{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T06:59:51Z","timestamp":1773212391296,"version":"3.50.1"},"reference-count":41,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2015,4,30]],"date-time":"2015-04-30T00:00:00Z","timestamp":1430352000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Renealmia alpinia (Rottb.) MAAS, obtained by micropropagation (in vitro) and wild forms have previously been shown to inhibit some toxic activities of Bothrops asper snake venom if preincubated before injection. In this study, assays were performed in a murine model in which extracts were administered for three days before venom injection.  R. alpinia extracts inhibited lethal activity of B. asper venom injected by intraperitoneal route. Median Effective Dose (ED50) values were 36.6 \u00b1 3.2 mg\/kg and 31.7 \u00b1 5.4 mg\/kg  (p &gt; 0.05) for R. alpinia wild and in vitro extracts, respectively. At a dose of 75 mg\/kg, both extracts totally inhibited the lethal activity of the venom. Moreover, this dose prolonged survival time of mice receiving a lethal dose of venom by the intravenous route. At 75 mg\/kg, both extracts of R. alpinia reduced the extent of venom-induced pulmonary hemorrhage by 48.0% (in vitro extract) and 34.7% (wild extract), in agreement with histological observations of lung tissue. R. alpinia extracts also inhibited hemorrhage in heart and kidneys, as evidenced by a decrease in mg of hemoglobin\/g of organ. These results suggest the possibility of using R. alpinia as a prophylactic agent in snakebite, a hypothesis that needs to be further explored.<\/jats:p>","DOI":"10.3390\/toxins7051532","type":"journal-article","created":{"date-parts":[[2015,4,30]],"date-time":"2015-04-30T08:58:53Z","timestamp":1430384333000},"page":"1532-1543","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Extracts of Renealmia alpinia (Rottb.) MAAS Protect against Lethality and Systemic Hemorrhage Induced by Bothrops asper Venom: Insights from a Model with Extract Administration before Venom Injection"],"prefix":"10.3390","volume":"7","author":[{"given":"Arley","family":"Pati\u00f1o","sequence":"first","affiliation":[{"name":"Food and Pharmaceutical Sciences Faculty, Pharmacy Department, University of Antioquia UdeA, Street 70 N\u00b0 52-21, Medell\u00edn 050010, Colombia"},{"name":"Ophidism\/Scorpionism Program, Food and Pharmaceutical Sciences Faculty,  University of Antioquia UdeA, Street 70 N\u00b0 52-21, Medell\u00edn 050010, Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7923-9158","authenticated-orcid":false,"given":"Juan","family":"Quintana","sequence":"additional","affiliation":[{"name":"School of Medicine, Universidad Cooperativa de Colombia, Sede Medell\u00edn, Street 50 A N\u00b0 41-20, Medell\u00edn 050010, Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8385-3081","authenticated-orcid":false,"given":"Jos\u00e9","family":"Guti\u00e9rrez","sequence":"additional","affiliation":[{"name":"Clodomiro Picado Institute, Microbiology Faculty, University of Costa Rica, Dulce Nombre, V\u00e1zquez de Coronado, San Jos\u00e9 11103, Costa Rica"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra","family":"Rucavado","sequence":"additional","affiliation":[{"name":"Clodomiro Picado Institute, Microbiology Faculty, University of Costa Rica, Dulce Nombre, V\u00e1zquez de Coronado, San Jos\u00e9 11103, Costa Rica"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dora","family":"Benjumea","sequence":"additional","affiliation":[{"name":"Food and Pharmaceutical Sciences Faculty, Pharmacy Department, University of Antioquia UdeA, Street 70 N\u00b0 52-21, Medell\u00edn 050010, Colombia"},{"name":"Ophidism\/Scorpionism Program, Food and Pharmaceutical Sciences Faculty,  University of Antioquia UdeA, Street 70 N\u00b0 52-21, Medell\u00edn 050010, Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaime","family":"Perea\u00f1ez","sequence":"additional","affiliation":[{"name":"Food and Pharmaceutical Sciences Faculty, Pharmacy Department, University of Antioquia UdeA, Street 70 N\u00b0 52-21, Medell\u00edn 050010, Colombia"},{"name":"Ophidism\/Scorpionism Program, Food and Pharmaceutical Sciences Faculty,  University of Antioquia UdeA, Street 70 N\u00b0 52-21, Medell\u00edn 050010, Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2015,4,30]]},"reference":[{"key":"ref_1","first-page":"80","article-title":"Snakebite envenoming from a global perspective: Towards an integrated approach","volume":"51","author":"Williams","year":"2010","journal-title":"Toxicon"},{"key":"ref_2","unstructured":"Campbell, J.A., and Lamar, W.W. (2004). The Venomous Reptiles of the Western Hemisphere, Comstock Publishing Associates."