Home A tablet derived from Andrographis paniculata complements dihydroartemisinin-piperaquine treatment of malaria in pregnant mice
Article
Licensed
Unlicensed Requires Authentication

A tablet derived from Andrographis paniculata complements dihydroartemisinin-piperaquine treatment of malaria in pregnant mice

  • Bastiana , Aty Widyawaruyanti , Hilkatul Ilmi , Lidya Tumewu , Budi Prasetyo , Achmad Fuad Hafid and Aryati
Published/Copyright: February 11, 2021

Abstract

Objectives

The use of standard antimalarial drugs, such as dihydroartemisinin-piperaquine (DHP) for the treatment of malaria during pregnancy is limited due to the risk of teratogenicity. The alternative is therefore required although few exist. Here we show a phytopharmaceutical drug derived from Andrographis paniculata (AS201-01), which is effective as herbal antimalarial both in vitro and in vivo and may be a suitable alternative when used in complementary treatment with DHP.

Methods

Plasmodium berghei 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-γ, TNF- α, IL-10, placental parasite counts and foetal morphology.

Results

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-γ and IL-10, whereas TNF-α 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.

Conclusions

A combination of A. paniculata tablet (AS201-01) with DHP has the potential to reduce the toxicity of DHP in malaria treatment.


Corresponding author: Aty Widyawaruyanti, Natural Product Medicine Research and Development, Institute of Tropical Disease, Universitas Airlangga, C Campus Universitas Airlangga, Mulyorejo, Surabaya 60115, Indonesia; and Department of Pharmacognosy and Phytochemistry, Faculty of Pharmacy, Universitas Airlangga, C Campus Universitas Airlangga, Mulyorejo, Surabaya 60115, Indonesia, Phone: +628113404171, E-mail:

Funding source: Universitas Airlangga

Award Identifier / Grant number: 564/UN3.14/LT/2016

Acknowledgments

The authors thank the management of Institute of Tropical Disease of Universitas Airlangga for providing support in terms of facilities.

  1. Research funding: This research was funded by Airlangga University through Mandat Research Grant 2016 contract no. 564/UN3.14/LT/2016.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Not applicable.

  5. Ethical approval: This experimental study has received ethical approval from the Ethics Committee of the Faculty of Veterinary Medicine, Universitas Airlangga No: 2.KE.185.10.2019.

References

1. McDonald, CR, Tran, V, Kain, KC. Complement activation in placental malaria. Front Microbiol 2015;6:1460. https://doi.org/10.3389/fmicb.2015.01460.Search in Google Scholar PubMed PubMed Central

2. 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;6:78–82. https://doi.org/10.1016/j.ijgo.2014.01.016.Search in Google Scholar PubMed PubMed Central

3. Yanow, SK, Gavina, K, Gnidehou, MA. Impact of malaria in pregnancy as Latin America approaches elimination. Trends Parasitol 2016;1480:12.10.1016/j.pt.2016.01.008Search in Google Scholar PubMed

4. World Health Organization. Antimalarial drug combination therapy, report of WHO technical consultation. Geneva: WHO Press; 2001.Search in Google Scholar

5. 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;90:1251–71. https://doi.org/10.1590/0001-3765201820170830.Search in Google Scholar PubMed

6. World Health Organization. Guidelines for the treatment of malaria, 3rd ed. Geneva: World Health Organization Press; 2015.Search in Google Scholar

7. Mishra, K, Dash, AP, Dey, N. Andrographolide: a novel antimalarial diterpene lactone compound from A. paniculata Nees and its interaction with curcumin and artesunate. J Trop Med 2011;2011:1–6. https://doi.org/10.1155/2011/579518.Search in Google Scholar PubMed PubMed Central

8. Widyawaruyanti, A, Asrory, M, Ekasari, W, Setyawan, D, Radjaram, A, Tumewu, L, et al.. In vivo antimalarial activity of A. paniculata tablet. Procedia Chem 2014;13:101–4. https://doi.org/10.1016/j.proche.2014.12.012.Search in Google Scholar

9. Widyawaruyanti, A, Astrianto, D, Ilmi, H, Tumewu, L, Setyawan, D, Widiastuti, E, et al.. Anti-malarial activity and survival time of A. paniculata fraction. (AS202-01) on Plasmodium berghei infected mice. Res J Pharmaceut Biol Chem Sci 2017;8:49–54.Search in Google Scholar

10. Jarukamjorn, K, Nemoto, N. Pharmacological aspects of A. paniculata on health and its major diterpenoid constituent andrographolide. J Health Sci 2008;54:370–81. https://doi.org/10.1248/jhs.54.370.Search in Google Scholar

11. Chao, WW, Lin, BF. Isolation and identification of bioactive compounds in A. paniculata (Chuanxinlian). Chin Med 2010;5:17. https://doi.org/10.1186/1749-8546-5-17.Search in Google Scholar PubMed PubMed Central

12. Akbar, S. A. paniculata: a review of pharmacological activities and clinical effects. Alternative Med Rev 2011;16:66–77.Search in Google Scholar

13. Adetutu, A, Olorunnisola, OS, Owoade, AO, Adegbola, P. Inhibition of in vivo 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.Search in Google Scholar PubMed PubMed Central

14. 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.Search in Google Scholar PubMed PubMed Central

15. Peter, W, Portus, H, Robinson, L. The four-day suppressive in vivo antimalarial test. Ann Trop Med Parasitol 1975;69:155–71.10.1080/00034983.1975.11686997Search in Google Scholar

16. Taylor, CR, Rudbeck, L. Immunohistochemical staining methods, 6th ed. Denmark: Dako; 2013.Search in Google Scholar

17. 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 4.10.22271/ed.book02.a04Search in Google Scholar

