New clinical application prospects of artemisinin and its derivatives: a scoping review

Abstract

Background

Recent research has suggested that artemisinin and its derivatives may have therapeutic effects on parasites, viruses, tumors, inflammation and skin diseases. This study aimed to review clinical research on artemisinin and its derivatives except anti-malaria and explore possible priority areas for future development.

Methods

Relevant articles in English and Chinese published before 28 October 2021 were reviewed. All articles were retrieved and obtained from databases including WanFang, PubMed/MEDLINE, the Cochrane Library, China National Knowledge International, Embase, OpenGrey, the Grey Literature Report, Grey Horizon, and ClinicalTrials.gov. Studies were selected for final inclusion based on predefined criteria. Information was then extracted and analyzed by region, disease, outcome, and time to identify relevant knowledge gaps.

Results

Seventy-seven studies on anti-parasitic (35), anti-tumor (16), anti-inflammatory (12), anti-viral (8), and dermatological treatments (7) focused on the safety and efficacy of artemisinin and its derivatives. The anti-parasitic clinical research developed rapidly, with a large number of trials, rapid clinical progress, and multiple research topics. In contrast, anti-viral research was limited and mainly stayed in phase I clinical trials (37.50%). Most of the studies were conducted in Asia (60%), followed by Africa (27%), Europe (8%), and the Americas (5%). Anti-parasite and anti-inflammatory research were mainly distributed in less developed continents such as Asia and Africa, while cutting-edge research such as anti-tumor has attracted more attention in Europe and the United States. At the safety level, 58 articles mentioned the adverse reactions of artemisinin and its derivatives, with only one study showing a Grade 3 adverse event, while the other studies did not show any related adverse reactions or required discontinuation. Most studies have discovered therapeutic effects of artemisinin or its derivatives on anti-parasitic (27), anti-tumor (9), anti-inflammatory (9) and dermatological treatment (6). However, the efficacy of artemisinin-based combination therapies (ACTs) for parasitic diseases (non-malaria) is still controversial.

Conclusions

Recent clinical studies suggest that artemisinin and its derivatives may be safe and effective candidates for anti-tumor, anti-parasitic, anti-inflammatory and dermatological drugs. More phase II/III clinical trials of artemisinin and its derivatives on antiviral effects are needed.

Supplementary Information

The online version contains supplementary material available at 10.1186/s40249-023-01152-6.

Background

Artemisinin is a natural sesquiterpene lactone obtained from Artemisia annua herb, which has been confirmed to be effective in the treatment of different forms of malarial parasites and thus has attracted much attention [1, 2]. Since the 1980s, artemisinin derivatives have gradually become the focus of research due to their low cost, good effect and ease of use [3–5]. In 2006, artemisinin-based combination therapies (ACTs) were recommended by the World Health Organization (WHO) as first-line treatment of falciparum malaria [6, 7]. At present, artemisinin and its derivatives have become the most important and effective antimalarial drugs [8]. However, the appearance of drug-resistant Plasmodium falciparum promotes the continuous improvement of antimalarial drug research and development, such as artemisinin-based combination therapies [8–10].

Early studies of artemisinin and its derivatives mainly focused on antimalarial effects. However, the low toxicity and immune regulation of artemisinin and its derivatives in the process of malaria treatment have lighted the interest of researchers in many other disease fields [11–15]. Over the past few decades, the therapeutic effects of artemisinin and its derivatives on various diseases have been discovered through a large amount of in vivo and in vitro studies, and have gradually led to the increase of clinical trials [16]. The possible effect of artemisinin and its derivatives for the treatment of Corona Virus Disease 2019 (COVID-19) has again attracted research interest.

To our knowledge, the results of these clinical studies have not yet been summarized. Thus, this scoping review aimed to overview the current status of clinical research on artemisinin and its derivatives on anti-parasite (non-malaria), antivirus, anti-tumor, inflammatory and dermatosis therapy and hope to explore potential priority areas for future development.

Methods

Inclusion and exclusion criteria

According to the review’s purpose, we conducted a scoping review guided by Arksey and O’Malley’s methodological framework [17]. We included all articles on the clinical use of artemisinin and its derivatives published before October 28, 2021. The following types of articles were excluded: studies on the antimalarial effects of artemisinin and its derivatives, conference papers, articles without research data, articles that did not address human diseases, duplicate publications, and studies that were not conducted based on clinical trials.

Retrieval and search method

Two authors searched for articles in the following databases: Wanfang (wanfangdata.com.cn), CNKI (cnki.net), PubMed/MEDLINE, the Cochrane Library, Embase, OpenGrey, the Grey Literature Report, Grey Horizon, and ClinicalTrials.gov. The search strategy was defined for each database by using a combination of MeSH terms or keywords including artemisinin, artemisinin derivatives, artesunate, dihydroartemisinin, artemether, clinical study, and diseases. The keywords were adapted for each database to be consistent with their indexing. The literature search was conducted on October 28, 2021. Mendeley 1.19.5 (Elsevier, Amsterdam, NL) and Endnote20 (Clarivate Analytics, Pennsylvania, US) software were used to manage references and remove duplicates.

Study selection

We performed a pilot selection study to evaluate consistency in the application of the above criteria and to identify discrepancies with 20 randomly selected references. For both abstract and full-text screening, two independent reviewers selected studies by title and abstract/full text, and the third reviewer resolved disagreements. Eligible clinical trials were screened by two independent reviewers (YY and GL) by title and abstract/full text based on study subjects, study diseases, study type, and details. In case of disagreement, a third reviewer (YH) was invited to review until a consensus was reached.

Data extraction, summary, and analysis

An extraction grid was created to record the following information for each of the selected studies: title, author, time, drug, disease, scale, safety, results, country, viewpoint, and conclusion. Initially, the three contributors extracted data from the same 10 articles independently to ensure harmonization. The other two participants resolved disagreements in the discussion. Subsequently, the remaining 67 articles were then summarized, their quality assessed by the same three contributors, and the results were recorded in the extraction grid (Additional file 1: Table S1). A quantitative conventional content analysis was employed to summarize and report the results. The key findings were classified into specific categories derived from the articles rather than a predefined framework. The categorization was revised with the advice of the panel of experts. Priority was given to the classification of the study itself. The remaining studies were classified into viral, parasitic, tumor, dermatologic, and inflammatory diseases using the International Classification of Diseases, 11th Revision (ICD-11) in combination with the disease classification of previous studies. As an emerging disease, COVID-19 was classified according to the primary outcome of the study.

