Due to a standardized and comprehensive dataset for export and wide use in academia, the Web of Science Core Collection (WoSCC) was used to compile the publication dataset in this study. The timespan of the retrieval was set between 2000 and 2021 to explore the global research trends in artemisinin study for a long time. The retrieval was carried out on 18 January 2022. At the initial stage of bibliometric analysis, “artemisinin” was used as the search term, and 9,449 publications were retrieved from the WoSCC database. Several queries were successively carried out as a part of retrieval. For example, “arteannuin” or “artemisinine” or “artemisine” or “artemisinin” were used as the search term. Finally, “artemisinin” was used as the retrieval term because it led to almost every relevant search result. In different types of relevant publications (i.e., meeting abstracts, editorial materials, preceding papers, letters, news items, corrections, book chapters, early access, book reviews, data papers, reprints, bibliographies, and biographical items), only articles and reviews written in English were included in the following analysis. A total of 7,346 articles and 1,120 reviews were retrieved and analyzed. Figure 1 shows the retrieval strategy in this research.

On the basis of WoSCC, text data were obtained, and further analysis was carried out with VOSviewer (version 1.6.10) and Citespace (version 5.7.R5). In accordance with the data, bibliometric indicators were extracted, including the number of publications (NPs) and the number of citations (NC) without self-citations. In 2005, Hirsch proposed the H-index (19), which introduced scientific measurement into a new context from the method and concept. According to its original definition, a researcher would have an H-index if he or she published H papers, and each of the papers at least had been cited H times. This simple, novel, and special method combines the NC with the number of papers, comprehensively considering the quantity and quality of scholars' papers, and breaks the phenomenon of paying too much attention to local citations in the past. As the most important breakthrough in scientometrics indicators since the 21st century, in the following 10 years, the research on H-index could become one of the most important hotspots in the field of scientometrics and academic evaluation (19, 20). A network of co-occurrence keywords, in which the research hotspots associated with artemisinin could be illustrated clearly, was also constructed, and the bursts of keywords and references are often used to detect new research trends in the field (21).

In accordance with the retrieval strategy, 8,466 articles and reviews published from 2000 to 2021 were retrieved, of which the total NC was 149,185 and the average NC per publication was 29.33. The H-index for all publications was 174.

Figure 2A shows the polynomial fitting curve of the annual trend of publication. The annual NP was obviously related to publication year, and the correlation coefficient R² reached 0.9727. Figure 2B shows the annual NP associated with artemisinin. In general, despite the fluctuation over the past 22 years, the annual NP rose from 98 in 2000 to 662 in 2021, reaching its peak in 2020.

Analysis of the publications in different countries could reflect the importance that a country attaches to this field and its influence in this field to some extent. From 2000 to 2021, 157 countries published research articles on artemisinin (Figure 3A). The top 10 output countries/regions according to the NP are listed in Figure 3B. Since 2000, the NP in the United States and China has maintained steady growth. Fluctuations could be observed in the NP from England, with the largest NP being 114 in 2015. In general, these findings showed that the research on artemisinin has entered a stage of rapid development and attracted extensive attention. As shown in Table 1, the United States had the most publications (2,050), followed by China (1,641) and England (1,347). Papers from the United States were cited 76,901 times, accounting for 51.55% of the total citations. England (56,951) and Thailand (31,993) ranked second and third, respectively. Besides, the United States achieved the highest H-index (131), more than two times the number for India (54) and Nigeria (31). England had a moderately lower NP but higher H-index, NC, and average per item than China. Thailand achieved the highest average per item (53.74), followed by England (49.06), indicating that the publications of the two countries were of high quality. The average per item in China, India, and Nigeria was relatively low, suggesting that the quality of publications in these countries needs to be improved. As shown in the visualized international collaboration network, close cooperation was found between countries (Figure 3C). India, France, Thailand, and Switzerland carried out research in this area earlier than other countries (Figure 3D).

The top 10 affiliations with the most publications associated with artemisinin are presented in Table 2. The University of Oxford had the highest NP (524), NC (30,311), and H-index (90), followed by Mahidol University and the University of London. In addition, the University of Oxford achieved the highest average per item (64.68), followed by Mahidol Oxford Tropical Medicine Research Unit (62.05) and Mahidol University (61.05). Moreover, 30% of the top 10 affiliations were from England. Mahidol University and the University of Oxford took up the core position (Figure 4A). Figure 4B shows the 20 most representative affiliations in terms of burst strength, burst duration, and burst time. Swiss Trop Instant had the highest burst strength. Eleven clusters were identified (Figure 4C), which included “uncomplicated Plasmodium falciparum malaria,” “birth outcome,” and “new guinea.” Table 3 shows the top 10 authors with the most publications. They published 988 papers, accounting for 11.67% of the total NP. Their NC was 76,490, accounting for 51.27% of the total NC. White, NJ from the Mahidol University in Thailand ranked first in the research field of artemisinin, followed by Nosten, F from the University of Oxford in England and Dondorp, AM from Mahidol University in Thailand. As shown in Table 3, Dondorp, AM had the highest average per item (108.36). Day, NPJ had the lowest number of documents. However, Day, NPJ ranked third in terms of average per item (98.03), showing that the quality of the author's publications was high. In addition, 30% of the top 10 authors were from Thailand. The co-occurrence network of authors is shown in Figure 4D. Among all authors, NJ White had the highest burst strength (Figure 4E). The cluster analysis of the authors showed 14 clusters, including “showing anticancer,” “ferrous iron-dependent delivery,” and “economic evaluation” (Figure 4F).

