Date Log
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Enhanced Malaria Survival: the Synergistic Effect of Aqueous Extracted a. Muricata Leaves with ACT
Corresponding Author(s) : Kis Djamiatun
International Journal of Allied Medical Sciences and Clinical Research,
Vol. 12 No. 2 (2024): 2024 Volume -12 - Issue 2
Abstract
Background: Combination therapy is essential for safeguarding both current and future antimalarial medications. Some argue that managing cerebral malaria necessitates adjunctive therapy. The efficacy of Annona muricata as an adjunct to Artemisinin-based-combination-therapy (ACT) remains uncertain, with evaluation based on host-survival in malaria.
Objective: To demonstrate the impact of aqueous extracted A. muricata leaf (AEAML) on the host-survival and parasite load in ACT-treated-malaria.
Method: A post-test-only-control-group-design-study was conducted and used 48-Swiss-mice which divided into four-groups. The K-group received water, whereas the P1-group was administered with AEAML. The P2-group received ACT, while the P3-group received an AEAML-ACT-combination. All mice were infected with 107 Plasmodium berghei ANKA (PbA). Parasitemia and survival were monitored. Results: The lowest-parasitemia-percentages of the P3 and P2-groups was no significant-different at day-5,7,9,17-PbA-infection (p>0.05). Conversely, both P1 and K-groups displayed the highest-parasitemia-percentages at these time-points, with no notable differences between them (p>0.05). From day-13-infection onward, the number of surviving-mice in P1-group significantly differed from that in K-group, marked by a notable decrease in K compared to P1-group. The survival-rate in P1-group sharply-declined in comparison to P2-group. By the end of the study, 11 mice in P2 and 10 in P3 survived. Notably, the mean-survival-time was higher in groups-P2 and P3, contrasting with the lower in groups-K and P1. Significantly differing outcomes among the four test groups were confirmed by the log-rank test (Mantel-Cox), with a p-value of 0.0001.
Conclusion: Annona muricata demonstrates a more significant impact on both the survival-rate and parasite-load of ACT-treated-malaria compared to those not receiving ACT.
Keywords
Download Citation
Endnote/Zotero/Mendeley (RIS)BibTeX
- WHO, Malaria. General Malaria Fact Sheet, 2023.
- WHO, Evidence-Informed Action to Eliminate Malaria in Indonesia. WHO Result Report 2020.
- Arya A, Kojom Foko LP, Chaudhry S, Sharma A, and Singh V, Artemisinin-Based Combination Therapy (Act) and Drug Resistance Molecular Markers: A Systematic Review of Clinical Studies from Two Malaria Endemic Regions - India and Sub-Saharan Africa. Int J Parasitol Drugs Drug Resist, 2021; 15.43-56.DOI: 10.1016/j.ijpddr.2020.11.006.
- Siddiqui FA, Liang X, and Cui L, Plasmodium Falciparum Resistance to Acts: Emergence, Mechanisms, and Outlook. International Journal for Parasitology: Drugs and Drug Resistance, 2021; 16.102-118.DOI: https://doi.org/10.1016/j.ijpddr.2021.05.007.
- Zhu L, van der Pluijm RW, Kucharski M, Nayak S, Tripathi J, White NJ, Day NPJ, Faiz A, Phyo AP, Amaratunga C, Lek D, Ashley EA, Nosten F, Smithuis F, Ginsburg H, von Seidlein L, Lin K, Imwong M, Chotivanich K, Mayxay M, Dhorda M, Nguyen HC, Nguyen TNT, Miotto O, Newton PN, Jittamala P, Tripura R, Pukrittayakamee S, Peto TJ, Hien TT, Dondorp AM, and Bozdech Z, Artemisinin Resistance in the Malaria Parasite, Plasmodium Falciparum, Originates from Its Initial Transcriptional Response. Communications Biology, 2022; 5(1).274.DOI: 10.1038/s42003-022-03215-0.
- Nguyen TD, Gao B, Amaratunga C, Dhorda M, Tran TN-A, White NJ, Dondorp AM, Boni MF, and Aguas R, Preventing Antimalarial Drug Resistance with Triple Artemisinin-Based Combination Therapies. Nature Communications, 2023; 14(1).4568.DOI: 10.1038/s41467-023-39914-3.
