Antifilarial activity of diterpenoids from Taxodium distichum
Identifieur interne : 000E11 ( Pmc/Curation ); précédent : 000E10; suivant : 000E12Antifilarial activity of diterpenoids from Taxodium distichum
Auteurs : Vikas Kushwaha [Inde] ; Kirti Saxena [Inde] ; Richa Verma [Inde] ; Shiv K. Verma [Inde, États-Unis] ; Deepali Katoch ; Neeraj Kumar ; Brij Lal ; P. Kalpana Murthy [Inde] ; Bikram SinghSource :
- Parasites & Vectors [ 1756-3305 ] ; 2016.
Abstract
Lymphatic filariasis caused by
Ethanolic extract (A001) of aerial parts of
A001 was effective in killing microfilariae (mf) and adult worms
Ethanolic extract of aerial parts of the plant
Url:
DOI: 10.1186/s13071-016-1592-4
PubMed: 27245322
PubMed Central: 4888613
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Deepali Katoch<affiliation><nlm:aff id="Aff2">Natural Product Chemistry and Process Development Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur, 176 061 HP India</nlm:aff>
<wicri:noCountry code="subfield">176 061 HP India</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="Aff2">Natural Product Chemistry and Process Development Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur, 176 061 HP India</nlm:aff>
<wicri:noCountry code="subfield">176 061 HP India</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="Aff3">Biodiversity Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur, 176 061 HP India</nlm:aff>
<wicri:noCountry code="subfield">176 061 HP India</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="Aff2">Natural Product Chemistry and Process Development Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur, 176 061 HP India</nlm:aff>
<wicri:noCountry code="subfield">176 061 HP India</wicri:noCountry>
</affiliation>
Le document en format XML
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Antifilarial activity of diterpenoids from <italic>Taxodium distichum</italic>
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<author><name sortKey="Kushwaha, Vikas" sort="Kushwaha, Vikas" uniqKey="Kushwaha V" first="Vikas" last="Kushwaha">Vikas Kushwaha</name>
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<country xml:lang="fr">Inde</country>
<wicri:regionArea>Division of Parasitology, CSIR-Central Drug Research Institute, New Campus, BS 10/1, Sector 10, Jankipuram Extension, Lucknow</wicri:regionArea>
</affiliation>
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<author><name sortKey="Saxena, Kirti" sort="Saxena, Kirti" uniqKey="Saxena K" first="Kirti" last="Saxena">Kirti Saxena</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1">Division of Parasitology, CSIR-Central Drug Research Institute, New Campus, BS 10/1, Sector 10, Jankipuram Extension, Lucknow, 226 031 India</nlm:aff>
<country xml:lang="fr">Inde</country>
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<author><name sortKey="Verma, Richa" sort="Verma, Richa" uniqKey="Verma R" first="Richa" last="Verma">Richa Verma</name>
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<country xml:lang="fr">Inde</country>
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<author><name sortKey="Verma, Shiv K" sort="Verma, Shiv K" uniqKey="Verma S" first="Shiv K." last="Verma">Shiv K. Verma</name>
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<author><name sortKey="Katoch, Deepali" sort="Katoch, Deepali" uniqKey="Katoch D" first="Deepali" last="Katoch">Deepali Katoch</name>
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<author><name sortKey="Kumar, Neeraj" sort="Kumar, Neeraj" uniqKey="Kumar N" first="Neeraj" last="Kumar">Neeraj Kumar</name>
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<wicri:noCountry code="subfield">176 061 HP India</wicri:noCountry>
</affiliation>
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<author><name sortKey="Lal, Brij" sort="Lal, Brij" uniqKey="Lal B" first="Brij" last="Lal">Brij Lal</name>
<affiliation><nlm:aff id="Aff3">Biodiversity Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur, 176 061 HP India</nlm:aff>
