{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T08:08:42Z","timestamp":1771661322992,"version":"3.50.1"},"reference-count":25,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,6,16]],"date-time":"2024-06-16T00:00:00Z","timestamp":1718496000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Support Program for Research and Technological Innovation Projects (PAPIIT-UNAM)","award":["TA200324"],"award-info":[{"award-number":["TA200324"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Haemonchus contortus, a blood-feeding parasite in grazing sheep, causes economic losses. Drug resistance necessitates exploring plant-based anthelmintics like Artemisia cina (Asteraceae). The plant, particularly its ethyl acetate extract, shows anthelmintic activity against H. contortus. However, there is limited information on pharmacodynamic interactions in ethyl acetate compounds. The study aims to identify pharmacodynamic interactions in the ethyl acetate extract of A. cina with anthelmintic effects on H. contortus eggs and L3 larvae using binary mixtures. Bioactive compounds were isolated via chromatography and identified using spectroscopic techniques. Pharmacodynamic interactions were assessed through binary mixtures with a main compound. Four bioactive compounds were identified: 1-nonacosanol, hentriacontane, peruvin, and cinic acid. Binary mixtures, with peruvin as the main compound, were performed. Peruvin\/1-nonacosanol-hentriacontane and peruvin\/cinic acid mixtures demonstrated 1.42-fold and 4.87-fold increased lethal effects in H. contortus L3 infective larvae, respectively, at a 0.50LC25\/0.50LC25 concentration. In this work, we determined the synergism between bioactive compounds isolated from the ethyl acetate extract of A. cina and identified unreported compounds for the specie.<\/jats:p>","DOI":"10.3390\/pathogens13060509","type":"journal-article","created":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T08:48:31Z","timestamp":1718614111000},"page":"509","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Understanding Artemisia cina Ethyl Acetate Extract\u2019s Anthelmintic Effect on Haemonchus contortus Eggs and L3 Larvae: The Synergism of Peruvin Binary Mixtures"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7871-1000","authenticated-orcid":false,"given":"Luis David","family":"Arango-De-la Pava","sequence":"first","affiliation":[{"name":"Facultad de Estudios Superiores Cuautitl\u00e1n, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Cuautitl\u00e1n 54714, Estado de M\u00e9xico, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3693-1670","authenticated-orcid":false,"given":"Manas\u00e9s","family":"Gonz\u00e1lez-Cortazar","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica del Sur, Instituto Mexicano del Seguro Social, Xochitepec 62790, Morelos, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2233-5958","authenticated-orcid":false,"given":"Alejandro","family":"Zamilpa","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica del Sur, Instituto Mexicano del Seguro Social, Xochitepec 62790, Morelos, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge Alfredo","family":"Cu\u00e9llar-Ordaz","sequence":"additional","affiliation":[{"name":"Facultad de Estudios Superiores Cuautitl\u00e1n, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Cuautitl\u00e1n 54714, Estado de M\u00e9xico, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9262-3111","authenticated-orcid":false,"given":"H\u00e9ctor Alejandro","family":"de la Cruz-Cruz","sequence":"additional","affiliation":[{"name":"Facultad de Estudios Superiores Cuautitl\u00e1n, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Cuautitl\u00e1n 54714, Estado de M\u00e9xico, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9231-1556","authenticated-orcid":false,"given":"Rosa Isabel","family":"Higuera-Piedrahita","sequence":"additional","affiliation":[{"name":"Facultad de Estudios Superiores Cuautitl\u00e1n, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Cuautitl\u00e1n 54714, Estado de M\u00e9xico, Mexico"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica del Sur, Instituto Mexicano del