{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:44:53Z","timestamp":1785426293414,"version":"3.56.0"},"reference-count":115,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Universidad Cooperativa de Colombia","award":["INV3799"],"award-info":[{"award-number":["INV3799"]}]},{"award":["INV3799"],"award-info":[{"award-number":["INV3799"]}],"id":[{"id":"https:\/\/ror.org\/04td15k45","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100019348","name":"Universidad del Tolima","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100019348","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/011bqgx84","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Leishmaniasis, a poorly studied tropical disease, has major therapeutic limitations, driving the search for safer, effective treatments. This review assessed scientific evidence on the antileishmanial activity of extracts, fractions, and bioactive compounds from Azadirachta indica and Cnidoscolus spp. in in vitro and in vivo studies. Following PRISMA 2020 guidelines, searches were conducted in PubMed\/MEDLINE, Scopus, ScienceDirect, and Google Scholar. Eligible studies reported quantitative outcomes, including IC50\/EC50 values, percentage inhibition, parasite load reduction, cytotoxicity, or selectivity index. Systematic reviews, studies without quantitative data, and unvalidated in silico studies were excluded. Overall, 87 records were identified, and 14 studies were included in the synthesis. Most evidence focused on A. indica derivatives tested against different Leishmania species, mainly in vitro, although some studies used BALB\/c and CD-1, mouse models. Active fractions generally showed greater potency against intracellular amastigotes than promastigotes, with activity varying by fraction and model. In vivo studies with A. indica preparations reported reduced parasite loads and improved lesions. Evidence for Cnidoscolus spp. was limited and variable. Overall, plant-derived compounds show promising antileishmanial potential, but rigorous comparative studies are needed to strengthen evidence-based phytopharmaceutical development for leishmaniasis and to clarify the most active compounds, doses, formulations, and therapeutic targets across models.<\/jats:p>","DOI":"10.3390\/molecules31152630","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T14:37:00Z","timestamp":1785249420000},"page":"2630","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Antileishmanial Activity of Bioactive Compounds Obtained from Azadirachta indica and Cnidoscolus spp.: Systematic Review"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8635-3306","authenticated-orcid":false,"given":"Jeison Alfonso","family":"Yaima-Yate","sequence":"first","affiliation":[{"name":"IMPRONTA Research Group, Faculty of Veterinary Medicine and Animal Science, Universidad Cooperativa de Colombia, Ibague 730006, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5672-9376","authenticated-orcid":false,"given":"Catalina","family":"Lapuente-Chala","sequence":"additional","affiliation":[{"name":"IMPRONTA Research Group, Faculty of Veterinary Medicine and Animal Science, Universidad Cooperativa de Colombia, Ibague 730006, Colombia"},{"name":"Neurodegenerative Diseases Research Group (END), Department of Animal Health, Universidad del Tolima, Ibague 730006, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3846-7143","authenticated-orcid":false,"given":"Daniel Alfonso","family":"Urrea-Montes","sequence":"additional","affiliation":[{"name":"Tropical Parasitology Research Laboratory (LIPT), Faculty of Sciences, Department of Biology, Universidad del Tolima, Ibague 730006, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0803-5008","authenticated-orcid":false,"given":"\u00c1ngel Enrique","family":"C\u00e9spedes-Rubio","sequence":"additional","affiliation":[{"name":"Neurodegenerative Diseases Research Group (END), Department of Animal Health, Universidad del Tolima, Ibague 730006, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"ref_1","first-page":"11","article-title":"Application of a sensitive and low-cost method for the extraction of DNA from canine blood to the molecular diagnosis of Leishmania sp","volume":"1","author":"Ascencio","year":"2017","journal-title":"Rev. Investig. Cient. Univ. Mor\u00f3n"},{"key":"ref_2","first-page":"1066","article-title":"In vivo evaluation of the antileishmanial activity of two immunomodulatory plants, Emblica officinalis and Azadirachta indica in balb\/c mice","volume":"3","author":"Kaur","year":"2013","journal-title":"Int. J. Ayurvedic Herb. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"fty025","DOI":"10.1093\/femspd\/fty025","article-title":"Leishmania (Viannia) guyanensis in Tegumentary Leishmaniasis","volume":"76","author":"Borges","year":"2018","journal-title":"Pathog. Dis."},{"key":"ref_4","first-page":"28","article-title":"An overview of the treatment of cutaneous leishmaniasis","volume":"9","author":"Arenas","year":"2020","journal-title":"Fac. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"161","DOI":"10.2478\/jvetres-2021-0028","article-title":"Canine leishmaniasis prevalence in the Slovenian dog population","volume":"65","author":"Kotnik","year":"2021","journal-title":"J. Vet. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1016\/j.pt.2019.06.008","article-title":"Leishmania Viannia\u00a0guyanensis","volume":"35","author":"Olivier","year":"2019","journal-title":"Trends Parasitol."},{"key":"ref_7","unstructured":"Instituto Nacional de Salud INS (2026, January 15). Protocolo de Vigilancia en Salud P\u00fablica de Leishmaniasis, Available online: https:\/\/www.ins.gov.co\/buscador-eventos\/Lineamientos\/Pro_Leishmaniasis.pdf."},{"key":"ref_8","unstructured":"WHO (2023). Leishmaniasis, World Health Organization. Available online: https:\/\/www.who.int\/es\/news-room\/fact-sheets\/detail\/leishmaniasis."},{"key":"ref_9","unstructured":"Pan American Health Organization PAHO (2024). Leishmaniases: Epidemiological Report of the Americas, OPAS. Available online: https:\/\/iris.paho.org\/handle\/10665.2\/51742."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s13071-020-04542-z","article-title":"Prevalence of asymptomatic visceral leishmaniasis in human and dog, Benishangul Gumuz regional state, Western Ethiopia","volume":"14","author":"Bejano","year":"2021","journal-title":"Parasites Vectors"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Santos, G.A., Mendes Sousa, J., Braga Martins de Aguiar, H.A., Silva Torres, K.C., Sousa Coelho, A.J., Ferreira, A.L., and Sousa Lima, M.I. (2023). Systematic Review of Treatment Failure and Clinical Relapses in Leishmaniasis from a Multifactorial Perspective: Clinical Aspects, Factors Associated with the Parasite and Host. Trop. Med. Infect. Dis., 8.","DOI":"10.3390\/tropicalmed8090430"},{"key":"ref_12","unstructured":"Bagchi, D., Das, A., and William, B. (2023). Viral, Parasitic, Bacterial, and Fungal Infections, Elsevier."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2605","DOI":"10.1038\/s41467-023-38221-1","article-title":"Translational reprogramming as a driver of antimony-drug resistance in Leishmania","volume":"14","author":"Guarnizo","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Karamysheva, Z.N., Guarnizo, S.A.G., and Karamyshev, A.L. (2020). Regulation of Translation in the Protozoan Parasite Leishmania. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21082981"},{"key":"ref_15","first-page":"25","article-title":"Leishmaniasis humana. Un problema de salud p\u00fablica","volume":"2","author":"Urmeneta","year":"2019","journal-title":"NPunto"},{"key":"ref_16","first-page":"151","article-title":"Novel detection of Leishmania RNA virus-1 (LRV-1) in clinical isolates of Leishmania Viannia panamensis","volume":"151","author":"Kariyawasam","year":"2024","journal-title":"Parasitology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1007\/s13205-021-02745-4","article-title":"Exploring the role of Azadirachta indica (neem) and its active compounds in the regulation of biological pathways: An update on molecular approach","volume":"11","author":"Sarkar","year":"2021","journal-title":"3 Biotech"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1017\/S0031182014000274","article-title":"In vitro cytokines profile and ultrastructural changes of microglia and macrophages following interaction with Leishmania","volume":"141","year":"2014","journal-title":"Parasitology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"41","DOI":"10.51584\/IJRIAS.2023.8704","article-title":"Phytochemical Screening, Antioxidant and Antimicrobial Activities of Neem Seed (Azadirachta indica) Extracts","volume":"VIII","author":"Awode","year":"2023","journal-title":"Int. J. Res. Innov. Appl. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"111","DOI":"10.4067\/S0716-97602012000200002","article-title":"The cytotoxic and antileishmanial activity of extracts and fractions of leaves and fruits of Azadirachta indica (A Juss.)","volume":"45","author":"Carneiro","year":"2012","journal-title":"Biol. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1186\/s13071-015-0788-3","article-title":"Apoptosis mediated leishmanicidal activity of Azadirachta indica bioactive fractions is accompanied by Th1 immunostimulatory potential and therapeutic cure in vivo","volume":"8","author":"Chouhan","year":"2015","journal-title":"Parasites Vectors"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"103919","DOI":"10.1016\/j.bioorg.2020.103919","article-title":"Hopane-type triterpenes from Cnidoscolus spinosus and their bioactivities","volume":"100","author":"Espinoza","year":"2020","journal-title":"Bioorganic Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2023620","DOI":"10.1155\/2024\/2023620","article-title":"A Comprehensive Review on Potential In Silico Screened Herbal Bioactive Compounds and Host Targets in the Cardiovascular Disease Therapy","volume":"2024","author":"Zarenezhad","year":"2024","journal-title":"BioMed Res. Int."},{"key":"ref_24","first-page":"6018","article-title":"Comparison of Silver, Copper and Iron Nano particles from Leaf Extract of Azadirachta indica and its Anti-microbial, Bio sensing activity and toxicity","volume":"8","author":"Balamurugan","year":"2019","journal-title":"Int. J. Innov. Res. Sci. Eng. Technol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Cervantes-Ceballos, L., Mercado-Camargo, J., Del Olmo-Fern\u00e1ndez, E., Serrano-Garc\u00eda, M.L., Robledo, S.M., and G\u00f3mez-Estrada, H. (2023). Antileishmanial Activity and In Silico Molecular Docking Studies of Malachra alceifolia Jacq. Fractions against Leishmania mexicana Amastigotes. Trop. Med. Infect. Dis., 8.","DOI":"10.3390\/tropicalmed8020115"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"278","DOI":"10.7705\/biomedica.v39i3.4312","article-title":"Geographical distribution of Leishmania species in Colombia, 1985\u20132017","volume":"39","author":"Ovalle","year":"2019","journal-title":"Biomedica"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"14741","DOI":"10.1021\/acsomega.0c01584","article-title":"Homology Modeling of Leishmanolysin (gp63) from Leishmania panamensis and Molecular Docking of Flavonoids","volume":"5","author":"Pedretti","year":"2020","journal-title":"ACS Omega"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6928","DOI":"10.1038\/s41598-023-34124-9","article-title":"In-vitro biological evaluation of 3,3\u2032,5,5\u2032-tetramethoxy-biphenyl-4,4\u2032-diol and molecular docking studies on trypanothione reductase and Gp63 from Leishmania amazonensis demonstrated anti-leishmania potential","volume":"13","author":"Schirmann","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Taheri, M., Iman, M., Khoobdel, M., Dehghan, O., and Zarei, S.M. (2020). Nanoemulsion Formulation of Cold Pressed Neem Oil As a Repellent Against Anopheles Stephensi, Research Square.","DOI":"10.21203\/rs.3.rs-134842\/v1"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"115283","DOI":"10.1016\/j.intimp.2025.115283","article-title":"Exploring the phytomedicine properties of azadiradione against leishmaniasis: In silico and in vitro insights","volume":"163","author":"Vijayakumar","year":"2025","journal-title":"Int. Immunopharmacol."},{"key":"ref_32","first-page":"347","article-title":"Leishmanicidal and anti-inflammatory activities of Lupeol Acetate isolated from Cnidoscolus tehuacanensis Breckon","volume":"9","year":"2020","journal-title":"Med. Aromat. Plants"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"5339","DOI":"10.1080\/14786419.2020.1758089","article-title":"Antiproliferative, antileishmanial and antimicrobial studies on Cnidoscolus quercifolius Pohl (Euphorbiaceae)","volume":"35","author":"Fernandes","year":"2021","journal-title":"Nat. Prod. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.sajb.2018.10.019","article-title":"Phytochemical analyses and pharmacological screening of Neem oil","volume":"120","author":"Cesa","year":"2019","journal-title":"S. Afr. J. Bot."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.jep.2016.01.012","article-title":"In vitro evaluation of traditionally used Surinamese medicinal plants for their potential anti-leishmanial efficacy","volume":"180","author":"Mans","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.exppara.2015.02.011","article-title":"In vitro and in vivo evaluation of anti-leishmanial and immunomodulatory activity of Neem leaf extract in Leishmania donovani infection","volume":"153","author":"Dayakar","year":"2015","journal-title":"Exp. Parasitol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Jumba, B.N., Anjili, C.O., Makwali, J., Ingonga, J., Nyamao, R., Marango, S., Choge, J.K., and Khayeka-Wandabwa, C. (2015). Evaluation of leishmanicidal activity and cytotoxicity of Ricinus communis and Azadirachta indica extracts from western Kenya: In vitro and in vivo assays Complementary and Alternative Medicine. BMC Res. Notes, 8.","DOI":"10.1186\/s13104-015-1605-y"},{"key":"ref_38","first-page":"104540","article-title":"Activity of Cuban Plants Extracts against Leishmania amazonensis","volume":"2012","author":"Monzote","year":"2012","journal-title":"ISRN Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/j.exppara.2010.10.014","article-title":"Leishmania donovani: Assessment of leishmanicidal effects of herbal extracts obtained from plants in the visceral leishmaniasis endemic area of Bihar, India","volume":"127","author":"Singh","year":"2011","journal-title":"Exp. Parasitol."