18. 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;51:275–9.Search in Google Scholar

19. Hafid, AF, Retnowati, D, Widyawaruyanti, A. The combination therapy model of A. paniculata extract and chloroquin on Plasmodium berghei infected mice. Asian J Pharmaceut Clin Res 2015;8:205–8.Search in Google Scholar

20. 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;26:83–90. https://doi.org/10.20473/mog.V26I22018.83-90.Search in Google Scholar

21. Kinansi, RR, Mayasari, R, Pratamawati, DA. Artemisinin-based combination of antimalaria theraphy (ACT) in West Papua at 2013. BALABA 2017;13:43–54. https://doi.org/10.22435/blb.V13il.4921.43-54.Search in Google Scholar

22. Zein, U, Fitri, LE, Saragih, A. Comparative study of anti-malarial effect of sambiloto (A. paniculata) extract, chloroquin and artemisinin and their combination against Plasmodium falciparum in-vitro. Acta Med Indones 2013;45:38–43.Search in Google Scholar

23. Widyawaruyanti, A, Rachmat, J, Viandika, N, Ilmi, H, Tumewu, L, Prasetyo, B. Effect of A. paniculata tablet (AS 201-01) on Transforming Growth Factor β (TGF-β) expression and parasite inhibition in mice placenta infected with Plasmodium berghei. Bali Med J 2018;7:210–4. https://doi.org/10.15562/bmj.v717.785.Search in Google Scholar

24. Widyawaruyanti, A, Safarianti, TL. Antimalarial effects of A. paniculata nees on Plasmodium falciparum food vacuole. Japan: Tokushima Bunri University; 2015.Search in Google Scholar

25. Septiana, E, Gianny, D, Simanjuntak, P. Toxicity and in vitro antimalarial heme polymerization inhibition activity of sambiloto (A. paniculata). Media Litbangkes 2017;27:255–62. https://doi.org/10.22435/mpk.v27i4.6499.255-262.Search in Google Scholar

26. Cui, L, Su, XZ. Discovery, mechanisms of action, and combination therapy of artemisinin. Expert Rev Anti-infect Ther 2009;7:999–1013. https://doi.org/10.1586/eri.09.68.NIH-PA.Search in Google Scholar

27. O’neil, PM, Barton, VE, Ward, SA. The molecular mechanism of action of artemisinin-the debatte continues. Molecules 2010;15:1705–21. https://doi.org/10.3390/molecules15031705.Search in Google Scholar PubMed PubMed Central

28. Lin, C. Antimalarial activity and toxicity of piperaquine in: artemisinin-based and other antimalarials, chapter 10. Elsevier; 2018:13–7 pp.Search in Google Scholar

29. Longo, M, Zanoncelli, S, Torre, PD, Riflettuto, M, Cocco, F, Pesenti, M, et al.. In vivo and in vitro investigation of the effects of the antimalarial drug dihydroartemisinin (DHA) on rat embryos. Reprod Toxicol 2006;22:797–810. https://doi.org/10.1016/j.reprotox.2006.08.001.Search in Google Scholar PubMed

30. 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;32:930–41. https://doi.org/10.1177/0960327113475678.Search in Google Scholar PubMed

31. 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;71:380–94. https://doi.org/10.1002/bdrb.20027.Search in Google Scholar PubMed

32. Mishra, K, Dash, AP, Swain, BK, Dey, N. Anti-malarial activities of A. paniculata and Hedyotis corymbosa extracts and their combination with curcumin. Malar J 2009;8:1–9. https://doi.org/10.1186/1475-2875-8-26.Search in Google Scholar PubMed PubMed Central

33. Mamatha, A. Brine shrimp lethality test of A. paniculata. Res J Pharm Technol 2014;7:743–5.Search in Google Scholar

34. Bardi, DA, Halabi, MF, Hassandarvish, P. A. paniculata leaf extract prevents thioacetamide-induced liver cirrhosis in rats. PloS One 2014;9:109424. https://doi.org/10.1371/journal.pone.0109424.Search in Google Scholar PubMed PubMed Central

35. 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;82:3783–9. https://doi.org/10.1128/IAI.01922-14.Search in Google Scholar PubMed PubMed Central

36. Abbas, AK, Lichtman, AH, Pillai, S. Basic immunology, function and disorders of the immune system, 5th ed. Philadelphia: Saunders Elsevier; 2016:55–79 pp.Search in Google Scholar

37. 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.Search in Google Scholar PubMed PubMed Central

38. 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;4:1–20. https://doi.org/10.7717/peerj.1965.Search in Google Scholar PubMed PubMed Central

39. Mens, PF, Bojtor, EC, Schallig, HD. Molecular interactions in the placenta during malaria infection. Eur J Obstet Gynecol Reprod Biol 2010;152:126–32. https://doi.org/10.1016/j.ejogrb.2010.05.013.Search in Google Scholar PubMed

40. White, TE, Bushdid, PB, Ritter, S. Artesunate-induced depletion of embryonic erythroblasts precedes embryolethality and teratogenicity in vivo. Birth Defects Res B 2006;77:413–7. https://doi.org/10.1002/bdrb.20092.Search in Google Scholar PubMed

41. Lin, FL, Wu, SJ, Lee, SC, Ng, IT. Anti-oxidant, anti-oedema and analgesic activities of A. paniculata extract and their active compound andrographolide. Phytother Res 2009;23:958–64. https://doi.org/10.1002/ptr.2701.Search in Google Scholar PubMed

Received: 2020-05-25
Accepted: 2020-11-04
Published Online: 2021-02-11

© 2021 Walter de Gruyter GmbH, Berlin/Boston

Downloaded on 10.9.2025 from https://www.degruyterbrill.com/document/doi/10.1515/jbcpp-2020-0162/html
Scroll to top button