chrysin and Parkinson-Disease

Parkinson's disease (PD) is the most common neurodegenerative movement disorder, with current treatment being mainly symptomatic and often accompanied by serious side effects. In search of novel and safe therapeutic agents for PD, natural flavonoids have been shown to exert significant neuroprotective effects. Among them, chrysin (5,7-dihydroxyflavone) has been demonstrated to exhibit anti-oxidative effects to dopaminergic neurons mainly by increasing the expression of Nuclear Factor Erythroid 2 -related factor 2 (NRF2) which reduces intracellular nitric oxide (NO) levels and regulates anti-oxidant pathways. Moreover, chrysin activates Myocyte Enhancer factor 2D (MEF2D), a critical transcription factor involved in dopaminergic survival. It suppresses the MPP-induced upregulation of c-caspase and Bax as well as the downregulation of anti-apoptotic protein Bcl 2. Chrysin also enhances the production of neurotrophic factors, contributing to neuronal survival. Of interest, the combination of chrysin with protocatechuic acid (PCA) has been demonstrated to inhibit neuronal loss in PD animal models. Along with anti-inflammatory properties, chrysin has also been shown to increase dopamine levels in the striatum via monoamino-oxidase B (MAO-B) inhibition while it restores the behavioral deficits in PD animal models. In this review, we discuss the molecular mechanisms that underlie the possible neuroprotective effects of chrysin in PD pathogenesis along with its therapeutic potential.

Topics: Animals; Antioxidants; Flavonoids; Humans; Neuroprotective Agents; NF-E2-Related Factor 2; Parkinson Disease; Proto-Oncogene Proteins c-bcl-2

Parkinson's disease (PD) is the second most progressive neurodegenerative disorder of the central nervous system in the elderly, causing motor impediments and cognitive dysfunctions. Dopaminergic (DA) neuron degeneration and α-synuclein (α-Syn) accumulation in substantia nigra pars compacta are the major contributors to this disease. At present, PD remains untreatable with a huge burden on the quality of life. Therefore, we attempt to explore novel treatment strategies by detecting effective drugs that stop or arrest PD's progression

Topics: alpha-Synuclein; Animals; Caenorhabditis elegans; Disease Models, Animal; Dopaminergic Neurons; Flavonoids; Parkinson Disease; Quality of Life

Chrysin, a flavonoid compound existing in several plants, is applied as a dietary supplement because of its beneficial effects on general human health and alleviation of neurological disorders. However, mechanisms underlying neuroprotection of chrysin has not been fully elucidated, and the effects of chrysin on the Parkinson's disease (PD) model in vivo have not been investigated. It is here shown that chrysin protects primary granular neurons against 1-methyl-4-phenylpyridinium ion insult via antiapoptosis by reversing the dysregulated expression of Bcl-2, Bax, and caspase 3. The mechanisms also involved activating transcriptional factor myocyte enhancer factor 2D (MEF2D) via regulation of AKT-GSK3β signaling. In this in vivo model of PD, chrysin rescued the dopaminergic neurons loss and alleviated the decrease in dopamine level induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mice. Moreover, chrysin markedly inhibited monoamine oxidase-B activity in vitro and in vivo. In conclusion, chrysin exerts beneficial effects to PD, possibly through multitarget mechanisms including antineuronal apoptosis, activation of the AKT-GSK3β/MEF2D pathway, and inhibition of the MAO-B activity.

Topics: Animals; Apoptosis; Cells, Cultured; Disease Models, Animal; Flavonoids; Humans; Male; MEF2 Transcription Factors; Mice; Mice, Inbred C57BL; Monoamine Oxidase; Neurons; Parkinson Disease; Rats; Rats, Sprague-Dawley

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 release from 6-hydroxydopamine-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 proteomic 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 protein expression and transcriptional activity; (ii) modulation of cellular redox status with the upregulated expression of hallmark antioxidant enzymes, including heme oxygenase-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 and expression of inducible nitric oxide synthase. Our findings suggest that natural products, when used in combination, can be effective potential therapeutic agents for treating diseases such as Parkinson disease. A therapy involving both PCA and chrysin exhibits its enhanced neuroprotective effects through a combination of cellular mechanisms: antioxidant cytoprotection and anti-inflammation.

Topics: Animals; Antiparkinson Agents; Dopaminergic Neurons; Drug Evaluation, Preclinical; Flavonoids; Heme Oxygenase-1; Hydroxybenzoates; Neuroprotective Agents; NF-E2-Related Factor 2; Nitric Oxide; Nitric Oxide Synthase Type II; Oxidative Stress; Parkinson Disease; PC12 Cells; Proteome; Proteomics; Rats; Transcription Factor RelA; Zebrafish