Characterization of the most promising fraction of Swietenia macrophylla active against myotoxic phospholipases A2: identification of catechin as one of the active compounds
Background: The pharmacological effects produced by snakebite accidents involve the actions of several enzymes, of which those of the phospholipases A2 (PLA2) exhibit a wide variety of effects such as edema and myotoxicity. Some plant extracts have been antagonists of crude snake venoms and toxins....
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Universidad de Antioquia
2016
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oai:doaj.org-article:0141fb3986d2429eace944e1f3f33f512021-11-19T04:09:42ZCharacterization of the most promising fraction of Swietenia macrophylla active against myotoxic phospholipases A2: identification of catechin as one of the active compounds0121-40042145-2660https://doaj.org/article/0141fb3986d2429eace944e1f3f33f512016-09-01T00:00:00Zhttps://revistas.udea.edu.co/index.php/vitae/article/view/25960https://doaj.org/toc/0121-4004https://doaj.org/toc/2145-2660 Background: The pharmacological effects produced by snakebite accidents involve the actions of several enzymes, of which those of the phospholipases A2 (PLA2) exhibit a wide variety of effects such as edema and myotoxicity. Some plant extracts have been antagonists of crude snake venoms and toxins. Based on promising bioactivity, Swietenia macrophylla King was selected for further studies. Objective: The purpose of this study was to identify the PLA2 inhibitors present in the crude extract of S. macrophylla that could be promising leads in neutralizing the local effects of ophidian accidents. Methods: Bioassay-guided fractionation of the ethanolic extract of the leaves of S. macrophylla lead to the detection of (+)-catechin, characterized through gas chromatography coupled with mass spectrometry (GC-MS), and confirmed by HPLC. The PLA2 inhibitory activity was measured with the Dole method and a spectrophotometric assay with 4-Nitro-3-octanoyloxy-benzoic acid (4N3OBA). Cytotoxicity was done on C2C12 murine myoblast. Results: Fraction F5 and (+)-Catechin inhibited the PLA2 activity of B. asper venom, in a dose-dependent way. In addition, (+)-Catechin showed an inhibition level of 83.1 ± 3.1 % of the enzymatic activity of one PLA2 purified from the venom of Crotalus durissus cumanensis using 4N3OBA as substrate. Also the ethanolic extract and fraction F5 showed inhibition of the cytotoxicity induced by the Bothrops atrox venom and their Lys 49 PLA2 (80 and 100% respectively). Molecular docking results suggested that that OH from 4´ and 5’ carbons of (+)-catechin could form hydrogen bonds with carboxylate moiety of residue Asp49, while OH from 5 could form a hydrogen bond with Asn 6. Additional Van der Waals interactions were also proposed. Conclusion: Swietenia macrophylla exhibited strong inhibitory activity against PLA2s enzymes. Catechin, the most abundant metabolite in the active fraction F5, is proposed as one of the compounds responsible for the bioactivity. Lina PRECIADOJaime Andrés PEREAÑEZVitelbina NUÑEZTatiana LOBO-ECHEVERRIUniversidad de AntioquiaarticleSwietenia macrophyllacatechinmolecular docking simulationsnakebiteViperidaeFood processing and manufactureTP368-456Pharmaceutical industryHD9665-9675ENVitae, Vol 23, Iss 2 (2016) |
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Swietenia macrophylla catechin molecular docking simulation snakebite Viperidae Food processing and manufacture TP368-456 Pharmaceutical industry HD9665-9675 |
| spellingShingle |
Swietenia macrophylla catechin molecular docking simulation snakebite Viperidae Food processing and manufacture TP368-456 Pharmaceutical industry HD9665-9675 Lina PRECIADO Jaime Andrés PEREAÑEZ Vitelbina NUÑEZ Tatiana LOBO-ECHEVERRI Characterization of the most promising fraction of Swietenia macrophylla active against myotoxic phospholipases A2: identification of catechin as one of the active compounds |
| description |