Results

Description and general characteristics of the included studies

Our study found 558 articles after matching the keywords. By title and abstract screening, 62 articles were excluded according to our inclusion and exclusion criteria. According to the inclusion and exclusion criteria, 77 articles were finally included after more detailed full-text assessment and reference review. The article search and selection processes are shown in Fig. 1. The diseases, target drugs and research time of this study are shown in Table 1 and Fig. 2.

Clinical research on artemisinin and its derivatives (except malaria treatment) began in the 1990s, and the number of studies has gradually increased (Additional file 1: Table S1). The main study subjects were artesunate and artemether (Fig. 2). Of the 77 retained studies, most were conducted in Asia (60%), followed by Africa (27%), Europe (8%), and the Americas (5%) (Table 2). Adverse events in all the included studies were graded according to the National Cancer Institute criteria, ranging from grade 1 (no events) to grade 5 (life-threatening events). Of the 59 studies with documented adverse events, only one reported a grade 3 adverse event without drug discontinuation, and all the rest 58 studies did not show any related adverse effects.

As for different disease types, studies on tumors are the most, covering 12 different diseases, such as breast cancer, liver cancer, ovarian cancer. In addition, studies on dermatology cover 10 different diseases, such as rosacea, eczema, and dermatitis (Fig. 3a). The number of clinical research on schistosomiasis, breast cancer, COVID-19, Human immunodeficiency virus (HIV) and dermatitis are relatively high (Fig. 3b). According to the Chord diagram (Fig. 3c), the effectiveness of artemisinin and its derivatives in the treatment of parasitosis, skin diseases, inflammatory diseases and tumors have received more attention, while the antiviral research still mainly focused on safety.

Antiparasitic effect

Artemisinin and its derivatives are known to be one of the most effective antimalarial drugs. Their use in the treatment of malaria has reduced the number of malaria-related cases and deaths worldwide by 30% and 37%, respectively, and reduced the number of deaths among children under 5 years of age by 11% as of 2019 [8]. In addition to their antimalarial effect, artemisinin and its derivatives also showed effects on other parasites, such as Schistosoma japonicum, Fasciola and Toxoplasma gondii [18, 19].

Anti-schistosomiasis effect

Clinical studies have suggested that artemisinin and its derivatives showed significant anti-S. japonicum properties, and were safe and cost-effective [20, 21]. Related research has entered phase III clinical trials. In terms of safety, repeated oral administration of artemisinin and its derivatives did not cause any related adverse reactions in phase I clinical trial. A single dose of 6 mg/kg of artemether, artesunate or artemisinin has been proven to be safe in many studies [22]. The study by Hua et al. suggested that this dose of artesunate was appropriate to be taken once a week for 4 weeks [23]. In terms of efficacy, most studies have suggested that artemether is effective in the early treatment of acute schistosomiasis, and can reduce the infection rate and intensity of the disease [20, 21, 24–27]. However, in some studies, the efficacy of artemisinin derivatives alone is not significant in clinical trials [28].

Artemisinin and its derivatives are also proven to be effective in schistosomiasis prevention. Lin et al. proved that taking a single dose of 6 mg/kg every 15 days has a preventive effect [29]. Other follow-up studies also supported that artemisinin and its derivatives have obvious preventive effects on residents in schistosomiasis-endemic areas [22, 25, 26, 29–35]. Research suggested that artemisinin derivatives had a wide range of prevention and protection rates, for example, the rates for artesunate reached 60.8–100% [29–34, 36, 37], and the rate for artemether reached 25–95% [25, 26, 35, 38]. It is noteworthy that the sensitivity of S. japonicum to artesunate decreased after its long-term use [39–41].

Artemisinin-based combination therapies (ACTs) may be used as an adjuvant measure for schistosomiasis treatment, but this approach is highly controversial. Researchers agreed that artemisinin-based combination therapies were safe and well tolerated, similar to praziquantel, the current preferred treatment for schistosomiasis [42, 43]. Some clinical studies found that ACTs can specifically reduce transmission and help eliminate schistosomiasis [44]. Their use in the treatment of urinary schistosomiasis [45] and intestinal schistosomiasis [46] were safe and effective. Notably, the curative rate was not significantly different from that of praziquantel alone [47], and even an open randomized controlled trial in western Kenya found that standard praziquantel therapy was more effective. The role of ACT for schistosomiasis needs to be further studied [48].

Anti-Toxoplasma gondii effect

Existing studies suggested that artemisinin and its derivatives are safe in the treatment of toxoplasmosis, but it is uncertain whether they can alleviate schizophrenia caused by T. gondii infection. In terms of safety, phase I clinical trials have shown that artemisinin and its derivatives are safe when use alone or in combination with antipsychotics. However, their efficacy in the treatment of toxoplasmosis is still controversial. Wang et al. [43] also confirmed that artemether could significantly improve some mental symptoms caused by T. gondii infection, and that combination with antipsychotics could effectively reduce the positivity rate of T. gondii antibodies. However, some studies have shown that this combination therapy did not improve clinical symptoms such as cognitive impairment in patients with schizophrenia [49, 50].

Anti-trematodes effect

Studies have suggested that artemisinin and its derivatives may also have some inhibitory effect on Fasciola hepatica [51], but there is a lack of research on the effect of ACTs [52]. A randomized controlled pilot study of human fascioliasis in central Vietnam found that artemisinin and its derivatives were effective against fascioliasis [51]. A subsequent clinical trial confirmed this result but found that the therapeutic effect was not sufficient to replace triclabendazole, the standard anti-fascioliasis drug. The role of artemisinin derivatives as matching drugs in combination therapies is not clear [52].

Study on the antitumor effect of artemisinin and its derivatives

Clinical studies have suggested that artemisinin and its derivatives are safe for tumor treatment, and might have effects on different kinds of tumors, including liver cancer, ovarian cancer, breast cancer, non-small cell lung cancer, colorectal cancer, cervical intraepithelial neoplasia, retinoblastoma, etc. [53–60]. A phase I clinical trial found that the apparent clearance rate increased with time after artesunate use in patients with breast cancer [61]. The Maximum tolerated dose (MTD) for intravenous injection was 18 mg/kg. At this dose, adverse reactions were mild and self-limited [62]. Under the clinically effective dose for the treatment of Cervical Intraepithelial Neoplasia (CIN)2/3, transvaginal injection of artesunate is safe and well tolerated [60]. Oral ART doses up to 200 mg per day are safe and well tolerable in patients with metastatic breast cancer [59, 63]. The recommended dose for phase II/III clinical trials is 200 mg/day [58]. Clinical studies have suggested that artemisinin and its derivatives might have a better clinical effect in tumor treatment by inhibiting tumor angiogenesis [64] and effectively improving immunity in patients with primary liver cancer and hematological diseases [54, 65]. In addition, a study found that hepatic arterial infusion of artesunate was similar to conventional Transcatheter arterial chemoembolization (TACE) therapy in reducing tumor size, reducing the short-term efficacy of AFP, and reducing interventional side effects [54].