},{"key":"ref_40","first-page":"3","article-title":"In vitro Assessment of Anti\u2014Cutaneous Leishmaniasis Activity of Some Sudanese Plants","volume":"29","author":"Khalid","year":"2005","journal-title":"Acta Parasitol. Turc."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Barrera-T\u00e9llez, F.J., Prieto-Mart\u00ednez, F.D., Hern\u00e1ndez-Campos, A., Mart\u00ednez-Mayorga, K., and Castillo-Bocanegra, R. (2023). In Silico Exploration of the Trypanothione Reductase (TryR) of L. mexicana. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242216046"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"vbaf318","DOI":"10.1093\/bioadv\/vbaf318","article-title":"Computational identification of Azadirachta indica compounds targeting trypanothione reductase in Leishmania infantum","volume":"6","author":"Samson","year":"2026","journal-title":"Bioinform. Adv."},{"key":"ref_43","first-page":"e2233","article-title":"In vitro and in silico antioxidant and antimicrobial activity of ethanolic extracts of Cnidoscolus cha-yamansa leaves","volume":"26","year":"2024","journal-title":"Biotecnia"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Ali, R., Tabrez, S., Kadir Akand, S., Rahman, F., Husein, A., Arish, M., Alqahtani, A.S., Ahmed, M.Z., Husain, M., and Rub, A. (2021). Sesamol Induces Apoptosis-Like Cell Death in Leishmania donovani. Front. Cell. Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.749420"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1111\/ced.14919","article-title":"Treatment options for leishmaniasis","volume":"47","author":"Pradhan","year":"2022","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Hassan, A.A., Khalid, H.E., Abdalla, A.H., Mukhtar, M.M., Osman, W.J., and Efferth, T. (2022). Antileishmanial Activities of Medicinal Herbs and Phytochemicals In Vitro and In Vivo: An Update for the Years 2015 to 2021. Molecules, 27.","DOI":"10.3390\/molecules27217579"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"108745","DOI":"10.1016\/j.biopha.2019.108745","article-title":"Quercetin promotes antipromastigote effect by increasing the ROS production and anti-amastigote by upregulating Nrf2\/HO-1 expression, affecting iron availability","volume":"113","author":"Cataneo","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2186","DOI":"10.1128\/AAC.02193-13","article-title":"Disuccinyl Betulin Triggers Metacaspase-Dependent Endonuclease G-Mediated Cell Death in Unicellular Protozoan Parasite Leishmania donovani","volume":"58","author":"Chowdhury","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1007\/s10495-008-0224-7","article-title":"Reactive oxygen species and imbalance of calcium homeostasis contributes to curcumin induced programmed cell death in Leishmania donovani","volume":"13","author":"Das","year":"2008","journal-title":"Apoptosis"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Fan, Y., Gu, Y., Tong, X., He, Y., Li, O., Chen, K., Cui, Z., Yang, Y., Xiang, Y., and Liu, Q. (2025). Efficacy and safety of different drugs for the treatment of leishmaniasis: A systematic review and network meta-analysis. Front. Cell. Infect. Microbiol., 15.","DOI":"10.3389\/fcimb.2025.1717863"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Fr\u00e9zard, F., Aguiar, M.M.G., Ferreira, L.A.M., Ramos, G.S., Santos, T.T., Borges, G.S.M., Vallejos, V.M.R., and De Morais, H.L.O. (2022). Liposomal Amphotericin B for Treatment of Leishmaniasis: From the Identification of Critical Physicochemical Attributes to the Design of Effective Topical and Oral Formulations. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15010099"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Zhang, H., Yan, R., Liu, Y., Yu, M., He, Z., Xiao, J., Li, K., Liu, G., Ning, Q., and Li, Y. (2025). Progress in antileishmanial drugs: Mechanisms, challenges, and prospects. PLoS Neglected Trop. Dis., 19.","DOI":"10.1371\/journal.pntd.0012735"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"227","DOI":"10.18006\/2022.10(1).227.247","article-title":"Leishmaniasis: Plants as a source of antileishmanial agents","volume":"10","author":"Singh","year":"2022","journal-title":"J. Exp. Biol. Agric. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1007\/s12639-023-01605-7","article-title":"In vitro screening of natural product-based compounds for leishmanicidal activity","volume":"47","author":"Tandon","year":"2023","journal-title":"J. Parasit. Dis."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e202100542","DOI":"10.1002\/cbdv.202100542","article-title":"An Update on Natural Antileishmanial Treatment Options from Plants, Fungi and Algae","volume":"19","author":"Koko","year":"2022","journal-title":"Chem. Biodivers."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Sette, K.M., Garcia, A.R., Tinoco, L.W., Pinheiro, A.S., and Rodrigues, I.A. (2025). Meliponini Geopropolis Extracts Induce ROS Production and Death in Leishmania amazonensis Promastigotes and Axenic Amastigotes In Vitro. Biology, 14.","DOI":"10.3390\/biology14020162"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"112156","DOI":"10.1016\/j.biopha.2021.112156","article-title":"Embilica officinalis L. inhibits the growth and proliferation of Leishmania donovani through the induction of ultrastructural changes, mitochondrial dysfunction, oxidative stress and apoptosis-like cell death","volume":"143","author":"Ali","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Gomes, V.E.D.S., B\u00f3coli, P.F.J., Iamarino, J.G., Grimaldi, R., Ribeiro, A.P.B., and Marangoni, L. (2025). Neem Oil: A Comprehensive Analysis of Quality and Identity Parameters. Lipidology, 2.","DOI":"10.3390\/lipidology2020009"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1007\/s00436-018-6157-3","article-title":"Berberine chloride mediates its antileishmanial activity by inhibiting Leishmania mitochondria","volume":"118","author":"Sarkar","year":"2019","journal-title":"Parasitol. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1017\/S003118201800183X","article-title":"The leishmanicidal activity of artemisinin is mediated by cleavage of the endoperoxide bridge and mitochondrial dysfunction","volume":"146","author":"Sarkar","year":"2019","journal-title":"Parasitology"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"36376","DOI":"10.1021\/acsomega.5c04741","article-title":"Kojic Acid Promotes Apoptosis-like Death and Cell Cycle Arrest in Leishmania (Leishmania) amazonensis Promastigotes","volume":"10","author":"Silva","year":"2025","journal-title":"ACS Omega"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Padilla-Camberos, E., Torres-Gonzalez, O.R., Sanchez-Hernandez, I.M., Diaz-Martinez, N.E., Hernandez-Perez, O.R., and Flores-Fernandez, J.M. (2021). Anti-Inflammatory Activity of Cnidoscolus aconitifolius (Mill.) Ethyl Acetate Extract on Croton Oil-Induced Mouse Ear Edema. Appl. Sci., 11.","DOI":"10.3390\/app11209697"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"6257","DOI":"10.1007\/s00253-021-11471-z","article-title":"Biotechnological processes to obtain bioactive secondary metabolites from some Mexican medicinal plants","volume":"105","year":"2021","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Zhang, J.J., Rizk, R., Li, X., Lee, B.G., Matthies, M.L., Bietz, K.A., Kim, K., Huard, J., Wang, Y., and Chen, W.C.W. (2024). Interleukin-10 exhibit dose-dependent effects on macrophage phenotypes and cardiac remodeling after myocardial infarction. Front. Physiol., 15.","DOI":"10.3389\/fphys.2024.1481460"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Gervazoni, L.F.O., Barcellos, G.B., Ferreira-Paes, T., and Almeida-Amaral, E.E. (2020). Use of Natural Products in Leishmaniasis Chemotherapy: An Overview. Front. Chem., 8.","DOI":"10.3389\/fchem.2020.579891"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1007\/7515_2020_27","article-title":"Heat Shock Proteins in Leishmania Parasites","volume":"Volume 22","author":"Asea","year":"2020","journal-title":"Heat Shock Proteins in Inflammatory Diseases"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Navarrete-Carriola, D.V., Rivera, G., Ortiz-P\u00e9rez, E., Paz-Gonz\u00e1lez, A.D., Mart\u00ednez-V\u00e1zquez, A.V., Aquino-Gonz\u00e1lez, L.V., Argueta-Figueroa, L., Doyle, M.P. (2025). Antiparasitic Effect of Polyphenols and Terpenes from Natural Products Against Trypanosoma cruzi and Leishmania mexicana. Metabolites, 15.","DOI":"10.3390\/metabo15080560"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Michels, P.A.M., Ginger, M.L., and Zilberstein, D. (2020). Trypanosomatids: Methods and Protocols, Springer. Available online: https:\/\/link.springer.com\/10.1007\/978-1-0716-0294-2.","DOI":"10.1007\/978-1-0716-0294-2"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1007\/s11686-024-00902-2","article-title":"Averrhoa carambola Leaf Extract Induces Apoptosis-Like Death with Increased ROS Generation in Leishmania donovani","volume":"69","author":"Ghosh","year":"2024","journal-title":"Acta Parasitol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.apjtb.2017.01.022","article-title":"Caffeic acid and quercetin exert caspases-independent apoptotic effects on Leishmania major promastigotes, and reactivate the death of infected phagocytes derived from BALB\/c mice","volume":"7","author":"Djerdjouri","year":"2017","journal-title":"Asian Pac. J. Trop. Biomed."