Document Type : Original Article(s)
Authors
1 Department of Parasitology, Faculty of Medicine, Maranatha Christian University (Universitas Kristen Maranatha), Bandung, Indonesia
2 Department of Pharmacology, Faculty of Pharmacy, Universitas Jenderal Achmad Yani, Bandung, Indonesia
3 Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran (Unpad), Bandung, Indonesia
Abstract
Background: Malaria drug resistance is one of the leading causes of malaria-related morbidity and mortality worldwide. Alpha-mangostin exhibits antimalarial and antioxidant activity in vitro. The soluble alpha-mangostin chitosan alginate nanoparticles (ACAN) exhibit proper antimalarial activity in vivo. This study aimed to explore the antimalarial activity of the chloroquine-ACAN combination and the interaction between them in various ratios.
Methods: A 4-day suppressive test, according to Peter’s test, was conducted using P. berghei-inoculated Swiss Webster mice in Bandung, 2024. It was done for six different concentrations (in triplicate) of three kinds of the combinations respectively i.e.: ½ effective dose 50 (ED50) ACAN:½ED50 chloroquine (ratio-1, ACAN and chloroquine were used in a weight ratio of 189:1), ¼ ED50 ACAN:¾ ED50 chloroquine (ratio-2, weight ratio of 63:1), ¾ ED50 ACAN:¼ ED50 chloroquine (ratio-3, weight ratio of 567:1) to find out growth inhibitory percentage of each concentration. ED50 of each combination was determined using probit analysis in IBM SPSS Statistics 27 software. The sum of fractional effective dose 50 (∑FED50) was determined using a specific formula. ∑FED50 indicates the kind of interaction: <1, >1, or =1 means synergistic, antagonistic, or additive.
Results: ED50 of ratio-1 (ACAN/Chloroquine weight ratio 189/1), ratio-2 (weight ratio 63/1), ratio-3 (weight ratio 567/1) is 9.196, 7.626, 82.13 mg/Kg BW (<100 mg/Kg BW). ∑FED50 of ratio-1, ratio-2, and ratio-3 is 0.069, 0.113, and 0.414 (far below 1).
Conclusion: ACAN-chloroquine exhibits good and marked synergistic antimalarial activity, especially in a ratio-1. It offers a glimmer of hope for future research to combat and ultimately eliminate malaria.
Highlights
Susy Tjahjani (Google Scholar)
Keywords
- Chora  F, Mota MM, Prudêncio M. The reciprocal influence of the liver and blood stages of the malaria parasite’s life cycle. Int J Parasitol. 2022;52:711-5. doi: 10.1016/j.ijpara.2022.02.002. PubMed PMID: 35367213.
- World Health Organization. World malaria report 2021. Geneva: WHO; 2021 [cited 03 September 2025]. Available from: https://www.who.int/teams/global-malaria-programme/reports/world-malaria-report-2021
- Centers for Disease Control and Prevention. Drug resistance in the malaria endemic world. Atlanta: CDC; 2019 [cited 18 September 2025]. Available from: https://www.cdc.gov/malaria/malaria_worldwide/reduction/drug_resistance.html
- Hassett MR, Roepe PD. Origin and Spread of Evolving Artemisinin-Resistant Plasmodium falciparum Malarial Parasites in Southeast Asia. Am J Trop Med Hyg. 2019;101:1204-11. doi: 10.4269/ajtmh.19-0379. PubMed PMID: 31642425; PubMed Central PMCID: PMC6896886.
- Siddiqui FA, Liang X, Cui L. Plasmodium falciparum resistance to ACTs: Emergence, mechanisms, and outlook. Int J Parasitol Drugs Drug Resist. 2021;16:102-18. doi: 10.1016/j.ijpddr.2021.05.007. PubMed PMID: 34090067; PubMed Central PMCID: PMC8188179.
- Balikagala B, Sakurai-Yatsushiro M, Tachibana SI, Ikeda M, Yamauchi M, Katuro OT, et al. Recovery and stable persistence of chloroquine sensitivity in Plasmodium falciparum parasites after its discontinued use in Northern Uganda. Malar J. 2020;19:76. doi: 10.1186/s12936-020-03157-0. PubMed PMID: 32070358; PubMed Central PMCID: PMC7026951.
- Asare KK, Africa J, Mbata J, Opoku YK. The emergence of chloroquine-sensitive Plasmodium falciparum is influenced by selected communities in some parts of the Central Region of Ghana. Malar J. 2021;20:447. doi: 10.1186/s12936-021-03985-8. PubMed PMID: 34823528; PubMed Central PMCID: PMC8620919.
