Riboflavin: The Health Benefits of a Forgotten Natural Vitamin
Identifieur interne : 000055 ( Pmc/Checkpoint ); précédent : 000054; suivant : 000056Riboflavin: The Health Benefits of a Forgotten Natural Vitamin
Auteurs : Nittiya Suwannasom [Thaïlande] ; Ijad Kao ; Axel Pru ; Radostina Georgieva [Bulgarie] ; Hans B UmlerSource :
- International Journal of Molecular Sciences [ 1422-0067 ] ; 2020.
Abstract
Riboflavin (RF) is a water-soluble member of the B-vitamin family. Sufficient dietary and supplemental RF intake appears to have a protective effect on various medical conditions such as sepsis, ischemia etc., while it also contributes to the reduction in the risk of some forms of cancer in humans. These biological effects of RF have been widely studied for their anti-oxidant, anti-aging, anti-inflammatory, anti-nociceptive and anti-cancer properties. Moreover, the combination of RF and other compounds or drugs can have a wide variety of effects and protective properties, and diminish the toxic effect of drugs in several treatments. Research has been done in order to review the latest findings about the link between RF and different clinical aberrations. Since further studies have been published in this field, it is appropriate to consider a re-evaluation of the importance of RF in terms of its beneficial properties.
Url:
DOI: 10.3390/ijms21030950
PubMed: 32023913
PubMed Central: 7037471
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Riboflavin: The Health Benefits of a Forgotten Natural Vitamin</title><author><name sortKey="Suwannasom, Nittiya" sort="Suwannasom, Nittiya" uniqKey="Suwannasom N" first="Nittiya" last="Suwannasom">Nittiya Suwannasom</name><affiliation><nlm:aff id="af1-ijms-21-00950">Institute of Transfusion Medicine, Center of Tumor Medicine, Charité—Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany;<email>nittiya.suwannasom@charite.de</email> (N.S.);<email>ijad.kao@charite.de</email> (I.K.);<email>axel.pruss@charite.de</email> (A.P.);<email>radostina.georgieva@charite.de</email> (R.G.)</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="af2-ijms-21-00950">School of Medical Sciences, University of Phayao, Phayao 56000, Thailand</nlm:aff><country xml:lang="fr">Thaïlande</country><wicri:regionArea>School of Medical Sciences, University of Phayao, Phayao 56000</wicri:regionArea><wicri:noRegion>Phayao 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(A.P.);<email>radostina.georgieva@charite.de</email> (R.G.)</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="af2-ijms-21-00950">School of Medical Sciences, University of Phayao, Phayao 56000, Thailand</nlm:aff><country xml:lang="fr">Thaïlande</country><wicri:regionArea>School of Medical Sciences, University of Phayao, Phayao 56000</wicri:regionArea><wicri:noRegion>Phayao 56000</wicri:noRegion></affiliation></author><author><name sortKey="Kao, Ijad" sort="Kao, Ijad" uniqKey="Kao I" first="Ijad" last="Kao">Ijad Kao</name><affiliation><nlm:aff id="af1-ijms-21-00950">Institute of Transfusion Medicine, Center of Tumor Medicine, Charité—Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany;<email>nittiya.suwannasom@charite.de</email> (N.S.);<email>ijad.kao@charite.de</email> (I.K.);<email>axel.pruss@charite.de</email> (A.P.);<email>radostina.georgieva@charite.de</email> (R.G.)</nlm:aff></affiliation></author><author><name sortKey="Pru, Axel" sort="Pru, Axel" uniqKey="Pru A" first="Axel" last="Pru">Axel Pru</name><affiliation><nlm:aff id="af1-ijms-21-00950">Institute of Transfusion Medicine, Center of Tumor Medicine, Charité—Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany;<email>nittiya.suwannasom@charite.de</email> (N.S.);<email>ijad.kao@charite.de</email> (I.K.);<email>axel.pruss@charite.de</email> (A.P.);<email>radostina.georgieva@charite.de</email> (R.G.)</nlm:aff></affiliation></author><author><name sortKey="Georgieva, Radostina" sort="Georgieva, Radostina" uniqKey="Georgieva R" first="Radostina" last="Georgieva">Radostina Georgieva</name><affiliation><nlm:aff id="af1-ijms-21-00950">Institute of Transfusion Medicine, Center of Tumor Medicine, Charité—Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany;<email>nittiya.suwannasom@charite.de</email> (N.S.);<email>ijad.kao@charite.de</email> (I.K.);<email>axel.pruss@charite.de</email> (A.P.);<email>radostina.georgieva@charite.de</email> (R.G.)