<wicri:noCountry code="subfield">176 061 HP India</wicri:noCountry>
</affiliation>
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<author><name sortKey="Murthy, P Kalpana" sort="Murthy, P Kalpana" uniqKey="Murthy P" first="P. Kalpana" last="Murthy">P. Kalpana Murthy</name>
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<author><name sortKey="Singh, Bikram" sort="Singh, Bikram" uniqKey="Singh B" first="Bikram" last="Singh">Bikram Singh</name>
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<series><title level="j">Parasites & Vectors</title>
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<front><div type="abstract" xml:lang="en"><sec><title>Background</title>
<p>Lymphatic filariasis caused by <italic>Wuchereria bancrofti</italic>
, <italic>Brugia malayi</italic>
and <italic>B. timori</italic>
, is a debilitating disease with an adverse social and economic impact. The infection remains unabated in spite of treatment with existing antifilarial drugs diethylcarbamazine (DEC) and ivermectin which are chiefly microfilaricides. There is therefore, need for macrofilaricides, embryostatic agents and better microfilaricides. In the present study we explored the antifilarial potential of crude extract and its molecular fractions of the plant <italic>Taxodium distichum</italic>
using <italic>in vitro</italic>
assay systems and rodent models of <italic>B. malayi</italic>
infection.</p>
</sec>
<sec><title>Methods</title>
<p>Ethanolic extract (A001) of aerial parts of <italic>T. distichum</italic>
was solvent fractionated and sub-fractionated. Four molecules, 3-Acetoxylabda-8(20), 13-diene-15-oic acid (K001), Beta-sitosterol (K002), labda-8(20),13-diene-15-oic acid (K003) and Metasequoic acid A (K004) were isolated from the fractions and their structure determined by spectroscopic analysis. The extract, subfractions and molecules were evaluated for antifilarial activity against <italic>B. malayi</italic>
by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) reduction and motility assays <italic>in vitro</italic>
and in two animal models, <italic>Meriones unguiculatus</italic>
and <italic>Mastomys coucha</italic>
, harbouring <italic>B. malayi</italic>
infection.</p>
</sec>
<sec><title>Results</title>
<p>A001 was effective in killing microfilariae (mf) and adult worms <italic>in vitro</italic>
. The diterpenoid K003 produced 100 % reduction in motility of both mf and adult worms and > 80 % inhibition in MTT reduction potential of adult female worms. In <italic>B. malayi</italic>
-<italic>M. unguiculatus</italic>
model, A001 killed all the adult worms in > 80 % of infected animals. K003 was embryostatic (> 95 %) in this model. In the <italic>B. malayi</italic>
-<italic>M. coucha</italic>
model, K003 killed ~54 % of adult worms (macrofilaricidal activity) and rendered > 36 % female worms sterile; it also stopped any further rise in microfilaraemia after day 42 post-initiation of treatment.</p>
</sec>
<sec><title>Conclusion</title>
<p>Ethanolic extract of aerial parts of the plant <italic>T. distichum</italic>
possesses potent antifilarial activity and the active principle was localised to K003 which showed significant macrofilaricidal activity and late suppression of peripheral microfilaraemia and some embryostatic activity. These findings indicate that labdane diterpenoid molecule(s) may provide valuable leads for design and development of new macrofilaricidal agent(s). To the best of our knowledge, this is the first report on antifilarial efficacy of products from the plant <italic>T. distichum</italic>
.</p>
</sec>
</div>
</front>
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</TEI>
<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Parasit Vectors</journal-id>
<journal-id journal-id-type="iso-abbrev">Parasit Vectors</journal-id>
<journal-title-group><journal-title>Parasites & Vectors</journal-title>
</journal-title-group>