Seguro Social, Xochitepec 62790, Morelos, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2050-6119","authenticated-orcid":false,"given":"Raquel","family":"L\u00f3pez-Arellano","sequence":"additional","affiliation":[{"name":"Facultad de Estudios Superiores Cuautitl\u00e1n, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Cuautitl\u00e1n 54714, Estado de M\u00e9xico, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,16]]},"reference":[{"key":"ref_1","first-page":"100938","article-title":"Benzimidazole-resistance associated mutation in Haemonchus contortus in Norwegian sheep, as detected by droplet digital PCR","volume":"46","author":"Gravdal","year":"2023","journal-title":"Vet. Parasitol. Reg. Stud. Rep."},{"key":"ref_2","first-page":"1","article-title":"Anthelmintic resistance in sheep gastrointestinal nematodes in Slovakia detected by in-vitro methods","volume":"10","year":"2014","journal-title":"BMC Vet. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.vetpar.2005.11.019","article-title":"The detection of anthelmintic resistance in nematodes of veterinary importance","volume":"136","author":"Coles","year":"2006","journal-title":"Vet. Parasitol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12639-016-0765-6","article-title":"Integrated parasite management with special reference to gastro-intestinal nematodes","volume":"41","author":"Maqbool","year":"2016","journal-title":"J. Parasit. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1007\/s11686-021-00364-w","article-title":"In Vitro Nematocidal Effect and Anthelmintic Activity of Artemisia cina Against Haemonchus contortus in Gerbils and Relative Expression of Hc29 Gene in Transitional Larvae (L3\u2013L4)","volume":"66","author":"Zamilpa","year":"2021","journal-title":"Acta Parasitol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Higuera-Piedrahita, R.I., Dolores-Hern\u00e1ndez, M., de la Cruz-Cruz, H.A., L\u00f3pez-Arellano, R., Gives, P.M.-D., Olmedo-Ju\u00e1rez, A., Cu\u00e9llar-Ordaz, J.A., Gonz\u00e1lez-Cortazar, M., Ble-Gonz\u00e1lez, E.A., and L\u00f3pez-Arellano, M.E. (2023). 3\u2032-Demethoxy-6-O-demethylisoguaiacin and norisoguaiacin nematocidal lignans from Artemisia cina against Haemonchus contortus Infective Larvae. Plants, 12.","DOI":"10.3390\/plants12040820"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Arango-De la Pava, L.D., Gonz\u00e1lez-Cort\u00e1zar, M., Zamilpa, A., Cu\u00e9llar-Ordaz, J.A., de la Cruz-Cruz, H.A., Higuera-Piedrahita, R.I., and L\u00f3pez-Arellano, R. (2024). Bio-guided isolation of a new sesquiterpene from Artemisia cina with anthelmintic activity against Haemonchus contortus L3 infective larvae. PLoS ONE, 19.","DOI":"10.1101\/2024.02.26.582230"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"109010","DOI":"10.1016\/j.vetpar.2019.109010","article-title":"Pharmacokinetic-pharmacodynamic assessment of the ivermectin and abamectin nematodicidal interaction in cattle","volume":"279","author":"Ballent","year":"2020","journal-title":"Vet. Parasitol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1002\/cpt.1434","article-title":"Pharmacodynamic Drug\u2013Drug Interactions","volume":"105","author":"Niu","year":"2019","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Arango-De la Pava, L.D., Zamilpa, A., Trejo-Espino, J.L., Dom\u00ednguez-Mendoza, B.E., Jim\u00e9nez-Ferrer, E., P\u00e9rez-Mart\u00ednez, L., and Trejo-Tapia, G. (2021). Synergism and subadditivity of verbascoside-lignans and-iridoids binary mixtures isolated from Castilleja tenuiflora benth. On NF-\u03baB\/ap-1 inhibition activity. Molecules, 26.","DOI":"10.3390\/molecules26030547"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/j.sajb.2007.05.006","article-title":"Verbascoside and luteolin-5-O-\u03b2-d-glucoside isolated from Halleria lucida L. exhibit antagonistic anti-oxidant properties in vitro","volume":"73","author":"Frum","year":"2007","journal-title":"S. Afr. J. Bot."},{"key":"ref_12","unstructured":"Patricia, V., Virginia, S., and Martino, S. (2018). Sesquiterpene Lactones Advances in their Chemistry and Biological Aspects, Springer."