{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T12:01:39Z","timestamp":1773144099849,"version":"3.50.1"},"reference-count":45,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2019,3,6]],"date-time":"2019-03-06T00:00:00Z","timestamp":1551830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["245416\/2012-9"],"award-info":[{"award-number":["245416\/2012-9"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Endopleura uchi (Huber) Cuatrec (Humiriaceae), known as uxi or uxi-amarelo in Brazil, is an endemic tree of the Amazon forest. In traditional medicine, its stem bark is used to treat a variety of health disorders, including cancer, diabetes, arthritis, uterine inflammation, and gynecological infections. According to HPLC analysis, the main constituent of the bark extract is the polyphenol bergenin. In the current study, we demonstrate by in vitro and in vivo experiments the antioxidant potential of a water extract from the stem bark of E. uchi. When tested in the model organism Caenorhabditis elegans, the extract enhanced stress resistance via the DAF-16\/FOXO pathway. Additionally, the extract promoted an increase in the lifespan of the worms independent from caloric restriction. It also attenuated the age-related muscle function decline and formation of polyQ40 plaques, as a model for Huntington\u2019s disease. Thus, these data support anti-aging and anti-oxidant properties of E. uchi, which has not yet been described. More studies are needed to assess the real benefits of E. uchi bark for human health and its toxicological profile.<\/jats:p>","DOI":"10.3390\/molecules24050915","type":"journal-article","created":{"date-parts":[[2019,3,7]],"date-time":"2019-03-07T10:52:22Z","timestamp":1551955942000},"page":"915","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Bark Extract of the Amazonian Tree Endopleura uchi (Humiriaceae) Extends Lifespan and Enhances Stress Resistance in Caenorhabditis elegans"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5538-0141","authenticated-orcid":false,"given":"Herbenya","family":"Peixoto","sequence":"first","affiliation":[{"name":"Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, INF 364, D-69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariana","family":"Roxo","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, INF 364, D-69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emerson","family":"Silva","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Science, Federal University of Amazonas (UFAM), 6200 General Rodrigo, Manaus 69077-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karla","family":"Valente","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Science, Federal University of Amazonas (UFAM), 6200 General Rodrigo, Manaus 69077-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus","family":"Braun","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, INF 364, D-69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6063-8303","authenticated-orcid":false,"given":"Xiaojuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, INF 364, D-69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7875-4510","authenticated-orcid":false,"given":"Michael","family":"Wink","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, INF 364, D-69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,3,6]]},"reference":[{"key":"ref_1","unstructured":"(1986). Food and Fruit-Bearing Forest Species, 3: Examples from Latin America\/F2911, Food and Agriculture Organization."},{"key":"ref_2","unstructured":"Shanley, P. (2011). Fruit Trees and Useful Plants in Amazonian Life, Food and Agriculture Organization of the United Nations (FAO)."},{"key":"ref_3","unstructured":"Correa, M., and Penna, L.d.A. (1974). Dicionario das plantas uteis do Brasil e das exoticas cultivadas: Volume 5. MR. Rio de Janeiro: Instituto Brasiliero de Desenvolvimento Florestal 687p.-illus. Por Icones. Geog, 4."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1002\/ptr.1866","article-title":"Plants and animals utilized as medicines in the Ja\u00fa National Park (JNP), Brazilian Amazon","volume":"20","author":"Rodrigues","year":"2006","journal-title":"Phytother. Res."},{"key":"ref_5","unstructured":"Scudeller, V.V., Veiga, J.B.d., and Ara\u00fajo-Jorge, L.d. (2009). Etnoconhecimento de plantas de uso medicinal nas comunidades S\u00e3o Jo\u00e3o do Tup\u00e9 e Central (Reserva de Desenvolvimento Sustent\u00e1vel do Tup\u00e9), UEA."},{"key":"ref_6","unstructured":"Pinto, A.Z.d.L., De Assis, A.F.S., Pereira, A.G., and Pasa, M.C. (2013). Levantamento etnobot\u00e2nico de plantas medicinais comercializadas no mercado do porto em Cuiab\u00e1, Mato Grosso, Brasil. FLOVET-Boletim do Grupo de Pesquisa da Flora, Vegeta\u00e7\u00e3o e Etnobot\u00e2nica, 1."},{"key":"ref_7","unstructured":"Caetano, R.S., de Souza, A.C.R., and Feitoza, L.F. (2014). O Uso de plantas medicinais utilizadas por frequentadores dos ambulat\u00f3rios Santa Marcelina, Porto Velho-RO. Sa\u00fade e Pesquisa, 7."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/j.apjtm.2015.10.013","article-title":"Phenolic profile and biological potential of Endopleura uchi extracts","volume":"8","author":"Silva","year":"2015","journal-title":"Asian Pac. J. Trop. Med."