Polyphenols: Multipotent Therapeutic Agents in Neurodegenerative Diseases
Identifieur interne : 000596 ( Pmc/Checkpoint ); précédent : 000595; suivant : 000597Polyphenols: Multipotent Therapeutic Agents in Neurodegenerative Diseases
Auteurs : Khushwant S. Bhullar [Canada] ; H. P. Vasantha Rupasinghe [Canada]Source :
- Oxidative Medicine and Cellular Longevity [ 1942-0900 ] ; 2013.
Abstract
Aging leads to numerous transitions in brain physiology including synaptic dysfunction and disturbances in cognition and memory. With a few clinically relevant drugs, a substantial portion of aging population at risk for age-related neurodegenerative disorders require nutritional intervention. Dietary intake of polyphenols is known to attenuate oxidative stress and reduce the risk for related neurodegenerative diseases such as Alzheimer's disease (AD), stroke, multiple sclerosis (MS), Parkinson's disease (PD), and Huntington's disease (HD). Polyphenols exhibit strong potential to address the etiology of neurological disorders as they attenuate their complex physiology by modulating several therapeutic targets at once. Firstly, we review the advances in the therapeutic role of polyphenols in cell and animal models of AD, PD, MS, and HD and activation of drug targets for controlling pathological manifestations. Secondly, we present principle pathways in which polyphenol intake translates into therapeutic outcomes. In particular, signaling pathways like PPAR, Nrf2, STAT, HIF, and MAPK along with modulation of immune response by polyphenols are discussed. Although current polyphenol researches have limited impact on clinical practice, they have strong evidence and testable hypothesis to contribute clinical advances and drug discovery towards age-related neurological disorders.
Url:
DOI: 10.1155/2013/891748
PubMed: 23840922
PubMed Central: 3690243
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Polyphenols: Multipotent Therapeutic Agents in Neurodegenerative Diseases</title><author><name sortKey="Bhullar, Khushwant S" sort="Bhullar, Khushwant S" uniqKey="Bhullar K" first="Khushwant S." last="Bhullar">Khushwant S. Bhullar</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, NS, Canada B2N 5E3</nlm:aff><country>Canada</country><wicri:regionArea>Department of Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, NS</wicri:regionArea><wicri:noRegion>NS</wicri:noRegion></affiliation></author><author><name sortKey="Rupasinghe, H P Vasantha" sort="Rupasinghe, H P Vasantha" uniqKey="Rupasinghe H" first="H. P. Vasantha" last="Rupasinghe">H. P. Vasantha Rupasinghe</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, NS, Canada B2N 5E3</nlm:aff><country>Canada</country><wicri:regionArea>Department of Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, NS</wicri:regionArea><wicri:noRegion>NS</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">23840922</idno><idno type="pmc">3690243</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3690243</idno><idno type="RBID">PMC:3690243</idno><idno type="doi">10.1155/2013/891748</idno><date when="2013">2013</date><idno type="wicri:Area/Pmc/Corpus">000C63</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000C63</idno><idno type="wicri:Area/Pmc/Curation">000C63</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000C63</idno><idno type="wicri:Area/Pmc/Checkpoint">000596</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000596</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Polyphenols: Multipotent Therapeutic Agents in Neurodegenerative Diseases</title><author><name sortKey="Bhullar, Khushwant S" sort="Bhullar, Khushwant S" uniqKey="Bhullar K" first="Khushwant S." last="Bhullar">Khushwant S. Bhullar</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, NS, Canada B2N 5E3</nlm:aff><country>Canada</country><wicri:regionArea>Department of Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, NS</wicri:regionArea><wicri:noRegion>NS</wicri:noRegion></affiliation></author><author><name sortKey="Rupasinghe, H P Vasantha" sort="Rupasinghe, H P Vasantha" uniqKey="Rupasinghe H" first="H. P. Vasantha" last="Rupasinghe">H. P. Vasantha Rupasinghe</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, NS, Canada B2N 5E3</nlm:aff><country>Canada</country><wicri:regionArea>Department of Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, NS</wicri:regionArea><wicri:noRegion>NS</wicri:noRegion></affiliation></author></analytic><series><title level="j">Oxidative Medicine and Cellular Longevity</title><idno type="ISSN">1942-0900</idno><idno type="eISSN">1942-0994</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Aging leads to numerous transitions in brain physiology including synaptic dysfunction and disturbances in cognition and memory. With a few clinically relevant drugs, a substantial portion of aging population at risk for age-related neurodegenerative disorders require nutritional intervention. Dietary intake of polyphenols is known to attenuate oxidative stress and reduce the risk for related neurodegenerative diseases such as Alzheimer's disease (AD), stroke, multiple sclerosis (MS), Parkinson's disease (PD), and Huntington's disease (HD). Polyphenols exhibit strong potential to address the etiology of neurological disorders as they attenuate their complex physiology by modulating several therapeutic targets at once. Firstly, we review the advances in the therapeutic role of polyphenols in cell and animal models of AD, PD, MS, and HD and activation of drug targets for controlling pathological manifestations. Secondly, we present principle pathways in which polyphenol intake translates into therapeutic outcomes. In particular, signaling pathways like PPAR, Nrf2, STAT, HIF, and MAPK along with modulation of immune response by polyphenols are discussed. