{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T16:06:00Z","timestamp":1776701160720,"version":"3.51.2"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,2,19]],"date-time":"2021-02-19T00:00:00Z","timestamp":1613692800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,2,19]],"date-time":"2021-02-19T00:00:00Z","timestamp":1613692800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009509","name":"Kementerian Riset Teknologi Dan Pendidikan Tinggi Republik Indonesia","doi-asserted-by":"crossref","award":["586\/UN3\/2017"],"award-info":[{"award-number":["586\/UN3\/2017"]}],"id":[{"id":"10.13039\/501100009509","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Complement Med Ther"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>In previous studies, <jats:italic>Cassia spectabilis<\/jats:italic> DC leaf has shown a good antiplasmodial activity. Therefore, this study is a follow-up study of the extract of leaf of <jats:italic>C. spectabilis<\/jats:italic> DC on its in vitro and in vivo antiplasmodial activity and mechanism as an antimalarial.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>The extract was fractionated, sub-fractionated and isolated to obtain the purified compound. In vitro antiplasmodial activity test against <jats:italic>Plasmodium falciparum<\/jats:italic> to find out the active compound. In vivo test against <jats:italic>P. berghei<\/jats:italic> ANKA-infected mice was conducted to determine prophylactic activity and antiplasmodial activity either alone or in combination with artesunate. The inhibition of heme detoxification test as one of the antimalarial mechanisms was carried out using the Basilico method.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The results showed that active antimalarial compound isolated from <jats:italic>C. spectabilis<\/jats:italic> DC leaf had a structural pattern that was identical to (\u2212)-7-hydroxycassine. Prophylactic test of 90% ethanolic extract of <jats:italic>C. spectabilis<\/jats:italic> DC leaf alone against <jats:italic>P. berghei<\/jats:italic> ANKA<jats:italic>-infected<\/jats:italic> mice obtained the highest percentage inhibition was 68.61%, while positive control (doxycycline 13\u2009mg\/kg) was 73.54%. In combination with artesunate, 150\u2009mg\/kg three times a day of <jats:italic>C. spectabilis<\/jats:italic> DC (D<jats:sub>0<\/jats:sub>-D<jats:sub>2<\/jats:sub>)\u2009+\u2009artesunate (D<jats:sub>2<\/jats:sub>) was better than the standard combination of amodiaquine + artesunate where the inhibition percentages were 99.18 and 92.88%, respectively. The IC<jats:sub>50<\/jats:sub> of the extract for the inhibitory activity of heme detoxification was 0.375\u2009mg\/ml which was better than chloroquine diphosphate (0.682\u2009mg\/ml).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p><jats:italic>C. spectabilis<\/jats:italic> DC leaf possessed potent antiplasmodial activity and may offer a potential agent for effective and affordable antimalarial phytomedicine.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12906-021-03239-9","type":"journal-article","created":{"date-parts":[[2021,2,21]],"date-time":"2021-02-21T00:11:41Z","timestamp":1613866301000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Antiplasmodial activity of Ethanolic extract of Cassia spectabilis DC leaf and its inhibition effect in Heme detoxification"],"prefix":"10.1186","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3163-5829","authenticated-orcid":false,"given":"Wiwied","family":"Ekasari","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dewi Resty","family":"Basuki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heny","family":"Arwati","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tutik Sri","family":"Wahyuni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,2,19]]},"reference":[{"issue":"1 Suppl","key":"3239_CR1","first-page":"110","volume":"12","author":"W Ekasari","year":"2018","unstructured":"Ekasari W, Wahyuni TS, Arwaty H, Putri NT. Determination of effective dose antimalarial from Cassia spectabilis leaf ethanol extract in Plasmodium berghei-infected mice. Afr J Infect Dis. 2018;12(1 Suppl):110\u20135.","journal-title":"Afr J Infect Dis"},{"issue":"18","key":"3239_CR2","doi-asserted-by":"publisher","first-page":"3691","DOI":"10.1021\/ol701623n","volume":"9","author":"H Morita","year":"2007","unstructured":"Morita H, Oshimi S, Hirasawa Y, Koyama K, Honda T, Ekasari W, et al. Cassiarins a and B, novel antiplasmodial alkaloids from Cassia siamea. Org Lett. 2007;9(18):3691\u20133.","journal-title":"Org Lett"},{"issue":"7","key":"3239_CR3","doi-asserted-by":"publisher","first-page":"1831","DOI":"10.3987\/COM-09-11680","volume":"78","author":"W Ekasari","year":"2009","unstructured":"Ekasari W, Widyawaruyanti A, Zaini NC. Antimalarial activity of cassiarin a from the leaves of Cassia siamea. Heterocycles. 