- Somsak V, Polwiang N, and Chachiyo S, In Vivo Antimalarial Activity of Annona Muricata Leaf Extract in Mice Infected with Plasmodium Berghei. J Pathog, 2016; 2016.3264070.DOI: 10.1155/2016/3264070.
- Nwonuma CO, Balogun EA, and Gyebi GA, Evaluation of Antimalarial Activity of Ethanolic Extract of Annona Muricata L.: An in Vivo and an in Silico Approach. Journal of Evidence-Based Integrative Medicine, 2023; 28.2515690X231165104.DOI: 10.1177/2515690x231165104.
- Djamiatun K, Abdulaziz KMA, Naamat WFA, Kristina TN, and Nugroho D, Annona Muricata Associated with Increase Phytohemaglutinin Induced Spleen Il-10 Production of Swiss Mice During Cerebral Malaria Phase. Advanced Science Letters, 2017; 23(4).3344-3348.DOI: 10.1166/asl.2017.9161.
- Djamiatun K, Naamat WFA, Dharmana E, Wijayahadi N, and Nugroho D, Reduce Spleen-Ifn-Gamma Correlated with Cxcl9 Levels During Cerebral Malaria Phase in Annona Muricata-Treated Swiss Mouse Study. Advanced Science Letters, 2017; 23(4).3380-3384.DOI: 10.1166/asl.2017.9179.
- Freitas do Rosário AP, Lamb T, Spence P, Stephens R, Lang A, Roers A, Muller W, O’Garra A, and Langhorne J, Il-27 Promotes Il-10 Production by Effector Th1 Cd4+ T Cells: A Critical Mechanism for Protection from Severe Immunopathology During Malaria Infection. The Journal of Immunology, 2012; 188(3).1178-1190.DOI: 10.4049/jimmunol.1102755.
- Surette FA, Guthmiller JJ, Li L, Sturtz AJ, Vijay R, Pope RL, McClellan BL, Pack AD, Zander R, Shao P, Lan L, Fernandez‐Ruiz D, Heath WR, Wilson PC, and Butler NS, Extrafollicular Cd4 T Cell-Derived Il-10 Functions Rapidly and Transiently to Support Anti-Plasmodium Humoral Immunity. PLOS Pathogens, 2021.DOI: 10.1371/journal.ppat.1009288.
- Wilson NO, Jain V, Roberts CE, Lucchi N, Joel PK, Singh MP, Nagpal AC, Dash AP, Udhayakumar V, Singh N, and Stiles JK, Cxcl4 and Cxcl10 Predict Risk of Fatal Cerebral Malaria. Dis Markers, 2011; 30(1).39-49.DOI: 10.3233/dma-2011-0763.
- Lekpor CE, Botchway F, Kusi KA, Adjei AA, Wilson MD, Stiles JK, and Wilson NO, Angiogenic and Angiostatic Factors Present in the Saliva of Malaria Patients. Malaria Journal, 2022; 21(1).220.DOI: 10.1186/s12936-022-04221-7.
- Wilson NO, Solomon W, Anderson L, Patrickson J, Pitts S, Bond V, Liu M, and Stiles JK, Pharmacologic Inhibition of Cxcl10 in Combination with Anti-Malarial Therapy Eliminates Mortality Associated with Murine Model of Cerebral Malaria. PLoS One, 2013; 8(4).e60898.DOI: 10.1371/journal.pone.0060898.
- Sulayman A, Djamiatun K, and Muniroh M, Effectivity of Annona Muricata and Artemisinin Combined Therapy on Brain Cxcl10 Expression (Study in Swiss Mice During Severe Plasmodium Berghei Anka Infection). Journal of Biomedicine and Translational Research, 2019; 5.47-52.DOI: 10.14710/jbtr.v5i2.4802.
- Tembo D, Harawa V, Tran TC, Afran L, Molyneux ME, Taylor TE, Seydel KB, Nyirenda T, Russell DG, and Mandala W, The Ability of Interleukin–10 to Negate Haemozoin-Related Pro-Inflammatory Effects Has the Potential to Restore Impaired Macrophage Function Associated with Malaria Infection. Malaria Journal, 2023; 22(1).125.DOI: 10.1186/s12936-023-04539-w.
- White NJ, Severe Malaria. Malaria Journal, 2022; 21(1).284.DOI: 10.1186/s12936-022-04301-8.