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Mehwish, S., Varikuti, S., Khan, M.A., Khan, T., Khan, I.U., Satoskar, A., Elserehy, H.A.E., and Ullah, N. (2021). Bioflavonoid-induced apoptosis and dna damage in amastigotes and promastigotes of Leishmania donovani: Iphering the mode of action. Molecules, 26.","DOI":"10.3390\/molecules26195843"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Fonseca-Silva, F., Inacio, J.D.F., Canto-Cavalheiro, M.M., and Almeida-Amaral, E.E. (2011). Reactive oxygen species production and mitochondrial dysfunction contribute to quercetin induced death in Leishmania amazonensis. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0014666"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1007\/978-1-0716-0294-2_47","article-title":"In Vitro Growth Inhibition Assays of Leishmania spp","volume":"Volume 2116","author":"Michels","year":"2020","journal-title":"Trypanosomatids"},{"key":"ref_74","first-page":"73","article-title":"In vitro efficacy of different concentrations of lupeol on old world Leishmania donovani","volume":"70","author":"Abbas","year":"2024","journal-title":"Ann. Parasitol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1080\/10942912.2022.2026953","article-title":"Phenolic acid and amino acid composition of Ethiopian Chaya (Cnidoscolus chayamansa)","volume":"25","author":"Temesgen","year":"2022","journal-title":"Int. J. Food Prop."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s13568-025-01877-7","article-title":"In vitro and in vivo evaluation of the leishmanicidal and cytotoxic activities of chitosan and chitosan\u2013amphotericin B","volume":"15","author":"Mousavi","year":"2025","journal-title":"AMB Express"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Fosse, V., Oldoni, E., Bietrix, F., Budillon, A., Daskalopoulos, E.P., Fratelli, M., Gerlach, B., Groenen, P.M.A., H\u00f6lter, S.M., and Menon, J.M.L. (2023). Recommendations for robust and reproducible preclinical research in personalised medicine. BMC Med., 21.","DOI":"10.1186\/s12916-022-02719-0"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Kousholt, B.S., Pr\u00e6stegaard, K.F., Stone, J.C., Thomsen, A.F., Johansen, T.T., Ritskes-Hoitinga, M., and Wegener, G. (2022). Reporting quality in preclinical animal experimental research in 2009 and 2018: A nationwide systematic investigation. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0275962"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Percie du Sert, N., Ahluwalia, A., Alam, S., Avey, M.T., Baker, M., Browne, W.J., Clark, A., Cuthill, I.C., Dirnagl, U., and Emerson, M. (2020). Reporting animal research: Explanation and elaboration for the arrive guidelines 2.0. PLoS Biol., 18.","DOI":"10.1371\/journal.pbio.3000411"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Mu\u00f1oz-Durango, N., G\u00f3mez, A., Garc\u00eda-Valencia, N., Rold\u00e1n, M., Ochoa, M., Bautista-Erazo, D.E., and Ram\u00edrez-Pineda, J.R. (2022). A Mouse Model of Ulcerative Cutaneous Leishmaniasis by Leishmania (Viannia) panamensis to Investigate Infection, Pathogenesis, Immunity, Therapeutics. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.907631"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Van der Ende, J., and Schallig, H.D.F.H. (2023). Leishmania Animal Models Used in Drug Discovery: A Systematic Review. Animals, 13.","DOI":"10.3390\/ani13101650"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Do Nascimento, J.B., Viturino, J.J.F., Ribeiro, M.A.M., and da Costa, J.G.M. (2025). Nutritional Value, Ethnopharmacology, Chemistry, and Biological Activities of Species of the Genus Cnidoscolus: An Updated Review. Foods, 14.","DOI":"10.3390\/foods14122092"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"190072","DOI":"10.1098\/rsob.190072","article-title":"Regulation of gene expression in Trypanosomatids: Living with polycistronic transcription","volume":"9","author":"Clayton","year":"2019","journal-title":"Open Biol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1186\/s13071-020-04056-8","article-title":"Prevalence and incidence of vector-borne pathogens in unprotected dogs in two Brazilian regions","volume":"13","author":"Ribeiro","year":"2020","journal-title":"Parasit. Vectors"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"113932","DOI":"10.1016\/j.celrep.2024.113932","article-title":"Leishmania braziliensis enhances monocyte responses to promote anti-tumor activity","volume":"43","author":"Moreno","year":"2024","journal-title":"Cell Rep."