</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="af3-ijms-21-00950">Biophysics and Radiology, Department of Medical Physics, Faculty of Medicine, Trakia University, 6000 Stara Zagora, Bulgaria</nlm:aff><country xml:lang="fr">Bulgarie</country><wicri:regionArea>Biophysics and Radiology, Department of Medical Physics, Faculty of Medicine, Trakia University, 6000 Stara Zagora</wicri:regionArea><wicri:noRegion>6000 Stara Zagora</wicri:noRegion></affiliation></author><author><name sortKey="B Umler, Hans" sort="B Umler, Hans" uniqKey="B Umler H" first="Hans" last="B Umler">Hans B Umler</name><affiliation><nlm:aff id="af1-ijms-21-00950">Institute of Transfusion Medicine, Center of Tumor Medicine, Charité—Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany;<email>nittiya.suwannasom@charite.de</email> (N.S.);<email>ijad.kao@charite.de</email> (I.K.);<email>axel.pruss@charite.de</email> (A.P.);<email>radostina.georgieva@charite.de</email> (R.G.)</nlm:aff></affiliation></author></analytic><series><title level="j">International Journal of Molecular Sciences</title><idno type="eISSN">1422-0067</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Riboflavin (RF) is a water-soluble member of the B-vitamin family. Sufficient dietary and supplemental RF intake appears to have a protective effect on various medical conditions such as sepsis, ischemia etc., while it also contributes to the reduction in the risk of some forms of cancer in humans. These biological effects of RF have been widely studied for their anti-oxidant, anti-aging, anti-inflammatory, anti-nociceptive and anti-cancer properties. Moreover, the combination of RF and other compounds or drugs can have a wide variety of effects and protective properties, and diminish the toxic effect of drugs in several treatments. Research has been done in order to review the latest findings about the link between RF and different clinical aberrations. Since further studies have been published in this field, it is appropriate to consider a re-evaluation of the importance of RF in terms of its beneficial properties.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Cardoso, D R" uniqKey="Cardoso D">D.R. Cardoso</name></author><author><name sortKey="Libardi, S H" uniqKey="Libardi S">S.H. Libardi</name></author><author><name sortKey="Skibsted, L H" uniqKey="Skibsted L">L.H. Skibsted</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dym, O" uniqKey="Dym O">O. Dym</name></author><author><name sortKey="Eisenberg, D" uniqKey="Eisenberg D">D. Eisenberg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Buehler, B A" uniqKey="Buehler B">B.A. Buehler</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, Y" uniqKey="Zhang Y">Y. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Int J Mol Sci</journal-id><journal-id journal-id-type="iso-abbrev">Int J Mol Sci</journal-id><journal-id journal-id-type="publisher-id">ijms</journal-id><journal-title-group><journal-title>International Journal of Molecular Sciences</journal-title></journal-title-group><issn pub-type="epub">1422-0067</issn><publisher><publisher-name>MDPI</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">32023913</article-id><article-id pub-id-type="pmc">7037471</article-id><article-id pub-id-type="doi">10.3390/ijms21030950</article-id><article-id pub-id-type="publisher-id">ijms-21-00950</article-id><article-categories><subj-group subj-group-type="heading"><subject>Review</subject></subj-group></article-categories><title-group><article-title>Riboflavin: The Health Benefits of a Forgotten Natural Vitamin</article-title></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0002-7069-5990</contrib-id><name><surname>Suwannasom</surname><given-names>Nittiya</given-names></name><xref ref-type="aff" rid="af1-ijms-21-00950">1</xref><xref ref-type="aff" rid="af2-ijms-21-00950">2</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0001-8447-2491</contrib-id><name><surname>Kao</surname><given-names>Ijad</given-names></name><xref ref-type="aff" rid="af1-ijms-21-00950">1</xref></contrib><contrib contrib-type="author"><name><surname>Pruß</surname><given-names>Axel</given-names></name><xref ref-type="aff" rid="af1-ijms-21-00950">1</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0003-1546-5540</contrib-id><name><surname>Georgieva</surname><given-names>Radostina</given-names></name><xref ref-type="aff" rid="af1-ijms-21-00950">1</xref><xref ref-type="aff" rid="af3-ijms-21-00950">3</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0002-2573-2289</contrib-id><name><surname>Bäumler</surname><given-names>Hans</given-names></name><xref ref-type="aff" rid="af1-ijms-21-00950">1</xref><xref rid="c1-ijms-21-00950" ref-type="corresp">*</xref></contrib></contrib-group><aff id="af1-ijms-21-00950"><label>1</label>Institute of Transfusion Medicine, Center of Tumor Medicine, Charité—Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany;<email>nittiya.suwannasom@charite.de</email> (N.S.);<email>ijad.kao@charite.de</email> (I.K.);<email>axel.pruss@charite.de</email> (A.P.);<email>radostina.georgieva@charite.de</email> (R.G.)