2009;78(7):1831\u20136.","journal-title":"Heterocycles."},{"key":"3239_CR4","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/B978-0-12-385897-9.00002-1","volume":"74","author":"IRF Elyazar","year":"2011","unstructured":"Elyazar IRF, Hay SI, Baird JK. Malaria distribution, prevalence, drug resistance and control in Indonesia. Adv Parasitol. 2011;74:41\u2013175.","journal-title":"Adv Parasitol"},{"issue":"4","key":"3239_CR5","doi-asserted-by":"publisher","first-page":"517","DOI":"10.4269\/ajtmh.2011.10-0285","volume":"84","author":"KR Tan","year":"2011","unstructured":"Tan KR, Magill AJ, Parise ME, Arguin PM. Doxycycline for malaria chemoprophylaxis and treatment: report from the CDC expert meeting on malaria chemoprophylaxis. Am J Trop Med Hyg. 2011;84(4):517\u201331.","journal-title":"Am J Trop Med Hyg"},{"issue":"14","key":"3239_CR6","doi-asserted-by":"publisher","first-page":"5392","DOI":"10.1073\/pnas.1218412110","volume":"110","author":"M Chugh","year":"2013","unstructured":"Chugh M, Sundararaman V, Kumar S, Reddy VS, Siddiqui WA, Stuart KD, et al. Protein complex directs hemoglobin-to-hemozoin formation in Plasmodium falciparum. Proc Natl Acad Sci U S A. 2013;110(14):5392\u20137.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"6356","key":"3239_CR7","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1038\/355167a0","volume":"355","author":"AF Slater","year":"1992","unstructured":"Slater AF, Cerami A. Inhibition by chloroquine of a novel haem polymerase enzyme activity in malaria trophozoites. Nature. 1992;355(6356):167\u20139.","journal-title":"Nature."},{"issue":"2","key":"3239_CR8","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1073\/pnas.88.2.325","volume":"88","author":"AF Slater","year":"1991","unstructured":"Slater AF, Swiggard WJ, Orton BR, Flitter WD, Goldberg DE, Cerami A, et al. An iron-carboxylate bond links the heme units of malaria pigment. Proc Natl Acad Sci U S A. 1991;88(2):325\u20139.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"3239_CR9","first-page":"497","volume":"572","author":"DS Bohle","year":"1994","unstructured":"Bohle DS, Conklin BJ, Cox D, Madsen SK, Paulson S, Stephens PW, et al. Structural and spectroscopic studies of \u03b2-hematin (the heme coordination polymer in malaria pigment). Inorganic and organometallic polymers II. ACS Symposium Series. Am Chem Soc. 1994;572:497\u2013515.","journal-title":"Am Chem Soc"},{"key":"3239_CR10","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1074\/jbc.272.2.713","volume":"272","author":"S Bohle","year":"1997","unstructured":"Bohle S, Dinnebier R, Madsen S, Stephens P, Bohle SD, Dinnebier RE, Madsen SK, Stephens PW. Characterization of the products of the heme detoxification pathway in malarial late trophozoites by X-ray diffraction. J Biol Chem. 1997;272:713\u20136.","journal-title":"J Biol Chem"},{"issue":"6775","key":"3239_CR11","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1038\/35005132","volume":"404","author":"S Pagola","year":"2000","unstructured":"Pagola S, Stephens PW, Bohle DS, Kosar AD, Madsen SK. The structure of malaria pigment beta-haematin. Nature. 2000;404(6775):307\u201310.","journal-title":"Nature."},{"issue":"12","key":"3239_CR12","doi-asserted-by":"publisher","first-page":"1437","DOI":"10.4155\/fmc.13.113","volume":"5","author":"KY Fong","year":"2013","unstructured":"Fong KY, Wright DW. Hemozoin and antimalarial drug discovery. Future Med Chem. 2013;5(12):1437\u201350.","journal-title":"Future Med Chem"},{"issue":"16","key":"3239_CR13","doi-asserted-by":"publisher","first-page":"4946","DOI":"10.1073\/pnas.1501023112","volume":"112","author":"KN Olafson","year":"2015","unstructured":"Olafson KN, Ketchum MA, Rimer JD, Vekilov PG. Mechanisms of hematin crystallization and inhibition by the antimalarial drug chloroquine. Proc Natl Acad Sci U S A. 2015;112(16):4946\u201351.