{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T12:31:22Z","timestamp":1765542682634,"version":"3.48.0"},"reference-count":41,"publisher":"Walter de Gruyter GmbH","issue":"2","funder":[{"DOI":"10.13039\/501100008463","name":"Universitas Airlangga","doi-asserted-by":"crossref","award":["564\/UN3.14\/LT\/2016"],"award-info":[{"award-number":["564\/UN3.14\/LT\/2016"]}],"id":[{"id":"10.13039\/501100008463","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,3,28]]},"abstract":"Abstract<\/jats:title>\n \n Objectives<\/jats:title>\n \n The use of standard antimalarial drugs, such as\u00a0dihydroartemisinin-piperaquine (DHP) for the treatment of malaria during pregnancy is limited due to the risk of teratogenicity. The alternative is therefore required although few\u00a0exist. Here we show a phytopharmaceutical drug derived from\n Andrographis paniculata<\/jats:italic>\n (AS201-01), which is effective as herbal antimalarial both\n in vitro<\/jats:italic>\n and\n in vivo<\/jats:italic>\n and may be a suitable alternative when used in complementary treatment with DHP.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Plasmodium berghei<\/jats:italic>\n infected pregnant BALB\/c mice were divided into four groups: G1 (negative control), G2 (AS201-01), G3 (DHP), and G4 (combination of DHP and AS201-01). Pheripheral blood was collected during therapy for counting parasitemia. Placental samples were analyzed for the expression of IFN-\u03b3, TNF- \u03b1, IL-10, placental parasite counts and foetal morphology.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Groups G4 and G3 both showed a 100% inhibition of peripheral parasitemia. However, the treatment in G4 was found to be less effective than that in G2 and G3 in preventing placental parasitemia. The G4 treatment was able to reduce the expression of IFN-\u03b3 and IL-10, whereas TNF-\u03b1 was not significantly different from the control group. Foetal morphologic abnormalities were observed in all groups except G2; G4 showed lower percentage of abnormalities compared to G3 and G1.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n A combination of\n A.\u00a0paniculata<\/jats:italic>\n tablet (AS201-01) with DHP has the potential to reduce the toxicity of DHP in malaria treatment.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1515\/jbcpp-2020-0162","type":"journal-article","created":{"date-parts":[[2021,2,14]],"date-time":"2021-02-14T01:39:38Z","timestamp":1613266778000},"page":"175-183","source":"Crossref","is-referenced-by-count":3,"title":["A tablet derived from\n Andrographis paniculata<\/i>\n complements dihydroartemisinin-piperaquine treatment of malaria in pregnant mice"],"prefix":"10.1515","volume":"33","author":[{"family":"Bastiana","sequence":"first","affiliation":[{"name":"Doctoral Student of Medicine Faculty , Universitas Airlangga , Surabaya , Indonesia"},{"name":"Department of Clinical Pathology, Faculty of Medicine , Universitas Nadhlatul Ulama\/Jemursari Islamic Hospital , Surabaya , Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aty","family":"Widyawaruyanti","sequence":"additional","affiliation":[{"name":"Natural Product Medicine Research and Development, Institute of Tropical Disease , Universitas Airlangga, C Campus Universitas Airlangga , Surabaya , Indonesia"},{"name":"Department of Pharmacognosy and Phytochemistry, Faculty of Pharmacy , Universitas Airlangga, C Campus Universitas Airlangga , Surabaya , Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hilkatul","family":"Ilmi","sequence":"additional","affiliation":[{"name":"Natural Product Medicine Research and Development, Institute of Tropical Disease , Universitas Airlangga, C Campus Universitas Airlangga , Surabaya , Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lidya","family":"Tumewu","sequence":"additional","affiliation":[{"name":"Natural Product Medicine