Artesunate combined with anti-tumor drug therapy was also safe and effective in ovarian cancer and non-small cell lung cancer [55]. In the treatment of ovarian cancer, artesunate increases sensitivity to cisplatin [55, 66]. Artesunate combined with NP and chemotherapy combined with sequential administration of artesunate can improve the disease control rate [55, 67].

Treatment of inflammatory diseases

Artemisinin and its derivatives have therapeutic effects on some infectious inflammatory diseases [68–70] and immune inflammatory diseases [71–76]. At present, few clinical trials have been conducted on the anti-inflammatory effects of artemisinin and its derivatives. Long-term clinical studies on artemisinin and its derivatives in the treatment of articular systemic lesions of Lupus nephritis (LN) [73, 76], Vogt-Koyanagi-Harada (VKH) syndrome [68, 77] and systemic lupus erythematosus suggested their safety with no obvious side effects [78]. It is worth noting that the pharmacokinetic parameters of artemether decreased significantly in tuberculosis treatment by rifampicin. This suggested that artemether should not be used in combination with rifampicin [79]. Other clinical studies have suggested that artemisinin derivatives are effective in the treatment of rheumatoid arthritis, joint systemic lesions of LN, VKH syndrome, COVID-19 and chronic simple otitis media [68–70, 74, 75]. In particular, the curative effect on rheumatoid arthritis was no less than that of the commonly used drug hydroxychloroquine [74, 75]. In addition, artemisinin could also inhibit the recurrence of lupus nephritis [71, 72, 80], further broadening its clinical application.

Antiviral effects of artemisinin and its derivatives

Research on the antiviral effects of artemisinin and its derivatives has mostly remained at the basic research stage, mainly in phase I clinical trials, and few clinical trials have been carried out. The phase I clinical trials showed that the combination with lopinavir and ritonavir significantly increased the exposure to clomiphene and decreased the exposure to artemether [81, 82]. It is predicted that 240 mg of artemether can achieve therapeutic plasma artemether concentrations [83]. In the case of the recommended dose of artemether-clomiphene, enhanced monitoring did not raise any safety concerns [82]. These results support for the continuation of phase II clinical trials. A prospective study on COVID-19 patients found that artemisinin combined with other drugs could clear pathogens from COVID-19 patients, shorten treatment time and improve prognosis [70]. However, another clinical study found that the standard 3-day artemisinin antimalarial regimen (4 mg/kg/day for 3 days) had no detectable effect on Cytomegalovirus (CMV) viremia in children with malaria. It is speculated that effective treatment of cytomegalovirus infection may require a longer course and/or a higher dose of artesunate than for conventional malaria [84].

Treatment of skin diseases

In clinical applications, artemisinin and its derivatives were found to be safe in the treatment of connective tissue diseases such as dermatitis (eczema), photosensitive dermatosis, summer blister disease, psoriasis vulgaris, and dermatomyositis [85–90]. Studies have found that artemisinin and its derivatives are effective [85] in treating some skin diseases. For example, the effective rate of artesunate in the treatment of eczema was 100%, and the effective rate in the treatment of pleomorphic erythema, pleomorphic solar eruption and summer blisters were 100% [86]. The effective rates for the treatment of psoriasis vulgaris and dermatomyositis were 60% and 75%, respectively [86]. In addition, artemisinin and its derivatives appeared to have good long-term efficacy in the treatment of skin diseases, such as eczema and photosensitive dermatoses with artemisinin [85], and rosacea with artesunate [88]. However, their efficacy in treating atopic dermatitis appeared to be poor [85]. Artemisinin and its derivatives appeared to have an advantage over some common dermatological drugs in the treatment of mild to moderate skin diseases. For rosacea, artesunate is similar in efficacy to doxycycline [87] and improves the condition earlier than metronidazole [88]. For acne vulgaris, artemether is more effective than fusidic acid [90].

Discussion

The purpose of this scoping review was to overview the current situation of the clinical application of artemisinin and its derivatives, and to seek how to maximize the utility of artemisinin within a range of therapeutic effects [91]. The main study subjects were artesunate and artemether. Even though research on the treatment of inflammatory diseases, tumors and skin diseases were developing relatively fast, the research related to anti-parasites were the most advanced in terms of clinical progress and quantity. The safety of artemisinin and its derivatives have been proven in most clinical trials [92], but the therapeutic effects vary in different disease areas. From the perspective of geographical distribution, studies on anti-parasitic and anti-inflammation were mainly in Asia, Africa and other developing areas, whereas the developed countries paid more attention to anti-tumor research. In addition, studies suggested that artemisinin and its derivatives might be more cost-effective compared with the existing standard treatments in various disease fields [5, 93–99]. In general, artemisinin and its derivatives have certain development prospects in the fields of anti-parasite, anti-virus, anti-inflammatory diseases, anti-tumor and skin diseases.

For parasites, the effect of artemisinin or its derivatives has been demonstrated, especially for artesunate and artemether. However, the efficacy of ACTs is still controversial [46, 48]. Some studies suggest that the occurrence of parasitic diseases can be explained by environmental epidemiology [100], and stratified sampling should be carried out in clinical research according to regional characteristics. It is worth noting that artemisinin and its derivatives are currently the most widely used antimalarial drugs, and widespread used in the treatment of other parasitic diseases may increase the risk of drug resistance in malaria parasites. Whether artesunate can be widely used to treat schistosomiasis in malaria-endemic areas requires further consideration and long-term monitoring [101–103].

For tumors, the clinical research of artemisinin and its derivatives was relatively mature, involving a wide range of diseases and their curative effects. However, their antitumor effect does not show absolute advantages compared with standard antitumor drugs [54, 65]. But with the emergence of drug resistance to standard anti-tumor drugs, it is imperative to explore new anti-tumor drugs with excellent efficacy and few side effects [104]. Related research should focus on exploring the tumor inhibition capabilities of artemisinin and its derivatives for further development, and focus on exploring the synergistic and sensitizing effects of them with standard antitumor treatments [105, 106].

For inflammation, compared with standard inflammatory treatments, artemisinin and its derivatives could significantly improve the curative effect, shorten the course of the disease, and reduce recurrence and complications, which is worth popularizing in public hospitals [69]. However, it is suggested that artemisinin and its derivatives might interact with some standard inflammatory drugs [79]. Therefore, attention should be given to drug-drug interactions. At the same time, more randomized clinical trials should be conducted to translate the plethora of preclinical results into clinical practice.