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Oxid Med Cell Longev</journal-id><journal-id journal-id-type="iso-abbrev">Oxid Med Cell Longev</journal-id><journal-id journal-id-type="publisher-id">OXIMED</journal-id><journal-title-group><journal-title>Oxidative Medicine and Cellular Longevity</journal-title></journal-title-group><issn pub-type="ppub">1942-0900</issn><issn pub-type="epub">1942-0994</issn><publisher><publisher-name>Hindawi Publishing Corporation</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">23840922</article-id><article-id pub-id-type="pmc">3690243</article-id><article-id pub-id-type="doi">10.1155/2013/891748</article-id><article-categories><subj-group subj-group-type="heading"><subject>Review Article</subject></subj-group></article-categories><title-group><article-title>Polyphenols: Multipotent Therapeutic Agents in Neurodegenerative Diseases</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Bhullar</surname><given-names>Khushwant S.</given-names></name><xref ref-type="aff" rid="I1"></xref></contrib><contrib contrib-type="author"><name><surname>Rupasinghe</surname><given-names>H. P. Vasantha</given-names></name><xref ref-type="aff" rid="I1"></xref><xref ref-type="corresp" rid="cor1">*</xref></contrib></contrib-group><aff id="I1">Department of Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, NS, Canada B2N 5E3</aff><author-notes><corresp id="cor1">*H. P. Vasantha Rupasinghe: <email>vrupasinghe@dal.ca</email></corresp><fn fn-type="other"><p>Academic Editor: Nilanjana Maulik</p></fn></author-notes><pub-date pub-type="ppub"><year>2013</year></pub-date><pub-date pub-type="epub"><day>6</day><month>6</month><year>2013</year></pub-date><volume>2013</volume><elocation-id>891748</elocation-id><history><date date-type="received"><day>10</day><month>3</month><year>2013</year></date><date date-type="accepted"><day>29</day><month>4</month><year>2013</year></date></history><permissions><copyright-statement>Copyright © 2013 K. S. Bhullar and H. P. V. Rupasinghe.</copyright-statement><copyright-year>2013</copyright-year><license license-type="open-access"><license-p>This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p></license></permissions><abstract><p>Aging leads to numerous transitions in brain physiology including synaptic dysfunction and disturbances in cognition and memory. With a few clinically relevant drugs, a substantial portion of aging population at risk for age-related neurodegenerative disorders require nutritional intervention. Dietary intake of polyphenols is known to attenuate oxidative stress and reduce the risk for related neurodegenerative diseases such as Alzheimer's disease (AD), stroke, multiple sclerosis (MS), Parkinson's disease (PD), and Huntington's disease (HD). Polyphenols exhibit strong potential to address the etiology of neurological disorders as they attenuate their complex physiology by modulating several therapeutic targets at once. Firstly, we review the advances in the therapeutic role of polyphenols in cell and animal models of AD, PD, MS, and HD and activation of drug targets for controlling pathological manifestations. Secondly, we present principle pathways in which polyphenol intake translates into therapeutic outcomes. In particular, signaling pathways like PPAR, Nrf2, STAT, HIF, and MAPK along with modulation of immune response by polyphenols are discussed. Although current polyphenol researches have limited impact on clinical practice, they have strong evidence and testable hypothesis to contribute clinical advances and drug discovery towards age-related neurological disorders.</p></abstract></article-meta></front><floats-group><fig id="fig1" orientation="portrait" position="float"><label>Figure 1</label><caption><p>Neuroprotection by polyphenols against neurological disorders.</p></caption><graphic xlink:href="OXIMED2013-891748.001"></graphic></fig><fig id="fig2" orientation="portrait" position="float"><label>Figure 2</label><caption><p>Chemical structure of polyphenols with therapeutic use in age-related neurological diseases.</p></caption><graphic xlink:href="OXIMED2013-891748.002"></graphic></fig><table-wrap id="tab1" orientation="portrait" position="float"><label>Table 1</label><caption><p>Neuroprotective signal transduction by polyphenols. </p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="1" colspan="1">Pathway</th><th align="center" rowspan="1" colspan="1">Polyphenol</th><th align="center" rowspan="1" colspan="1">References</th></tr></thead><tbody><tr><td align="left" rowspan="1" colspan="1">P13K/AkT pathway</td><td align="center" rowspan="1" colspan="1">Resveratrol</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B134">99</xref>, <xref ref-type="bibr" rid="B100">100</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1"> </td><td align="center" rowspan="1" colspan="1">Baicalein</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B97">97</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1">NF<italic>κ</italic>B pathway</td><td align="center" rowspan="1" colspan="1">Kaempferol, acacetin, apigenin, luteolin</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B136">101</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1"> </td><td align="center" rowspan="1" colspan="1">Soybean isoflavones</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B137">102</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1"> </td><td align="center" rowspan="1" colspan="1">Fisetin</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B94">94</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1"> </td><td align="center" rowspan="1" colspan="1">Resveratrol</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B138">103</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1"> </td><td align="center" rowspan="1" colspan="1">Baicalein</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B142">104</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1"> </td><td