Background: The pharmacological effects produced by snakebite accidents involve the actions of several enzymes, of which those of the phospholipases A2 (PLA2) exhibit a wide variety of effects such as edema and myotoxicity. Some plant extracts have been antagonists of crude snake venoms and toxins. Based on promising bioactivity, Swietenia macrophylla King was selected for further studies. Objective: The purpose of this study was to identify the PLA2 inhibitors present in the crude extract of S. macrophylla that could be promising leads in neutralizing the local effects of ophidian accidents. Methods: Bioassay-guided fractionation of the ethanolic extract of the leaves of S. macrophylla lead to the detection of (+)-catechin, characterized through gas chromatography coupled with mass spectrometry (GC-MS), and confirmed by HPLC. The PLA2 inhibitory activity was measured with the Dole method and a spectrophotometric assay with 4-Nitro-3-octanoyloxy-benzoic acid (4N3OBA). Cytotoxicity was done on C2C12 murine myoblast. Results: Fraction F5 and (+)-Catechin inhibited the PLA2 activity of B. asper venom, in a dose-dependent way. In addition, (+)-Catechin showed an inhibition level of 83.1 ± 3.1 % of the enzymatic activity of one PLA2 purified from the venom of Crotalus durissus cumanensis using 4N3OBA as substrate. Also the ethanolic extract and fraction F5 showed inhibition of the cytotoxicity induced by the Bothrops atrox venom and their Lys 49 PLA2 (80 and 100% respectively). Molecular docking results suggested that that OH from 4´ and 5’ carbons of (+)-catechin could form hydrogen bonds with carboxylate moiety of residue Asp49, while OH from 5 could form a hydrogen bond with Asn 6. Additional Van der Waals interactions were also proposed. Conclusion: Swietenia macrophylla exhibited strong inhibitory activity against PLA2s enzymes. Catechin, the most abundant metabolite in the active fraction F5, is proposed as one of the compounds responsible for the bioactivity.
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article |
| author |
Lina PRECIADO Jaime Andrés PEREAÑEZ Vitelbina NUÑEZ Tatiana LOBO-ECHEVERRI |
| author_facet |
Lina PRECIADO Jaime Andrés PEREAÑEZ Vitelbina NUÑEZ Tatiana LOBO-ECHEVERRI |
| author_sort |
Lina PRECIADO |
| title |
Characterization of the most promising fraction of Swietenia macrophylla active against myotoxic phospholipases A2: identification of catechin as one of the active compounds |
| title_short |
Characterization of the most promising fraction of Swietenia macrophylla active against myotoxic phospholipases A2: identification of catechin as one of the active compounds |
| title_full |
Characterization of the most promising fraction of Swietenia macrophylla active against myotoxic phospholipases A2: identification of catechin as one of the active compounds |
| title_fullStr |
Characterization of the most promising fraction of Swietenia macrophylla active against myotoxic phospholipases A2: identification of catechin as one of the active compounds |
| title_full_unstemmed |
Characterization of the most promising fraction of Swietenia macrophylla active against myotoxic phospholipases A2: identification of catechin as one of the active compounds |
| title_sort |
characterization of the most promising fraction of swietenia macrophylla active against myotoxic phospholipases a2: identification of catechin as one of the active compounds |
| publisher |
Universidad de Antioquia |
| publishDate |
2016 |
| url |
https://doaj.org/article/0141fb3986d2429eace944e1f3f33f51 |
| work_keys_str_mv |
AT linapreciado characterizationofthemostpromisingfractionofswieteniamacrophyllaactiveagainstmyotoxicphospholipasesa2identificationofcatechinasoneoftheactivecompounds AT jaimeandrespereanez characterizationofthemostpromisingfractionofswieteniamacrophyllaactiveagainstmyotoxicphospholipasesa2identificationofcatechinasoneoftheactivecompounds AT vitelbinanunez characterizationofthemostpromisingfractionofswieteniamacrophyllaactiveagainstmyotoxicphospholipasesa2identificationofcatechinasoneoftheactivecompounds AT tatianaloboecheverri characterizationofthemostpromisingfractionofswieteniamacrophyllaactiveagainstmyotoxicphospholipasesa2identificationofcatechinasoneoftheactivecompounds |
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