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Zebrafish bioassay-guided microfractionation identifies anticonvulsant steroid glycosides from the Philippine medicinal plant Solanum torvum

Challal, Soura and Buenafe, Olivia Erin M and Queiroz, Emerson Ferreira and Maljevic, Snezana and Marcourt, Laurence and Bock, Merle and Kloeti, Werner and Dayrit, Fabian Millar and Harvey, Alan L and Lerche, Holger and Esguerra, Camila V and de Witte, Peter A M and Wolfender, Jean-Luc and Crawford, Alexander D (2014) Zebrafish bioassay-guided microfractionation identifies anticonvulsant steroid glycosides from the Philippine medicinal plant Solanum torvum. ACS Chemical Neuroscience, 5 (10). pp. 993-1004. ISSN 1948-7193

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    Medicinal plants used for the treatment of epilepsy are potentially a valuable source of novel anti-epileptic 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 on-line 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.