Repurposing Artemisinin-Based Drugs from Antimalarial to Pan-Therapeutic: Pharmacological Promise and Therapeutic Challenges

Di Wu,1,* Hong Zeng,2,* Jiachen Tan,1 Qinzheng Xu,1,3 Faheem Ahmed Khan,4 Nuruliarizki Shinta Pandupuspitasari,5 Shengqiang Yang,2 Chunjie Huang1 1School of Medicine, Nantong University, Nantong, 226001, People’s Republic of China; 2School of Basic Medicine, Youjiang Medical University for Nationalities, Baise, 533000, People’s Republic of China; 3Department of Obstetrics and Gynecology, Affiliated Hospital of Nantong University, Nantong, 226001, People’s Republic of China; 4Research Center for Animal Husbandry, National Research and Innovation Agency, Jakarta Pusat, 10340, Indonesia; 5Faculty of Animal and Agricultural Sciences, Universitas Diponegoro, Semarang, 50275, Indonesia*These authors contributed equally to this workCorrespondence: Shengqiang Yang, Email [email protected] Chunjie Huang, Email [email protected]: The sourcing of pharmaceutical agents from natural products remains a cornerstone of drug discovery. For millennia, herbal remedies have served as foundational therapeutic interventions, yet their mechanisms of action often remain elusive. Artemisinin (ART, or “Qinghaosu”) and its derivatives, collectively known as ARTs, exemplify this paradigm. Originating from traditional Chinese medicine, these well-established antimalarial compounds exhibit potent cytotoxicity, positioning them as promising anti-cancer agents. ARTs operate through multiple cancer cell-intrinsic mechanisms and demonstrate synergistic effects with conventional therapies, even against chemoresistant malignancies. Beyond oncology, the therapeutic portfolio of ART-based drugs is rapidly expanding. This review synthesizes recent advancements in the application of ARTs for treating various cancers, Alzheimer’s disease, and reproductive disorders. Furthermore, we explore the frontier of ART drug development, focusing on the rational design of ART-derived molecular hybrids and the engineering of nano-enabled delivery systems. These innovative strategies are pivotal for enhancing anti-cancer efficacy and achieving cancer-specific targeting. Ultimately, this work aims to guide the innovation of ART-based precision medicine, revitalizing the exploration and development of natural products in modern pharmacotherapy.Keywords: artemisinin, malignancy, neurodegenerative disease, reproductive disorder, drug delivery