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1586\/epr.11.61","article-title":"Proteomic tools against the neglected pathology of snake bite envenoming","volume":"8","author":"Calvete","year":"2011","journal-title":"Expert Rev. Proteomics"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1016\/j.toxicon.2009.07.001","article-title":"Epidemiological, clinical and therapeutic aspects of Bothrops asper bites","volume":"54","year":"2009","journal-title":"Toxicon"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1016\/j.toxicon.2009.01.039","article-title":"Experimental pathophysiology of systemic alterations induced by Bothrops asper snake venom","volume":"54","author":"Escalante","year":"2009","journal-title":"Toxicon"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/0041-0101(96)83647-6","article-title":"The serum\u2014Therapie was discovered 100 years ago","volume":"34","author":"Bon","year":"1996","journal-title":"Toxicon"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1016\/S0041-0101(98)00145-7","article-title":"Neutralization of local tissue damage induced by Bothrops asper (terciopelo) snake venom","volume":"36","author":"Rojas","year":"1998","journal-title":"Toxicon"},{"key":"ref_8","unstructured":"WHO (2007). Rabies and Envenomings: A Neglected Public Health Issue: Report of a Consultative Meeting, WHO."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2625","DOI":"10.2174\/092986705774370655","article-title":"Medicinal plants with inhibitory properties against snake venoms","volume":"12","author":"Soares","year":"2005","journal-title":"Curr. Med. Chem."},{"key":"ref_10","unstructured":"Villalobos, G. (1994). Plantas Comestibles en dos Comunidades de la Sierra Norte de Puebla: Xochitl\u00e1n de Vicente Su\u00e1rez y Zapotitl\u00e1n de M\u00e9ndez. [Tesis de Licenciatura, Universidad Nacional Aut\u00f3noma de M\u00e9xico]."},{"key":"ref_11","unstructured":"Acero, L.E. (1979). Principales Plantas \u00datiles de la Amazonia Colombiana, Editora Guadalupe. [Primera ed.]."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Standley, P.C., and Steyermark, J.A. (1952). Flora of Guatemala, Chicago Natural History Museum. Fieldiana: Botany Vol 24, part III.","DOI":"10.5962\/bhl.title.2255"},{"key":"ref_13","unstructured":"Otero, R., Fonnegra, R., and Jim\u00e9nez, S.L. (2000). Plantas Utilizadas Contra Mordeduras de Serpientes en Antioquia y Choc\u00f3, Colombia, Granda-color. [Primera ed.]."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1590\/S0100-879X2004000700005","article-title":"Neutralization of the edema-forming, defibrinating and coagulant effects of Bothrops asper venom by extracts of plants used by healers in Colombia","volume":"37","author":"Otero","year":"2004","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/S0378-8741(00)00243-9","article-title":"Snakebites and ethnobotany in the northwest regi\u00f3n of Colombia. Part I: Traditional use of plants","volume":"71","author":"Otero","year":"2000","journal-title":"J. Ethnopharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/S0378-8741(00)00321-4","article-title":"Snakebites and ethnobotany in the northwest regi\u00f3n of Colombia. Part III: Neutralization of the haemorrhagic effect of Bothrops atrox venom","volume":"73","author":"Otero","year":"2000","journal-title":"J. Ethnopharmacol."},{"key":"ref_17","first-page":"61","article-title":"Propagaci\u00f3n in vitro de Renealmia alpinia (Rottb), planta con actividad antiof\u00eddica","volume":"15","author":"Quintana","year":"2008","journal-title":"Vitae"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"75","DOI":"10.17533\/udea.vitae.4979","article-title":"Antiophidian properties evaluation of ethanol extract and fractions obtained from Renealmia alpinia (Rottb) Mass (Zingiberaceae) cultivated in vitro","volume":"17","author":"Ortiz","year":"2010","journal-title":"Vitae"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1016\/j.jep.2014.08.002","article-title":"Inhibition of the toxic effects of Bothrops asper venom by pinostrobin, a flavanone isolated from Renealmia alpinia (Rottb.) MAAS","volume":"155","author":"Benjumea","year":"2014","journal-title":"J. Ethnopharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1016\/j.jep.2013.07.033","article-title":"Inhibition of venom serine proteinase and metalloproteinase activities by Renealmia alpinia (Zingiberaceae) extracts: Comparison of wild and in vitro propagated plants","volume":"149","author":"Benjumea","year":"2013","journal-title":"J. Ethnopharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0003-9861(03)00385-0","article-title":"Characterization of \u201cbasparin A\u201d, a prothrombin-activating metalloproteinase, from the venom of the snake Bothrops asper that inhibits platelet aggregation and induces defibrination and thrombosis","volume":"418","author":"Rucavado","year":"2003","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/S0041-0101(99)00127-0","article-title":"Purification and characterization of BaH4, a hemorrhagic metalloproteinase from the venom of the snake Bothrops asper","volume":"38","author":"Franceschi","year":"2000","journal-title":"Toxicon"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1016\/S0041-0101(97)00012-3","article-title":"Systemic hemorrhage induced by proteinase H from Crotalus adamanteus (eastern diamondback rattlesnake) venom","volume":"35","author":"Anderson","year":"1997","journal-title":"Toxicon"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1016\/0041-0101(91)90207-8","article-title":"Systemic haemorrhage in rats induced by a haemorrhagic fraction from Bothrops jararaca venom","volume":"29","author":"Kamiguti","year":"1991","journal-title":"Toxicon"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S0041-008X(03)00337-5","article-title":"Pulmonary hemorrhage induced by jararhagin, a metalloproteinase from Bothrops jararaca venom","volume":"193","author":"Escalante","year":"2003","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_26","unstructured":"Rosenberg, P. (1978). Toxins: Animal, Plant and Microbial, Pergamon Press."