Cardenolide-rich fraction of Pergularia tomentosa as a novel Antiangiogenic agent mainly targeting endothelial cell migration
Purpose Angiogenesis related abnormalities underlie several life-threatening disorders. Despite approved therapies, scientists have yet to develop highly efficient, low cost approaches with minimal side effects. Methods We evaluated the antiangiogenic activity of 50% hydroalcoholic extracts of Pergu...
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| Veröffentlicht in: | Daru 2020-12, Vol.28 (2), p.533-543 |
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| creator | Hosseini, Mahya Ayyari, Mahdi Meyfour, Anna Piacente, Sonia Cerulli, Antonietta Crawford, Alexander Pahlavan, Sara |
| description | Purpose
Angiogenesis related abnormalities underlie several life-threatening disorders. Despite approved therapies, scientists have yet to develop highly efficient, low cost approaches with minimal side effects.
Methods
We evaluated the antiangiogenic activity of 50% hydroalcoholic extracts of
Pergularia tomentosa
L. root and aerial parts along with their EtOAc and water fractions, in vivo and in vitro. Transgenic zebrafish line
Tg(fli1:EGFP)
was used for in vivo assay and human umbilical vein endothelial cell (HUVEC) migration test along with possibility of tube formation were performed as in vitro tests. Furthermore, microvasculature in chicken chorioallantoic membrane (CAM) was assessed under
P. tomentosa
treatment. The fractionation of the 50% hydroalcoholic extracts was led to the identification of the best active fraction in this study. The metabolite profiling of the active fraction was also carried out using LC-HRESIMS analysis.
Results
Pergularia tomentosa
markedly inhibited intersegmental vessel (ISV) formation at 48 h post-fertilization (hpf) embryos in zebrafish. The water fraction of root hydroalcoholic extract (PtR2), showed strong antiangiogenic effect with minimal adverse viability impacts. Over 80% of embryos showed more than 50% inhibition in their ISV development at 20 and 40 μg/mL. PtR2 at 20 μg/mL substantially reduced human umbilical vein endothelial cell (HUVEC) migration up to 40%, considerable destruction of the formed tubes in the tube formation and microvasculature in CAM assays. Immunocytochemistry showed a marked reduction in vascular endothelial cadherin (VE-cadherin) abundance at cell junctions concurrent with substantial reduction of phospho-Akt (p-Akt) and β-catenin protein expressions. Phytochemical profile of PtR2 showed a rich source of cardenolide structures, including ghalakinoside, calactin and calotropin derivatives.
Conclusion
Thus, the
P. tomentosa
cardenolide-rich fraction (PtR2) may hold a considerable promise for an antiangiogenic impact by impairment of endothelial cell (EC) migration and viability.
Graphical abstract |
| doi_str_mv | 10.1007/s40199-020-00356-7 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7704873</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A628471490</galeid><sourcerecordid>A628471490</sourcerecordid><originalsourceid>FETCH-LOGICAL-c521t-69b9d9d2c29ae7c1ffa1ebae2934da2c2273a6d6229b64d30216bfb808cf132d3</originalsourceid><addsrcrecordid>eNp9ks-L1TAQx4so7rr6D3gKCOKla5L2Nc1FeDzWH7CgBz2HaTLty5Ima5Iu7MH_3dQusg9Ecpgw-cw3M8m3ql4zeskoFe9TS5mUNeW0prTZdbV4Up1zSvua84Y9fbQ_q16kdFOgvu348-qs4R0VctedV78OEA364KzBOlp9JGMEnW3wJIzkG8ZpcRAtkBxm9DkkIJAIEB_u0JG9zxb8ZMOE3moCJWQyg_XunmSIE2brJ4LehHxEZ8ERjc6R2U4R1jteVs9GcAlfPcSL6sfHq--Hz_X1109fDvvrWu84y3UnB2mk4ZpLQKHZOALDAZDLpjVQ0lw00JmOczl0rWkoZ90wDj3t9cgabpqL6sOme7sMMxpd2ozg1G20M8R7FcCq0xNvj2oKd0oI2vaiKQLvHgRi-Llgymq2aZ0FPIYlKd4y2fLy1KKgbzZ0AofK-jEURb3iat_xvhWslbRQl_-gyjI4Wx08jrbkTwrePio4Irh8TMEt6zOmU5BvoI4hpYjj3zEZVatv1OYbVXyj_vhGrU03W1EqsJ8wqpuwRF_-5H9VvwHBKcXt</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2419422237</pqid></control><display><type>article</type><title>Cardenolide-rich fraction of Pergularia tomentosa as a novel Antiangiogenic agent mainly targeting endothelial cell migration</title><source>Springer Nature - Complete Springer Journals</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><source>Free Full-Text Journals in Chemistry</source><creator>Hosseini, Mahya ; Ayyari, Mahdi ; Meyfour, Anna ; Piacente, Sonia ; Cerulli, Antonietta ; Crawford, Alexander ; Pahlavan, Sara</creator><creatorcontrib>Hosseini, Mahya ; Ayyari, Mahdi ; Meyfour, Anna ; Piacente, Sonia ; Cerulli, Antonietta ; Crawford, Alexander ; Pahlavan, Sara</creatorcontrib><description>Purpose
Angiogenesis related abnormalities underlie several life-threatening disorders. Despite approved therapies, scientists have yet to develop highly efficient, low cost approaches with minimal side effects.