As presented in Table 4, MALARIA JOURNAL (1,021 publications, IF: 2.979) published the greatest number of papers related to artemisinin. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (337 publications, IF: 5.191) and PLOS ONE (231 publications, IF: 3.24) ranked second and third, respectively. The top 10 journals published approximately 30% of the papers (2,390/28.23%). Of these top 10 journals, except for ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (IF: 5.191) and JOURNAL OF MEDICINAL CHEMISTRY (IF: 7.446), the rest were journals with low IF (defined as lower than 5.000), indicating that researchers should improve the quality of their papers and conduct more in-depth and valuable research. MALARIA JOURNAL notably had the highest H-index and NC, and JOURNAL OF MEDICINAL CHEMISTRY exhibited the highest average per item. Although BIOORGANIC MEDICINAL CHEMISTRY had the lowest NP, its H-index was higher than that of BIOORGANIC MEDICINAL CHEMISTRY LETTERS, SCIENTIFIC REPORTS, ACTA TROPICA, and MOLECULES. The co-occurrence network of the cited journals is shown in Figure 5A. The top three journals with the highest citations were MALARIA JOURNAL, ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, and PLOS ONE. When two articles appear in the references of the third citation together, a co-citation relationship is formed (22). Figure 5B shows the 20 most representative journals in terms of burst strength, burst duration, and burst time. In the co-citation network, the line between two nodes implies that two papers were cited in one publication. The size of nodes represented the total number of co-citations of a document. Besides, nodes were divided into different clusters by using different colors. In view of the great number of cited references, 100 was set as the minimum NC of a reference. Among the 174,484 references cited by the retrieved publications, 206 references were selected for co-citation analysis (Figure 5C). The top 10 co-cited references are shown in Supplementary Table 1. The co-citation of the paper written by Dondorp in 2009 was cited 1,360 times and in the first place, followed by the paper written by Klayman in 1985 and by Ashley in 2014. A total of 75 references were included in cluster 1 (in red), which mainly concentrated on the research on the synthesis, mechanism, efficacy, and pharmacokinetics of artemisinin. Cluster 2 (in green) was mainly about the study of antimalarial methods and drug resistance. Cluster 3 (in blue) paid attention to resistance in Plasmodium falciparum malaria and countermeasures. The main content of cluster 4 (in yellow) focused on the biosynthesis, extraction, and separation of artemisinin. Among all co-cited references, the paper written by Eckstein-Ludwig in 2003 had the highest burst strength (Figure 5D). The minimum number of co-citations of an author was set as 193 due to the large amounts of authors. Among the 104,510 authors cited by retrieved publications, 158 co-cited authors were selected for analysis (Figure 5E). The top 10 co-cited authors are shown in Supplementary Table 2. White, NJ had the most citations (2,924), followed by WHO (2,233) and Efferth, T (2,103). In terms of total link strength, White, NJ ranked first (45,050), followed by Posner, GH (33,037), and Haynes, RK (30,363). Although Posner, GH had a slightly low citation, the author's total link strength (33,037) was higher than that of WHO, Efferth T, and Dondorp AM.