For skin diseases, artemisinin and its derivatives seem to be more effective than some dermatological drugs; in the treatment of papulopustular rosacea, the disease improved earlier and the beneficial effect lasted longer [86]. Currently, topical or oral corticosteroids are often used to treat skin diseases, which can easily cause various adverse reactions [107], but artemisinin and its derivatives are rare. Therefore, in terms of cost, safety and efficacy, artemisinin and its derivatives might have more advantages than some dermatological drugs in the treatment of skin diseases. More clinical trials are recommended to explore their mechanism of action and therapeutic potential [101, 108].

For viruses, artemisinin and its derivatives may also have broad application prospects, particularly in the control of COVID-19 [109, 110]. However, relevant clinical studies are still in the exploratory stage, and lack serious phase I clinical trials. Studies have suggested that artemisinin and its derivatives have an inhibitory effect on novel coronavirus [70], and might have the potential to treat COVID-19 [111, 112]. In addition, in the study of the antiviral effects of artemisinin and its derivatives, the results of some clinical trials might be contrary to the results of basic research and animal trials, such as cytomegalovirus. This might be due to improper course of treatment or dose design [84]. Therefore, attention should be paid to the structure-tissue exposure/selectivity relationship, that is, the delicate balance between clinical dose/efficacy/toxicity [113]. At the same time, the scope of randomized clinical trials should be expanded based on the basic research results.

Artemisinin and its derivatives represent a new beginning for antimalarial treatment worldwide, and great efforts have been made for their pharmacological study and mechanism exploration [114]. As a "modern traditional Chinese medicine", artemisinin provided a model for the development of traditional medicine using modern science and technology [115, 116]. Traditional medicine might be more suitable for the research and development of pharmaceutical products related to parasitic and other complex diseases [115, 116].

Clinical studies on malaria treatment with artemisinin and its derivatives are relatively mature and have been conducted on a large scale. Therefore, malaria-related studies were excluded from the literature search to limit the number of studies. Additionally, our included studies themselves might have some limitations to influence our conclusion. For example, the sample sizes for some studies were too small, so the results might have been due to chance; while some studies did not report the sampling strategies. Clinical trials of antiparasitic effects are mainly conducted in China, and there are almost no co-epidemic areas of schistosomiasis japonica and falciparum malaria. Thus, risk for drug resistance may not be taken into account [117]. In addition, most of the included studies involved randomized controlled trials (44, 57.1%), followed by quasi-experiment studies (28, 36.4%), and others (5, 6.5%). The overall quality of the included studies was good, but the quality of other types of evidence was relatively general, which may affect the credibility of the results to some extent.

Conclusions

Except antimalarial effects, current clinical research suggested that artemisinin and its derivatives might be safe and effective on anti-tumor, anti-virus, anti-parasite, anti-inflammatory and skin disease treatment. The potential to treat inflammatory diseases may provide a promising candidate to treat and suppress the recurrence of inflammatory and autoimmune diseases, and could potentially be an option for the urgent treatment for the COVID-19 pandemic. However, the underlying mechanism is not clear and more phase II/III clinical trials on the antiviral effects of artemisinin and its derivatives are needed to promote the translation from laboratory to population. Artemisinin and its derivatives provided a model for the development of traditional medicine using modern science and technology. With the features of complex components and multiple targets and pathways, Traditional Chinese Medicine need extensive research on pharmacological and mechanism studies to maximize their clinical potentials [118–120].

Supplementary Information

Acknowledgements

AcknowledgementsNot applicable.

Competing interests

Competing interestsThe authors declare that they do not have any competing interests. Yangmu Huang and Yang Yang contributed to the work equally and should be regarded as co-first authors.