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Edo, M., Mar\u00edn-Garc\u00eda, P.J., and Llobat, L. (2021). Is the prevalence of Leishmania infantum linked to breeds in dogs? Characterization of seropositive dogs in ibiza. Animals, 11.","DOI":"10.3390\/ani11092579"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"112110","DOI":"10.1016\/j.colsurfb.2021.112110","article-title":"Response of RAW 264.7 and J774A.1 macrophages to particles and nanoparticles of a mesoporous bioactive glass: A comparative study","volume":"208","author":"Feito","year":"2021","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_88","first-page":"22","article-title":"Perfil proteico de aislados de Leishmania mexicana con diferente virulencia","volume":"34","year":"2023","journal-title":"Rev. Biom\u00e9d."},{"key":"ref_89","first-page":"379","article-title":"High prevalence of Leishmania spp. in dogs from Central West Colombia","volume":"58","year":"2022","journal-title":"Vet. Ital."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1002\/pst.426","article-title":"Guidelines for accurate EC50\/IC50 estimation","volume":"10","author":"Sebaugh","year":"2011","journal-title":"Pharm. Stat."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Portuondo-Mallet, L.M.D.L.C., Mollineda-Diogo, N., Orozco-Morales, R., and Lorenzo-Ginori, J.V. (2024). Detection and counting of Leishmania intracellular parasites in microscopy images. Front. Med. Technol., 6.","DOI":"10.3389\/fmedt.2024.1360280"},{"key":"ref_92","unstructured":"Marques, M.C.S., Yoshida, N.C., Torres-Santos, E.C., Garcez, F.R., and Garcez, W.S. (2021). Bioassay-guided isolation of leishmanicidal cucurbitacins from Momordica charantia. Front. Pharmacol., 19."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Fanelli, G., Romano, M., Nova-Lamperti, E., Werner Sunderland, M., Nerviani, A., Scott\u00e0, C., Bombardieri, M., Quezada, S.A., Sacks, S.H., and Noelle, R.J. (2021). PD-L1 signaling on human memory CD4+ T cells induces a regulatory phenotype. PLoS Biol., 19.","DOI":"10.1371\/journal.pbio.3001199"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1007\/s00436-017-5454-6","article-title":"Detection and identification of Leishmania spp.: Application of two hsp70-based PCR-RFLP protocols to clinical samples from the New World","volume":"116","author":"Montalvo","year":"2017","journal-title":"Parasitol. Res."},{"key":"ref_95","first-page":"1","article-title":"Anxiolytic effects of Leishmania braziliensis proteins in a zebrafish animal model","volume":"31","author":"Gurgel","year":"2023","journal-title":"Rev. Neuroci\u00eancias"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s43538-023-00153-1","article-title":"Therapeutic potential of Indian medicinal plants against Leishmania donovani: A review","volume":"89","author":"Pyne","year":"2023","journal-title":"Proc. Indian Natl. Sci. Acad. USA"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.jep.2006.04.003","article-title":"Anti-infective potential of natural products: How to develop a stronger in vitro \u2018proof-of-concept\u2019","volume":"106","author":"Cos","year":"2006","journal-title":"J. Ethnopharmacol."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Corman, H.N., McNamara, C.W., and Bakowski, M.A. (2023). Drug Discovery for Cutaneous Leishmaniasis: A Review of Developments in the Past 15 Years. Microorganisms, 11.","DOI":"10.3390\/microorganisms11122845"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s00403-018-1872-2","article-title":"Gene expression analysis of antimony resistance in Leishmania tropica using quantitative real-time PCR focused on genes involved in trypanothione metabolism and drug transport","volume":"311","author":"Mohebali","year":"2019","journal-title":"Arch. Dermatol. Res."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"108554","DOI":"10.1016\/j.exppara.2023.108554","article-title":"Promising natural products for the treatment of cutaneous leishmaniasis: A review of in vitro and in vivo studies","volume":"251","author":"Afonso","year":"2023","journal-title":"Exp. Parasitol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.rvsc.2022.10.012","article-title":"Absolute quantification of gene expression in drug discovery using RT-qPCR: Case of a drug used in the treatment of leishmaniasis","volume":"153","author":"Nemer","year":"2022","journal-title":"Res. Vet. Sci."