- Uddin TM, Chakraborty AJ, Khusro A, Zidan BRM, Mitra S, Emran TB, et al. Antibiotic resistance in microbes: History, mechanisms, therapeutic strategies and future prospects. J Infect Public Health. 2021;14:1750-66. doi: 10.1016/j.jiph.2021.10.020. PubMed PMID: 34756812.
- Zhou W, Wang H, Yang Y, Chen ZS, Zou C, Zhang J. Chloroquine against malaria, cancers and viral diseases. Drug Discov Today. 2020;25:2012-22. doi: 10.1016/j.drudis.2020.09.010. PubMed PMID: 32947043; PubMed Central PMCID: PMC7492153.
- Andayani R, Armin F, Mardhiyah A. Determination of the total phenolics and antioxidant activity in the rind extracts of Garcinia mangostana L., Garcinia cowa Roxb., and Garcinia atroviridis Griff. ex T. Anders. Asian J Pharm Clin Res. 2020;13:149-52. doi: 10.22159/ajpcr.2020.v13i8.36525.
- Tjahjani S. Antimalarial activity of Garcinia mangostana L rind and its synergistic effect with artemisinin in vitro. BMC Complement Altern Med. 2017;17:131. doi: 10.1186/s12906-017-1649-8. PubMed PMID: 28241761; PubMed Central PMCID: PMC5329916.
- John OD, Mouatt P, Panchal SK, Brown L. Rind from Purple Mangosteen (Garcinia mangostana) Attenuates Diet-Induced Physiological and Metabolic Changes in Obese Rats. Nutrients. 2021;13. doi: 10.3390/nu13020319. PubMed PMID: 33499382; PubMed Central PMCID: PMC7912346.
- Suhandi C, Wilar G, Narsa AC, Mohammed AFA, El-Rayyes A, Muchtaridi M, et al. Updating the Pharmacological Effects of α-Mangostin Compound and Unraveling Its Mechanism of Action: A Computational Study Review. Drug Des Devel Ther. 2024;18:4723-48. doi: 10.2147/dddt.s478388. PubMed PMID: 39469723; PubMed Central PMCID: PMC11514645.
- Kuncoro H, Widyawaruyanti A, Ersam T. α-Mangostin effect on inhibition development stadium and globin accumulation against Plasmodium falciparum. Pharmacogn J. 2018;10:783-8. doi: 10.5530/pj.2018.4.132.
- Pratama AA, Jumina J, Anwar C. Synthesis, biological activity, and molecular docking study of xanthenol and its disproportionation products as anticancer and antimalarial agents. Makara J Sci. 2024;28:110-8. doi: 10.7454/mss.v28i2.2314.
- Vasquez M, Zuniga M, Rodriguez A. Oxidative Stress and Pathogenesis in Malaria. Front Cell Infect Microbiol. 2021;11:768182. doi: 10.3389/fcimb.2021.768182. PubMed PMID: 34917519; PubMed Central PMCID: PMC8669614.
- Bhalani DV, Nutan B, Kumar A, Singh Chandel AK. Bioavailability Enhancement Techniques for Poorly Aqueous Soluble Drugs and Therapeutics. Biomedicines. 2022;10. doi: 10.3390/biomedicines10092055. PubMed PMID: 36140156; PubMed Central PMCID: PMC9495787.
- Herdiana Y, Handaresta DF, Joni IM, Wathoni N, Muchtaridi M. Synthesis of nano-α mangostin based on chitosan and Eudragit S 100. J Adv Pharm Technol Res. 2020;11:95-100. doi: 10.4103/japtr.JAPTR_182_19. PubMed PMID: 33102191; PubMed Central PMCID: PMC7574733.
- Wathoni N, Rusdin A, Febriani E, Purnama D, Daulay W, Azhary SY, et al. Formulation and Characterization of α-Mangostin in Chitosan Nanoparticles Coated by Sodium Alginate, Sodium Silicate, and Polyethylene Glycol. J Pharm Bioallied Sci. 2019;11:S619-s27. doi: 10.4103/jpbs.JPBS_206_19. PubMed PMID: 32148373; PubMed Central PMCID: PMC7020839.
- Teimouri A, Haghi AM, Nateghpour M, Farivar L, Hanifian H, Mavi SA, et al. Antimalarial efficacy of low molecular weight chitosan against Plasmodium berghei infection in mice. J Vector Borne Dis. 2016;53:312-6. PubMed PMID: 28035107.
- Tjahjani S, Hermanto F, Muchtaridi M, Aulifa DL, Haq FA. The ins and outs of alpha-mangostin’s potential as an antimalarial. J Kesehat Masy. 2025;20:841-7. doi: 10.15294/kemas.v20i4.19307.