Research and Development, Institute of Tropical Disease , Universitas Airlangga, C Campus Universitas Airlangga , Surabaya , Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Budi","family":"Prasetyo","sequence":"additional","affiliation":[{"name":"Natural Product Medicine Research and Development, Institute of Tropical Disease , Universitas Airlangga, C Campus Universitas Airlangga , Surabaya , Indonesia"},{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine , Universitas Airlangga , Surabaya , Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Achmad Fuad","family":"Hafid","sequence":"additional","affiliation":[{"name":"Natural Product Medicine Research and Development, Institute of Tropical Disease , Universitas Airlangga, C Campus Universitas Airlangga , Surabaya , Indonesia"},{"name":"Department of Pharmacognosy and Phytochemistry, Faculty of Pharmacy , Universitas Airlangga, C Campus Universitas Airlangga , Surabaya , Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"family":"Aryati","sequence":"additional","affiliation":[{"name":"Natural Product Medicine Research and Development, Institute of Tropical Disease , Universitas Airlangga, C Campus Universitas Airlangga , Surabaya , Indonesia"},{"name":"Department of Clinical Pathology, Faculty of Medicine , Universitas Airlangga , Surabaya , Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2021,2,11]]},"reference":[{"doi-asserted-by":"crossref","unstructured":"McDonald, CR, Tran, V, Kain, KC. Complement activation in placental malaria. Front Microbiol 2015;6:1460. https:\/\/doi.org\/10.3389\/fmicb.2015.01460.","key":"2025121209250618664_j_jbcpp-2020-0162_ref_001","DOI":"10.3389\/fmicb.2015.01460"},{"doi-asserted-by":"crossref","unstructured":"McClure, EM, Meshnick, SR, Lazebnik, N, Mungai, P, King, CL, Hudgens, M, et al.. A cohort study of Plasmodium falciparum malaria in pregnancy and associations with uteroplacental blood flow and foetal anthropometrics in Kenya. Int J Gynecol Obstet 2014;6:78\u201382. https:\/\/doi.org\/10.1016\/j.ijgo.2014.01.016.","key":"2025121209250618664_j_jbcpp-2020-0162_ref_002","DOI":"10.1016\/j.ijgo.2014.01.016"},{"doi-asserted-by":"crossref","unstructured":"Yanow, SK, Gavina, K, Gnidehou, MA. Impact of malaria in pregnancy as Latin America approaches elimination. Trends Parasitol 2016;1480:12.","key":"2025121209250618664_j_jbcpp-2020-0162_ref_003","DOI":"10.1016\/j.pt.2016.01.008"},{"unstructured":"World Health Organization. Antimalarial drug combination therapy, report of WHO technical consultation. Geneva: WHO Press; 2001.","key":"2025121209250618664_j_jbcpp-2020-0162_ref_004"},{"doi-asserted-by":"crossref","unstructured":"Pinheiro, LCS, Livia, MF, Da Silveira, FF, Boechat, N. Current anti-malarial theraphies and advances in the development of semi-synthetic artemisinin derivatives. An Acad Bras Cienc 2018;90:1251\u201371. https:\/\/doi.org\/10.1590\/0001-3765201820170830.","key":"2025121209250618664_j_jbcpp-2020-0162_ref_005","DOI":"10.1590\/0001-3765201820170830"},{"unstructured":"World Health Organization. Guidelines for the treatment of malaria, 3rd ed. Geneva: World Health Organization Press; 2015.","key":"2025121209250618664_j_jbcpp-2020-0162_ref_006"},{"doi-asserted-by":"crossref","unstructured":"Mishra, K, Dash, AP, Dey, N. Andrographolide: a novel antimalarial\u00a0diterpene lactone compound from A.\u00a0paniculata Nees and its interaction with curcumin and artesunate. J Trop Med 2011;2011:1\u20136. https:\/\/doi.org\/10.1155\/2011\/579518.","key":"2025121209250618664_j_jbcpp-2020-0162_ref_007","DOI":"10.1155\/2011\/579518"},{"doi-asserted-by":"crossref","unstructured":"Widyawaruyanti, A, Asrory, M, Ekasari, W, Setyawan, D, Radjaram, A, Tumewu, L, et al.. In vivo antimalarial activity of A.