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"9430","key":"3239_CR14","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/S0140-6736(04)16680-4","volume":"364","author":"PG Kremsner","year":"2004","unstructured":"Kremsner PG, Krishna S. Antimalarial combinations. Lancet. 2004;364(9430):285\u201394.","journal-title":"Lancet."},{"issue":"5","key":"3239_CR15","doi-asserted-by":"publisher","first-page":"1859","DOI":"10.1128\/AAC.50.5.1859-1860.2006","volume":"50","author":"DN Nandakumar","year":"2006","unstructured":"Nandakumar DN, Nagaraj VA, Vathsala PG, Rangarajan P, Padmanaban G. Curcumin-artemisinin combination therapy for malaria. Antimicrob Agents Chemother. 2006;50(5):1859\u201360.","journal-title":"Antimicrob Agents Chemother"},{"key":"3239_CR16","unstructured":"WHO. Artemisinin resistance and artemisinin-based combination therapy efficacy: status report, vol. 2018. Geneva: World Health Organization; 2018. Contract No.: WHO\/CDS\/GMP\/2018.18"},{"issue":"1","key":"3239_CR17","doi-asserted-by":"publisher","first-page":"90","DOI":"10.4269\/ajtmh.2010.09-0286","volume":"83","author":"G Alvarez","year":"2010","unstructured":"Alvarez G, Tob\u00f3n A, Pi\u00f1eros J-G, R\u00edos A, Blair S. Dynamics of Plasmodium falciparum parasitemia regarding combined treatment regimens for acute uncomplicated malaria, Antioquia, Colombia. Am J Trop Med Hyg. 2010;83(1):90\u20136.","journal-title":"Am J Trop Med Hyg"},{"issue":"3","key":"3239_CR18","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1645\/0022-3395(2005)091[0484:HMPICC]2.0.CO;2","volume":"91","author":"W Trager","year":"2005","unstructured":"Trager W, Jensen JB. Human malaria parasites in continuous culture. 1976. J Parasitol. 2005;91(3):484\u20136.","journal-title":"J Parasitol"},{"issue":"3","key":"3239_CR19","first-page":"352","volume":"51","author":"L Carbone","year":"2012","unstructured":"Carbone L, Carbone ET, Yi EM, Bauer DB, Lindstrom KA, Parker JM, et al. Assessing cervical dislocation as a humane euthanasia method in mice. J Am Assoc Lab Anim Sci. 2012;51(3):352\u20136.","journal-title":"J Am Assoc Lab Anim Sci"},{"key":"3239_CR20","doi-asserted-by":"publisher","first-page":"7390385","DOI":"10.1155\/2019\/7390385","volume":"2019","author":"W Ekasari","year":"2019","unstructured":"Ekasari W, Widya Pratiwi D, Amanda Z, Suciati WA, Arwati H. Various parts of Helianthus annuus plants as new sources of antimalarial drugs. Evid Based Complement Alternat Med. 2019;2019:7390385.","journal-title":"Evid Based Complement Alternat Med"},{"issue":"2","key":"3239_CR21","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1080\/00034983.1975.11686997","volume":"69","author":"W Peters","year":"1975","unstructured":"Peters W. The chemotherapy of rodent malaria, XXII. The value of drug-resistant strains of P. berghei in screening for blood schizontocidal activity. Ann Trop Med Parasitol. 1975;69(2):155\u201371.","journal-title":"Ann Trop Med Parasitol"},{"key":"3239_CR22","volume-title":"Adequacy of sample size in health studies \/ Stanley Lemeshow","author":"S Lemeshow","year":"1990","unstructured":"Lemeshow S, Hosmer DW, Klar J, Lwanga SK, World HO. Adequacy of sample size in health studies \/ Stanley Lemeshow. Chichester: Wiley; 1990."},{"issue":"1","key":"3239_CR23","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1093\/jac\/42.1.55","volume":"42","author":"N Basilico","year":"1998","unstructured":"Basilico N, Pagani E, Monti D, Olliaro P, Taramelli D. A microtitre-based method for measuring the haem polymerization inhibitory activity (HPIA) of antimalarial drugs. J Antimicrob Chemother. 1998;42(1):55\u201360.","journal-title":"J Antimicrob Chemother"},{"issue":"8054","key":"3239_CR24","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/S0140-6736(78)90365-3","volume":"1","author":"KH Rieckmann","year":"1978","unstructured":"Rieckmann KH, Campbell GH, Sax LJ, Mrema JE. Drug sensitivity of Plasmodium falciparum. An in-vitro microtechnique. Lancet. 