Evaluation of The Chloroquine and Resveratrol Combination in Inhibiting β-Hematin Formation In Vitro

Authors

  • Faizal Hermanto Universitas Jenderal achmad Yani
  • Sri Wahyuningsih Universitas Jenderal achmad Yani
  • Risky Zamzami Adnan Universitas Jenderal achmad Yani

DOI:

https://doi.org/10.35451/jxpeda42

Keywords:

beta-hematin, malaria, Chloroquine, Resveratrol, Drug Resistance

Abstract

Malaria, caused by the Plasmodium parasite, remains a significant global health issue, exacerbated by drug resistance. This study aimed to explore the potential of combining chloroquine (CQ) and resveratrol in inhibiting β-hematin formation, a key process in the parasite's detoxification mechanism. The research began with the preparation of various concentrations of CQ and resveratrol, which were then combined and tested for their effects on inhibiting β-hematin in vitro using an ELISA reader. The results showed that both CQ and resveratrol individually inhibited β-hematin formation at moderate levels. However, their combination demonstrated a significant increase in inhibition, with the most effective combination being CQ at 164.03 μM and resveratrol at 0.98 μM. Statistical analysis confirmed that this combination was far more effective than using each compound separately. The study concluded that the combination of CQ and resveratrol can enhance the inhibition of β-hematin formation, providing a promising approach to improving malaria treatment efficacy, especially in the face of increasing drug resistance.

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References

[1] Balaji S, Deshmukh R, Trivedi V. Severe malaria: Biology, clinical manifestation, pathogenesis and consequences. J Vector Borne Dis. 2020;57(1):1–13.

[2] WHO. World Malaria Report 2024. 2023. 283 p.

[3] Kemenkes. Laporan Tahunan 2022 Malaria. Kemenkes RI. 2022;1–51.

[4] Zambare KK, Thalkari AB, Tour NS. A Review on Pathophysiology of Malaria: A Overview of Etiology, Life Cycle of Malarial Parasite, Clinical Signs, Diagnosis and Complications. Asian J Res Pharm Sci. 2019;9(3):226.

[5] Nqoro X, Tobeka N, Aderibigbe BA. Quinoline-Based Hybrid Compounds with Antimalarial Activity. Molecules. 2017 Dec 1;22(12).

[6] Sekihara M, Tachibana SI, Yamauchi M, Yatsushiro S, Tiwara S, Fukuda N, et al. Lack of significant recovery of chloroquine sensitivity in Plasmodium falciparum parasites following discontinuance of chloroquine use in Papua New Guinea. Malar J. 2018;17(1).

[7] Plowe C V. Malaria chemoprevention and drug resistance: a review of the literature and policy implications. Malar J. 2022 Dec 1;21(1).

[8] WHO. Antimalarial Drug Combination Therapy - Report of a WHO Technical Consultation. World Heal Organ Geneva WHO. 2001;36.

[9] Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020;56(1).

[10] Alhazzani W, Møller MH, Arabi YM, Loeb M, Gong MN, Fan E, et al. Surviving Sepsis Campaign: guidelines on the management of critically ill adults with Coronavirus Disease 2019 (COVID-19). Intensive Care Med. 2020;46(5).

[11] Rathore D, McCutchan TF, Sullivan M, Kumar S. Antimalarial drugs: Current status and new developments. Vol. 14, Expert Opinion on Investigational Drugs. 2005.

[12] Hermanto F, Nur Anisa I, Wahyuningsih S, Alatas F, Suryani S, Rachmawan RL, et al. Antiplasmodium Activity and The Effect of Resveratrol on Index Organs of Mice Infected with Plasmodium berghei ANKA. Pharm J Farm Indones (Pharmaceutical J Indones. 2022;19(1):28.

[13] Hermanto F, Sari Dewi P, Ahsanul Haq F, Melsandy N, Farmakologi dan Toksikologi B, Farmasi F, et al. Potensi Resveratrol Dalam Mengurangi Keparahan Malaria Serebral Pada Mencit Yang Terinfeksi Plasmodium berghei ANKA. Med Sains J Ilm Kefarmasian. 2023;8(4):1481–8.

[14] Hermanto F, Refiani A, Ahsanul Haq F. Resveratrol Reduce the Severity of Anemia and Thrombocytopenia in Plasmodium berghei ANKA-Infected Mice. J Farm Dan Ilmu Kefarmasian Indones. 2023;10(3):266–71.

[15] Haq FA, Hermanto F, Sutjiatmo AB, Lutfi MH, Farmasi F, Jenderal U, et al. Pengaruh resveratrol terhadap jalur permeabilitas baru sebagai target kerja antimalaria. 2024;4(4).

