Zebrafish Bioassay-Guided Microfractionation Identifies Anticonvulsant Steroid Glycosides from the Philippine Medicinal Plant Solanum torvum

Medicinal plants used for the treatment of epilepsy are potentially a valuable source of novel antiepileptic small molecules. To identify anticonvulsant secondary metabolites, we performed an in vivo, zebrafish-based screen of medicinal plants used in Southeast Asia for the treatment of seizures. So...

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Main Authors: Challal, Soura, Buenafe, Olivia Erin M, Quiroz, Emerson F, Maljevic, Snezana, Marcourt, Laurence, Bock, Merle, Kloeti, Werner, Dayrit, Fabian M, Harvey, Alan L, Lerche, Holger, Esguerra, Camila V, de Witte, Peter A M, Wolfender, Jean-Luc, Crawford, Alexander D
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Published: Archīum Ateneo 2014
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Online Access:https://archium.ateneo.edu/chemistry-faculty-pubs/111
https://pubs.acs.org/doi/abs/10.1021/cn5001342
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spelling ph-ateneo-arc.chemistry-faculty-pubs-11102020-07-27T08:09:15Z Zebrafish Bioassay-Guided Microfractionation Identifies Anticonvulsant Steroid Glycosides from the Philippine Medicinal Plant Solanum torvum Challal, Soura Buenafe, Olivia Erin M Quiroz, Emerson F Maljevic, Snezana Marcourt, Laurence Bock, Merle Kloeti, Werner Dayrit, Fabian M Harvey, Alan L Lerche, Holger Esguerra, Camila V de Witte, Peter A M Wolfender, Jean-Luc Crawford, Alexander D Medicinal plants used for the treatment of epilepsy are potentially a valuable source of novel antiepileptic small molecules. To identify anticonvulsant secondary metabolites, we performed an in vivo, zebrafish-based screen of medicinal plants used in Southeast Asia for the treatment of seizures. Solanum torvum Sw. (Solanaceae) was identified as having significant anticonvulsant activity in zebrafish larvae with seizures induced by the GABAA antagonist pentylenetetrazol (PTZ). This finding correlates well with the ethnomedical use of this plant in the Philippines, where a water decoction of S. torvum leaves is used to treat epileptic seizures. HPLC microfractionation of the bioactive crude extract, in combination with the in vivo zebrafish seizure assay, enabled the rapid localization of several bioactive compounds that were partially identified online by UHPLC-TOF-MS as steroid glycosides. Targeted isolation of the active constituents from the methanolic extract enabled the complete de novo structure identification of the six main bioactive compounds that were also present in the traditional preparation. To partially mimic the in vivo metabolism of these triterpene glycosides, their common aglycone was generated by acid hydrolysis. The isolated molecules exhibited significant anticonvulsant activity in zebrafish seizure assays. These results underscore the potential of zebrafish bioassay-guided microfractionation to rapidly identify novel bioactive small molecules of natural origin. 2014-01-01T08:00:00Z text https://archium.ateneo.edu/chemistry-faculty-pubs/111 https://pubs.acs.org/doi/abs/10.1021/cn5001342 Chemistry Faculty Publications Archīum Ateneo Zebrafish HPLC microfractionation Solanum torvum Solanaceae saponins antiepileptic activity Chemistry Medicinal and Pharmaceutical Chemistry
institution Ateneo De Manila University
building Ateneo De Manila University Library
country Philippines
collection archium.Ateneo Institutional Repository
topic Zebrafish HPLC microfractionation Solanum torvum Solanaceae saponins antiepileptic activity
Chemistry
Medicinal and Pharmaceutical Chemistry
spellingShingle Zebrafish HPLC microfractionation Solanum torvum Solanaceae saponins antiepileptic activity
Chemistry
Medicinal and Pharmaceutical Chemistry
Challal, Soura
Buenafe, Olivia Erin M
Quiroz, Emerson F
Maljevic, Snezana
Marcourt, Laurence
Bock, Merle
Kloeti, Werner
Dayrit, Fabian M
Harvey, Alan L
Lerche, Holger
Esguerra, Camila V
de Witte, Peter A M
Wolfender, Jean-Luc
Crawford, Alexander D
Zebrafish Bioassay-Guided Microfractionation Identifies Anticonvulsant Steroid Glycosides from the Philippine Medicinal Plant Solanum torvum
description Medicinal plants used for the treatment of epilepsy are potentially a valuable source of novel antiepileptic small molecules. To identify anticonvulsant secondary metabolites, we performed an in vivo, zebrafish-based screen of medicinal plants used in Southeast Asia for the treatment of seizures. Solanum torvum Sw. (Solanaceae) was identified as having significant anticonvulsant activity in zebrafish larvae with seizures induced by the GABAA antagonist pentylenetetrazol (PTZ). This finding correlates well with the ethnomedical use of this plant in the Philippines, where a water decoction of S. torvum leaves is used to treat epileptic seizures. HPLC microfractionation of the bioactive crude extract, in combination with the in vivo zebrafish seizure assay, enabled the rapid localization of several bioactive compounds that were partially identified online by UHPLC-TOF-MS as steroid glycosides. Targeted isolation of the active constituents from the methanolic extract enabled the complete de novo structure identification of the six main bioactive compounds that were also present in the traditional preparation. To partially mimic the in vivo metabolism of these triterpene glycosides, their common aglycone was generated by acid hydrolysis. The isolated molecules exhibited significant anticonvulsant activity in zebrafish seizure assays. These results underscore the potential of zebrafish bioassay-guided microfractionation to rapidly identify novel bioactive small molecules of natural origin.
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author Challal, Soura
Buenafe, Olivia Erin M
Quiroz, Emerson F
Maljevic, Snezana
Marcourt, Laurence
Bock, Merle
Kloeti, Werner
Dayrit, Fabian M
Harvey, Alan L
Lerche, Holger
Esguerra, Camila V
de Witte, Peter A M
Wolfender, Jean-Luc
Crawford, Alexander D
author_facet Challal, Soura
Buenafe, Olivia Erin M
Quiroz, Emerson F
Maljevic, Snezana
Marcourt, Laurence
Bock, Merle
Kloeti, Werner
Dayrit, Fabian M
Harvey, Alan L
Lerche, Holger
Esguerra, Camila V
de Witte, Peter A M
Wolfender, Jean-Luc
Crawford, Alexander D
author_sort Challal, Soura
title Zebrafish Bioassay-Guided Microfractionation Identifies Anticonvulsant Steroid Glycosides from the Philippine Medicinal Plant Solanum torvum
title_short Zebrafish Bioassay-Guided Microfractionation Identifies Anticonvulsant Steroid Glycosides from the Philippine Medicinal Plant Solanum torvum
title_full Zebrafish Bioassay-Guided Microfractionation Identifies Anticonvulsant Steroid Glycosides from the Philippine Medicinal Plant Solanum torvum
title_fullStr Zebrafish Bioassay-Guided Microfractionation Identifies Anticonvulsant Steroid Glycosides from the Philippine Medicinal Plant Solanum torvum
title_full_unstemmed Zebrafish Bioassay-Guided Microfractionation Identifies Anticonvulsant Steroid Glycosides from the Philippine Medicinal Plant Solanum torvum
title_sort zebrafish bioassay-guided microfractionation identifies anticonvulsant steroid glycosides from the philippine medicinal plant solanum torvum
publisher Archīum Ateneo
publishDate 2014
url https://archium.ateneo.edu/chemistry-faculty-pubs/111
https://pubs.acs.org/doi/abs/10.1021/cn5001342
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