1978;1(8054):22\u20133.","journal-title":"Lancet"},{"issue":"1","key":"3239_CR25","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/0001-706X(94)90041-8","volume":"56","author":"MC Gessler","year":"1994","unstructured":"Gessler MC, Nkunya MH, Mwasumbi LB, Heinrich M, Tanner M. Screening Tanzanian medicinal plants for antimalarial activity. Acta Trop. 1994;56(1):65\u201377.","journal-title":"Acta Trop"},{"key":"3239_CR26","first-page":"230","volume":"24","author":"C Viegas Junior","year":"2013","unstructured":"Viegas Junior C, Pivatto M, Ad R, Hamerski L, DHS S, VdS B. (\u2212)-7-hydroxycassine: a new 2,6-dialkylpiperidin-3-ol alkaloid and other constituents isolated from flowers and fruits of Senna spectabilis (Fabaceae). J Braz Chem Soc. 2013;24:230\u20135.","journal-title":"J Braz Chem Soc"},{"issue":"2","key":"3239_CR27","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/S0378-8741(99)00096-3","volume":"69","author":"V Munoz","year":"2000","unstructured":"Munoz V, Sauvain M, Bourdy G, Callapa J, Rojas I, Vargas L, et al. The search for natural bioactive compounds through a multidisciplinary approach in Bolivia. Part II. Antimalarial activity of some plants used by Mosetene indians. J Ethnopharmacol. 2000;69(2):139\u201355.","journal-title":"J Ethnopharmacol"},{"issue":"1","key":"3239_CR28","doi-asserted-by":"publisher","first-page":"63","DOI":"10.2174\/1386207053328101","volume":"8","author":"BL Tekwani","year":"2005","unstructured":"Tekwani BL, Walker LA. Targeting the hemozoin synthesis pathway for new antimalarial drug discovery: technologies for in vitro beta-hematin formation assay. Comb Chem High Throughput Screen. 2005;8(1):63\u201379.","journal-title":"Comb Chem High Throughput Screen"},{"key":"3239_CR29","doi-asserted-by":"publisher","first-page":"8031392","DOI":"10.1155\/2016\/8031392","volume":"2016","author":"V Somsak","year":"2016","unstructured":"Somsak V, Borkaew P, Klubsri C, Dondee K, Bootprom P, Saiphet B. Antimalarial properties of aqueous crude extracts of Gynostemma pentaphyllum and Moringa oleifera leaves in combination with artesunate in Plasmodium berghei-infected mice. J Trop Med. 2016;2016:8031392.","journal-title":"J Trop Med"},{"key":"3239_CR30","volume-title":"rd, editor. Guidelines for the Treatment of Malaria","author":"WHO","year":"2015","unstructured":"WHO. Guidelines Approved by the Guidelines Review Committee. In: rd, editor. Guidelines for the Treatment of Malaria, vol. 2015. Geneva: World Health Organization. Copyright (c) World Health Organization; 2015."},{"issue":"4","key":"3239_CR31","doi-asserted-by":"publisher","first-page":"714","DOI":"10.2165\/00003495-199550040-00009","volume":"50","author":"LB Barradell","year":"1995","unstructured":"Barradell LB, Fitton A. Artesunate. A review of its pharmacology and therapeutic efficacy in the treatment of malaria. Drugs. 1995;50(4):714\u201341.","journal-title":"Drugs."},{"key":"3239_CR32","volume-title":"Handbook of Medical Parasitology: Churchill Livingstone","author":"V Zaman","year":"1990","unstructured":"Zaman V, Keong LA. Handbook of Medical Parasitology: Churchill Livingstone; 1990."}],"container-title":["BMC Complementary Medicine and Therapies"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12906-021-03239-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12906-021-03239-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12906-021-03239-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,21]],"date-time":"2021-02-21T00:11:55Z","timestamp":1613866315000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmccomplementalternmed.biomedcentral.com\/articles\/10.1186\/s12906-021-03239-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,19]]},"references-count":32,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["3239"],"URL":"https:\/\/doi.org\/10.1186\/s12906-021-03239-9","relation":{},"ISSN":["2662-7671"],"issn-type":[{"value":"2662-7671","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,19]]},"assertion":[{"value":"2 March 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 February 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 February 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This work was approved by Animal care and Use Committee, Airlangga University, No 2.KE.181.10.2018.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing of interest.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"71"}}