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1016\/j.toxicon.2005.02.012","article-title":"Structural considerations of the snake venom metalloproteinases, key members of the M12 reprolysin family of metalloproteinases","volume":"45","author":"Fox","year":"2005","journal-title":"Toxicon"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1016\/j.toxicon.2005.02.029","article-title":"Hemorrhage induced by snake venom metalloproteinases: Biochemical and biophysical mechanisms involved in microvessel damage","volume":"45","author":"Rucavado","year":"2005","journal-title":"Toxicon"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1016\/j.toxicon.2005.02.026","article-title":"Platelets as targets of snake venom metalloproteinases","volume":"45","author":"Kamiguti","year":"2005","journal-title":"Toxicon"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/0304-4165(94)90172-4","article-title":"Ineffectiveness of the inhibition of the main haemorrhagic metalloproteinase from Bothrops jararaca venom by its only plasma inhibtor, a2-macroglobulin","volume":"1200","author":"Kamiguti","year":"1994","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1160\/TH05-02-0112","article-title":"Thrombocytopenia and platelet hypoggregation induced by Bothrops asper snake venom: Toxins involved and their contribution to metalloproteinase-induced pulmonary hemorrhage","volume":"94","author":"Rucavado","year":"2005","journal-title":"Thromb. Haemost."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1002\/ffj.2730060113","article-title":"On the characterization of some terpenes from Renealmia alpinia Rottb. (Maas) Oleoresin","volume":"6","author":"Lognay","year":"1991","journal-title":"Flavour Frag. J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1021\/np990055i","article-title":"A new labdane diterpenoid from Renealmia alpinia collected in the Suriname rainforest","volume":"62","author":"Yang","year":"1999","journal-title":"J. Nat. Prod."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1021\/np970233c","article-title":"Bioactive labdane diterpenoids from Renealmia alpinia collected in the Suriname rainforest","volume":"60","author":"Zhou","year":"1997","journal-title":"J. Nat. Prod."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/S0162-0134(02)00511-1","article-title":"Iron and copper chelation by flavonoids: An electrospray mass spectrometry study","volume":"92","author":"Fernandez","year":"2002","journal-title":"J. Inorg. Biochem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1080\/1071576021000016463","article-title":"Interactions of flavonoids with iron and copper ions: A mechanism for their antioxidant activity","volume":"36","author":"Mira","year":"2002","journal-title":"Free Radic. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.toxicon.2007.03.024","article-title":"Triterpenoid saponins, new metalloprotease snake venom inhibitors isolated from Pentaclethra macroloba","volume":"50","author":"Fernandes","year":"2007","journal-title":"Toxicon"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3781","DOI":"10.2174\/1381612043382684","article-title":"Coumarin and isocoumarin as serine protease inhibitors","volume":"10","author":"Pochet","year":"2004","journal-title":"Curr. Pharm. Des."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1716","DOI":"10.1248\/bpb.33.1716","article-title":"Isofraxidin, a coumarin component from Acanthopanax senticosus, inhibits matrix metalloproteinase-7 expression and cell invasion of human hepatoma cells","volume":"33","author":"Yamazaki","year":"2010","journal-title":"Biol. Pharm. Bull."},{"key":"ref_40","first-page":"365","article-title":"Evaluation of the inhibitory effect of extracts from leaves of Renealmia alpinia Rottb. Maas (Zingiberaceae) on the venom of Bothrops asper (mapan\u00e1)","volume":"32","author":"Quintana","year":"2012","journal-title":"Biomedica"},{"key":"ref_41","unstructured":"Finney, D.J. (1971). Probit Analysis, Cambridge University Press. [3rd ed.]."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/7\/5\/1532\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:45:37Z","timestamp":1760215537000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/7\/5\/1532"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,4,30]]},"references-count":41,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2015,5]]}},"alternative-id":["toxins7051532"],"URL":"https:\/\/doi.org\/10.3390\/toxins7051532","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,4,30]]}}}