Tricin promoted ATG-7 dependent autophagic degradation of α-synuclein and dopamine release for improving cognitive and motor deficits in Parkinson's disease

Xingxia Wang; Wei Hu; Liqun Qu; Jian Wang; Anguo Wu; Hang Hong Lo; Jerome P L Ng; Yong Tang; Xiaoyun Yun; Jianhui Wu; Vincent Kam Wai Wong; Sookja Kim Chung; Linna Wang; Weidan Luo; Xiang Ji; Betty Yuen Kwan Law

doi:10.1016/j.phrs.2023.106874

Tricin promoted ATG-7 dependent autophagic degradation of α-synuclein and dopamine release for improving cognitive and motor deficits in Parkinson's disease

Pharmacol Res. 2023 Oct:196:106874. doi: 10.1016/j.phrs.2023.106874. Epub 2023 Aug 14.

Authors

Xingxia Wang¹, Wei Hu², Liqun Qu³, Jian Wang², Anguo Wu⁴, Hang Hong Lo², Jerome P L Ng², Yong Tang⁵, Xiaoyun Yun², Jianhui Wu², Vincent Kam Wai Wong², Sookja Kim Chung⁶, Linna Wang², Weidan Luo², Xiang Ji², Betty Yuen Kwan Law⁷

Affiliations

¹ Neher's Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau Special Administrative Region of China; Department of Neurology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China.
² Neher's Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau Special Administrative Region of China.
³ Neher's Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau Special Administrative Region of China; Marine Traditional Chinese Medicine Research Center, Key Laboratory of Marine Traditional Chinese Medicine in Shandong Universities, Shandong Engineering and Technology Research Center on Omics of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, China.
⁴ Sichuan Key Medical Laboratory of New Drug Discovery and Drug ability Evaluation, Luzhou Key Laboratory of Activity Screening and Draggability Evaluation for Chinese Materia Medica, Key Laboratory of Medical Electrophysiology of Ministry of Education, School of Pharmacy, Southwest Medical University, Luzhou, China.
⁵ Neher's Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau Special Administrative Region of China; Sichuan Key Medical Laboratory of New Drug Discovery and Drug ability Evaluation, Luzhou Key Laboratory of Activity Screening and Draggability Evaluation for Chinese Materia Medica, Key Laboratory of Medical Electrophysiology of Ministry of Education, School of Pharmacy, Southwest Medical University, Luzhou, China.
⁶ Neher's Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau Special Administrative Region of China; Faculty of Medicine, Macau University of Science and Technology, Macau Special Administrative Region of China.
⁷ Neher's Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau Special Administrative Region of China. Electronic address: yklaw@must.edu.mo.

PMID: 37586619
DOI: 10.1016/j.phrs.2023.106874

Abstract

Tricin, a natural nontoxic flavonoid distributed in grasses and euphorbia plants, has been reported to scavenge free radicals, possess anti-inflammatory and antioxidative effects. However, its autophagic effect on Parkinson's disease (PD) has not been elucidated. By adopting cellular and C. elegans models of PD, the autophagic effect of tricin was identified based on the level of autophagy markers (LC3-II and p62). Besides, the pharmacological effects on neurotransmitters (dopamine), inflammatory cytokines (IFN γ, TNFα, MCP-1, IL-10, IL-6 and IL-17A), histology (hematoxylin & eosin and Nissl staining) and behavioural pathology (open-field test, hindlimb clasping, Y-maze, Morris water-maze and nest building test) were also confirmed in the A53T-α-synuclein transgenic PD mouse model. Further experiments demonstrated that tricin induced autophagic flux and lowered the level of α-synuclein through AMPK-p70s6K- and ATG7-dependent mechanism. Compared to the existing clinical PD drugs, tricin mitigated pathogenesis and symptoms of PD with no observable side effects. In summary, tricin is proposed as a potential adjuvant remedy or nutraceutical for the prevention and treatment of PD.

Keywords: AMPK-p70s6K; ATG7; Autophagy; Parkinson’s disease; Tricin.