References

1. Badshah SL, Ullah A, Ahmad N, Almarhoon ZM, Mabkhot Y. Increasing the strength and production of artemisinin and its derivatives. Molecules 2018, 23(1).10.3390/molecules23010100PMC601743229301383 doi:10.3390/molecules23010100 PubMed
2. Talman AM, Clain J, Duval R, Ménard R, Ariey F. Artemisinin bioactivity and resistance in malaria parasites. Trends Parasitol. 2019 doi:10.1016/j.pt.2019.09.005 PubMed
3. Shi C, Li H, Yang Y, Hou L. Anti-inflammatory and immunoregulatory functions of artemisinin and its derivatives. Mediat Inflamm. 2015 doi:10.1155/2015/435713 PubMed
4. Wang JG, Zhu XX. Advances in the study of artemisinin targets and mechanisms in chemical biology. Kexue Tongbao (Chin Ed). 2017
5. Guo HQ, Liu SZ, Wang L, Liu ZY, Wang ZH. Research progress of artemisinin and its derivatives against coccidiosis of chicken. Poult Sci. 2020
6. Isba R, Zani B, Gathu M, Sinclair D. Artemisinin-naphthoquine for treating uncomplicated Plasmodium falciparum malaria. Cochrane Database Syst Rev. 2015 doi:10.1002/14651858.CD011547 PubMed
7. Naing C, Whittaker MA, Mak JW, Aung K. A systematic review of the efficacy of a single dose artemisinin-naphthoquine in treating uncomplicated malaria. Malar J. 2015 doi:10.1186/s12936-015-0919-5 PubMed
8. World malaria report 2022. WHO. 2022. https://www.who.int/publications/i/item/9789240064898. Accessed 15 Sep 2023.
9. Garcia LS. Malaria. Clin Lab Med. 2010 doi:10.1016/j.cll.2009.10.001 PubMed
10. Ward KE, Fidock DA, Bridgford JL. Plasmodium falciparum resistance to artemisinin-based combination therapies. Curr Opin Microbiol. 2022 doi:10.1016/j.mib.2022.102193 PubMed
11. Firestone GL, Sundar SN. Anticancer activities of artemisinin and its bioactive derivatives. Expert Rev Mol Med. 2009 doi:10.1017/S1462399409001239 PubMed
12. Crespo-Ortiz MP, Wei MQ. Antitumor activity of artemisinin and its derivatives: from a well-known antimalarial agent to a potential anticancer drug. J Biomed Biotechnol. 2012 doi:10.1155/2012/247597 PubMed
13. Lai HC, Singh NP, Sasaki T. Development of artemisinin compounds for cancer treatment. Invest New Drugs. 2013 doi:10.1007/s10637-012-9873-z PubMed
14. Ho WE, Peh HY, Chan TK, Wong WS. Artemisinins: pharmacological actions beyond anti-malarial. Pharmacol Ther. 2014 doi:10.1016/j.pharmthera.2013.12.001 PubMed
15. Li Y, Shan NN, Sui XH. Research progress on artemisinin and its derivatives against hematological malignancies. Chin J Integr Med. 2020 doi:10.1007/s11655-019-3207-3 PubMed
16. Wang Y, Wang Y, You F, Xue J. Novel use for old drugs: the emerging role of artemisinin and its derivatives in fibrosis. Pharmacol Res. 2020 doi:10.1016/j.phrs.2020.104829 PubMed
17. Levac D, Colquhoun H, O'Brien KK. Scoping studies: advancing the methodology. Implement Sci. 2010 doi:10.1186/1748-5908-5-69 PubMed
18. Lam NS, Long X, Su XZ, Lu F. Artemisinin and its derivatives in treating helminthic infections beyond schistosomiasis. Pharmacol Res. 2018 doi:10.1016/j.phrs.2018.04.025 PubMed
19. Pérez del Villar L, Burguillo FJ, López-Abán J, Muro A. Systematic review and meta-analysis of artemisinin based therapies for the treatment and prevention of schistosomiasis. PLoS ONE. 2012 doi:10.1371/journal.pone.0045867 PubMed
20. De Clercq D, Vercruysse J, Kongs A, Verlé P, Dompnier JP, Faye PC. Efficacy of artesunate and praziquantel in Schistosoma haematobium infected schoolchildren. Acta Trop. 2002 doi:10.1016/S0001-706X(02)00003-7 PubMed
21. Boulanger D, Dieng Y, Cisse B, Remoue F, Capuano F, Dieme JL. Antischistosomal efficacy of artesunate combination therapies administered as curative treatments for malaria attacks. Trans R Soc Trop Med Hyg. 2007 doi:10.1016/j.trstmh.2006.03.003 PubMed
22. Goran EK, Jürg U, Gnaka HN, Ahoa Y, Guessan NA. Randomized, double-blind, placebo-controlled trial of oral artemether for the prevention of patent Schistosoma haematobium infections. Am J Trop Med Hyg. 2003 doi:10.4269/ajtmh.2003.68.24 PubMed
23. Hua HY, An N, Wu HZ, Gao ZL, Zhang Y, Liang YS. Clinical trials on preventive effect of artesunate against reinfection of Schistosoma japonicum. Zhongguo Xuexichongbing Fangzhi Zazhi. 2010
24. Xiao S, Shi Z, Zhuo S, Wang C, Zhang Z, Chu B. Field studies on the preventive effect of oral artemether against schistosomal infection. Chin Med J. 1996 PubMed
25. Song Y, Xiao S, Wu W, Zhang S, Xie H, Xu X. Preventive effect of artemether on schistosome infection. Chin Med J. 1998 PubMed
26. Li YS, Chen HG, He HB, Hou XY, Ellis M, McManus DP. A double-blind field trial on the effects of artemether on Schistosoma japonicum infection in a highly endemic focus in southern China. Acta Trop. 2005 doi:10.1016/j.actatropica.2005.07.013 PubMed
27. Yi ZH, Lu M, Feng DC, Wang ZH, Xiang CP, Gou ZQ. Clinical observation on prevention of schistosomiasis by oral artesunate in people exposed to epidemic water for a short time. Zhongguo Xuexichongbing Fangzhi Zazhi. 2000
28. Borrmann S, Szlezák N, Faucher JF, Matsiegui PB, Neubauer R, Binder RK. Artesunate and praziquantel for the treatment of Schistosoma haematobium infections: a double-blind, randomized, placebo-controlled study. J Infect Dis. 2001 doi:10.1086/324004 PubMed
29. Lin DD, Zhang SJ, Liu YM, Li SW, Wu LJ, Gao ZL. Field observation on the prophylaxis of artesunate with 15 days interval against infection of schtstosoma japonicum. Zhongguo Renshou Gonghuanbing Zazhi. 1999
30. Lu RG, Wang XY, Li ZH, Yan JL, Huang YN, Liu ZD. Clinical validation of artesunate against Schistosomiasis japonicum. Jishengchongbing Yu Ganranxingjibing. 1997
31. Xu MS, Zhang SQ, Wang TP, Fang GR, Wang QZ, He JX. Field appliance of oral artesunate for prevention of schistosomiasis japonica. Redaibing Yu Jishengchongxue. 1998
32. Liu HY, Li SW. Observation on the prevention of schistosomiasis japonica by administration of artesunate long term. J Pathogen Biol. 1999