- O'Neal KA, Zeltner SL, Foscue CL, and Stumhofer JS, Bhlhe40 Limits Early Il-10 Production from Cd4(+) T Cells During Plasmodium Yoelii 17x Infection. Infect Immun, 2023; 91(11).e0036723.DOI: 10.1128/iai.00367-23.
- Guiyedi V, Bécavin C, Herbert F, Gray J, Cazenave P-A, Kombila M, Crisanti A, Fesel C, and Pied S, Asymptomatic Plasmodium Falciparum Infection in Children Is Associated with Increased Auto-Antibody Production, High Il-10 Plasma Levels and Antibodies to Merozoite Surface Protein 3. Malaria Journal, 2015; 14(1).162.DOI: 10.1186/s12936-015-0658-7.
- Badell E, Oeuvray C, Moreno Sabater A, Soe S, Van Rooijen N, Bouzidi A, and Druilhe P, Human Malaria in Immunocompromised Mice: An in Vivo Model to Study Defense Mechanisms against Plasmodium Falciparum. The Journal of Experimental Medicine, 2000; 192.1653-1660.DOI: 10.1084/jem.192.11.1653.
- Mbengue B, Sylla Niang M, Ndiaye Diallo R, Diop G, Thiam A, Ka O, Touré A, Tall A, Perraut R, and Dièye A, [Igg Responses to Candidate Malaria Vaccine Antigens in the Urban Area of Dakar (Senegal): Evolution According to Age and Parasitemia in Patients with Mild Symptoms]. Bull Soc Pathol Exot, 2015; 108(2).94-101.DOI: 10.1007/s13149-015-0419-4.
- Rambhatla JS, Tonkin-Hill GQ, Takashima E, Tsuboi T, Noviyanti R, Trianty L, Sebayang BF, Lampah DA, Marfurt J, Price RN, Anstey NM, Papenfuss AT, Damelang T, Chung AW, Duffy MF, and Rogerson SJ, Identifying Targets of Protective Antibodies against Severe Malaria in Papua, Indonesia, Using Locally Expressed Domains of Plasmodium Falciparum Erythrocyte Membrane Protein 1. Infect Immun, 2022; 90(2).e0043521.DOI: 10.1128/iai.00435-21.
- Surette FA, Guthmiller JJ, Li L, Sturtz AJ, Vijay R, Pope RL, McClellan BL, Pack AD, Zander RA, Shao P, Lan LY-L, Fernandez-Ruiz D, Heath WR, Wilson PC, and Butler NS, Extrafollicular Cd4 T Cell-Derived Il-10 Functions Rapidly and Transiently to Support Anti-Plasmodium Humoral Immunity. PLOS Pathogens, 2021; 17(2).e1009288.DOI: 10.1371/journal.ppat.1009288.
- Mukherjee D, Chora ÂF, Lone J-C, Ramiro RS, Blankenhaus B, Serre K, Ramirez M, Gordo I, Veldhoen M, Varga-Weisz P, and Mota MM, Host Lung Microbiota Promotes Malaria-Associated Acute Respiratory Distress Syndrome. Nature Communications, 2022; 13(1).3747.DOI: 10.1038/s41467-022-31301-8.
- Djamiatun K, Wirman RP, and Wijayahadi N, Effect of Combination Songga-Wood-Stem (Strychnos Ligustrina Blume) and Antimalaria-Act on Il-10 Production of Malaria. Journal of Biomedicine and Translational Research, 2022.
References
WHO, Malaria. General Malaria Fact Sheet, 2023.
WHO, Evidence-Informed Action to Eliminate Malaria in Indonesia. WHO Result Report 2020.
Arya A, Kojom Foko LP, Chaudhry S, Sharma A, and Singh V, Artemisinin-Based Combination Therapy (Act) and Drug Resistance Molecular Markers: A Systematic Review of Clinical Studies from Two Malaria Endemic Regions - India and Sub-Saharan Africa. Int J Parasitol Drugs Drug Resist, 2021; 15.43-56.DOI: 10.1016/j.ijpddr.2020.11.006.
Siddiqui FA, Liang X, and Cui L, Plasmodium Falciparum Resistance to Acts: Emergence, Mechanisms, and Outlook. International Journal for Parasitology: Drugs and Drug Resistance, 2021; 16.102-118.DOI: https://doi.org/10.1016/j.ijpddr.2021.05.007.