[16] Hermanto F, Haq FA, Khasanah R. The effect of resveratrol on the relationship of antioxidant activity and beta-hematin inhibition as an antimalarial action target. J Adv Pharm Technol Res. 2024;15(4):359–63.

[17] Sucilestari R, Dj DS, Bachtiar I. Uji Aktivitas Antimalaria Fraksi Triterpenoid dari Ekstrak Metanol Daun Artocarpus camansi terhadap Plasmodium berghei Secara In Vivo. 2013;2(2):196–9.

[18] Salkeld J, Duncan A, Minassian AM. Malaria: Past, present and future. Clin Med (Northfield Il). 2024 Nov 1;24(6):100258.

[19] Figueiredo A, Rastogi ST, Ramos S, Nogueira F, De Villiers K, de Sousa AGG, et al. A metabolite-based resistance mechanism against malaria. Science. 2025 Jun 12;388(6752):eadq6741.

[20] Alven S, Aderibigbe B. Combination therapy strategies for the treatment of malaria. Molecules. 2019;24(19).

[21] Acosta ME, Gotopo L, Gamboa N, Rodrigues JR, Henriques GC, Cabrera G, et al. Antimalarial Activity of Highly Coordinative Fused Heterocycles Targeting β-Hematin Crystallization. ACS omega. 2022 Mar 8;7(9):7499–514.

[22] Sahoo P, Pathak NK, Scott Bohle D, Dodd EL, Tripathy U. Hematin anhydride (β-hematin): An analogue to malaria pigment hemozoin possesses nonlinearity. Spectrochim Acta Part A Mol Biomol Spectrosc. 2024 Apr 5;310:123902.

[23] Cruz JN, Mali SN. Antimalarial Hemozoin Inhibitors (β-Hematin Formation Inhibition): Latest Updates. Comb Chem High Throughput Screen. 2022 Jan 18;25(12):1987–90.

[24] Villarreal W, Castro W, González S, Madamet M, Amalvict R, Pradines B, et al. Copper (I)-Chloroquine Complexes: Interactions with DNA and Ferriprotoporphyrin, Inhibition of β-Hematin Formation and Relation to Antimalarial Activity. Pharmaceuticals (Basel). 2022 Jul 25 [cited 2025 Aug 31];15(8).

[25] Jimoh A, Abdullahi S, Dawoud F, Jimoh AO, Tanko Y. Evaluation of the effect of resveratrol on parasitaemia in Plasmodium berghei-induced malaria in diabetic male Wistar rats A. 2022;10(1):44–57. ]

[26] Dawud FA, Abdullahi S, Abdulazeez J, Usman F, Ayo JO. Effect of resveratrol on haematological changes in diabetic-malaria infected wistar rats. Niger J Biochem Mol Biol. 2023;38(3).

[27] Schwager J, Seifert N, Bompard A, Raederstorff D, Bendik I. Resveratrol, egcg and vitamins modulate activated t lymphocytes. Molecules. 2021 Sep 1;26(18).

[28] Aisya Maulidia, Wijayanti S, Mustamin F, Ubrusun J. Testing the Antioxidant Activity of Ethanol Extract on Terap Fruit Seeds (Artocarpus odoratissimus) using the DPPH Method. J Farm. 2024 Oct 31;7(1):73–80.

[29] Kaban VE, Yusmarlisa S. Uji Aktivitas Kandungan Antioksidan Pada Daun Bangun-Bangun (Plectranthus Amboinicus) Secara Spektrofotometri Ultraviolet-Visible. Vol. 1, Jurnal Farmasimed (JFM). 2018.

[30] Handayani F, Fatimah N, Ansyori AK, Sari PE, Agustina I. Aktivitas Antioksidan dan Antibakteri Ekstrak Etanol Daun Selutui Puka (Tabernaemontana macrocarpa Jack.) terhadap Propionibacterium acnes. J Farm. 2024;7(1):1–6.

[31] Abdulai SI, Ishola AA, Bewaji CO. Antimalarial Activities of a Therapeutic Combination of Azadirachta indica, Mangifera indica and Morinda lucida Leaves: A Molecular View of its Activity on Plasmodium falciparum Proteins. Acta Parasitol. 2023 Sep 1;68(3):659–75.

[32] Nguyen TD, Gao B, Amaratunga C, Dhorda M, Tran TNA, White NJ, et al. Preventing antimalarial drug resistance with triple artemisinin-based combination therapies. Nat Commun. 2023 Dec 1;14(1).

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Published

2025-11-13

How to Cite

Evaluation of The Chloroquine and Resveratrol Combination in Inhibiting β-Hematin Formation In Vitro. (2025). JURNAL FARMASIMED (JFM), 8(1), 243-249. https://doi.org/10.35451/jxpeda42