align="center" rowspan="1" colspan="1">Silymarin</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B140">105</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1"> </td><td align="center" rowspan="1" colspan="1">Tetrahydroxystilbene</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B58">58</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1"> </td><td align="center" rowspan="1" colspan="1">Quercetin</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B136">101</xref>, <xref ref-type="bibr" rid="B141">106</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1"> </td><td align="center" rowspan="1" colspan="1">Catechin hydrate</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B94">94</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1">STAT pathway</td><td align="center" rowspan="1" colspan="1">Silymarin</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B140">105</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1">PPAR pathway</td><td align="center" rowspan="1" colspan="1">Baicalein</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B142">104</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1"> </td><td align="center" rowspan="1" colspan="1">Resveratrol</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B143">107</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1"> </td><td align="center" rowspan="1" colspan="1">Pterostilbene</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B144">108</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1">Nrf2/HO1/ARE pathway</td><td align="center" rowspan="1" colspan="1">Epicatechin</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B146">109</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1"> </td><td align="center" rowspan="1" colspan="1">Resveratrol</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B147">110</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1">HIF-1<italic>α</italic></td><td align="center" rowspan="1" colspan="1">Xanthohumol</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B148">111</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1"> </td><td align="center" rowspan="1" colspan="1">Resveratrol</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B149">112</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1">MAPK</td><td align="center" rowspan="1" colspan="1">Flavone glycoside</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B204">113</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1"> </td><td align="center" rowspan="1" colspan="1">Quercetin</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B124">114</xref>]</td></tr></tbody></table></table-wrap><table-wrap id="tab2" orientation="portrait" position="float"><label>Table 2</label><caption><p>Modulation of cytokines and inflammatory targets by polyphenols. </p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="1" colspan="1">Polyphenol</th><th align="center" rowspan="1" colspan="1">Target</th><th align="center" rowspan="1" colspan="1">References</th></tr></thead><tbody><tr><td align="left" rowspan="1" colspan="1">EGCG</td><td align="center" rowspan="1" colspan="1">IL-1<italic>β</italic></td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B157">115</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1"> </td><td align="center" rowspan="1" colspan="1">IL-6</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B151">116</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1"> </td><td align="center" rowspan="1" colspan="1">MCP-1</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B157">115</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1"> </td><td align="center" rowspan="1" colspan="1">CXCL 10, </td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B151">116</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1"> </td><td align="center" rowspan="1" colspan="1">CCL22, CCL 17</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B154">117</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1"> </td><td align="center" rowspan="1" colspan="1">TGF <italic>β</italic></td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B154">117</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1">Resveratrol</td><td align="center" rowspan="1" colspan="1">MCP-1</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B152">118</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1">Catechin</td><td align="center" rowspan="1" colspan="1">MCP-1 (<italic>α</italic> and <italic>β</italic>)</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B153">119</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1">Caffeic acid</td><td align="center" rowspan="1" colspan="1">CCR1, CCR2</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B153">119</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1">Quercetin</td><td align="center" rowspan="1" colspan="1">IL-1<italic>β</italic>, IL-6</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B155">120</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1"> </td><td align="center" rowspan="1" colspan="1">COX-2</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B155">120</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1"> </td><td align="center" rowspan="1" colspan="1">COX-20, TRAF1</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B156">121</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1">Apple polyphenols</td><td align="center" rowspan="1" colspan="1">IL-1<italic>β</italic>, IL-6, IL-17, IL-22<break></break>CXCL-9, CXCL-10, CXCL-11, </td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B159">122</xref>, <xref ref-type="bibr" rid="B212">123</xref>]</td></tr></tbody></table></table-wrap><table-wrap id="tab3" orientation="portrait" position="float"><label>Table 3</label><caption><p>Modulation of mitochondrial targets by polyphenols. </p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="1" colspan="1">Target</th><th