{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:57:16Z","timestamp":1787029036057,"version":"build-2736575974"},"reference-count":52,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2014,5,6]],"date-time":"2014-05-06T00:00:00Z","timestamp":1399334400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Snakebite is a neglected disease and serious health problem in Brazil, with most bites being caused by snakes of the genus Bothrops. Although serum therapy is the primary treatment for systemic envenomation, it is generally ineffective in neutralizing the local effects of these venoms. In this work, we examined the ability of 7,8,3'-trihydroxy-4'-methoxyisoflavone (TM), an isoflavone from Dipteryx alata, to neutralize the neurotoxicity (in mouse phrenic nerve-diaphragm preparations) and myotoxicity (assessed by light microscopy) of Bothrops jararacussu snake venom in vitro. The toxicity of TM was assessed using the Salmonella microsome assay (Ames test). Incubation with TM alone (200 \u03bcg\/mL) did not alter the muscle twitch tension whereas incubation with venom  (40 \u03bcg\/mL) caused irreversible paralysis. Preincubation of TM (200 \u03bcg\/mL) with venom attenuated the venom-induced neuromuscular blockade by 84% \u00b1 5% (mean \u00b1 SEM;  n = 4). The neuromuscular blockade caused by bothropstoxin-I (BthTX-I), the major myotoxic PLA2 of this venom, was also attenuated by TM. Histological analysis of diaphragm muscle incubated with TM showed that most fibers were preserved (only  9.2% \u00b1 1.7% were damaged; n = 4) compared to venom alone (50.3% \u00b1 5.4% of fibers damaged; n = 3), and preincubation of TM with venom significantly attenuated the  venom-induced damage (only 17% \u00b1 3.4% of fibers damaged; n = 3; p &lt; 0.05 compared to venom alone). TM showed no mutagenicity in the Ames test using Salmonella strains TA98 and TA97a with (+S9) and without (\u2212S9) metabolic activation. These findings indicate that TM is a potentially useful compound for antagonizing the neuromuscular effects (neurotoxicity and myotoxicity) of B. jararacussu venom.<\/jats:p>","DOI":"10.3390\/molecules19055790","type":"journal-article","created":{"date-parts":[[2014,5,6]],"date-time":"2014-05-06T11:18:15Z","timestamp":1399375095000},"page":"5790-5805","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["An Isoflavone from Dipteryx alata Vogel is Active against the  in Vitro Neuromuscular Paralysis of Bothrops jararacussu Snake Venom and Bothropstoxin I, and Prevents  Venom-Induced Myonecrosis"],"prefix":"10.3390","volume":"19","author":[{"given":"Miri\u00e9le","family":"Ferraz","sequence":"first","affiliation":[{"name":"Post-Graduate Program in Pharmaceutical Sciences, University of Sorocaba (UNISO),  Rodovia Raposo Tavares, Km 92.5, 18023-000 Sorocaba, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edson","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Post-Graduate Program in Pharmaceutical Sciences, University of Sorocaba (UNISO),  Rodovia Raposo Tavares, Km 92.5, 18023-000 Sorocaba, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"Tavares","sequence":"additional","affiliation":[{"name":"Post-Graduate Program in Technological and Environmental Processes,  University of Sorocaba (UNISO), Rodovia Raposo Tavares, Km 92.5,  18023-000 Sorocaba, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Cogo","sequence":"additional","affiliation":[{"name":"Serpentarium of the Vale do Para\u00edba University (CEN\u2014UNIVAP), Av Shishima Hifumi 2911, 12244-000 S\u00e3o Jos\u00e9 dos Campos, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ad\u00e9lia","family":"Cintra","sequence":"additional","affiliation":[{"name":"Department of Clinical, Toxicological and Bromatological Analysis,  Faculty of Pharmaceutical Sciences, S\u00e3o Paulo University (USP), Via do Caf\u00e9 S\/N,  14040-903 Ribeir\u00e3o Preto, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ch\u00e1riston","family":"Dal Belo","sequence":"additional","affiliation":[{"name":"LANETOX, Federal University of Pampa (UNIPAMPA), Avenida Antonio Trilha 1847,  97300-000 S\u00e3o Gabriel, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiz","family":"Franco","sequence":"additional","affiliation":[{"name":"Methodist University of Piracicaba, Rodovia do A\u00e7ucar, Km 156, 13423-170 Piracicaba, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e1rcio","family":"Dos Santos","sequence":"additional","affiliation":[{"name":"Post-Graduate Course in Environmental Sciences, Federal University of Tocantins (UFT),  Av NS 15 ALC NO 14, 109 Norte, 77001-090 Palmas, TO, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fl\u00e1via","family":"Resende","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, S\u00e3o Paulo State University (UNESP), Rodovia Araraquara-Jau, Km 1, 14801-902 Araraquara, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliana","family":"Varanda","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, S\u00e3o Paulo State University (UNESP), Rodovia Araraquara-Jau, Km 1, 14801-902 Araraquara, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Hyslop","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medical Sciences,  State University of Campinas (UNICAMP), Rua Tess\u00e1lia Vieira de Camargo, 126,  13083-887 Campinas, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar","family":"Puebla","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Salamanca University, CIETUS, IBSAL,  Salamanca 37007, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0578-0611","authenticated-orcid":false,"given":"Arturo","family":"San Feliciano","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Salamanca University, CIETUS, IBSAL,  Salamanca 37007, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Oshima-Franco","sequence":"additional","affiliation":[{"name":"Post-Graduate Program in Pharmaceutical Sciences, University of Sorocaba (UNISO),  Rodovia Raposo Tavares, Km 92.5, 18023-000 Sorocaba, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2014,5,6]]},"reference":[{"key":"ref_1","first-page":"709","article-title":"Snakebites in central and south america: Epidemiology, clinical features and clinical management","volume":"Volume 2","author":"Campbell","year":"2004","journal-title":"The Venomous Reptiles of the Western Hemisphere"},{"key":"ref_2","unstructured":"Campbell, J.A., and Lamar, W.W. 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