Anticancer power of Artemisia annua: A preclinical systematic review

Cancer remains a leading global health challenge, and treatment efficacy is often limited by resistance to conventional therapies and their associated toxicities. These limitations have intensified the exploration of alternative strategies, particularly natural compounds with antitumor potential such as Artemisia annua (AA). This review aimed to systematically evaluate the antitumor efficacy and mechanisms of action of AA extracts and derivatives in preclinical animal models. A structured literature search was conducted in PubMed, Scopus, and Web of Science for studies published between 2019 and August 2025, following PRISMA 2020 guidelines with the protocol prospectively registered in PROSPERO (CRD420251113840). Original in vivo investigations reporting the anticancer activity of AA or its derivatives were considered eligible. Of the 176 records initially identified, 21 underwent full-text review, and seven studies met the inclusion criteria for synthesis. Among the included studies, six of seven eligible studies (86%) reported measurable reductions in tumor size or volume, and four documented apoptosis induction. Additional mechanisms included angiogenesis inhibition and ferroptosis activation. Dihydroartemisinin was the most frequently investigated derivative, while novel compounds such as ZQJ29 also showed promising activity. Importantly, no notable systemic toxicity was reported at the administered doses among the seven included in vivo studies available. This finding reflects only the data available across the seven eligible studies, demonstrates a potentially favorable safety profile. So far, the possibility of dose- or regimen-dependent toxicities reported elsewhere in the literature is not excluded; however, further comprehensive studies are needed to confirm this. This review is the first to consolidate recent preclinical evidence highlighting ferroptosis as one of the key mechanisms of AA derivatives, thereby expanding the understanding of their multifaceted anticancer activity. Collectively, the findings underscore the therapeutic promise of AA derivatives and advocate for further investigation into their pharmacokinetics, safety, and integration into regimens with established therapies. These results demonstrate that AA compounds have significant potential as adjuncts or alternatives in cancer management and warrant rigorous evaluation in standardized clinical trials.