Zhu L, van der Pluijm RW, Kucharski M, Nayak S, Tripathi J, White NJ, Day NPJ, Faiz A, Phyo AP, Amaratunga C, Lek D, Ashley EA, Nosten F, Smithuis F, Ginsburg H, von Seidlein L, Lin K, Imwong M, Chotivanich K, Mayxay M, Dhorda M, Nguyen HC, Nguyen TNT, Miotto O, Newton PN, Jittamala P, Tripura R, Pukrittayakamee S, Peto TJ, Hien TT, Dondorp AM, and Bozdech Z, Artemisinin Resistance in the Malaria Parasite, Plasmodium Falciparum, Originates from Its Initial Transcriptional Response. Communications Biology, 2022; 5(1).274.DOI: 10.1038/s42003-022-03215-0.
Nguyen TD, Gao B, Amaratunga C, Dhorda M, Tran TN-A, White NJ, Dondorp AM, Boni MF, and Aguas R, Preventing Antimalarial Drug Resistance with Triple Artemisinin-Based Combination Therapies. Nature Communications, 2023; 14(1).4568.DOI: 10.1038/s41467-023-39914-3.
Somsak V, Polwiang N, and Chachiyo S, In Vivo Antimalarial Activity of Annona Muricata Leaf Extract in Mice Infected with Plasmodium Berghei. J Pathog, 2016; 2016.3264070.DOI: 10.1155/2016/3264070.
Nwonuma CO, Balogun EA, and Gyebi GA, Evaluation of Antimalarial Activity of Ethanolic Extract of Annona Muricata L.: An in Vivo and an in Silico Approach. Journal of Evidence-Based Integrative Medicine, 2023; 28.2515690X231165104.DOI: 10.1177/2515690x231165104.
Djamiatun K, Abdulaziz KMA, Naamat WFA, Kristina TN, and Nugroho D, Annona Muricata Associated with Increase Phytohemaglutinin Induced Spleen Il-10 Production of Swiss Mice During Cerebral Malaria Phase. Advanced Science Letters, 2017; 23(4).3344-3348.DOI: 10.1166/asl.2017.9161.
Djamiatun K, Naamat WFA, Dharmana E, Wijayahadi N, and Nugroho D, Reduce Spleen-Ifn-Gamma Correlated with Cxcl9 Levels During Cerebral Malaria Phase in Annona Muricata-Treated Swiss Mouse Study. Advanced Science Letters, 2017; 23(4).3380-3384.DOI: 10.1166/asl.2017.9179.
Freitas do Rosário AP, Lamb T, Spence P, Stephens R, Lang A, Roers A, Muller W, O’Garra A, and Langhorne J, Il-27 Promotes Il-10 Production by Effector Th1 Cd4+ T Cells: A Critical Mechanism for Protection from Severe Immunopathology During Malaria Infection. The Journal of Immunology, 2012; 188(3).1178-1190.DOI: 10.4049/jimmunol.1102755.
Surette FA, Guthmiller JJ, Li L, Sturtz AJ, Vijay R, Pope RL, McClellan BL, Pack AD, Zander R, Shao P, Lan L, Fernandez‐Ruiz D, Heath WR, Wilson PC, and Butler NS, Extrafollicular Cd4 T Cell-Derived Il-10 Functions Rapidly and Transiently to Support Anti-Plasmodium Humoral Immunity. PLOS Pathogens, 2021.DOI: 10.1371/journal.ppat.1009288.
Wilson NO, Jain V, Roberts CE, Lucchi N, Joel PK, Singh MP, Nagpal AC, Dash AP, Udhayakumar V, Singh N, and Stiles JK, Cxcl4 and Cxcl10 Predict Risk of Fatal Cerebral Malaria. Dis Markers, 2011; 30(1).39-49.DOI: 10.3233/dma-2011-0763.
Lekpor CE, Botchway F, Kusi KA, Adjei AA, Wilson MD, Stiles JK, and Wilson NO, Angiogenic and Angiostatic Factors Present in the Saliva of Malaria Patients. Malaria Journal, 2022; 21(1).220.DOI: 10.1186/s12936-022-04221-7.
Wilson NO, Solomon W, Anderson L, Patrickson J, Pitts S, Bond V, Liu M, and Stiles JK, Pharmacologic Inhibition of Cxcl10 in Combination with Anti-Malarial Therapy Eliminates Mortality Associated with Murine Model of Cerebral Malaria. PLoS One, 2013; 8(4).e60898.DOI: 10.1371/journal.pone.0060898.