33. Lu GY, Lin GJ, Sun MX, Jiang J, Cui JF, Wu QZ. Optimization of oral artesunate to prevent schistosoma schistosoma infection. J Pathogen Biol. 2000
34. Zhang SJ, Lin DD, Liu YM, Liu HY, Liu ZD, Hu LS. Clinical trials on preventive effect of artesunate on Schistosomiasis Japonica. Xiandai Zhenduan Yu Zhiliao. 2000
35. Hou XY. Clinical study on acute schistosomiasis japonica treatment with artemether and praziquantel. Master. Central South University; 2006 (in Chinese).
36. Wu LJ, Li SW, Xuan XY, Xu PS, Liu ZD, Hu LS. Field application of artesunate in prophylaxis of schistosomiasis: an observation of 346 cases. Zhongguo Xuexichongbing Fangzhi Zazhi. 1995
37. Liu ZD, Hu F, Zhou SY, Liu YM, Hu LS, Su LH. Clinical validation of artesunate against Schistosomiasis japonicum in Rocky Mountains. Zhongguo Xuexichongbing Fangzhi Zazhi. 1996
38. N'Goran EK, Utzinger J, Gnaka HN, Yapi A, N'Guessan NA, Kigbafori SD. Randomized, double-blind, placebo-controlled trial of oral artemether for the prevention of patent Schistosoma haematobium infections. Am J Trop Med Hyg. 2003 doi:10.4269/ajtmh.2003.68.24 PubMed
39. Utzinger J, N'Goran EK, N'Dri A, Lengeler C, Xiao S, Tanner M. Oral artemether for prevention of Schistosoma mansoni infection: randomised controlled trial. Lancet. 2000 doi:10.1016/S0140-6736(00)02114-0 PubMed
40. Hua HY, Liang YS, Zhang Y, Wei JF, Guo HX. The sensitivity of artesunate against Schistosoma japonicum decreased after 10 years of use in China. J Parasitol Res. 2010 doi:10.1007/s00436-010-1944-5 PubMed
41. Liu R, Dong HF, Jiang MS. The sensitivity of artesunate against Schistosoma japonicum decreased after 10 years of use in China?. Parasitol Res. 2012 doi:10.1007/s00436-011-2641-8 PubMed
42. Sissoko MS, Dabo A, Traoré H, Diallo M, Traoré B, Konaté D. Efficacy of artesunate + sulfamethoxypyrazine/pyrimethamine versus praziquantel in the treatment of Schistosoma haematobium in children. PLoS ONE. 2009 doi:10.1371/journal.pone.0006732 PubMed
43. Wang DG, Wang GH, Wang HL, Wang B, Xu AR, Li XS. A control study of artemether auxiliary treatment for schizophrenia with toxoplasmosis gondii antibody positive. Linchuang Xinshen Jibing Zazhi. 2012
44. Elmorshedy H, Tanner M, Bergquist RN, Sharaf S, Barakat R. Prophylactic effect of artemether on human schistosomiasis mansoni among Egyptian children: a randomized controlled trial. Acta Trop. 2016 doi:10.1016/j.actatropica.2016.02.015 PubMed
45. Inyang-Etoh PC, Ejezie GC, Useh MF, Inyang-Etoh EC. Efficacy of a combination of praziquantel and artesunate in the treatment of urinary schistosomiasis in Nigeria. Trans R Soc Trop Med Hyg. 2009 doi:10.1016/j.trstmh.2008.08.002 PubMed
46. Mnkugwe RH, Minzi O. Kinung’hi S, Kamuhabwa A, Aklillu E: Efficacy and safety of praziquantel and dihydroartemisinin piperaquine combination for treatment and control of intestinal schistosomiasis: a randomized, non-inferiority clinical trial. PLoS Negl Trop Dis. 2020 doi:10.1371/journal.pntd.0008619 PubMed
47. Hou XY, Li YS, Luo XS, He KY, Yu XL, Fu X. Clinical study on acute schistosomiasis japonica treatment with artemether and praziquantel. Zhongguo Xuexichongbing Fangzhi Zazhi. 2006
48. Obonyo CO, Muok EMO, Mwinzi PNM. Efficacy of artesunate with sulfalene plus pyrimethamine versus praziquantel for treatment of Schistosoma mansoni in Kenyan children: an open-label randomised controlled trial. Lancet Infect Dis. 2010 doi:10.1016/S1473-3099(10)70161-4 PubMed
49. Wang HL, Xiang YT, Li QY, Wang XP, Liu ZC, Hao SS. The effect of artemether on psychotic symptoms and cognitive impairment in first-episode, antipsychotic drug-naive persons with schizophrenia seropositive to Toxoplasma gondii. J Psychiatr Res. 2014 doi:10.1016/j.jpsychires.2014.02.016 PubMed
50. Dickerson F, Stallings C, Vaughan C, Origoni A, Goga J, Khushalani S. Artemisinin reduces the level of antibodies to gliadin in schizophrenia. Schizophr Res. 2011 doi:10.1016/j.schres.2011.04.010 PubMed
51. Tran TH, Ng TT, Nguyen HM, Hoang DD, Nguyen TD, Nguyen TH. A randomized controlled pilot study of artesunate versus triclabendazole for human fascioliasis in central Vietnam. Am J Trop Med Hyg. 2008 doi:10.4269/ajtmh.2008.78.388 PubMed
52. Keiser J, Sayed H, El-Ghanam M, Sabry H, Anani S, El-Wakeel A. Efficacy and safety of artemether in the treatment of chronic fascioliasis in Egypt: exploratory phase-2 trials. PLoS Negl Trop Dis. 2011 doi:10.1371/journal.pntd.0001285 PubMed
53. Efferth T, Dunstan H, Sauerbrey A, Miyachi H, Chitambar CR. The anti-malarial artesunate is also active against cancer. Int J Oncol. 2001 doi:10.3892/ijo.18.4.767 PubMed
54. Luo YC. Effect of artesunate hepatic artery infusion on immune function in patients with primary liver cancer. Master. Guangzhou University of Chinese Medicine; 2008 (in Chinese).
55. Yu S-Q, Zhang Z-Y. Artesunate combined with vinorelbine plus cisplatin in treatment of advanced non-small cell lung cancer: a randomized controlled trial. Zhong Xi Yi Jie He Xue Bao. 2008 doi:10.3736/jcim20080206 PubMed
56. Zhang YY. Clinical efficacy and safety of artesunate in the treatment of advanced retinoblastoma. Master. Anhui Medical University; 2015 (in Chinese).
57. Krishna S, Ganapathi S, Ster IC, Saeed MEM, Cowan M, Finlayson C. A randomised, double blind, placebo-controlled pilot study of oral artesunate therapy for colorectal cancer. EBioMedicine. 2015 doi:10.1016/j.ebiom.2014.11.010 PubMed
58. von Hagens C, Walter-Sack I, Goeckenjan M, Osburg J, Storch-Hagenlocher B, Sertel S. Prospective open uncontrolled phase I study to define a well-tolerated dose of oral artesunate as add-on therapy in patients with metastatic breast cancer (ARTIC M33/2). Breast Cancer Res Treat. 2017 doi:10.1007/s10549-017-4261-1 PubMed