</aff><aff id="af2-ijms-21-00950"><label>2</label>School of Medical Sciences, University of Phayao, Phayao 56000, Thailand</aff><aff id="af3-ijms-21-00950"><label>3</label>Biophysics and Radiology, Department of Medical Physics, Faculty of Medicine, Trakia University, 6000 Stara Zagora, Bulgaria</aff><author-notes><corresp id="c1-ijms-21-00950"><label>*</label>Correspondence: <email>hans.baeumler@charite.de</email></corresp></author-notes><pub-date pub-type="epub"><day>31</day><month>1</month><year>2020</year></pub-date><pub-date pub-type="collection"><month>2</month><year>2020</year></pub-date><volume>21</volume><issue>3</issue><elocation-id>950</elocation-id><history><date date-type="received"><day>03</day><month>1</month><year>2020</year></date><date date-type="accepted"><day>29</day><month>1</month><year>2020</year></date></history><permissions><copyright-statement>© 2020 by the authors.</copyright-statement><copyright-year>2020</copyright-year><license license-type="open-access"><license-p>Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>).</license-p></license></permissions><abstract><p>Riboflavin (RF) is a water-soluble member of the B-vitamin family. Sufficient dietary and supplemental RF intake appears to have a protective effect on various medical conditions such as sepsis, ischemia etc., while it also contributes to the reduction in the risk of some forms of cancer in humans. These biological effects of RF have been widely studied for their anti-oxidant, anti-aging, anti-inflammatory, anti-nociceptive and anti-cancer properties. Moreover, the combination of RF and other compounds or drugs can have a wide variety of effects and protective properties, and diminish the toxic effect of drugs in several treatments. Research has been done in order to review the latest findings about the link between RF and different clinical aberrations. Since further studies have been published in this field, it is appropriate to consider a re-evaluation of the importance of RF in terms of its beneficial properties.</p></abstract><kwd-group><kwd>riboflavin</kwd><kwd>vitamin B2</kwd><kwd>complementary medicine</kwd><kwd>functional food</kwd><kwd>oxidative stress</kwd><kwd>cancer</kwd><kwd>neurodegeneration</kwd><kwd>muscular degeneration</kwd></kwd-group></article-meta></front><floats-group><fig id="ijms-21-00950-f001" orientation="portrait" position="float"><label>Figure 1</label><caption><p>Structure of (<bold>a</bold>) Riboflavin (RF), (<bold>b</bold>) Flavin monophosphate (FMN), and (<bold>c</bold>) Flavin adenine dinucleotide (FAD). ChemDraw (PerkinElmer Informatics, Inc. MA, USA).</p></caption><graphic xlink:href="ijms-21-00950-g001"></graphic></fig><fig id="ijms-21-00950-f002" orientation="portrait" position="float"><label>Figure 2</label><caption><p>RF is an essential vitamin for multiple physiological aspects in the body.</p></caption><graphic xlink:href="ijms-21-00950-g002"></graphic></fig><fig id="ijms-21-00950-f003" orientation="portrait" position="float"><label>Figure 3</label><caption><p>Flavin adenine dinucleotide (FAD) activates the glutathione reductase (GR) by transferring hydrogen for conversion of glutathione disulfide (GSSG) to glutathione (GSH).</p></caption><graphic xlink:href="ijms-21-00950-g003"></graphic></fig><fig id="ijms-21-00950-f004" orientation="portrait" position="float"><label>Figure 4</label><caption><p>RF is converted by RFK into FMN and FAD, which is essential cofactor the phagocytic NADPH oxidase 2 (Nox2) to generate ROS. Therefore, RF deficiency is incapable of ROS production by the phagocyte Nox2, which is crucial to inactivate phagocytosed microbes and to regulate the inflammatory response in innate immune cells. TNF, tumor necrosis factor; TNFR1, tumor necrosis factor receptor 1.