\u00a0paniculata tablet. Procedia Chem 2014;13:101\u20134. https:\/\/doi.org\/10.1016\/j.proche.2014.12.012.","key":"2025121209250618664_j_jbcpp-2020-0162_ref_008","DOI":"10.1016\/j.proche.2014.12.012"},{"unstructured":"Widyawaruyanti, A, Astrianto, D, Ilmi, H, Tumewu, L, Setyawan, D, Widiastuti, E, et al.. Anti-malarial activity and survival time of A.\u00a0paniculata fraction. (AS202-01) on Plasmodium berghei infected mice. Res J Pharmaceut Biol Chem Sci 2017;8:49\u201354.","key":"2025121209250618664_j_jbcpp-2020-0162_ref_009"},{"doi-asserted-by":"crossref","unstructured":"Jarukamjorn, K, Nemoto, N. Pharmacological aspects of A.\u00a0paniculata on health and its major diterpenoid constituent andrographolide. J Health Sci 2008;54:370\u201381. https:\/\/doi.org\/10.1248\/jhs.54.370.","key":"2025121209250618664_j_jbcpp-2020-0162_ref_010","DOI":"10.1248\/jhs.54.370"},{"doi-asserted-by":"crossref","unstructured":"Chao, WW, Lin, BF. Isolation and identification of bioactive compounds in A.\u00a0paniculata (Chuanxinlian). Chin Med 2010;5:17. https:\/\/doi.org\/10.1186\/1749-8546-5-17.","key":"2025121209250618664_j_jbcpp-2020-0162_ref_011","DOI":"10.1186\/1749-8546-5-17"},{"unstructured":"Akbar, S. A.\u00a0paniculata: a review of pharmacological activities and clinical effects. Alternative Med Rev 2011;16:66\u201377.","key":"2025121209250618664_j_jbcpp-2020-0162_ref_012"},{"doi-asserted-by":"crossref","unstructured":"Adetutu, A, Olorunnisola, OS, Owoade, AO, Adegbola, P. Inhibition of in\u00a0vivo growth of Plasmodium berghei by Launaea taraxacifolia and Amaranthus viridis in Mice. Malar Res Treat 2016;2016:9248024 https:\/\/doi.org\/10.1155\/2016\/9248024.","key":"2025121209250618664_j_jbcpp-2020-0162_ref_013","DOI":"10.1155\/2016\/9248024"},{"doi-asserted-by":"crossref","unstructured":"Somsak, V, Polwiang, N, Chachiyo, S. In vivo antimalarial activity of Annona muricata leaf extract in mice infected with Plasmodium berghei. J Pathog 2016;2016:3264070 https:\/\/doi.org\/10.1155\/2016\/3264070.","key":"2025121209250618664_j_jbcpp-2020-0162_ref_014","DOI":"10.1155\/2016\/3264070"},{"doi-asserted-by":"crossref","unstructured":"Peter, W, Portus, H, Robinson, L. The four-day suppressive in\u00a0vivo antimalarial test. Ann Trop Med Parasitol 1975;69:155\u201371.","key":"2025121209250618664_j_jbcpp-2020-0162_ref_015","DOI":"10.1080\/00034983.1975.11686997"},{"unstructured":"Taylor, CR, Rudbeck, L. Immunohistochemical staining methods, 6th ed. Denmark: Dako; 2013.","key":"2025121209250618664_j_jbcpp-2020-0162_ref_016"},{"doi-asserted-by":"crossref","unstructured":"Rohlan, K, Choudhary, S, Kumar, V, Shringi, N. Embedding techniques in tissue histological process. In: Ganguly, S, editor. Latest trends in zoology and entomology sciences. New Delhi: AkiNik Publication; 2018, vol 1, Chapter 4.","key":"2025121209250618664_j_jbcpp-2020-0162_ref_017","DOI":"10.22271\/ed.book02.a04"},{"unstructured":"Nowak, M, Madej, JA, Dziegeil, P. Intensity of cox 2 expression in cell of soft tissue fibrosarcomas in dog as related to grade of tumor malignation. Bull Vet Inst Pulawy 2007;51:275\u20139.","key":"2025121209250618664_j_jbcpp-2020-0162_ref_018"},{"unstructured":"Hafid, AF, Retnowati, D, Widyawaruyanti, A. The combination therapy model of A.\u00a0paniculata extract and chloroquin on Plasmodium berghei infected mice. Asian J Pharmaceut Clin Res 2015;8:205\u20138.","key":"2025121209250618664_j_jbcpp-2020-0162_ref_019"},{"doi-asserted-by":"crossref","unstructured":"Wahdi, N, Widjiati, WA, Prasetyo, B. The effect of sambiloto tablet (AS201-01) on placental chondroitin sulfate A (CSA) expression of pregnant mice infected by Plasmodium berghei. Maj Obstet Ginekol 2018;26:83\u201390. https:\/\/doi.org\/10.20473\/mog.V26I22018.83-90.","key":"2025121209250618664_j_jbcpp-2020-0162_ref_020","DOI":"10.20473\/mog.V26I22018.83-90"},{"doi-asserted-by":"crossref","unstructured":"Kinansi, RR, Mayasari, R, Pratamawati, DA. Artemisinin-based combination of antimalaria theraphy (ACT) in West Papua at 2013. BALABA 2017;13:43\u201354. https:\/\/doi.org\/10.22435\/blb.V13il.4921.43-54.","key":"2025121209250618664_j_jbcpp-2020-0162_ref_021","DOI":"10.22435\/blb.v13i1.255"},{"unstructured":"Zein, U, Fitri, LE, Saragih, A. Comparative study of anti-malarial effect of sambiloto (A.