59. von Hagens C, Walter-Sack I, Goeckenjan M, Storch-Hagenlocher B, Sertel S, Elsässer M. Long-term add-on therapy (compassionate use) with oral artesunate in patients with metastatic breast cancer after participating in a phase I study (ARTIC M33/2). Phytomedicine. 2019 doi:10.1016/j.phymed.2018.09.178 PubMed
60. Trimble CL, Levinson K, Maldonado L, Donovan M, Clark KT, Fu J. A first-in-human proof-of-concept trial of intravaginal artesunate to treat cervical intraepithelial neoplasia (CIN2/3). Gynecol Oncol. 2020 doi:10.1016/j.ygyno.2020.06.078 PubMed
61. Ericsson T, Blank A, Von Hagens C, Ashton M, Äbelö A. Population pharmacokinetics of artesunate and dihydroartemisinin during long-term oral administration of artesunate to patients with metastatic breast cancer. Eur J Clin Pharmacol. 2014 doi:10.1007/s00228-014-1754-2 PubMed
62. Deeken JF, Wang H, Hartley M, Cheema AK, Smaglo B, Hwang JJ. A phase I study of intravenous artesunate in patients with advanced solid tumor malignancies. Cancer Chemother Pharmacol. 2018 doi:10.1007/s00280-018-3533-8 PubMed
63. König M, Von Hagens C, Hoth S, Baumann I, Walter-Sack I, Edler L. Investigation of ototoxicity of artesunate as add-on therapy in patients with metastatic or locally advanced breast cancer: new audiological results from a prospective, open, uncontrolled, monocentric phase i study. Cancer Chemother Pharmacol. 2016 doi:10.1007/s00280-016-2960-7 PubMed
64. Zhou WJ. Study on the clinical efficacy of anti-tumor angiogenesis drugs. China Pract Med. 2017
65. Zhang XJ. Therapeutic effect of artesunate on acute leukemia and its effect on intracellular calcium concentration. Master. Guangzhou University of Chinese Medicine; 2008 (in Chinese).
66. Wang M, Luo HJ, Lin Y. The chemotherapy effect and safety of artesunate/cisplatin-paclitaxel for ovarian cancer. Xibei Yaoxue Zazhi. 2016
67. Xiao XP, Zhang ZY, Yu SQ, Zhou SX. The curative effect of chemotherapy combined with sequential administration of artesu-nate in non - small cell lung cancer. Mod Oncol. 2015
68. Zhang H. Analysis of 134 cases of uveitis complicated by malaria. Chin N Med. 2009
69. Li DZ. Observation on the efficacy of artesunate boric acid powder combined with microwave irradiation in the treatment of chronic suppurative otitis media in malaria area. Zhongguo Yaowu Yu Linchuang. 2015
70. Lin YR, Wu FY, Xie HZ, Song XL, Zhu QD, Wei J. Clinical study of artesunate in the treatment of coronavirus disease 2019. Zhonghua Weizhongbing Jijiu Yixue. 2020 doi:10.3760/cma.j.cn121430-20200312-00412 PubMed
71. Liu HJ. Clinical study of artesunate in the treatment of systemic lupus erythematosus. Master. Guangzhou University of Chinese Medicine; 2002 (in Chinese).
72. Lu L. Study on effect of Cordyceps Sinensis and artemisinin in preventing recurrence of lupus nephritis. Zhongguo Zhongxiyi Jiehe Zazhi. 2002 PubMed
73. Du AH, He YQ, Chen LP. Clinical nursing of severe lupus nephritis treated by combination of traditional Chinese and Western Medicine. Xiandai Zhongxiyi Jiehe Zazhi. 2004
74. Cui XJ, Wang YY, Hou XQ, Pan L, Fu JX. Clinical observation of artesunate in the treatment of rheumatoid arthritis. Zhongguo Yiyuan Yaoxue Zazhi. 2007
75. Wei S, Xu GG. Clinical observation of artesunate in the treatment of rheumatoid arthritis. Shanxi Yiyao Zazhi. 2008
76. Huang XX. Clinical study on the effect of artesunate on immune function in patients with lupus nephritis. Shizhen Guoyi Guoyao. 2011
77. Zhao YJ, Liu XR. Clinical observation on 25 cases of VKH syndrome treated by artemether soft capsule combined with glucocorticoid. Pract Clin J Integr Tradit Chin West Med. 2016
78. Zhong JX, Liu YM, Liu HJ, Yang DF, Lin XD, Fu CL. Safety of artesunate in the treatment of systemic lupus erythematosus. Zhongyao Xinyao Yu Linchuang Yaoli. 2000
79. Lamorde M, Byakika-Kibwika P, Mayito J, Nabukeera L, Ryan M, Hanpithakpong W. Lower artemether, dihydroartemisinin and lumefantrine concentrations during rifampicin-based tuberculosis treatment. AIDS. 2013 doi:10.1097/QAD.0b013e32835cae3b PubMed
80. Yu QB, Jin HL. Systemic lupus erythematosus treated with artesunate. Bengbu Yixueyuan Xuebao. 1996
81. Byakika-Kibwika P, Lamorde M, Okaba-Kayom V, Mayanja-Kizza H, Katabira E, Hanpithakpong W. Lopinavir/ritonavir significantly influences pharmacokinetic exposure of artemether/lumefantrine in HIV-infected Ugandan adults. J Antimicrob Chemother. 2012 doi:10.1093/jac/dkr596 PubMed
82. Kredo T, Mauff K, Workman L, Vander Walt JS, Wiesner L. The interaction between artemether-lumefantrine and lopinavir/ritonavir-based antiretroviral therapy in HIV-1 infected patients. BMC Infect Dis. 2016 doi:10.1186/s12879-016-1345-1 PubMed
83. Siccardi M, Olagunju A, Seden K, Ebrahimjee F, Rannard S, Back D. Use of a physiologically-based pharmacokinetic model to simulate artemether dose adjustment for overcoming the drug-drug interaction with efavirenz. In Silico Pharmacol. 2013 doi:10.1186/2193-9616-1-4 PubMed
84. Soren G. An artesunate-containing antimalarial treatment regimen did not suppress cytomegalovirus viremia. J Clin Virol. 2013 doi:10.1016/j.jcv.2013.06.008 PubMed
85. Chen H, Gao YX. Artesunate therapy in eczema-dermatitis and photoallergic skin diseases (preliminary observation). Bengbu Yixueyuan Xuebao. 1991
86. Yu QB, Jin HL. Clinical analysis of 90 cases of dermatosis treated with artesunate. Bengbu Yixueyuan Xuebao. 1997
87. Li T, Hu Y, Yu AH, Chen XM, Zhang HQ, Wang GJ. Clinical research of the efficacy of artesunate in 31 patients with rosacea. Zhongguo Pifu Xingbingxue Zazhi. 2015
88. Wang GJ, Gao XY, Wu Y, He HQ, Yu Y, Qin HH. Evaluation of the efficacy and tolerance of artemether emulsion for the treatment of papulopustular rosacea: a randomized pilot study. J Dermatolog Treat. 2019 doi:10.1080/09546634.2019.1610549 PubMed
89. Shen WT, Wu Y, He HQ, Yu Y, Qin HH, Fei JB. Efficacy and safety of artemether emulsion for the treatment of mild-to-moderate acne vulgaris: a randomized pilot study. J Dermatolog Treat. 2021 doi:10.1080/09546634.2019.1710447 PubMed