</p></caption><graphic xlink:href="ijms-21-00950-g004"></graphic></fig><fig id="ijms-21-00950-f005" orientation="portrait" position="float"><label>Figure 5</label><caption><p>Activation of NADPH oxidase and microbicidal systems during phagocytosis. Complement and antibody receptors (CRs and FcRs) promote the uptake of micro-organisms by neutrophils, which, in turn, trigger the degranulation and production of ROS.</p></caption><graphic xlink:href="ijms-21-00950-g005"></graphic></fig><fig id="ijms-21-00950-f006" orientation="portrait" position="float"><label>Figure 6</label><caption><p>Role of RF as an adjuvant in cisplatin based chemo radiotherapy [<xref rid="B75-ijms-21-00950" ref-type="bibr">75</xref>]. RF stimulates apoptotic factors and downregulates anti-apoptotic factors. Additionally, it activates p53, which also results in an amplification of apoptosis. The inhibitory effects of RF in respect to the deteriorate effect of cisplatin are also shown. On the one hand, it inhibits the downregulation of antioxidant enzymes and proteins; on the other, RF downregulates pro-inflammatory cytokines.</p></caption><graphic xlink:href="ijms-21-00950-g006"></graphic></fig><fig id="ijms-21-00950-f007" orientation="portrait" position="float"><label>Figure 7</label><caption><p>Implications of RF deficiency on health [<xref rid="B75-ijms-21-00950" ref-type="bibr">75</xref>].</p></caption><graphic xlink:href="ijms-21-00950-g007"></graphic></fig><fig id="ijms-21-00950-f008" orientation="portrait" position="float"><label>Figure 8</label><caption><p>Conversion oxidized glutathione (GSSG) to the reduced form (GSH) by glutathione reductase requires RF in the FAD co-enzyme form for its activity. G-6P-D, glucose-6-phosphate dehydrogenase [<xref rid="B98-ijms-21-00950" ref-type="bibr">98</xref>].</p></caption><graphic xlink:href="ijms-21-00950-g008"></graphic></fig><fig id="ijms-21-00950-f009" orientation="portrait" position="float"><label>Figure 9</label><caption><p>RF in functional food and encapsulation products.</p></caption><graphic xlink:href="ijms-21-00950-g009"></graphic></fig><table-wrap id="ijms-21-00950-t001" orientation="portrait" position="float"><object-id pub-id-type="pii">ijms-21-00950-t001_Table 1</object-id><label>Table 1</label><caption><p>Flavin content of selected human body fluids (mol L<sup>−1</sup>) and organs (mol per kg of dry matter) [<xref rid="B1-ijms-21-00950" ref-type="bibr">1</xref>].</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1"></th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Riboflavin</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">FAD</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">FMN</th></tr></thead><tbody><tr><td align="center" valign="middle" rowspan="1" colspan="1">Skin</td><td align="center" valign="middle" rowspan="1" colspan="1">7.6 × 10<sup>−6</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">—</td><td align="center" valign="middle" rowspan="1" colspan="1">—</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">Cerebral cortex</td><td align="center" valign="middle" rowspan="1" colspan="1">7.2 × 10<sup>−6</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">—</td><td align="center" valign="middle" rowspan="1" colspan="1">—</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">Myocardium</td><td align="center" valign="middle" rowspan="1" colspan="1">3.2 × 10<sup>−5</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">—</td><td align="center" valign="middle" rowspan="1" colspan="1">—</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">Pectoral muscle</td><td align="center" valign="middle" rowspan="1" colspan="1">7.2 × 10<sup>−6</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">—</td><td align="center" valign="middle" rowspan="1" colspan="1">—</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">Aortic tissue</td><td align="center" valign="middle" rowspan="1" colspan="1">4.8 × 10<sup>−7</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">9.7 × 10<sup>−7</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">2.2 × 10<sup>−7</sup></td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">Erythrocyte</td><td align="center" valign="middle" rowspan="1" colspan="1">1.4 × 10<sup>−7</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">4.3 × 10<sup>−7</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">2.8 × 10<sup>−8</sup></td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">Plasma</td><td align="center" valign="middle" rowspan="1" colspan="1">1.0 × 