Methods
We evaluated the antiangiogenic activity of 50% hydroalcoholic extracts of
Pergularia tomentosa
L. root and aerial parts along with their EtOAc and water fractions, in vivo and in vitro. Transgenic zebrafish line
Tg(fli1:EGFP)
was used for in vivo assay and human umbilical vein endothelial cell (HUVEC) migration test along with possibility of tube formation were performed as in vitro tests. Furthermore, microvasculature in chicken chorioallantoic membrane (CAM) was assessed under
P. tomentosa
treatment. The fractionation of the 50% hydroalcoholic extracts was led to the identification of the best active fraction in this study. The metabolite profiling of the active fraction was also carried out using LC-HRESIMS analysis.
Results
Pergularia tomentosa
markedly inhibited intersegmental vessel (ISV) formation at 48 h post-fertilization (hpf) embryos in zebrafish. The water fraction of root hydroalcoholic extract (PtR2), showed strong antiangiogenic effect with minimal adverse viability impacts. Over 80% of embryos showed more than 50% inhibition in their ISV development at 20 and 40 μg/mL. PtR2 at 20 μg/mL substantially reduced human umbilical vein endothelial cell (HUVEC) migration up to 40%, considerable destruction of the formed tubes in the tube formation and microvasculature in CAM assays. Immunocytochemistry showed a marked reduction in vascular endothelial cadherin (VE-cadherin) abundance at cell junctions concurrent with substantial reduction of phospho-Akt (p-Akt) and β-catenin protein expressions. Phytochemical profile of PtR2 showed a rich source of cardenolide structures, including ghalakinoside, calactin and calotropin derivatives.
Conclusion
Thus, the
P. tomentosa
cardenolide-rich fraction (PtR2) may hold a considerable promise for an antiangiogenic impact by impairment of endothelial cell (EC) migration and viability.
Graphical abstract</description><identifier>ISSN: 2008-2231</identifier><identifier>ISSN: 1560-8115</identifier><identifier>EISSN: 2008-2231</identifier><identifier>DOI: 10.1007/s40199-020-00356-7</identifier><identifier>PMID: 32607956</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Animal genetic engineering ; Antineoplastic agents ; Biomedical and Life Sciences ; Biomedicine ; Endothelium ; Medicinal Chemistry ; Metabolites ; Pharmaceutical Sciences/Technology ; Pharmacology/Toxicology ; Research Article</subject><ispartof>Daru, 2020-12, Vol.28 (2), p.533-543</ispartof><rights>Springer Nature Switzerland AG 2020</rights><rights>COPYRIGHT 2020 BioMed Central Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c521t-69b9d9d2c29ae7c1ffa1ebae2934da2c2273a6d6229b64d30216bfb808cf132d3</citedby><cites>FETCH-LOGICAL-c521t-69b9d9d2c29ae7c1ffa1ebae2934da2c2273a6d6229b64d30216bfb808cf132d3</cites><orcidid>0000-0002-8854-2626</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704873/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704873/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,41467,42536,51297,53769,53771</link.rule.ids></links><search><creatorcontrib>Hosseini, Mahya</creatorcontrib><creatorcontrib>Ayyari, Mahdi</creatorcontrib><creatorcontrib>Meyfour, Anna</creatorcontrib><creatorcontrib>Piacente, Sonia</creatorcontrib><creatorcontrib>Cerulli, Antonietta</creatorcontrib><creatorcontrib>Crawford, Alexander</creatorcontrib><creatorcontrib>Pahlavan, Sara</creatorcontrib><title>Cardenolide-rich fraction of Pergularia tomentosa as a novel Antiangiogenic agent mainly targeting endothelial cell migration</title><title>Daru</title><addtitle>DARU J Pharm Sci</addtitle><description>Purpose
Angiogenesis related abnormalities underlie several life-threatening disorders. Despite approved therapies, scientists have yet to develop highly efficient, low cost approaches with minimal side effects.
