PUBLICATION
Theacrine, a purine alkaloid from kucha, protects against Parkinson's disease through SIRT3 activation
- Authors
- Duan, W.J., Liang, L., Pan, M.H., Lu, D.H., Wang, T.M., Li, S.B., Zhong, H.B., Yang, X.J., Cheng, Y., Liu, B., Li, W.X., Kurihara, H., Bi, W., Li, Y.F., He, R.R.
- ID
- ZDB-PUB-200728-11
- Date
- 2020
- Source
- Phytomedicine : international journal of phytotherapy and phytopharmacology 77: 153281 (Journal)
- Registered Authors
- Keywords
- Dopaminergic neurons, Mitochondrial dysfunction, Oxidative damage, Parkinson's disease, SIRT3, Theacrine
- MeSH Terms
-
- Animals
- Apoptosis/drug effects
- Behavior, Animal/drug effects
- Camellia/chemistry
- Dopaminergic Neurons/drug effects
- Embryo, Nonmammalian/drug effects
- Humans
- Male
- Mice, Inbred C57BL
- Mitochondria/drug effects
- Neuroprotective Agents/pharmacology*
- Oxidopamine/pharmacology
- Parkinsonian Disorders/drug therapy*
- Parkinsonian Disorders/pathology
- Rats, Sprague-Dawley
- Sirtuin 1/metabolism*
- Uric Acid/analogs & derivatives*
- Uric Acid/pharmacology
- Zebrafish/embryology
- PubMed
- 32707370 Full text @ Phytomedicine
Citation
Duan, W.J., Liang, L., Pan, M.H., Lu, D.H., Wang, T.M., Li, S.B., Zhong, H.B., Yang, X.J., Cheng, Y., Liu, B., Li, W.X., Kurihara, H., Bi, W., Li, Y.F., He, R.R. (2020) Theacrine, a purine alkaloid from kucha, protects against Parkinson's disease through SIRT3 activation. Phytomedicine : international journal of phytotherapy and phytopharmacology. 77:153281.
Abstract
Background Oxidative damage of dopaminergic neurons is the fundamental causes of Parkinson's disease (PD) that has no standard cure at present. Theacrine, a purine alkaloid from Chinese tea Kucha, has been speculated to benefit the neurodegeneration in PD, through similar actions to its chemical analogue caffeine, albeit excluding side effects. Theacrine has nowadays gained a lot of interest for its multiple benefits, while the investigations are weak and insufficient.
Hypothesis/purpose It is well-known that tea has a wide range of functions, especially in the prevention and treatment of neurodegenerative diseases. Theacrine is an active monomer compound in Camellia assamica var. kucha Hung T. Chang & H.S.Wang (Kucha), which appears to be effective and safe in PD therapy. The aim of this study is to examine its actions in diverse PD models and explore the mechanisms.
Study design For determination of theacrine's effects, we employed diverse oxidative damage-associated PD models, including 6-OHDA-treated rats, MPTP-treated mice/zebrafish and MPP+-treated SH-SY5Y cells, and using caffeine, selegiline and depranyl as positve control. For investigation and verification of the mechanisms, we utilized approaches testing mitochondrial function-related parameters and enzyme activity as well as applied gene knockdown and overexpression.
Methods We employed behavioral tests including spontaneous activity, pole, swimming, rotarod and gait, immunohistochemistry, HPLC, flow cytometry, immunohistochemistry, Western blot, gene knockdown by siRNA and overexpression by plasmid in this study.
Results Theacrine is demonstrated to retrieve the loss of dopaminergic neurons and the damages of behavioral performance in multiple animal models of PD (6-OHDA-treated rats and in MPTP-treated mice and zebrafish). The followed data of MPP+-treated SH-SY5Y cells indicate that theacrine relieves apoptosis resulted from oxidative damage and mitochondrial dysfunction. Further investigations illustrate that theacrine activates SIRT3 directly. It is of advantage to prevent apoptosis through SIRT3-mediated SOD2 deacetylation that reduces ROS accumulation and restores mitochondrial function. This concept is elaborated by 3TYP that inhibits SIRT3 enzyme activity and knockdown/overexpression of SIRT3 gene, demonstrating a crucial role of SIRT3 in theacrine-benefited dopaminergic neurons.
Conclusion Theacrine prevents apoptosis of dopaminergic neurons through directly activating SIRT3 which deacetylating SOD2 and restoring mitochondrial functions.
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Sequence Targeting Reagents
Fish
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