<issn pub-type="epub">1756-3305</issn>
<publisher><publisher-name>BioMed Central</publisher-name>
<publisher-loc>London</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">27245322</article-id>
<article-id pub-id-type="pmc">4888613</article-id>
<article-id pub-id-type="publisher-id">1592</article-id>
<article-id pub-id-type="doi">10.1186/s13071-016-1592-4</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research</subject>
</subj-group>
</article-categories>
<title-group><article-title>Antifilarial activity of diterpenoids from <italic>Taxodium distichum</italic>
</article-title>
</title-group>
<contrib-group><contrib contrib-type="author" equal-contrib="yes"><name><surname>Kushwaha</surname>
<given-names>Vikas</given-names>
</name>
<xref ref-type="aff" rid="Aff1"></xref>
</contrib>
<contrib contrib-type="author" equal-contrib="yes"><name><surname>Saxena</surname>
<given-names>Kirti</given-names>
</name>
<xref ref-type="aff" rid="Aff1"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Verma</surname>
<given-names>Richa</given-names>
</name>
<xref ref-type="aff" rid="Aff1"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Verma</surname>
<given-names>Shiv K.</given-names>
</name>
<xref ref-type="aff" rid="Aff1"></xref>
<xref ref-type="aff" rid="Aff4"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Katoch</surname>
<given-names>Deepali</given-names>
</name>
<xref ref-type="aff" rid="Aff2"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kumar</surname>
<given-names>Neeraj</given-names>
</name>
<xref ref-type="aff" rid="Aff2"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Lal</surname>
<given-names>Brij</given-names>
</name>
<xref ref-type="aff" rid="Aff3"></xref>
</contrib>
<contrib contrib-type="author" corresp="yes"><name><surname>Murthy</surname>
<given-names>P. Kalpana</given-names>
</name>
<address><email>drpkmurthy@yahoo.com</email>
<email>drpkmurthy@gmail.com</email>
<email>psr_murthy@yahoo.com</email>
</address>
<xref ref-type="aff" rid="Aff1"></xref>
</contrib>
<contrib contrib-type="author" corresp="yes"><name><surname>Singh</surname>
<given-names>Bikram</given-names>
</name>
<address><email>bikramsingh@ihbt.res.in</email>
<email>bikram_npp@rediffmail.com</email>
</address>
<xref ref-type="aff" rid="Aff2"></xref>
</contrib>
<aff id="Aff1"><label></label>
Division of Parasitology, CSIR-Central Drug Research Institute, New Campus, BS 10/1, Sector 10, Jankipuram Extension, Lucknow, 226 031 India</aff>
<aff id="Aff2"><label></label>
Natural Product Chemistry and Process Development Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur, 176 061 HP India</aff>
<aff id="Aff3"><label></label>
Biodiversity Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur, 176 061 HP India</aff>
<aff id="Aff4"><label></label>
Present Address: USDA, ARS, APDL, BARC-East Bldg 1001, 10300 Baltimore Avenue, Beltsville, MD 20705 USA</aff>
</contrib-group>
<pub-date pub-type="epub"><day>31</day>
<month>5</month>
<year>2016</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>31</day>
<month>5</month>
<year>2016</year>
</pub-date>
<pub-date pub-type="collection"><year>2016</year>
</pub-date>
<volume>9</volume>
<elocation-id>312</elocation-id>
<history><date date-type="received"><day>27</day>
<month>10</month>
<year>2015</year>
</date>
<date date-type="accepted"><day>13</day>
<month>5</month>
<year>2016</year>
</date>
</history>
<permissions><copyright-statement>© Kushwaha et al. 2016</copyright-statement>
<license license-type="OpenAccess"><license-p><bold>Open Access</bold>
This article is distributed under the terms of the Creative Commons Attribution 4.0 International 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>
), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/publicdomain/zero/1.0/">http://creativecommons.org/publicdomain/zero/1.0/</ext-link>
) applies to the data made available in this article, unless otherwise stated.</license-p>
</license>
</permissions>