Methods
We evaluated the antiangiogenic activity of 50% hydroalcoholic extracts of
Pergularia tomentosa
L. root and aerial parts along with their EtOAc and water fractions, in vivo and in vitro. Transgenic zebrafish line
Tg(fli1:EGFP)
was used for in vivo assay and human umbilical vein endothelial cell (HUVEC) migration test along with possibility of tube formation were performed as in vitro tests. Furthermore, microvasculature in chicken chorioallantoic membrane (CAM) was assessed under
P. tomentosa
treatment. The fractionation of the 50% hydroalcoholic extracts was led to the identification of the best active fraction in this study. The metabolite profiling of the active fraction was also carried out using LC-HRESIMS analysis.
Results
Pergularia tomentosa
markedly inhibited intersegmental vessel (ISV) formation at 48 h post-fertilization (hpf) embryos in zebrafish. The water fraction of root hydroalcoholic extract (PtR2), showed strong antiangiogenic effect with minimal adverse viability impacts. Over 80% of embryos showed more than 50% inhibition in their ISV development at 20 and 40 μg/mL. PtR2 at 20 μg/mL substantially reduced human umbilical vein endothelial cell (HUVEC) migration up to 40%, considerable destruction of the formed tubes in the tube formation and microvasculature in CAM assays. Immunocytochemistry showed a marked reduction in vascular endothelial cadherin (VE-cadherin) abundance at cell junctions concurrent with substantial reduction of phospho-Akt (p-Akt) and β-catenin protein expressions. Phytochemical profile of PtR2 showed a rich source of cardenolide structures, including ghalakinoside, calactin and calotropin derivatives.
Conclusion
Thus, the
P. tomentosa
cardenolide-rich fraction (PtR2) may hold a considerable promise for an antiangiogenic impact by impairment of endothelial cell (EC) migration and viability.
Graphical abstract</description><subject>Animal genetic engineering</subject><subject>Antineoplastic agents</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Endothelium</subject><subject>Medicinal Chemistry</subject><subject>Metabolites</subject><subject>Pharmaceutical Sciences/Technology</subject><subject>Pharmacology/Toxicology</subject><subject>Research Article</subject><issn>2008-2231</issn><issn>1560-8115</issn><issn>2008-2231</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp9ks-L1TAQx4so7rr6D3gKCOKla5L2Nc1FeDzWH7CgBz2HaTLty5Ima5Iu7MH_3dQusg9Ecpgw-cw3M8m3ql4zeskoFe9TS5mUNeW0prTZdbV4Up1zSvua84Y9fbQ_q16kdFOgvu348-qs4R0VctedV78OEA364KzBOlp9JGMEnW3wJIzkG8ZpcRAtkBxm9DkkIJAIEB_u0JG9zxb8ZMOE3moCJWQyg_XunmSIE2brJ4LehHxEZ8ERjc6R2U4R1jteVs9GcAlfPcSL6sfHq--Hz_X1109fDvvrWu84y3UnB2mk4ZpLQKHZOALDAZDLpjVQ0lw00JmOczl0rWkoZ90wDj3t9cgabpqL6sOme7sMMxpd2ozg1G20M8R7FcCq0xNvj2oKd0oI2vaiKQLvHgRi-Llgymq2aZ0FPIYlKd4y2fLy1KKgbzZ0AofK-jEURb3iat_xvhWslbRQl_-gyjI4Wx08jrbkTwrePio4Irh8TMEt6zOmU5BvoI4hpYjj3zEZVatv1OYbVXyj_vhGrU03W1EqsJ8wqpuwRF_-5H9VvwHBKcXt</recordid><startdate>20201201</startdate><enddate>20201201</enddate><creator>Hosseini, Mahya</creator><creator>Ayyari, Mahdi</creator><creator>Meyfour, Anna</creator><creator>Piacente, Sonia</creator><creator>Cerulli, Antonietta</creator><creator>Crawford, Alexander</creator><creator>Pahlavan, Sara</creator><general>Springer International Publishing</general><general>BioMed Central Ltd</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-8854-2626</orcidid></search><sort><creationdate>20201201</creationdate><title>Cardenolide-rich fraction of Pergularia tomentosa as a novel Antiangiogenic agent mainly targeting endothelial cell migration</title><author>Hosseini, Mahya ; Ayyari, Mahdi ; Meyfour, Anna ; Piacente, Sonia ; Cerulli, Antonietta ; Crawford, Alexander ; Pahlavan, Sara</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c521t-69b9d9d2c29ae7c1ffa1ebae2934da2c2273a6d6229b64d30216bfb808cf132d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animal genetic engineering</topic><topic>Antineoplastic agents</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Endothelium</topic><topic>Medicinal