Examining the neuroprotective effects of protocatechuic acid and chrysin on in vitro and in vivo models of Parkinson disease.
Identifieur interne : 000731 ( Main/Exploration ); précédent : 000730; suivant : 000732Examining the neuroprotective effects of protocatechuic acid and chrysin on in vitro and in vivo models of Parkinson disease.
Auteurs : Zaijun Zhang [République populaire de Chine] ; Guohui Li [République populaire de Chine] ; Samuel S W. Szeto [République populaire de Chine] ; Cheong Meng Chong [République populaire de Chine] ; Quan Quan [République populaire de Chine] ; Chen Huang [République populaire de Chine] ; Wei Cui [République populaire de Chine] ; Baojian Guo [République populaire de Chine] ; Yuqiang Wang [République populaire de Chine] ; Yifan Han [République populaire de Chine] ; K W Michael Siu [Canada] ; Simon Ming Yuen Lee [République populaire de Chine] ; Ivan K. Chu [République populaire de Chine]Source :
- Free radical biology & medicine [ 1873-4596 ] ; 2015.
English descriptors
- KwdEn :
- 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.
- MESH :
- chemical , metabolism : Heme Oxygenase-1, NF-E2-Related Factor 2, Nitric Oxide, Nitric Oxide Synthase Type II, Proteome, Transcription Factor RelA.
- chemical , pharmacology : Antiparkinson Agents, Flavonoids, Hydroxybenzoates, Neuroprotective Agents.
- chemical , therapeutic use : Antiparkinson Agents, Flavonoids, Hydroxybenzoates, Neuroprotective Agents.
- drug effects : Dopaminergic Neurons.
- drug therapy : Parkinson Disease.
- physiology : Dopaminergic Neurons.
- Animals, Drug Evaluation, Preclinical, Oxidative Stress, PC12 Cells, Proteomics, Rats, Zebrafish.
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 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.
DOI: 10.1016/j.freeradbiomed.2015.02.030
PubMed: 25769424
Affiliations:
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Szeto</name><affiliation wicri:level="1"><nlm:affiliation>Department of Chemistry, The University of Hong Kong, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Chemistry, The University of Hong Kong, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Chong, Cheong Meng" sort="Chong, Cheong Meng" uniqKey="Chong C" first="Cheong Meng" last="Chong">Cheong Meng Chong</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao</wicri:regionArea><wicri:noRegion>Macao</wicri:noRegion></affiliation></author><author><name sortKey="Quan, Quan" sort="Quan, Quan" uniqKey="Quan Q" first="Quan" last="Quan">Quan Quan</name><affiliation wicri:level="1"><nlm:affiliation>Department of Chemistry, The University of Hong Kong, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Chemistry, The University of Hong Kong, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Huang, Chen" sort="Huang, Chen" uniqKey="Huang C" first="Chen" last="Huang">Chen Huang</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao</wicri:regionArea><wicri:noRegion>Macao</wicri:noRegion></affiliation></author><author><name sortKey="Cui, Wei" sort="Cui, Wei" uniqKey="Cui W" first="Wei" last="Cui">Wei Cui</name><affiliation wicri:level="1"><nlm:affiliation>Department of Applied Biology and Chemical Technology, Institute of Modern Medicine, The Hong Kong Polytechnic University, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Applied Biology and Chemical Technology, Institute of Modern Medicine, The Hong Kong Polytechnic University, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Guo, Baojian" sort="Guo, Baojian" uniqKey="Guo B" first="Baojian" last="Guo">Baojian Guo</name><affiliation wicri:level="1"><nlm:affiliation>Institute of New Drug Research and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine, College of Pharmacy, Jinan University, Guangdong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Institute of New Drug Research and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine, College of Pharmacy, Jinan University, Guangdong</wicri:regionArea><wicri:noRegion>Guangdong</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Yuqiang" sort="Wang, Yuqiang" uniqKey="Wang Y" first="Yuqiang" last="Wang">Yuqiang Wang</name><affiliation wicri:level="1"><nlm:affiliation>Institute of New Drug Research and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine, College of Pharmacy, Jinan University, Guangdong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Institute of New Drug Research and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine, College of Pharmacy, Jinan University, Guangdong</wicri:regionArea><wicri:noRegion>Guangdong</wicri:noRegion></affiliation></author><author><name sortKey="Han, Yifan" sort="Han, Yifan" uniqKey="Han Y" first="Yifan" last="Han">Yifan Han</name><affiliation wicri:level="1"><nlm:affiliation>Department of Applied Biology and Chemical Technology, Institute of Modern Medicine, The Hong Kong Polytechnic University, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Applied Biology and Chemical Technology, Institute of Modern Medicine, The Hong Kong Polytechnic University, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Michael Siu, K W" sort="Michael Siu, K W" uniqKey="Michael Siu K" first="K W" last="Michael Siu">K W Michael Siu</name><affiliation wicri:level="1"><nlm:affiliation>Department of Chemistry and Biochemistry, University of Windsor, Windsor, ON, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Chemistry and Biochemistry, University of Windsor, Windsor, ON</wicri:regionArea><wicri:noRegion>ON</wicri:noRegion></affiliation></author><author><name sortKey="Yuen Lee, Simon Ming" sort="Yuen Lee, Simon Ming" uniqKey="Yuen Lee S" first="Simon Ming" last="Yuen Lee">Simon Ming Yuen Lee</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China. Electronic address: simonlee@umac.mo.