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

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          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.

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          Supplementary Information

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

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          Most cited references111

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          Scoping studies: advancing the methodology

          Background Scoping studies are an increasingly popular approach to reviewing health research evidence. In 2005, Arksey and O'Malley published the first methodological framework for conducting scoping studies. While this framework provides an excellent foundation for scoping study methodology, further clarifying and enhancing this framework will help support the consistency with which authors undertake and report scoping studies and may encourage researchers and clinicians to engage in this process. Discussion We build upon our experiences conducting three scoping studies using the Arksey and O'Malley methodology to propose recommendations that clarify and enhance each stage of the framework. Recommendations include: clarifying and linking the purpose and research question (stage one); balancing feasibility with breadth and comprehensiveness of the scoping process (stage two); using an iterative team approach to selecting studies (stage three) and extracting data (stage four); incorporating a numerical summary and qualitative thematic analysis, reporting results, and considering the implications of study findings to policy, practice, or research (stage five); and incorporating consultation with stakeholders as a required knowledge translation component of scoping study methodology (stage six). Lastly, we propose additional considerations for scoping study methodology in order to support the advancement, application and relevance of scoping studies in health research. Summary Specific recommendations to clarify and enhance this methodology are outlined for each stage of the Arksey and O'Malley framework. Continued debate and development about scoping study methodology will help to maximize the usefulness and rigor of scoping study findings within healthcare research and practice.
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            Why 90% of clinical drug development fails and how to improve it?

            Ninety percent of clinical drug development fails despite implementation of many successful strategies, which raised the question whether certain aspects in target validation and drug optimization are overlooked? Current drug optimization overly emphasizes potency/specificity using structure‒activity-relationship (SAR) but overlooks tissue exposure/selectivity in disease/normal tissues using structure‒tissue exposure/selectivity–relationship (STR), which may mislead the drug candidate selection and impact the balance of clinical dose/efficacy/toxicity. We propose structure‒tissue exposure/selectivity–activity relationship (STAR) to improve drug optimization, which classifies drug candidates based on drug's potency/selectivity, tissue exposure/selectivity, and required dose for balancing clinical efficacy/toxicity. Class I drugs have high specificity/potency and high tissue exposure/selectivity, which needs low dose to achieve superior clinical efficacy/safety with high success rate. Class II drugs have high specificity/potency and low tissue exposure/selectivity, which requires high dose to achieve clinical efficacy with high toxicity and needs to be cautiously evaluated. Class III drugs have relatively low (adequate) specificity/potency but high tissue exposure/selectivity, which requires low dose to achieve clinical efficacy with manageable toxicity but are often overlooked. Class IV drugs have low specificity/potency and low tissue exposure/selectivity, which achieves inadequate efficacy/safety, and should be terminated early. STAR may improve drug optimization and clinical studies for the success of clinical drug development.
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              Antitumor Activity of Artemisinin and Its Derivatives: From a Well-Known Antimalarial Agent to a Potential Anticancer Drug

              Improvement of quality of life and survival of cancer patients will be greatly enhanced by the development of highly effective drugs to selectively kill malignant cells. Artemisinin and its analogs are naturally occurring antimalarials which have shown potent anticancer activity. In primary cancer cultures and cell lines, their antitumor actions were by inhibiting cancer proliferation, metastasis, and angiogenesis. In xenograft models, exposure to artemisinins substantially reduces tumor volume and progression. However, the rationale for the use of artemisinins in anticancer therapy must be addressed by a greater understanding of the underlying mechanisms involved in their cytotoxic effects. The primary targets for artemisinin and the chemical base for its preferential effects on heterologous tumor cells need yet to be elucidated. The aim of this paper is to provide an overview of the recent advances and new development of this class of drugs as potential anticancer agents.
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                Author and article information

                Contributors
                ymhuang@bjmu.edu.cn
                hudan@bjmu.edu.cn
                Journal
                Infect Dis Poverty
                Infect Dis Poverty
                Infectious Diseases of Poverty
                BioMed Central (London )
                2095-5162
                2049-9957
                11 December 2023
                11 December 2023
                2023
                : 12
                : 115
                Affiliations
                [1 ]School of Public Health, Peking University, ( https://ror.org/02v51f717) 38 Xue Yuan Road, Haidian District, Beijing, 100191 China
                [2 ]Institute for Global Health and Development, Peking University, ( https://ror.org/02v51f717) 38 Xue Yuan Road, Haidian District, Beijing, 100191 China
                [3 ]China Center for Health Development Studies, Peking University, ( https://ror.org/02v51f717) 38 Xue Yuan Road, Haidian District, Beijing, 100191 China
                [4 ]Energy Saving and Environmental Protection and Occupational Safety and Health Research Institute, China Academy of Railway Sciences Co., Ltd, ( https://ror.org/051wv2j09) No. 2 Daliushu Road, Beijing, 100081 China
                Article
                1152
                10.1186/s40249-023-01152-6
                10712159
                38072951
                51e1a061-a2aa-4195-9d84-565cd298a69d
                © The Author(s) 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 22 May 2023
                : 2 November 2023
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000865, Bill and Melinda Gates Foundation;
                Award ID: No. INV-018913
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100020347, Steel and Iron Foundation of Hebei Province;
                Award ID: No. 71503015
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100019053, Capacity Building Plan for some Non-military Universities and Colleges of Shanghai Scientific Committee;
                Funded by: FundRef http://dx.doi.org/10.13039/501100013077, National Science and Technology Planning Project;
                Categories
                Scoping Review
                Custom metadata
                © National Institute of Parasitic Diseases 2023

                artemisinin,derivatives,medicinal effect,clinical application,clinical study,scoping review

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