ORIGINAL RESEARCH article
Front. Immunol.
Sec. Parasite Immunology
Proteomics-driven screening of artemisinin-based combination ratios and mechanistic insights into Plasmodium berghei infection in mice
Provisionally accepted
Liyu Hao1Jianhui Sun2Jianliang Li2
Zongyuan Li2*Zeyue Yu2Hanhui Huang2Guimin Liu2Zhenru Shen2Hairu Huo2Qili Yuan3
Hongmei Li2
Luqi Huang1,3- 1Shenyang Pharmaceutical University, Shenyang, China
- 2China Academy of Chinese Medical Sciences Institute of Chinese Materia Medica, Beijing, China
- 3China Academy of Chinese Medical Sciences, Beijing, China
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Malaria, a life-threatening mosquito-borne disease caused by Plasmodium falciparum, poses a substantial health burden on tropical and subtropical regions. Artemisinin, a sesquiterpene lactone isolated from Artemisia annua L., and its derivatives were initially used as monotherapies for malaria treatment. However, limitations such as short pharmacokinetic half-life and emerging drug resistance have driven the widespread adoption of artemisinin-based combination therapies (ACTs) as first-line interventions. A. annua contains other bioactive compounds such as arteannuin B, artemisinic acid, and scopoletin that exhibit distinct pharmacological properties. In this study, we aimed to devise a new strategy for treatment of malaria to overcome artemisinin resistance in Plasmodium species. We systematically screened antimalarial compound ratios using murine malaria models and optimized a formula comprising arteannuin B, artemisinic acid, and scopoletin. Through integrated proteomic profiling and western blot validation, we elucidated the immunomodulatory mechanisms underlying the antimalarial efficacy of this combination. Specifically, the formula strengthened host defense by modulating phagocytic activity in splenic macrophages, dendritic cells, and natural killer cells via Fcγ receptor-mediated pathways. These findings provide mechanistic insights into artemisinin-associated immune potentiation. Moreover, we have proposed a novel ACT strategy targeting host-parasite interactions, offering a promising approach to circumvent emerging artemisinin resistance in Plasmodium species.
Keywords: Artemisinin, artemisinin-based combination therapy, Drug resistance reversal, Fcγ receptor signaling, Malaria
Received: 30 Sep 2025; Accepted: 21 Nov 2025.
Copyright: © 2025 Hao, Sun, Li, Li, Yu, Huang, Liu, Shen, Huo, Yuan, Li and Huang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Zongyuan Li, lizongyuan0921@163.com
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