10<sup>−8</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">6.3 × 10<sup>−8</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">7.5 × 10<sup>−9</sup></td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Eye-fluid</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">4.5 × 10<sup>−6</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">—</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">—</td></tr></tbody></table></table-wrap><table-wrap id="ijms-21-00950-t004" orientation="portrait" position="float"><object-id pub-id-type="pii">ijms-21-00950-t004_Table 4</object-id><label>Table 4</label><caption><p>Antinociception and anti-inflammation effects of RF in animal model.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Animal Model</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">RF Doses/Models</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Major Outcome</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">References</th></tr></thead><tbody><tr><td colspan="2" align="center" valign="middle" style="border-bottom:solid thin" rowspan="1"><bold>Inflammation-Related Pain</bold></td><td colspan="2" align="center" valign="middle" style="border-bottom:solid thin" rowspan="1"></td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Acetic acid-induced abdominal constructions, formaldehyde-induced nociceptive response and hot-plate models in mice</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF at 3–100 mg/kg i.p. injection 1 h before acetic acid-induced model, RF at 6 or12 mg/kg i.p. injection 1 h before formaldehyde-induced nociceptive response, and RF at 50 mg/kg i.p. injection 1 h before formaldehyde-induced hindpaw edema</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">A dose-dependent RF inhibited the nociceptive response produced by acetic acid. Pre-treatment RF remarkably reduced the acute nociceptive response induced by formaldehyde in the second phase, but not in the hot-plate model. RF moderately inhibited formaldehyde-induced hindpaw edema.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B37-ijms-21-00950" ref-type="bibr">37</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Formalin-induced and carrageenan-induced paw edema, and spinal nerve ligation models in rat</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF at 1–50 mg/kg oral administration 30 min before formalin test and 6.25–150 mg/kg immediately after carrageenan injection</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Second phase treatment with RF produced a significant dose-dependent inhibition in flinching behavior produced by formalin and RF at 25 mg/kg dose had peak antinociceptive effect in formalin-induced model. RF reduced hyperalgesic effect, highest effect at 75 mg/kg dose. In addition, a dose- and time-dependent RF treatment reduced by carrageenan-induced edema, but not tactile allodynia in the spinal nerve ligation models. Moreover, antinociceptive effect of RF can be reversed by glibenclamide and NG-L-nitro-aeginie methyl ester.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B41-ijms-21-00950" ref-type="bibr">41</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Formalin-induced nociceptive response, carrageenan-induced paw edema, LPS-induced febrile response, and cotton pellet-induced formation of fibrovascular tissue models in rat</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF at 25, 50, 100 mg/kg i.p. injection 30 min before formalin-induced nociceptive response, carrageenan-induced paw edema, RF at 50 or 100 mg/kg immediately or 2 hr after LPS-induced the febrile response, and RF at 50 or 100 mg/kg i.p. 7 days after s.c. implantation of a cotton pellet-induced fibrovascular tissue</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF inhibited the nociceptive response in the mouse formalin test, markedly in second phase. RF was dose-dependently reduced the mechanical allodynia and the paw edema induced by carrageenan and inhibited the fever induced by LPS. Moreover, the formation of fibrovascular tissue induced by s.c. implant of a cotton pellet was inhibited. Therefore, RF prevents prolonged inflammatory response.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B36-ijms-21-00950" ref-type="bibr">36</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Zymosan-induced peritonitis in Swiss mice</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF at 20, 50, 100 mg/kg i.p. injection 30 min before zymosan administration; RF at 50 mg/kg in combination with 5 mg/kg morphine</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF at 50 and 100 mg/kg induced antinociceptive-related body writhes and RF at 100 mg/kg dose suppressed intraperitoneal PMN influx. On the other hand, RF co-injected with morphine at low dose had antinociceptive effect and also reduced levels of proinflammatory cytikines such as TNF-α, IL-12p07, and IFN-γ according to RF dose and the time of injection.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B39-ijms-21-00950" ref-type="bibr">39</xref>]</td></tr><tr><td colspan="2" align="center" valign="middle" style="border-bottom:solid thin" rowspan="1"><bold>Anti-Inflammatory Effect</bold></td><td colspan="2" align="center" valign="middle" style="border-bottom:solid thin" rowspan="1"></td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Toxin-induced shock (LPS-induced shock and <italic>S. aureus</italic> enterotoxin B (SEB)-induced shock) and bacterial infection in mice</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF at 2.5, 5, 10, and 20 mg/kg bolus injection 6 h after LPS injection or SEB–D-galactosamine injection. RF at 2.5, 5, 10, 20 mg/kg 1 day before <italic>E. coli</italic> inoculation or 1 and 2 days after <italic>S. aureus</italic> inoculation.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF decreased the mortality of endotoxin- and exotoxin-induced shock, gram-negative and gram-positive bacterial infection including long-term treatment. In addition, RF reduced levels of plasma inflammatory cytokines, including TNF-, IL-1β, IL-6, IFN-γ, MCP-1, MIP-2, and NO level. Moreover, co-administration RF with APC ameliorated survival rate of toxin-induced shock.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B42-ijms-21-00950" ref-type="bibr">42</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">LPS-induced shock model and bacterial infection model in mice</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF at 2.5, 5, 10, 20, 40, and 80 mg/kg/6h i.v. infusion after 6 h LPS injection. RF at 80 mg/kg/6 h after 1 h <italic>E.coli</italic> infection or RF at 20, 40, 80 mg/kg/6 h after 1 h <italic>S.aureus</italic> infection.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF protected mice against the mortality in both toxin shock and infection models, but RF reduced only the level of IL-6 and NO in plasma. In addition, RF decreased the elevation of TNF-α, IL-1β, MPC-1, IL-6, and NO level in plasma.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B8-ijms-21-00950" ref-type="bibr">8</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">LPS-induced shock model in mice</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF at 2.5 or 10 mg/kg for 6 h continuous i.v bolus administration with or without aminolevane<sup>®</sup> or single dose injection with or without amino acids or valine after 6 h LPS injection.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF at 10 mg/kg administered continuously for 6 h reduced morbidities on LPS- induced shock model, and was better with aminolevane<sup>®</sup> combination treatment. RF treatment in combination with tryptophan, isoleucine, proline, threonine, alanine or valine had improved the survival rate, but only valine was significantly effective. Moreover, RF reduced IL-6, lactic acid level, but increased glucose level.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B9-ijms-21-00950" ref-type="bibr">9</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Endotoxin-induced shock in mice</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF at 20 mg/kg i.v. administered after 6 h LPS injection</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF decreased the number of IL-6 and MIP-2 and NO levels in plasma. RF also reduced IL-6 and MIP-2 levels in lung, but inhibited only MIP-2 level in liver. However, RF reduced IL-6 mRNA expression in lung, but MIP-2 mRNA expression was inhibited in liver and kidney. Additionally, iNO expression was inhibited by RF.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B43-ijms-21-00950" ref-type="bibr">43</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Olive oil-triggered paw swelling and collagen-induced arthritis models in mice</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF at 20 mg/kg i.p. administration before oil injection or after collagen-induced arthritis</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF inhibited the paw swelling induced by olive oil, affecting a reduction in neutrophil-dependent reaction. However, RF could not inhibit delayed type hypersensitivity reactivity and collagen II arthritis.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B33-ijms-21-00950" ref-type="bibr">33</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">LPS-induced shock model in mice</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF at 1 and 10 mg/kg i.p. injection at 2 and 0 h before LPS administration</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF significantly suppressed the LPS-induced lethality in mice septic shock model and RF have protective effect through up-regulated the expression of HSP25 in the lung and heart.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B44-ijms-21-00950" ref-type="bibr">44</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Zymosan-induced peritonitis in different C57BL/6J, BALB/c and CBA mice strains</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF at 50 mg/kg i.p. co-injection with zymosan (40 mg/kg)</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF co-treatment with zymosan reduced pain symptoms. Anti-inflammatory effects of RF are strain-specific manner. Particularly, peritoneal leukocytes (PTL) accumulation was inhibited in BALB/c and CBA strains, but was prolonged in C57BL/6J strain. The expression of iNOS was delayed (C57BL/6J) or inhibited (BALB/c and CBA) in PTL lysates as well as the prolonged (C57BL/6) or inhibited (BALB/c) intraperitoneal accumulation of MMP-9.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B38-ijms-21-00950" ref-type="bibr">38</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Zymosan-induced peritonitis in Swiss mice</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF at 0, 20, 50, or 100 mg/kg by co-injection, pre-injection or post-injection in zymosan-induced peritonitis</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF itself induced nociceptive-related body writhes, but effectively reduces zymosan-induced writhing response on influence of pre-injection or post- injection. RF also reduced the evaluation number of PLTs, mainly PMN and an increase in inflammation-related cytokines and MMP-9 with dose- and administration time-dependent effect.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B40-ijms-21-00950" ref-type="bibr">40</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">LPS-induced acute lungs injury in rat</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF at 30 mg/kg, p.o. for 7 days before LPS intranasally (i.n.)</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF reduced interstitial edema, hemorrhage, infiltration of inflammatory PMNs, and destruction of lung parenchyma as well as decreased the iNOS level, but enhanced GSH, GR, GRx, and CAT expression.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B45-ijms-21-00950" ref-type="bibr">45</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Zymosan-induced inflammation in mice and in vitro macrophages</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF at 50 mg/kg i.p. injection 30 min either before zymosan, together with zymosan, or 2, 4, 6 h after i.p. zymosan injection.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF causes both the inhibition of expression and release of HMGB1 in time-dependent manner.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B46-ijms-21-00950" ref-type="bibr">46</xref>]</td></tr></tbody></table></table-wrap></floats-group></pmc><affiliations><list><country><li>Bulgarie</li><li>Thaïlande</li></country></list><tree><noCountry><name sortKey="B Umler, Hans" sort="B Umler, Hans" uniqKey="B Umler H" first="Hans" last="B Umler">Hans B Umler</name><name sortKey="Kao, Ijad" sort="Kao, Ijad" uniqKey="Kao I" first="Ijad" last="Kao">Ijad Kao</name><name sortKey="Pru, Axel" sort="Pru, Axel" uniqKey="Pru A" first="Axel" last="Pru">Axel Pru</name></noCountry><country name="Thaïlande"><noRegion><name sortKey="Suwannasom, Nittiya" sort="Suwannasom, Nittiya" uniqKey="Suwannasom N" first="Nittiya" last="Suwannasom">Nittiya Suwannasom</name></noRegion></country><country name="Bulgarie"><noRegion><name sortKey="Georgieva, Radostina" sort="Georgieva, Radostina" uniqKey="Georgieva R" first="Radostina" last="Georgieva">Radostina Georgieva</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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