align="center" rowspan="1" colspan="1">Polyphenol</th><th align="center" rowspan="1" colspan="1">Effect</th><th align="center" rowspan="1" colspan="1">References</th></tr></thead><tbody><tr><td align="left" rowspan="1" colspan="1">AP-1</td><td align="center" rowspan="1" colspan="1">EGCG</td><td align="center" rowspan="1" colspan="1">Downregulation</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B151">116</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1">Bad/Bax</td><td align="center" rowspan="1" colspan="1">Resveratrol</td><td align="center" rowspan="1" colspan="1">Downregulation</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B149">112</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1"> </td><td align="center" rowspan="1" colspan="1">Ferulic acid</td><td align="center" rowspan="1" colspan="1">Downregulation</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B104">124</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1">Bcl-2</td><td align="center" rowspan="1" colspan="1">Lutein</td><td align="center" rowspan="1" colspan="1">Upregulation</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B197">125</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1"> </td><td align="center" rowspan="1" colspan="1">Baicalein</td><td align="center" rowspan="1" colspan="1">Upregulation</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B135">126</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1">Cox-2</td><td align="center" rowspan="1" colspan="1">Lutein</td><td align="center" rowspan="1" colspan="1">Downregulation</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B197">125</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1"> </td><td align="center" rowspan="1" colspan="1">Hesperidin</td><td align="center" rowspan="1" colspan="1">Downregulation</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B205">127</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1"> </td><td align="center" rowspan="1" colspan="1"><italic>Hibiscus sabdariffa</italic> polyphenols</td><td align="center" rowspan="1" colspan="1">Downregulation</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B203">128</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1">GCLM</td><td align="center" rowspan="1" colspan="1">Chrysin, apigenin, luteolin</td><td align="center" rowspan="1" colspan="1">Upregulation</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B198">129</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1">GCLC</td><td align="center" rowspan="1" colspan="1">Chrysin, apigenin, luteolin</td><td align="center" rowspan="1" colspan="1">Upregulation</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B198">129</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1">GPX</td><td align="center" rowspan="1" colspan="1">EGCG</td><td align="center" rowspan="1" colspan="1">Upregulation</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B211">130</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1"> </td><td align="center" rowspan="1" colspan="1">Red wine polyphenols</td><td align="center" rowspan="1" colspan="1">Upregulation</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B194">131</xref>, <xref ref-type="bibr" rid="B199">132</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1"> </td><td align="center" rowspan="1" colspan="1">3,3′,5,5′-tetra-t-butyl-biphenyl-4,4′-diol</td><td align="center" rowspan="1" colspan="1">Upregulation</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B200">133</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1">HO-1</td><td align="center" rowspan="1" colspan="1">Butein, apigenin</td><td align="center" rowspan="1" colspan="1">Upregulation</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B198">129</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1"> </td><td align="center" rowspan="1" colspan="1">Luteolin</td><td align="center" rowspan="1" colspan="1">Upregulation</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B201">134</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1">IFN-<italic>γ</italic></td><td align="center" rowspan="1" colspan="1">Quercetin</td><td align="center" rowspan="1" colspan="1">Downregulation</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B202">135</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1">JNK</td><td align="center" rowspan="1" colspan="1">Quercetin</td><td align="center" rowspan="1" colspan="1">Downregulation</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B202">135</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1"> </td><td align="center" rowspan="1" colspan="1">EGCG</td><td align="center" rowspan="1" colspan="1">Downregulation</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B151">116</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1"> </td><td align="center" rowspan="1" colspan="1"><italic>Hibiscus sabdariffa</italic> polyphenols</td><td align="center" rowspan="1" colspan="1">Downregulation</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B203">128</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1">JUN</td><td align="center" rowspan="1" colspan="1">Quercetin</td><td align="center" rowspan="1" colspan="1">Downregulation</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B202">135</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1">SOD </td><td align="center" rowspan="1" colspan="1">Phloridzin</td><td align="center" rowspan="1" colspan="1">Upregulation</td><td align="center" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="B129">136</xref>]</td></tr></tbody></table></table-wrap></floats-group></pmc><affiliations><list><country><li>Canada</li></country></list><tree><country name="Canada"><noRegion><name sortKey="Bhullar, Khushwant S" sort="Bhullar, Khushwant S" uniqKey="Bhullar K" first="Khushwant S." last="Bhullar">Khushwant S. 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