Sulayman A, Djamiatun K, and Muniroh M, Effectivity of Annona Muricata and Artemisinin Combined Therapy on Brain Cxcl10 Expression (Study in Swiss Mice During Severe Plasmodium Berghei Anka Infection). Journal of Biomedicine and Translational Research, 2019; 5.47-52.DOI: 10.14710/jbtr.v5i2.4802.
Tembo D, Harawa V, Tran TC, Afran L, Molyneux ME, Taylor TE, Seydel KB, Nyirenda T, Russell DG, and Mandala W, The Ability of Interleukin–10 to Negate Haemozoin-Related Pro-Inflammatory Effects Has the Potential to Restore Impaired Macrophage Function Associated with Malaria Infection. Malaria Journal, 2023; 22(1).125.DOI: 10.1186/s12936-023-04539-w.
White NJ, Severe Malaria. Malaria Journal, 2022; 21(1).284.DOI: 10.1186/s12936-022-04301-8.
O'Neal KA, Zeltner SL, Foscue CL, and Stumhofer JS, Bhlhe40 Limits Early Il-10 Production from Cd4(+) T Cells During Plasmodium Yoelii 17x Infection. Infect Immun, 2023; 91(11).e0036723.DOI: 10.1128/iai.00367-23.
Guiyedi V, Bécavin C, Herbert F, Gray J, Cazenave P-A, Kombila M, Crisanti A, Fesel C, and Pied S, Asymptomatic Plasmodium Falciparum Infection in Children Is Associated with Increased Auto-Antibody Production, High Il-10 Plasma Levels and Antibodies to Merozoite Surface Protein 3. Malaria Journal, 2015; 14(1).162.DOI: 10.1186/s12936-015-0658-7.
Badell E, Oeuvray C, Moreno Sabater A, Soe S, Van Rooijen N, Bouzidi A, and Druilhe P, Human Malaria in Immunocompromised Mice: An in Vivo Model to Study Defense Mechanisms against Plasmodium Falciparum. The Journal of Experimental Medicine, 2000; 192.1653-1660.DOI: 10.1084/jem.192.11.1653.
Mbengue B, Sylla Niang M, Ndiaye Diallo R, Diop G, Thiam A, Ka O, Touré A, Tall A, Perraut R, and Dièye A, [Igg Responses to Candidate Malaria Vaccine Antigens in the Urban Area of Dakar (Senegal): Evolution According to Age and Parasitemia in Patients with Mild Symptoms]. Bull Soc Pathol Exot, 2015; 108(2).94-101.DOI: 10.1007/s13149-015-0419-4.
Rambhatla JS, Tonkin-Hill GQ, Takashima E, Tsuboi T, Noviyanti R, Trianty L, Sebayang BF, Lampah DA, Marfurt J, Price RN, Anstey NM, Papenfuss AT, Damelang T, Chung AW, Duffy MF, and Rogerson SJ, Identifying Targets of Protective Antibodies against Severe Malaria in Papua, Indonesia, Using Locally Expressed Domains of Plasmodium Falciparum Erythrocyte Membrane Protein 1. Infect Immun, 2022; 90(2).e0043521.DOI: 10.1128/iai.00435-21.
Surette FA, Guthmiller JJ, Li L, Sturtz AJ, Vijay R, Pope RL, McClellan BL, Pack AD, Zander RA, Shao P, Lan LY-L, Fernandez-Ruiz D, Heath WR, Wilson PC, and Butler NS, Extrafollicular Cd4 T Cell-Derived Il-10 Functions Rapidly and Transiently to Support Anti-Plasmodium Humoral Immunity. PLOS Pathogens, 2021; 17(2).e1009288.DOI: 10.1371/journal.ppat.1009288.
Mukherjee D, Chora ÂF, Lone J-C, Ramiro RS, Blankenhaus B, Serre K, Ramirez M, Gordo I, Veldhoen M, Varga-Weisz P, and Mota MM, Host Lung Microbiota Promotes Malaria-Associated Acute Respiratory Distress Syndrome. Nature Communications, 2022; 13(1).3747.DOI: 10.1038/s41467-022-31301-8.
Djamiatun K, Wirman RP, and Wijayahadi N, Effect of Combination Songga-Wood-Stem (Strychnos Ligustrina Blume) and Antimalaria-Act on Il-10 Production of Malaria. Journal of Biomedicine and Translational Research, 2022.