PUBLICATION
Examining the neuroprotective effects of protocatechuic acid and chrysin on in vitro and in vivo models of Parkinson's disease
- Authors
- Zhang, Z., Li, G., Szeto, S.S., Chong, C., Quan, Q., Huang, C., Cui, W., Guo, B., Wang, Y., Han, Y., Michael Siu, K.W., Lee, S.M., Chu, I.K.
- ID
- ZDB-PUB-150315-4
- Date
- 2015
- Source
- Free radical biology & medicine 84: 331-43 (Journal)
- Registered Authors
- Szeto, Samuel
- Keywords
- Anti-inflammation, NF-κB, Neuroprotection, Nrf2, Parkinson's disease, Proteomics
- MeSH Terms
-
- Animals
- Antiparkinson Agents/pharmacology*
- Antiparkinson Agents/therapeutic use
- Dopaminergic Neurons/drug effects
- Dopaminergic Neurons/physiology
- Drug Evaluation, Preclinical
- Flavonoids/pharmacology*
- Flavonoids/therapeutic use
- Heme Oxygenase-1/metabolism
- Hydroxybenzoates/pharmacology*
- Hydroxybenzoates/therapeutic use
- NF-E2-Related Factor 2/metabolism
- Neuroprotective Agents/pharmacology*
- Neuroprotective Agents/therapeutic use
- Nitric Oxide/metabolism
- Nitric Oxide Synthase Type II/metabolism
- Oxidative Stress
- PC12 Cells
- Parkinson Disease/drug therapy*
- Proteome/metabolism
- Proteomics
- Rats
- Transcription Factor RelA/metabolism
- Zebrafish
- PubMed
- 25769424 Full text @ Free Radic. Biol. Med.
Citation
Zhang, Z., Li, G., Szeto, S.S., Chong, C., Quan, Q., Huang, C., Cui, W., Guo, B., Wang, Y., Han, Y., Michael Siu, K.W., Lee, S.M., Chu, I.K. (2015) Examining the neuroprotective effects of protocatechuic acid and chrysin on in vitro and in vivo models of Parkinson's disease. Free radical biology & medicine. 84:331-43.
Abstract
Polypharmacology-based strategies using drug combinations with different mechanisms of action are gaining increasing attention as a novel methodology to discover potentially innovative medicines for neurodegenerative disorders. We used this approach to examine the combined neuroprotective effects of two polyphenols, protocatechuic acid (PCA) and chrysin, identified from the fruits of Alpinia oxyphylla. Our results demonstrated synergistic neuroprotective effects, with chrysin enhancing the protective effects of PCA, resulting in greater cell viability and decreased lactate dehydrogenase (LDH) release from 6-hydroxydopamine (6-OHDA)-treated PC12 cells. Their combination also significantly attenuated chemically induced dopaminergic neuron loss in both zebrafish and mice. We examined the molecular mechanisms underlying these collective cytoprotective effects through proteomics analysis of treated PC12 cells, resulting in the identification of 12 regulated proteins. Two were further characterized, leading to the determination that pretreatment with PCA and chrysin resulted in (i) increased nuclear factor-erythroid 2-related factor 2 (Nrf2) protein expression and transcriptional activity; (ii) modulation of cellular redox status with the upregulated expression of hallmark antioxidant enzymes, including heme oxygenase-1 (HO-1), superoxide dismutase, and catalase; and (iii) decreased levels of malondialdehyde, a known lipid peroxidation product. Treatment with PCA and chrysin also inhibited activation of nuclear factor-κB (NF-κB) and expression of inducible nitric oxide synthase (iNOS). Our findings suggest that natural products, when used in combination, can be effective potential therapeutic agents for treating diseases such as Parkinson's disease. A therapy involving both PCA and chrysin exhibits its enhanced neuroprotective effects through combination of cellular mechanisms: antioxidant cytoprotection and anti-inflammation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping