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A comparative study on root and bark extracts of Eleutherococcus senticosus and their effects on human macrophages.

Identifieur interne : 000235 ( Main/Exploration ); précédent : 000234; suivant : 000236

A comparative study on root and bark extracts of Eleutherococcus senticosus and their effects on human macrophages.

Auteurs : Lu Jin [Allemagne] ; Michael Schmiech [Allemagne] ; Menna El Gaafary [Égypte] ; Xinlei Zhang [République populaire de Chine] ; Tatiana Syrovets [Allemagne] ; Thomas Simmet [Allemagne]

Source :

RBID : pubmed:32065954

Descripteurs français

English descriptors

Abstract

BACKGROUND

Eleutherococcus senticosus or Siberian ginseng is a medicinal plant containing adaptogenic substances believed to regulate immune responses. Both, the root and stem bark are commonly used in traditional medicines.

PURPOSE

The purpose of the present study is to chemically characterize E. senticosus root and bark extracts and to compare their effects on functions of human primary macrophages.

STUDY DESIGN AND METHODS

HPLC-DAD-MS analysis was used to characterize chemical constituents of alcoholic extracts from E. senticosus root and bark. The data obtained and available databases were combined for network pharmacology analysis. Involvement of predicted pathways was further functionally confirmed by using monocyte-derived human macrophages and endotoxin-free E. senticosus root and bark extracts.

RESULTS

Chemical analysis showed that the root extract contained more syringin, caffeic acid, and isofraxidin than the bark extract. At variance, bark extract contained more sesamin and oleanolic acid. Coniferyl aldehyde and afzelin were below the limit of quantification in both extracts. Network pharmacology analysis indicated that constituents of E. senticosus might affect the immune cell phenotype and signaling pathways involved in cell metabolism and cytoskeleton regulation. Indeed, both extracts promoted actin polymerization, migration, and phagocytosis of E. coli by macrophages pointing to macrophage polarization towards the M2 phenotype. In addition, treatment with E. senticosus root and bark extracts decreased phosphorylation of Akt on Ser473 and significantly reduced expression of the hemoglobin scavenger receptor CD163 by macrophages. Neither extract affected expression of CD11b, CD80, or CD64 by macrophages. In addition, macrophages treated with the bark extract, but not with the root extract, exhibited activated p38 MAPK and NF-κB and released increased, but still moderate, amounts of proinflammatory TNF-α and IL-6, anti-inflammatory IL-10, and chemotactic CCL1, which all together point to a M2b-like macrophage polarization. Differently, the root extract increased the IL-4-induced expression of anti-inflammatory CD200R. These changes in monocytes are in agreement with an increased M2a macrophage polarization.

CONCLUSION

The ability of E. senticosus root and bark extracts to promote polarization of human macrophages towards anti-inflammatory M2a and M2b phenotypes, respectively, might underlay the immunoregulatory activities and point to potential wound healing promoting effects of this medicinal plant.


DOI: 10.1016/j.phymed.2020.153181
PubMed: 32065954


Affiliations:


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<p>
<b>BACKGROUND</b>
</p>
<p>Eleutherococcus senticosus or Siberian ginseng is a medicinal plant containing adaptogenic substances believed to regulate immune responses. Both, the root and stem bark are commonly used in traditional medicines.</p>
</div>
<div type="abstract" xml:lang="en">
<p>
<b>PURPOSE</b>
</p>
<p>The purpose of the present study is to chemically characterize E. senticosus root and bark extracts and to compare their effects on functions of human primary macrophages.</p>
</div>
<div type="abstract" xml:lang="en">
<p>
<b>STUDY DESIGN AND METHODS</b>
</p>
<p>HPLC-DAD-MS analysis was used to characterize chemical constituents of alcoholic extracts from E. senticosus root and bark. The data obtained and available databases were combined for network pharmacology analysis. Involvement of predicted pathways was further functionally confirmed by using monocyte-derived human macrophages and endotoxin-free E. senticosus root and bark extracts.</p>
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<p>
<b>RESULTS</b>
</p>
<p>Chemical analysis showed that the root extract contained more syringin, caffeic acid, and isofraxidin than the bark extract. At variance, bark extract contained more sesamin and oleanolic acid. Coniferyl aldehyde and afzelin were below the limit of quantification in both extracts. Network pharmacology analysis indicated that constituents of E. senticosus might affect the immune cell phenotype and signaling pathways involved in cell metabolism and cytoskeleton regulation. Indeed, both extracts promoted actin polymerization, migration, and phagocytosis of E. coli by macrophages pointing to macrophage polarization towards the M2 phenotype. In addition, treatment with E. senticosus root and bark extracts decreased phosphorylation of Akt on Ser473 and significantly reduced expression of the hemoglobin scavenger receptor CD163 by macrophages. Neither extract affected expression of CD11b, CD80, or CD64 by macrophages. In addition, macrophages treated with the bark extract, but not with the root extract, exhibited activated p38 MAPK and NF-κB and released increased, but still moderate, amounts of proinflammatory TNF-α and IL-6, anti-inflammatory IL-10, and chemotactic CCL1, which all together point to a M2b-like macrophage polarization. Differently, the root extract increased the IL-4-induced expression of anti-inflammatory CD200R. These changes in monocytes are in agreement with an increased M2a macrophage polarization.</p>
</div>
<div type="abstract" xml:lang="en">
<p>
<b>CONCLUSION</b>
</p>
<p>The ability of E. senticosus root and bark extracts to promote polarization of human macrophages towards anti-inflammatory M2a and M2b phenotypes, respectively, might underlay the immunoregulatory activities and point to potential wound healing promoting effects of this medicinal plant.</p>
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<NlmUniqueID>9438794</NlmUniqueID>
<ISSNLinking>0944-7113</ISSNLinking>
</MedlineJournalInfo>
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<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D000893">Anti-Inflammatory Agents</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D003374">Coumarins</NameOfSubstance>
</Chemical>
<Chemical>
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<Chemical>
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<NameOfSubstance UI="D016328">NF-kappa B</NameOfSubstance>
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<NameOfSubstance UI="D010666">Phenylpropionates</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D010936">Plant Extracts</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>304915F056</RegistryNumber>
<NameOfSubstance UI="C008182">isofraxidin</NameOfSubstance>
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<NameOfSubstance UI="C054125">sesamin</NameOfSubstance>
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<MeshHeadingList>
<MeshHeading>
<DescriptorName UI="D000893" MajorTopicYN="N">Anti-Inflammatory Agents</DescriptorName>
<QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D016764" MajorTopicYN="N">Cell Polarity</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D003374" MajorTopicYN="N">Coumarins</DescriptorName>
<QualifierName UI="Q000032" MajorTopicYN="N">analysis</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D004149" MajorTopicYN="N">Dioxoles</DescriptorName>
<QualifierName UI="Q000032" MajorTopicYN="N">analysis</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D028001" MajorTopicYN="N">Eleutherococcus</DescriptorName>
<QualifierName UI="Q000737" MajorTopicYN="Y">chemistry</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D005960" MajorTopicYN="N">Glucosides</DescriptorName>
<QualifierName UI="Q000032" MajorTopicYN="N">analysis</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D017705" MajorTopicYN="N">Lignans</DescriptorName>
<QualifierName UI="Q000032" MajorTopicYN="N">analysis</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D008264" MajorTopicYN="N">Macrophages</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D016328" MajorTopicYN="N">NF-kappa B</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D010666" MajorTopicYN="N">Phenylpropionates</DescriptorName>
<QualifierName UI="Q000032" MajorTopicYN="N">analysis</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D024301" MajorTopicYN="N">Plant Bark</DescriptorName>
<QualifierName UI="Q000737" MajorTopicYN="Y">chemistry</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D010936" MajorTopicYN="N">Plant Extracts</DescriptorName>
<QualifierName UI="Q000032" MajorTopicYN="N">analysis</QualifierName>
<QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName>
<QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D018517" MajorTopicYN="N">Plant Roots</DescriptorName>
<QualifierName UI="Q000737" MajorTopicYN="Y">chemistry</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D010946" MajorTopicYN="N">Plants, Medicinal</DescriptorName>
<QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName>
</MeshHeading>
</MeshHeadingList>
<KeywordList Owner="NOTNLM">
<Keyword MajorTopicYN="N">Adaptogen</Keyword>
<Keyword MajorTopicYN="N">Alternatively activated macrophages</Keyword>
<Keyword MajorTopicYN="N">Cytoskeleton</Keyword>
<Keyword MajorTopicYN="N">Eleutherococcus senticosus</Keyword>
<Keyword MajorTopicYN="N">Network pharmacology</Keyword>
<Keyword MajorTopicYN="N">Wound healing</Keyword>
</KeywordList>
<CoiStatement>Declaration of Competing Interest The authors have stated that there is no conflict of interest associated with the publication and no financial support, which could have influenced the outcome.</CoiStatement>
</MedlineCitation>
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<Year>2019</Year>
<Month>10</Month>
<Day>31</Day>
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<PubMedPubDate PubStatus="revised">
<Year>2020</Year>
<Month>01</Month>
<Day>24</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="accepted">
<Year>2020</Year>
<Month>02</Month>
<Day>05</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="pubmed">
<Year>2020</Year>
<Month>2</Month>
<Day>18</Day>
<Hour>6</Hour>
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<PubMedPubDate PubStatus="medline">
<Year>2020</Year>
<Month>7</Month>
<Day>14</Day>
<Hour>6</Hour>
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<PubMedPubDate PubStatus="entrez">
<Year>2020</Year>
<Month>2</Month>
<Day>18</Day>
<Hour>6</Hour>
<Minute>0</Minute>
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</History>
<PublicationStatus>ppublish</PublicationStatus>
<ArticleIdList>
<ArticleId IdType="pubmed">32065954</ArticleId>
<ArticleId IdType="pii">S0944-7113(20)30014-3</ArticleId>
<ArticleId IdType="doi">10.1016/j.phymed.2020.153181</ArticleId>
</ArticleIdList>
</PubmedData>
</pubmed>
<affiliations>
<list>
<country>
<li>Allemagne</li>
<li>République populaire de Chine</li>
<li>Égypte</li>
</country>
<region>
<li>Bade-Wurtemberg</li>
<li>District de Tübingen</li>
</region>
<settlement>
<li>Ulm</li>
</settlement>
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<tree>
<country name="Allemagne">
<region name="Bade-Wurtemberg">
<name sortKey="Jin, Lu" sort="Jin, Lu" uniqKey="Jin L" first="Lu" last="Jin">Lu Jin</name>
</region>
<name sortKey="Schmiech, Michael" sort="Schmiech, Michael" uniqKey="Schmiech M" first="Michael" last="Schmiech">Michael Schmiech</name>
<name sortKey="Simmet, Thomas" sort="Simmet, Thomas" uniqKey="Simmet T" first="Thomas" last="Simmet">Thomas Simmet</name>
<name sortKey="Syrovets, Tatiana" sort="Syrovets, Tatiana" uniqKey="Syrovets T" first="Tatiana" last="Syrovets">Tatiana Syrovets</name>
</country>
<country name="Égypte">
<noRegion>
<name sortKey="El Gaafary, Menna" sort="El Gaafary, Menna" uniqKey="El Gaafary M" first="Menna" last="El Gaafary">Menna El Gaafary</name>
</noRegion>
</country>
<country name="République populaire de Chine">
<noRegion>
<name sortKey="Zhang, Xinlei" sort="Zhang, Xinlei" uniqKey="Zhang X" first="Xinlei" last="Zhang">Xinlei Zhang</name>
</noRegion>
</country>
</tree>
</affiliations>
</record>

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