},{"key":"ref_9","unstructured":"Bento, J.F. (2013). Caracteriza\u00e7\u00e3o de polissacar\u00eddeos e metab\u00f3licos secund\u00e1rios da casca de Endopleura uchi (Huber) cuatrec: Avalia\u00e7\u00e3o dos efeitos do decocto e de fra\u00e7\u00f5es polissacar\u00eddicas em c\u00e9lulas hela e macr\u00f3fagos. [Ph.D. Thesis, Federal University of Paran\u00e1]."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"223","DOI":"10.5897\/AJPP2014.4220","article-title":"Subchronic toxicity evaluation of the hydroethanolic extract from Endopleura uchi (Huber) Cuatrec in Wistar rats","volume":"9","author":"Lima","year":"2015","journal-title":"Afr. J. Pharm. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"187","DOI":"10.5123\/S2176-62232010000100026","article-title":"Preliminary tests on acute oral toxicity and intestinal motility with extract of pulverized bark of Endopleura uchi (Huber) Cuatrec. (Humiriaceae) in mice","volume":"1","author":"Politi","year":"2010","journal-title":"Rev. Pan-Amaz. Saude"},{"key":"ref_12","first-page":"123","article-title":"Isolamento e identifica\u00e7\u00e3o estrutural dos constituintes qu\u00edmicos de Endopleura uchi (Humiriaceae)","volume":"2","author":"Luna","year":"2000","journal-title":"Reuni\u00e3o Anual da Sociedade Brasileira de Qu\u00edmica, Minas Gerais, Brasil"},{"key":"ref_13","unstructured":"Politi, F.A.S. (2009). Estudos farmacogn\u00f3sticos e avalia\u00e7\u00e3o de atividades biol\u00f3gicas de extratos obtidos das cascas pulverizadas de Endopleura uchi (Huber) Cuatrec. (Humiriaceae). [Master\u2019s Thesis, Universidade Estadual Paulista]."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1590\/S0044-59672013000400015","article-title":"Pentacyclic triterpenes and steroids from the stem bark of uchi (Sacoglottis uchi, Humiriaceae)","volume":"43","author":"Abreu","year":"2013","journal-title":"Acta Amazonica"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2713","DOI":"10.1039\/b804385j","article-title":"Antioxidant activity of (+)-bergenin\u2014a phytoconstituent isolated from the bark of Sacoglottis uchi Huber (Humireaceae)","volume":"6","author":"Lago","year":"2008","journal-title":"Org. Biomol. Chem."},{"key":"ref_16","first-page":"1303","article-title":"Antinociceptive activity of acetylbergenin in mice","volume":"30","author":"Borges","year":"2011","journal-title":"Lat. Am. J. Pharm."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1590\/S0102-695X2012005000134","article-title":"Box-Behnken design to study the bergenin content and antioxidant activity of Endopleura uchi bark extracts obtained by dynamic maceration","volume":"23","author":"Tacon","year":"2013","journal-title":"Revista Brasileira de Farmacognosia"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Blois, M.S. (1958). Antioxidant determinations by the use of a stable free radical. Nature.","DOI":"10.1038\/1811199a0"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1590\/S0103-50532009000600009","article-title":"Characterization of bergenin in Endopleura uchi bark and its anti-inflammatory activity","volume":"20","author":"Nunomura","year":"2009","journal-title":"J. Braz. Chem. Soc."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1021\/acs.jafc.5b05812","article-title":"An anthocyanin-rich extract of acai (Euterpe precatoria Mart.) increases stress resistance and retards aging-related markers in Caenorhabditis elegans","volume":"64","author":"Peixoto","year":"2016","journal-title":"J. Agric. Food Chem."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Stiernagle, T. (2005). Maintenance of C. elegans. WormBook.","DOI":"10.1895\/wormbook.1.101.1"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Peixoto, H., Roxo, M., R\u00f6hrig, T., Richling, E., Wang, X., and Wink, M. (2017). Anti-Aging and antioxidant potential of Paullinia cupana var. sorbilis: Findings in Caenorhabditis elegans indicate a new utilization for roasted seeds of Guarana. Medicines, 4.","DOI":"10.3390\/medicines4030061"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Peixoto, H., Roxo, M., Koolen, H., da Silva, F., Silva, E., Braun, M.S., Wang, X., and Wink, M.J.M. (2018). Calycophyllum spruceanum (Benth.), the amazonian \u201ctree of youth\u201d prolongs longevity and enhances stress resistance in Caenorhabditis elegans. Molecules, 23.","DOI":"10.3390\/molecules23030534"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1749-8546-9-4","article-title":"Anti-infective and cytotoxic properties of Bupleurum marginatum","volume":"9","author":"Ashour","year":"2014","journal-title":"Chin. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1021\/np960074h","article-title":"Constituents of Ardisia japonica and their in vitro anti-HIV activity","volume":"59","author":"Piacente","year":"1996","journal-title":"J. Nat. Prod."},{"key":"ref_26","first-page":"1080","article-title":"Antiulcer activity of naturally occurring pyrano-coumarin and isocoumarins and their effect on prostanoid synthesis using human colonic mucosa","volume":"35","author":"Goel","year":"1997","journal-title":"Ind. J. Exp. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1016\/S0968-0896(02)00666-1","article-title":"Synthesis and neuroprotective activity of bergenin derivatives with antioxidant activity","volume":"11","author":"Takahashi","year":"2003","journal-title":"Bioorg. Med. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/S0378-8741(00)00260-9","article-title":"Hepatoprotective effects of bergenin, a major constituent of Mallotus japonicus, on carbon tetrachloride-intoxicated rats","volume":"72","author":"Lim","year":"2000","journal-title":"J. Ethnopharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.jep.2007.02.023","article-title":"Immunomodulatory effect of bergenin and norbergenin against adjuvant-induced arthritis\u2014A flow cytometric study","volume":"112","author":"Nazir","year":"2007","journal-title":"J. Ethnopharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1016\/j.cellbi.2009.06.018","article-title":"Juglone, a naphthoquinone from walnut, exerts cytotoxic and genotoxic effects against cultured melanoma tumor cells","volume":"33","author":"Aithal","year":"2009","journal-title":"Cell Biol. Int."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2305","DOI":"10.1096\/fj.03-0376fje","article-title":"Expression of the small heat-shock protein HSP 16-2 in Caenorhabditis elegans is suppressed by Ginkgo biloba extract EGb 761","volume":"17","author":"Strayer","year":"2003","journal-title":"FASEB J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"573","DOI":"10.18632\/aging.100058","article-title":"Heat shock proteins in long-lived worms and mice with insulin\/insulin-like signaling mutations","volume":"1","author":"Swindell","year":"2009","journal-title":"Aging"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1093\/ajcn\/81.1.215S","article-title":"Polyphenols: Antioxidants and beyond","volume":"81","author":"Scalbert","year":"2005","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.exger.2006.04.010","article-title":"Genetic control of longevity in C. elegans","volume":"42","author":"Braeckman","year":"2007","journal-title":"Exp. Gerontol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1016\/j.exger.2006.05.020","article-title":"Worming pathways to and from DAF-16\/FOXO","volume":"41","author":"Mukhopadhyay","year":"2006","journal-title":"Exp. Gerontol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1055\/s-0028-1088378","article-title":"Epigallocatechin gallate from green tea (Camellia sinensis) increases lifespan and stress resistance in Caenorhabditis elegans","volume":"75","author":"Abbas","year":"2009","journal-title":"Planta Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.tcb.2016.05.002","article-title":"Does longer lifespan mean longer healthspan?","volume":"26","author":"Hansen","year":"2016","journal-title":"Trends Cell Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1073\/pnas.1412192112","article-title":"Uncoupling lifespan and healthspan in Caenorhabditis elegans longevity mutants","volume":"112","author":"Bansal","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Cui, H., Kong, Y., and Zhang, H. (2011). Oxidative stress, mitochondrial dysfunction, and aging. J. Signal Transduct., 2012.","DOI":"10.1155\/2012\/646354"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.jff.2016.08.012","article-title":"Anthocyanin-rich extract of Acai (Euterpe precatoria Mart.) mediates neuroprotective activities in Caenorhabditis elegans","volume":"26","author":"Peixoto","year":"2016","journal-title":"J. Funct. Foods"},{"key":"ref_41","unstructured":"Collins, J.J., Huang, C., Hughes, S., and Kornfeld, K. (2005). The measurement and analysis of age-related changes in Caenorhabditis elegans. WormBook."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.arr.2015.09.005","article-title":"Successful aging: Advancing the science of physical independence in older adults","volume":"24","author":"Anton","year":"2015","journal-title":"Ageing Res. Rev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1126\/science.1172539","article-title":"Extending healthy life span\u2014from yeast to humans","volume":"328","author":"Fontana","year":"2010","journal-title":"Science"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"7476","DOI":"10.1101\/cshperspect.a007476","article-title":"Huntington\u2019s disease","volume":"3","author":"Finkbeiner","year":"2011","journal-title":"Cold Spring Harb Perspect. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1038\/nrn2474","article-title":"The insulin paradox: Aging, proteotoxicity and neurodegeneration","volume":"9","author":"Cohen","year":"2008","journal-title":"Nat. Rev. Neurosci."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/5\/915\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:36:34Z","timestamp":1760186194000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/5\/915"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,6]]},"references-count":45,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2019,3]]}},"alternative-id":["molecules24050915"],"URL":"https:\/\/doi.org\/10.3390\/molecules24050915","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,6]]}}}