- Muchtaridi M, Suryani AI, Wathoni N, Herdiana Y, Mohammed AFA, Gazzali AM, et al. Chitosan/Alginate Polymeric Nanoparticle-Loaded α-Mangostin: Characterization, Cytotoxicity, and In Vivo Evaluation against Breast Cancer Cells. Polymers (Basel). 2023;15. doi: 10.3390/polym15183658. PubMed PMID: 37765512; PubMed Central PMCID: PMC10538075.
- Ahmad SJ, Abdul Rahim MBH, Baharum SN, Baba MS, Zin NM. Discovery of Antimalarial Drugs from Streptomycetes Metabolites Using a Metabolomic Approach. J Trop Med. 2017;2017:2189814. doi: 10.1155/2017/2189814. PubMed PMID: 29123551; PubMed Central PMCID: PMC5662797.
- Weichbrod RH, Thompson GA, Norton JN. Husbandry. In: Management of Animal Care and Use Programs in Research, Education, and Testing. 2nd ed. Boca Raton (FL): CRC Press; 2018. doi: 10.1201/9781315152189. PubMed PMID: 29787045.
- Mazhari N, Nateghpour M, Heydarian P, Farivar L, Souri E, Motevalli Haghi A. In Vivo Anti-Malarial Activity of Heracleum persicum Fruit Extract, in Combination with Chloroquine against Chloroquine-Sensitive Strain of Plasmodium berghei. Iran J Public Health. 2018;47:868-74. PubMed PMID: 30087873; PubMed Central PMCID: PMC6077635.
- Jia N, Zuo X, Guo C, Li Y, Cui J, Zhao C, et al. Synergistic antinociceptive effects of alfentanil and propofol in the formalin test. Mol Med Rep. 2017;15:1893-9. doi: 10.3892/mmr.2017.6174. PubMed PMID: 28259933.
- Ounjaijean S, Lektip C, Somsak V. In vivo antimalarial activity of Cyperus rotundus and its combination with dihydroartemisinin against Plasmodium berghei. Adv Pharmacol Pharm Sci. 2024;2024:6249977. doi: 10.1155/2024/6249977.
- Edington FLB, Gadellha SR, Santiago MB. Safety of treatment with chloroquine and hydroxychloroquine: A ten-year systematic review and meta-analysis. Eur J Intern Med. 2021;88:63-72. doi: 10.1016/j.ejim.2021.03.028. PubMed PMID: 33832827.
- Alkandahri MY, Yuniarsih N, Berbudi A, Subarnas A. Antimalaria activities of several active compounds from medicinal plants. Pharmacogn J. 2022;14:245-52. doi: 10.5530/pj.2022.14.30.
- Pillat MM, Krüger A, Guimarães LMF, Lameu C, de Souza EE, Wrenger C, et al. Insights in Chloroquine Action: Perspectives and Implications in Malaria and COVID-19. Cytometry A. 2020;97:872-81. doi: 10.1002/cyto.a.24190. PubMed PMID: 32686260; PubMed Central PMCID: PMC7404934.
- Li C, Wang X, Deng M, Luo Q, Yang C, Gu Z, et al. Antiepileptic Drug Combinations for Epilepsy: Mechanisms, Clinical Strategies, and Future Prospects. Int J Mol Sci. 2025;26. doi: 10.3390/ijms26094035. PubMed PMID: 40362274; PubMed Central PMCID: PMC12071858.
- Ibraheem SO, Abdul Majid R, Alapid A, Mohammad Sedik H, Sabariah M, Faruq M, et al. In vitro antiplasmodium and chloroquine resistance reversal effects of mangostin. Pharmacogn Mag. 2020;16 Suppl 2:S276-83. doi: 10.4103/pm.pm_510_19.
- Gomes ARQ, Cunha N, Varela ELP, Brígido HPC, Vale VV, Dolabela MF, et al. Oxidative Stress in Malaria: Potential Benefits of Antioxidant Therapy. Int J Mol Sci. 2022;23. doi: 10.3390/ijms23115949. PubMed PMID: 35682626; PubMed Central PMCID: PMC9180384.
- Momenfam F, Nateghpour M, Haghi AM, Farivar L, Mohebali M, Hajjaran H, et al. Interaction between Chitosan and Chloroquine against Plasmodium berghei and P. falciparum Using In-Vivo and In-Vitro Tests. Iran J Parasitol. 2021;16:261-9. doi: 10.18502/ijpa.v16i2.6320. PubMed PMID: 34557241; PubMed Central PMCID: PMC8418647.
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