese MedicineGuangzhouChina

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