<abstract id="Abs1"><sec><title>Background</title>
<p>Lymphatic filariasis caused by <italic>Wuchereria bancrofti</italic>
, <italic>Brugia malayi</italic>
and <italic>B. timori</italic>
, is a debilitating disease with an adverse social and economic impact. The infection remains unabated in spite of treatment with existing antifilarial drugs diethylcarbamazine (DEC) and ivermectin which are chiefly microfilaricides. There is therefore, need for macrofilaricides, embryostatic agents and better microfilaricides. In the present study we explored the antifilarial potential of crude extract and its molecular fractions of the plant <italic>Taxodium distichum</italic>
using <italic>in vitro</italic>
assay systems and rodent models of <italic>B. malayi</italic>
infection.</p>
</sec>
<sec><title>Methods</title>
<p>Ethanolic extract (A001) of aerial parts of <italic>T. distichum</italic>
was solvent fractionated and sub-fractionated. Four molecules, 3-Acetoxylabda-8(20), 13-diene-15-oic acid (K001), Beta-sitosterol (K002), labda-8(20),13-diene-15-oic acid (K003) and Metasequoic acid A (K004) were isolated from the fractions and their structure determined by spectroscopic analysis. The extract, subfractions and molecules were evaluated for antifilarial activity against <italic>B. malayi</italic>
by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) reduction and motility assays <italic>in vitro</italic>
and in two animal models, <italic>Meriones unguiculatus</italic>
and <italic>Mastomys coucha</italic>
, harbouring <italic>B. malayi</italic>
infection.</p>
</sec>
<sec><title>Results</title>
<p>A001 was effective in killing microfilariae (mf) and adult worms <italic>in vitro</italic>
. The diterpenoid K003 produced 100 % reduction in motility of both mf and adult worms and > 80 % inhibition in MTT reduction potential of adult female worms. In <italic>B. malayi</italic>
-<italic>M. unguiculatus</italic>
model, A001 killed all the adult worms in > 80 % of infected animals. K003 was embryostatic (> 95 %) in this model. In the <italic>B. malayi</italic>
-<italic>M. coucha</italic>
model, K003 killed ~54 % of adult worms (macrofilaricidal activity) and rendered > 36 % female worms sterile; it also stopped any further rise in microfilaraemia after day 42 post-initiation of treatment.</p>
</sec>
<sec><title>Conclusion</title>
<p>Ethanolic extract of aerial parts of the plant <italic>T. distichum</italic>
possesses potent antifilarial activity and the active principle was localised to K003 which showed significant macrofilaricidal activity and late suppression of peripheral microfilaraemia and some embryostatic activity. These findings indicate that labdane diterpenoid molecule(s) may provide valuable leads for design and development of new macrofilaricidal agent(s). To the best of our knowledge, this is the first report on antifilarial efficacy of products from the plant <italic>T. distichum</italic>
.</p>
</sec>
</abstract>
<kwd-group xml:lang="en"><title>Keywords</title>
<kwd><italic>Taxodium distichum</italic>
</kwd>
<kwd><italic>Brugia malayi</italic>
</kwd>
<kwd>Labdane diterpenoids</kwd>
<kwd><italic>In vitro</italic>
assays</kwd>
<kwd>Macrofilaricide</kwd>
<kwd>Embryostatic</kwd>
<kwd><italic>Mastomys coucha</italic>
</kwd>
<kwd><italic>Meriones unguiculatus</italic>
</kwd>
<kwd>Diethylcarbamazine</kwd>
<kwd>Ivermectin</kwd>
</kwd-group>
<funding-group><award-group><funding-source><institution-wrap><institution-id institution-id-type="FundRef">http://dx.doi.org/http://dx.doi.org/10.13039/501100001412</institution-id>
<institution>Council of Scientific and Industrial Research</institution>
</institution-wrap>
</funding-source>
<award-id>SPLENDID and NWP 0037</award-id>
</award-group>
</funding-group>
<custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name>
<meta-value>© The Author(s) 2016</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
</front>
</pmc>
</record>
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