\u00a0paniculata) extract, chloroquin and artemisinin and their combination against Plasmodium falciparum in-vitro. Acta Med Indones 2013;45:38\u201343.","key":"2025121209250618664_j_jbcpp-2020-0162_ref_022"},{"doi-asserted-by":"crossref","unstructured":"Widyawaruyanti, A, Rachmat, J, Viandika, N, Ilmi, H, Tumewu, L, Prasetyo, B. Effect of A.\u00a0paniculata tablet (AS 201-01) on Transforming Growth Factor \u03b2 (TGF-\u03b2) expression and parasite inhibition in mice placenta infected with Plasmodium berghei. Bali Med J 2018;7:210\u20134. https:\/\/doi.org\/10.15562\/bmj.v717.785.","key":"2025121209250618664_j_jbcpp-2020-0162_ref_023","DOI":"10.15562\/bmj.v7i1.785"},{"unstructured":"Widyawaruyanti, A, Safarianti, TL. Antimalarial effects of A. paniculata nees on Plasmodium falciparum food vacuole. Japan: Tokushima Bunri University; 2015.","key":"2025121209250618664_j_jbcpp-2020-0162_ref_024"},{"doi-asserted-by":"crossref","unstructured":"Septiana, E, Gianny, D, Simanjuntak, P. Toxicity and in\u00a0vitro antimalarial heme polymerization inhibition activity of sambiloto (A.\u00a0paniculata). Media Litbangkes 2017;27:255\u201362. https:\/\/doi.org\/10.22435\/mpk.v27i4.6499.255-262.","key":"2025121209250618664_j_jbcpp-2020-0162_ref_025","DOI":"10.22435\/mpk.v27i4.6499.255-262"},{"doi-asserted-by":"crossref","unstructured":"Cui, L, Su, XZ. Discovery, mechanisms of action, and combination therapy of artemisinin. Expert Rev Anti-infect Ther 2009;7:999\u20131013. https:\/\/doi.org\/10.1586\/eri.09.68.NIH-PA.","key":"2025121209250618664_j_jbcpp-2020-0162_ref_026","DOI":"10.1586\/eri.09.68"},{"doi-asserted-by":"crossref","unstructured":"O\u2019neil, PM, Barton, VE, Ward, SA. The molecular mechanism of action of artemisinin-the debatte continues. Molecules 2010;15:1705\u201321. https:\/\/doi.org\/10.3390\/molecules15031705.","key":"2025121209250618664_j_jbcpp-2020-0162_ref_027","DOI":"10.3390\/molecules15031705"},{"unstructured":"Lin, C. Antimalarial activity and toxicity of piperaquine in: artemisinin-based and other antimalarials, chapter 10. Elsevier; 2018:13\u20137 pp.","key":"2025121209250618664_j_jbcpp-2020-0162_ref_028"},{"doi-asserted-by":"crossref","unstructured":"Longo, M, Zanoncelli, S, Torre, PD, Riflettuto, M, Cocco, F, Pesenti, M, et al.. In vivo and in\u00a0vitro investigation of the effects of the antimalarial drug dihydroartemisinin (DHA) on rat embryos. Reprod Toxicol 2006;22:797\u2013810. https:\/\/doi.org\/10.1016\/j.reprotox.2006.08.001.","key":"2025121209250618664_j_jbcpp-2020-0162_ref_029","DOI":"10.1016\/j.reprotox.2006.08.001"},{"doi-asserted-by":"crossref","unstructured":"Boareto, AC, Mueller, JC, Lourenco, ELB, Lombardi, N, Lourenco, AC, Rabitto, I, et al.. Effects of the combined artesunate and mefloquine anti-malarial drugs on rat embryos. Hum Exp Toxicol 2013;32:930\u201341. https:\/\/doi.org\/10.1177\/0960327113475678.","key":"2025121209250618664_j_jbcpp-2020-0162_ref_030","DOI":"10.1177\/0960327113475678"},{"doi-asserted-by":"crossref","unstructured":"Clark, RL, White, TEK, Cloude, SA, Gaunt, I, Winstanley, P, Ward, SA. Developmental toxicity of artesunate and artesunate combination in the rat and rabbit. Birth Defects Res B 2004;71:380\u201394. https:\/\/doi.org\/10.1002\/bdrb.20027.","key":"2025121209250618664_j_jbcpp-2020-0162_ref_031","DOI":"10.1002\/bdrb.20027"},{"doi-asserted-by":"crossref","unstructured":"Mishra, K, Dash, AP, Swain, BK, Dey, N. Anti-malarial activities of A.