Figure 6 shows the annual number of global citation scores (GCS) of the top 10 publications. The paper written by Ashley in 2014 had the highest GCS (1,231). In this study, E.A. Ashley concluded that the prevalent resistance of Plasmodium falciparum to artemisinin in Southeast Asia was related to kelch13 mutations. Extended courses of ACTs were effective in areas where the standard 3-day treatment has failed (23). Ariey et al. linked artemisinin resistance to mutations in the PF3D7_1343700 Kelch propeller domain (“K13-Propper”) through whole-genome sequencing of the artemisinin-resistant parasite in Cambodia and parasite strains in Africa. Kelch13 (K13) propeller allele mutation was concentrated in Cambodia, and resistance was widespread. As a useful molecular marker, K13 polymorphism was conducive to controlling artemisinin resistance and avoiding its global spread (24). Paddon et al. proved the complete biosynthetic pathway of artemisinin. In addition, they developed a chemical process that could convert artemisinic acid to artemisinin with a chemical source of singlet oxygen (25). Tu described the discovery and application of artemisinin (2). White et al. reviewed the clinical, pathological, and epidemiological features of malaria and the means of prevention and treatment; they pointed out that a high supply of ACT is an effective means to reduce the incidence rate and mortality of malaria (26). Phyo et al. found that parasite clearance half-lives greatly lengthened and identified 148 multi-locus parasite genotypes (27). Bousema et al. summarized the epidemiology and infectivity of Plasmodium falciparum and Plasmodium vivax gametocytes in relation to malaria control and elimination (28). Westfall et al. described the progress toward the goal of developing semisynthetic artemisinin by fermenting the artemisinin precursor from engineered Saccharomyces cerevisiae and chemically converting it to dihydroartemisinin acid, which could then be converted to artemisinin (29). Straimer et al. provided solid evidence to identify and eliminate artemisinin-resistant malaria parasites (30). Achan et al. reviewed the historical uses of quinine, and its current use was considered. ACT offered a better choice than quinine, although in resource-limited settings, maintaining a stable supply of ACT was difficult (31). In any case, the focuses of artemisinin research in these publications were different, but they were all pioneering, which had a good guiding significance for the follow-up research in this field.

The keywords extracted from abstracts and titles of the 8,466 publications were analyzed (Figure 7). As shown in Figure 7A, cluster 1 majorly focused on clinical research of artemisinin on malaria treatment, especially for children in Africa, including efficacy and drug resistance. Cluster 2 mainly reflected on basic research and explored the main mechanism of artemisinin in the treatment of diseases. Cluster 3 focused on the biosynthesis mechanism of artemisinin. The top 20 keywords in frequency are shown in Supplementary Table 3. The most frequent keywords were “artemisinin,” “malaria,” “artesunate,” “plasmodium-falciparum,” “in-vitro,” “artemisinin resistance,” “plasmodium falciparum,” “resistance,” and “artemether-lumefantrine,” indicating that studies associated with artemisinin mainly involved basic research, clinical research, and structure modification. As shown in Figure 7B, in accordance with the average publication year (APY), all keywords were divided into different types of colors through VOSviewer. Compared with artemisinin, artesunate, and other earlier research keywords, nanoparticle (2017.37), piperaquine (2016.51), artemisinin biosynthesis (2016.88), and drug discovery (2016.11) have become major topics in this field. Comparison between Figures 7A,B showed that artemisinin combination and biosynthesis were the research hotspots in recent years. Figure 7C shows the 20 most representative keywords in terms of burst strength, burst duration, and burst time. The findings showed that in the early stage of artemisinin research, the chemical synthesis of artemisinin and its derivatives, antimalaria, and combination drugs are the research hotspots.

Bibliographic coupling denotes that if two documents cite the same references, they have a coupling relationship. In addition, on the basis of the latest version of Journal Citation Reports, the impact factor (IF), which has been widely used as the main indicator to measure the quality and impact of journals, was obtained (32). The network of bibliographic coupling analysis is shown in Figure 8, and the top 10 countries are shown in Supplementary Table 4. The United States had the most documents, citations, and total link strength. China ranked second in documents, but its total link strength was lower than that of England and Thailand. The citations of China were also lower than those in England. Except for the United States, China, and England, the documents of other countries were <1,000. In terms of affiliation (Supplementary Table 5), Mahidol University ranked first in terms of documents, citations, and total link strength, followed by the University of Oxford and London School of Hygiene & Tropical Medicine. Although the Chinese Academy of Sciences had high documents, its total link strength was lower than that of other institutions. As shown in Supplementary Table 6, White had the most documents, citations, and total link strength. Nosten ranked second in number of documents, but the author's total link strength was lower than that of Dondorp, Fidock, David and Menard; Dier had low documents, but their citations and total link strength were relatively high. The top 10 journals are shown in Supplementary Table 7. MALARIA JOURNAL has published the most documents, which have the most citations and total link strength, followed by ANTIMICROBIAL AGENTS and CHEMOTHERAPY and PLOS ONE. A paper written by Dondorp published in 2009 had the most citation, while the paper written by Ariey in 2014 had the highest total link strength (Supplementary Table 8).

During the coronavirus disease 2019 (COVID-19) pandemic, researchers are looking for effective treatments, and the therapeutic effect of artemisinin on COVID-19 was studied. A total of 48 papers about the therapeutic effect of artemisinin on COVID-19 were screened and analyzed in this study, with 316 keywords in total. As shown in Figure 9, except for COVID-19 and artemisinin, SARS-CoV-2, coronavirus, malaria, chloroquine, artesunate, hydroxychloroquine, and in-vitro appeared most frequently. Figure 9 shows the research on artemisinin for COVID-19 treatment, including the efficacy and mechanism of action in vivo and in vitro, immunity, gene expression, and cytokines.