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s13643-020-01542-z","article-title":"PRISMA-S: An extension to the PRISMA Statement for Reporting Literature Searches in Systematic Reviews","volume":"10","author":"Rethlefsen","year":"2021","journal-title":"Syst. Rev."},{"key":"ref_103","first-page":"200091","article-title":"Search strategy formulation for systematic reviews: Issues, challenges and opportunities","volume":"15","author":"MacFarlane","year":"2022","journal-title":"Intell. Syst. Appl."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s13643-021-01877-1","article-title":"Where to prospectively register a systematic review","volume":"11","author":"Pieper","year":"2022","journal-title":"Syst. Rev."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Min, S.N., Duangthip, D., and Detsomboonrat, P. (2024). Effects of light curing on silver diamine fluoride-treated carious lesions: A systematic review. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0306367"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s13643-021-01583-y","article-title":"Considerations for conducting systematic reviews: Evaluating the performance of different methods for de-duplicating references","volume":"10","author":"McKeown","year":"2021","journal-title":"Syst. Rev."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1002\/jrsm.1378","article-title":"Which academic search systems are suitable for systematic reviews or meta-analyses? Evaluating retrieval qualities of Google Scholar, PubMed, and 26 other resources","volume":"11","author":"Gusenbauer","year":"2020","journal-title":"Res. Synth. Methods"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.jclinepi.2022.10.009","article-title":"Deduplicating records in systematic reviews: There are free, accurate automated ways to do so","volume":"152","author":"Ferreira","year":"2022","journal-title":"J. Clin. Epidemiol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"l6890","DOI":"10.1136\/bmj.l6890","article-title":"Synthesis without meta-analysis (SWiM) in systematic reviews: Reporting guideline","volume":"368","author":"Campbell","year":"2020","journal-title":"BMJ"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Hooijmans, C.R., Rovers, M.M., De Vries, R.B.M., Leenaars, M., Ritskes-Hoitinga, M., and Langendam, M.W. (2014). SYRCLE\u2019s risk of bias tool for animal studies. BMC Med. Res. Methodol., 14.","DOI":"10.1186\/1471-2288-14-43"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1016\/j.prosdent.2022.05.019","article-title":"Development and validation of a risk-of-bias tool for assessing in vitro studies conducted in dentistry: The QUIN","volume":"131","author":"Sheth","year":"2024","journal-title":"J. Prosthet. Dent."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Andersen, M.S., Kofoed, M.S., Paludan-M\u00fcller, A.S., Pedersen, C.B., Mathiesen, T., Mawrin, C., Olsen, B.B., Halle, B., and Poulsen, F.R. (2024). CRIME-Q\u2014A unifying tool for critical appraisal of methodological (technical) quality, quality of reporting and risk of bias in animal research. BMC Med. Res. Methodol., 24.","DOI":"10.1186\/s12874-024-02413-0"},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Neira, L.F., Mantilla, J.C., and Escobar, P. (2023). Monitoring Cutaneous Leishmaniasis Lesions in Mice Undergoing Topical Miltefosine Treatment. Sci. Pharm., 91.","DOI":"10.3390\/scipharm91040054"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/s41432-025-01186-9","article-title":"Mapping risk of bias criteria in systematic reviews of in vitro endodontic studies: An umbrella review","volume":"26","author":"Piva","year":"2025","journal-title":"Evid. Based. Dent."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1055\/s-0030-1250027","article-title":"Potential of Cameroonian plants and derived products against microbial infections: A review","volume":"76","author":"Kuete","year":"2010","journal-title":"Planta Medica"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/15\/2630\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T04:28:16Z","timestamp":1785385696000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/15\/2630"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,28]]},"references-count":115,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["molecules31152630"],"URL":"https:\/\/doi.org\/10.3390\/molecules31152630","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,28]]}}}