\u00a0paniculata and Hedyotis corymbosa extracts and their combination with curcumin. Malar J 2009;8:1\u20139. https:\/\/doi.org\/10.1186\/1475-2875-8-26.","key":"2025121209250618664_j_jbcpp-2020-0162_ref_032","DOI":"10.1186\/1475-2875-8-26"},{"unstructured":"Mamatha, A. Brine shrimp lethality test of A.\u00a0paniculata. Res J Pharm Technol 2014;7:743\u20135.","key":"2025121209250618664_j_jbcpp-2020-0162_ref_033"},{"doi-asserted-by":"crossref","unstructured":"Bardi, DA, Halabi, MF, Hassandarvish, P. A.\u00a0paniculata leaf extract prevents thioacetamide-induced liver cirrhosis in rats. PloS One 2014;9:109424. https:\/\/doi.org\/10.1371\/journal.pone.0109424.","key":"2025121209250618664_j_jbcpp-2020-0162_ref_034","DOI":"10.1371\/journal.pone.0109424"},{"doi-asserted-by":"crossref","unstructured":"Chene, A, Brian, V, Ibitikou, S, Dechavanne, S, Massougbodji, A, Deloron, P, et al.. Placental cytokine and chemokine profiles reflect pregnancy outcomes in women exposed to Plasmodium falciparum infection. Infect Immun 2014;82:3783\u20139. https:\/\/doi.org\/10.1128\/IAI.01922-14.","key":"2025121209250618664_j_jbcpp-2020-0162_ref_035","DOI":"10.1128\/IAI.01922-14"},{"unstructured":"Abbas, AK, Lichtman, AH, Pillai, S. Basic immunology, function and disorders of the immune system, 5th ed. Philadelphia: Saunders Elsevier; 2016:55\u201379 pp.","key":"2025121209250618664_j_jbcpp-2020-0162_ref_036"},{"doi-asserted-by":"crossref","unstructured":"Gowda, DC, Wu, X. Parasite recognition and signaling mechanisms in innate immune responses to malaria. Front Immunol 2018;9:3006. https:\/\/doi.org\/10.3389\/fimmu.2018.03006.","key":"2025121209250618664_j_jbcpp-2020-0162_ref_037","DOI":"10.3389\/fimmu.2018.03006"},{"doi-asserted-by":"crossref","unstructured":"Dieye, Y, Mbengue, B, Damagajal, S, Fall, MM, Loke, MF, Nguer, CM, et al.. Cytokine response during non cerebral and cerebral malaria: evidence of a failure to control inflammation as a cause of death in African adults. Peer J 2016;4:1\u201320. https:\/\/doi.org\/10.7717\/peerj.1965.","key":"2025121209250618664_j_jbcpp-2020-0162_ref_038","DOI":"10.7717\/peerj.1965"},{"doi-asserted-by":"crossref","unstructured":"Mens, PF, Bojtor, EC, Schallig, HD. Molecular interactions in the placenta during malaria infection. Eur J Obstet Gynecol Reprod Biol 2010;152:126\u201332. https:\/\/doi.org\/10.1016\/j.ejogrb.2010.05.013.","key":"2025121209250618664_j_jbcpp-2020-0162_ref_039","DOI":"10.1016\/j.ejogrb.2010.05.013"},{"doi-asserted-by":"crossref","unstructured":"White, TE, Bushdid, PB, Ritter, S. Artesunate-induced depletion of embryonic erythroblasts precedes embryolethality and teratogenicity in\u00a0vivo. Birth Defects Res B 2006;77:413\u20137. https:\/\/doi.org\/10.1002\/bdrb.20092.","key":"2025121209250618664_j_jbcpp-2020-0162_ref_040","DOI":"10.1002\/bdrb.20092"},{"doi-asserted-by":"crossref","unstructured":"Lin, FL, Wu, SJ, Lee, SC, Ng, IT. Anti-oxidant, anti-oedema and analgesic activities of A.\u00a0paniculata extract and their active compound andrographolide. Phytother Res 2009;23:958\u201364. https:\/\/doi.org\/10.1002\/ptr.2701.","key":"2025121209250618664_j_jbcpp-2020-0162_ref_041","DOI":"10.1002\/ptr.2701"}],"container-title":["Journal of Basic and Clinical Physiology and Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/jbcpp-2020-0162\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/jbcpp-2020-0162\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T12:26:29Z","timestamp":1765542389000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/jbcpp-2020-0162\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,11]]},"references-count":41,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,2,10]]},"published-print":{"date-parts":[[2022,3,28]]}},"alternative-id":["10.1515\/jbcpp-2020-0162"],"URL":"https:\/\/doi.org\/10.1515\/jbcpp-2020-0162","relation":{},"ISSN":["2191-0286"],"issn-type":[{"type":"electronic","value":"2191-0286"}],"subject":[],"published":{"date-parts":[[2021,2,11]]}}}