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao</wicri:regionArea><wicri:noRegion>Macao</wicri:noRegion></affiliation></author><author><name sortKey="Chu, Ivan K" sort="Chu, Ivan K" uniqKey="Chu I" first="Ivan K" last="Chu">Ivan K. Chu</name><affiliation wicri:level="1"><nlm:affiliation>Department of Chemistry, The University of Hong Kong, Hong Kong, China. Electronic address: ivankchu@hku.hk.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Chemistry, The University of Hong Kong, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author></analytic><series><title level="j">Free radical biology & medicine</title><idno type="eISSN">1873-4596</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antiparkinson Agents (pharmacology)</term><term>Antiparkinson Agents (therapeutic use)</term><term>Dopaminergic Neurons (drug effects)</term><term>Dopaminergic Neurons (physiology)</term><term>Drug Evaluation, Preclinical</term><term>Flavonoids (pharmacology)</term><term>Flavonoids (therapeutic use)</term><term>Heme Oxygenase-1 (metabolism)</term><term>Hydroxybenzoates (pharmacology)</term><term>Hydroxybenzoates (therapeutic use)</term><term>NF-E2-Related Factor 2 (metabolism)</term><term>Neuroprotective Agents (pharmacology)</term><term>Neuroprotective Agents (therapeutic use)</term><term>Nitric Oxide (metabolism)</term><term>Nitric Oxide Synthase Type II (metabolism)</term><term>Oxidative Stress</term><term>PC12 Cells</term><term>Parkinson Disease (drug therapy)</term><term>Proteome (metabolism)</term><term>Proteomics</term><term>Rats</term><term>Transcription Factor RelA (metabolism)</term><term>Zebrafish</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Heme Oxygenase-1</term><term>NF-E2-Related Factor 2</term><term>Nitric Oxide</term><term>Nitric Oxide Synthase Type II</term><term>Proteome</term><term>Transcription Factor RelA</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antiparkinson Agents</term><term>Flavonoids</term><term>Hydroxybenzoates</term><term>Neuroprotective Agents</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antiparkinson Agents</term><term>Flavonoids</term><term>Hydroxybenzoates</term><term>Neuroprotective Agents</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Dopaminergic Neurons</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Dopaminergic Neurons</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Drug Evaluation, Preclinical</term><term>Oxidative Stress</term><term>PC12 Cells</term><term>Proteomics</term><term>Rats</term><term>Zebrafish</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><affiliations><list><country><li>Canada</li><li>République populaire de Chine</li></country></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Zhang, Zaijun" sort="Zhang, Zaijun" uniqKey="Zhang Z" first="Zaijun" last="Zhang">Zaijun Zhang</name></noRegion><name sortKey="Chong, Cheong Meng" sort="Chong, Cheong Meng" uniqKey="Chong C" first="Cheong Meng" last="Chong">Cheong Meng Chong</name><name sortKey="Chu, Ivan K" sort="Chu, Ivan K" uniqKey="Chu I" first="Ivan K" last="Chu">Ivan K. Chu</name><name sortKey="Cui, Wei" sort="Cui, Wei" uniqKey="Cui W" first="Wei" last="Cui">Wei Cui</name><name sortKey="Guo, Baojian" sort="Guo, Baojian" uniqKey="Guo B" first="Baojian" last="Guo">Baojian Guo</name><name sortKey="Han, Yifan" sort="Han, Yifan" uniqKey="Han Y" first="Yifan" last="Han">Yifan Han</name><name sortKey="Huang, Chen" sort="Huang, Chen" uniqKey="Huang C" first="Chen" last="Huang">Chen Huang</name><name sortKey="Li, Guohui" sort="Li, Guohui" uniqKey="Li G" first="Guohui" last="Li">Guohui Li</name><name sortKey="Quan, Quan" sort="Quan, Quan" uniqKey="Quan Q" first="Quan" last="Quan">Quan Quan</name><name sortKey="Szeto, Samuel S W" sort="Szeto, Samuel S W" uniqKey="Szeto S" first="Samuel S W" last="Szeto">Samuel S W. Szeto</name><name sortKey="Wang, Yuqiang" sort="Wang, Yuqiang" uniqKey="Wang Y" first="Yuqiang" last="Wang">Yuqiang Wang</name><name sortKey="Yuen Lee, Simon Ming" sort="Yuen Lee, Simon Ming" uniqKey="Yuen Lee S" first="Simon Ming" last="Yuen Lee">Simon Ming Yuen Lee</name></country><country name="Canada"><noRegion><name sortKey="Michael Siu, K W" sort="Michael Siu, K W" uniqKey="Michael Siu K" first="K W" last="Michael Siu">K W Michael Siu</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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|texte= Examining the neuroprotective effects of protocatechuic acid and chrysin on in vitro and in vivo models of Parkinson disease.
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