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1135\/cccc19921092","article-title":"Sesquiterpene lactones of Ambrosia artemisiifolia L. and Ambrosia trifda L. species","volume":"57","author":"Szczepanska","year":"1992","journal-title":"Collect. Czechoslov. Chem. Commun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e00149","DOI":"10.1002\/prp2.149","article-title":"Analysis of drug combinations: Current methodological landscape","volume":"3","author":"Foucquier","year":"2015","journal-title":"Pharmacol. Res. Perspect."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Krakowska-Sieprawska, A., Kie\u0142basa, A., Rafi\u0144ska, K., Ligor, M., and Buszewski, B. (2022). Modern Methods of Pre-Treatment of Plant Material for the Extraction of Bioactive Compounds. Molecules, 27.","DOI":"10.3390\/molecules27030730"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"De Carvalho, C.C.C.R., and Caramujo, M.J. (2018). The various roles of fatty acids. Molecules, 23.","DOI":"10.3390\/molecules23102583"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e135","DOI":"10.1017\/S0022149X20000152","article-title":"In vitro nematocidal activity of commercial fatty acids and \u03b2-sitosterol against Haemonchus contortus","volume":"94","author":"Zamilpa","year":"2020","journal-title":"J. Helminthol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Cross, M.E., and Plunkett, E.V.E. (2014). Affinity, Efficacy and Potency. Physics, Pharmacology and Physiology for Anaesthetists: Key Concepts for the FRCA, Cambridge University Press. [2nd ed.].","DOI":"10.1017\/CBO9781107326200"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.vetpar.2011.03.013","article-title":"In vitro analysis of the anthelmintic activity of forage chicory (Cichorium intybus L.) sesquiterpene lactones against a predominantly Haemonchus contortus egg population","volume":"180","author":"Foster","year":"2011","journal-title":"Vet. Parasitol."},{"key":"ref_20","first-page":"6","article-title":"Biomedical properties and origins of sesquiterpene lactones, with a focus on dehydroleucodine","volume":"12","author":"Abood","year":"2017","journal-title":"Nat. Prod. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Atif, M., Estrada-Mondragon, A., Nguyen, B., Lynch, J.W., and Keramidas, A. (2017). Effects of glutamate and ivermectin on single glutamate-gated chloride channels of the parasitic nematode H. contortus. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006663"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.micpath.2017.05.048","article-title":"In vitro assessment of Argemone mexicana, Taraxacum officinale, Ruta chalepensis and Tagetes filifolia against Haemonchus contortus nematode eggs and infective (L3) larvae","volume":"109","author":"Zamilpa","year":"2017","journal-title":"Microb. Pathog."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1007\/s11250-010-9727-7","article-title":"Anthelminthic activity of acetone extract and fractions of Vernonia amygdalina against Haemonchus contortus eggs and larvae","volume":"43","author":"Ademola","year":"2011","journal-title":"Trop. Anim. Health Prod."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.9734\/EJMP\/2014\/10421","article-title":"In vitro Anthelmintic Activity of Bidens pilosa Linn. (Asteraceae) Leaf Extracts against Haemonchus contortus Eggs and Larvae","volume":"4","author":"Jeannette","year":"2014","journal-title":"Eur. J. Med. Plants"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1051\/parasite\/2018008","article-title":"Antiparasitic activity in Asteraceae with special attention to ethnobotanical use by the tribes of Odisha, India","volume":"25","author":"Panda","year":"2018","journal-title":"Parasite"}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/13\/6\/509\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:59:39Z","timestamp":1760108379000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/13\/6\/509"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,16]]},"references-count":25,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["pathogens13060509"],"URL":"https:\/\/doi.org\/10.3390\/pathogens13060509","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,16]]}}}