Chemistry</topic><topic>Metabolites</topic><topic>Pharmaceutical Sciences/Technology</topic><topic>Pharmacology/Toxicology</topic><topic>Research Article</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hosseini, Mahya</creatorcontrib><creatorcontrib>Ayyari, Mahdi</creatorcontrib><creatorcontrib>Meyfour, Anna</creatorcontrib><creatorcontrib>Piacente, Sonia</creatorcontrib><creatorcontrib>Cerulli, Antonietta</creatorcontrib><creatorcontrib>Crawford, Alexander</creatorcontrib><creatorcontrib>Pahlavan, Sara</creatorcontrib><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Daru</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hosseini, Mahya</au><au>Ayyari, Mahdi</au><au>Meyfour, Anna</au><au>Piacente, Sonia</au><au>Cerulli, Antonietta</au><au>Crawford, Alexander</au><au>Pahlavan, Sara</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cardenolide-rich fraction of Pergularia tomentosa as a novel Antiangiogenic agent mainly targeting endothelial cell migration</atitle><jtitle>Daru</jtitle><stitle>DARU J Pharm Sci</stitle><date>2020-12-01</date><risdate>2020</risdate><volume>28</volume><issue>2</issue><spage>533</spage><epage>543</epage><pages>533-543</pages><issn>2008-2231</issn><issn>1560-8115</issn><eissn>2008-2231</eissn><abstract>Purpose
Angiogenesis related abnormalities underlie several life-threatening disorders. Despite approved therapies, scientists have yet to develop highly efficient, low cost approaches with minimal side effects.
Methods
We evaluated the antiangiogenic activity of 50% hydroalcoholic extracts of
Pergularia tomentosa
L. root and aerial parts along with their EtOAc and water fractions, in vivo and in vitro. Transgenic zebrafish line
Tg(fli1:EGFP)
was used for in vivo assay and human umbilical vein endothelial cell (HUVEC) migration test along with possibility of tube formation were performed as in vitro tests. Furthermore, microvasculature in chicken chorioallantoic membrane (CAM) was assessed under
P. tomentosa
treatment. The fractionation of the 50% hydroalcoholic extracts was led to the identification of the best active fraction in this study. The metabolite profiling of the active fraction was also carried out using LC-HRESIMS analysis.
Results
Pergularia tomentosa
markedly inhibited intersegmental vessel (ISV) formation at 48 h post-fertilization (hpf) embryos in zebrafish. The water fraction of root hydroalcoholic extract (PtR2), showed strong antiangiogenic effect with minimal adverse viability impacts. Over 80% of embryos showed more than 50% inhibition in their ISV development at 20 and 40 μg/mL. PtR2 at 20 μg/mL substantially reduced human umbilical vein endothelial cell (HUVEC) migration up to 40%, considerable destruction of the formed tubes in the tube formation and microvasculature in CAM assays. Immunocytochemistry showed a marked reduction in vascular endothelial cadherin (VE-cadherin) abundance at cell junctions concurrent with substantial reduction of phospho-Akt (p-Akt) and β-catenin protein expressions. Phytochemical profile of PtR2 showed a rich source of cardenolide structures, including ghalakinoside, calactin and calotropin derivatives.
Conclusion
Thus, the
P. tomentosa
cardenolide-rich fraction (PtR2) may hold a considerable promise for an antiangiogenic impact by impairment of endothelial cell (EC) migration and viability.
Graphical abstract</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>32607956</pmid><doi>10.1007/s40199-020-00356-7</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-8854-2626</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Springer Nature - Complete Springer Journals; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Animal genetic engineering Antineoplastic agents Biomedical and Life Sciences Biomedicine Endothelium Medicinal Chemistry Metabolites Pharmaceutical Sciences/Technology Pharmacology/Toxicology Research Article |
| title | Cardenolide-rich fraction of Pergularia tomentosa as a novel Antiangiogenic agent mainly targeting endothelial cell migration |
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