90. Deng DQ, Chen H, Zhou XO, Li HY, Xie HY, Zhang PL. Clinical observation of polymorphous light eruption and chronic actinic dermatitis treated with artemtherin. Kunming Yike Daxue Xuebao. 2006
91. Wang J, Xu C, Wong YK, Li Y, Liao F, Jiang T. Artemisinin, the magic drug discovered from traditional Chinese medicine—sciencedirect. Engineering. 2019 doi:10.1016/j.eng.2018.11.011
92. Jiang WQ, Dong YJ, Zhou FJ, Chen JP, Zhou YT, Tian CW. Research progress of artemisinin and its derivatives. Zhongcaoyao. 2022
93. Inyang-Etoh PC, Ejezie GC, Useh MF, Inyang-Etoh EC. Efficacy of artesunate in the treatment of urinary schistosomiasis, in an endemic community in Nigeria. Ann Trop Med Parasitol. 2004 doi:10.1179/000349804225003460 PubMed
94. Zhang TJ, Wang YF, Liu D, Li LG, Guo RX, Shi QW. History of natural medicine chemistry: artemisinin—a monument of traditional Chinese medicine research. Zhongcaoyao. 2016
95. Sun X, Yan P, Zou C, Wong YK, Shu Y, Lee YM et al. Targeting autophagy enhances the anticancer effect of artemisinin and its derivatives. Med Res Rev. 2019 doi:10.1002/med.21580 PubMed
96. Augustin Y, Staines HM, Krishna S. Artemisinins as a novel anti-cancer therapy: targeting a global cancer pandemic through drug repurposing. Pharmacol Ther. 2020 doi:10.1016/j.pharmthera.2020.107706 PubMed
97. Luo J, Zhang Y, Wang Y, Liu Q, Li J, He H et al. Artesunate and dihydroartemisinin inhibit rabies virus replication. Virol Sin. 2021 doi:10.1007/s12250-021-00349-z PubMed
98. Machín L, Nápoles R, Gille L, Monzote L. Leishmania amazonensis response to artemisinin and derivatives. Parasitol Int. 2021 doi:10.1016/j.parint.2020.102218 PubMed
99. Nair MS, Huang Y, Fidock DA, Towler MJ, Weathers PJ. Artemisia annua L. hot-water extracts show potent activity in vitro against Covid-19 variants including delta. J Ethnopharmacol. 2022 doi:10.1016/j.jep.2021.114797 PubMed
100. Chen YL, Guo Y. Epidemic characteristics and influencing factors of parasitic diseases. Gansu Anim Husb Vet Med. 2023
101. Liang YJ, Peng Y, Han XP. Research progress of artemisinin and its derivatives in dermatosis. J Pract Dermatol. 2021
102. Li H-M, Arthur Djibougou D, Lu S-N, Lv S, Zongo D, Wang D-Q. Strengthening capacity-building in malaria and schistosomiasis control under China-Africa cooperation: assessing a case study of Burkina Faso. Sci One Health. 2022 doi:10.1016/j.soh.2023.100009 PubMed
103. Guo Z-Y, Zheng J, Li S-Z, Zhou X-N. Orientation of One Health development: think globally and act locally. Sci One Health. 2023 doi:10.1016/j.soh.2023.100042 PubMed
104. Zhang B. Artemisinin-derived dimers as potential anticancer agents: current developments, action mechanisms, and structure-activity relationships. Arch Pharm (Weinheim). 2020 doi:10.1002/ardp.201900240 PubMed
105. Lou ZH, Bao JF, Guo JC. Artemisinin derivatives may assist in the treatment of liver cancer. Liver Doctor. 2023
106. Shen XD, Cao YO, Su C. Research progress on the effect of artemisinin and its derivatives on gastrointestinal tumors. J Tradit Chin Med. 2022
107. Zhang LJ, Zhuang KY. Research and application of artemisinin and its derivatives in dermatology. Yixue Zongshu. 2014
108. Jiang L, Sun LY. General situation of research on Artemisia annua and its derivatives in the treatment of skin diseases. Zhonghua Zhongyiyao Zazhi. 2018
109. Liu GM, Cai N, Xie J, Xin C, Li RM, Zhou HY. Application of artemisinin and its derivatives in the treatment of COVID-19. Yaowu Pingjia Yanjiu. 2020
110. Yang YM, Chen LN, Qu SQ, Deng QS, Liu H, Wang Q. Based on the cardiovascular protective effects of artemisinin and its derivatives, the feasibility of artemisinin in the intervention of cardiovascular complications in COVID-19 was discussed. Zhongguo Zhongyao Zazhi. 2020 doi:10.19540/j.cnki.cjcmm.20200828.601 PubMed
111. Liu W, Gong PY, Gu J, Yuan ZX. Application of traditional Chinese medicine with antipyretic, anti-inflammatory and immunomodulatory effects in the treatment of COVID-19 (COVID-19). Zhongyaocai. 2020
112. Guo FQ. Preparation and preliminary evaluation of dihydroartemisinin sustained release tablets. M.s. China Acad Chin Med Sci. 2020 (in Chinese).
113. Sun D, Gao W, Hu H, Zhou S. Why 90% of clinical drug development fails and how to improve it?. Acta Pharm Sin B. 2022 doi:10.1016/j.apsb.2022.02.002 PubMed
114. Kumari A, Karnatak M, Singh D, Shankar R, Jat JL, Sharma S et al. Current scenario of artemisinin and its analogues for antimalarial activity. Eur J Med Chem. 2019 doi:10.1016/j.ejmech.2018.12.007 PubMed
115. Efferth T, Zacchino S, Georgiev MI, Liu L, Wagner H, Panossian A. Nobel Prize for artemisinin brings phytotherapy into the spotlight. Phytomedicine. 2015 doi:10.1016/j.phymed.2015.10.003 PubMed
116. Huang YM, Cao J. China's contribution to the research and development of medical products against parasitic diseases: inspiration from the 2015 Nobel Prize in Physiology or Medicine. Zhongguo Xuexichongbing Fangzhi Zazhi. 2016 doi:10.16250/j.32.1374.2016161 PubMed
117. Liu YX, Wu W, Liang YJ, Jie ZL, Wang H, Wang W. New uses for old drugs: the tale of artemisinin derivatives in the elimination of schistosomiasis japonica in China. Molecules. 2014 doi:10.3390/molecules190915058 PubMed
118. Ma BL, Ma YM. Pharmacokinetic herb-drug interactions with traditional Chinese medicine: progress, causes of conflicting results and suggestions for future research. Drug Metab Rev. 2016 doi:10.3109/03602532.2015.1124888 PubMed
119. Wu S, Luo H, Zhong Z, Ai Y, Zhao Y, Liang Q et al. Phytochemistry, pharmacology and quality control of Xiasangju: a traditional Chinese medicine formula. Front Pharmacol. 2022 doi:10.3389/fphar.2022.930813 PubMed
120. Chen X, Ung CY, Chen Y. Can an in silico drug-target search method be used to probe potential mechanisms of medicinal plant ingredients?. Nat Prod Rep. 2003 doi:10.1039/b303745b PubMed