Advances in the study of artemisinin and its derivatives for the treatment of rheumatic skeletal disorders, autoimmune inflammatory diseases, and autoimmune disorders: a comprehensive review
Artemisinin and its derivatives are widely recognized as first-line treatments for malaria worldwide. Recent studies have demonstrated that artemisinin-based antimalarial drugs, such as artesunate, dihydroartemisinin, and artemether, not only possess excellent antimalarial properties but also exhibi...
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Frontiers Media S.A.
2024-10-01
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| author | Zhiyong Long Wang Xiang Wei Xiao Yu Min Fei Qu Bolin Zhang Liuting Zeng |
| author_facet | Zhiyong Long Wang Xiang Wei Xiao Yu Min Fei Qu Bolin Zhang Liuting Zeng |
| author_sort | Zhiyong Long |
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| description | Artemisinin and its derivatives are widely recognized as first-line treatments for malaria worldwide. Recent studies have demonstrated that artemisinin-based antimalarial drugs, such as artesunate, dihydroartemisinin, and artemether, not only possess excellent antimalarial properties but also exhibit antitumor, antifungal, and immunomodulatory effects. Researchers globally have synthesized artemisinin derivatives like SM735, SM905, and SM934, which offer advantages such as low toxicity, high bioavailability, and potential immunosuppressive properties. These compounds induce immunosuppression by inhibiting the activation of pathogenic T cells, suppressing B cell activation and antibody production, and enhancing the differentiation of regulatory T cells. This review summarized the mechanisms by which artemisinin and its analogs modulate excessive inflammation and immune responses in rheumatic and skeletal diseases, autoimmune inflammatory diseases, and autoimmune disorders, through pathways including TNF, Toll-like receptors, IL-6, RANKL, MAPK, PI3K/AKT/mTOR, JAK/STAT, and NRF2/GPX4. Notably, in the context of the NF-κB pathway, artemisinin not only inhibits NF-κB expression by disrupting upstream cascades and/or directly binding to NF-κB but also downregulates multiple downstream genes controlled by NF-κB, including inflammatory chemokines and their receptors. These downstream targets regulate various immune cell functions, apoptosis, proliferation, signal transduction, and antioxidant responses, ultimately intervening in systemic autoimmune diseases and autoimmune responses in organs such as the kidneys, nervous system, skin, liver, and biliary system by modulating immune dysregulation and inflammatory responses. Ongoing multicenter randomized clinical trials are investigating the effects of these compounds on rheumatic, inflammatory, and autoimmune diseases, with the aim of translating promising preclinical data into clinical applications. |
| format | Article |
| id | doaj-art-a0ec83ddc57b47f1abed1b7296f50f9f |
| institution | OA Journals |
| issn | 1664-3224 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-a0ec83ddc57b47f1abed1b7296f50f9f2025-08-20T02:11:38ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-10-011510.3389/fimmu.2024.14326251432625Advances in the study of artemisinin and its derivatives for the treatment of rheumatic skeletal disorders, autoimmune inflammatory diseases, and autoimmune disorders: a comprehensive reviewZhiyong Long0Wang Xiang1Wei Xiao2Yu Min3Fei Qu4Bolin Zhang5Liuting Zeng6Department of Physical Medicine and Rehabilitation, The Affiliated Panyu Central Hospital, Guangzhou Medical University, Guangzhou, ChinaDepartment of Rheumatology, Changde Hospital, Xiangya School of Medicine, Central South University, Changde, ChinaDepartment of Rheumatology, Changde Hospital, Xiangya School of Medicine, Central South University, Changde, ChinaDepartment of Physical Medicine and Rehabilitation, The Affiliated Panyu Central Hospital, Guangzhou Medical University, Guangzhou, ChinaDepartment of Acupuncture and Massage, The Affiliated Panyu Central Hospital, Guangzhou Medical University, Guangzhou, ChinaHainan Normal University, Haikou, ChinaDepartment of Physical Medicine and Rehabilitation, The Affiliated Panyu Central Hospital, Guangzhou Medical University, Guangzhou, ChinaArtemisinin and its derivatives are widely recognized as first-line treatments for malaria worldwide. Recent studies have demonstrated that artemisinin-based antimalarial drugs, such as artesunate, dihydroartemisinin, and artemether, not only possess excellent antimalarial properties but also exhibit antitumor, antifungal, and immunomodulatory effects. Researchers globally have synthesized artemisinin derivatives like SM735, SM905, and SM934, which offer advantages such as low toxicity, high bioavailability, and potential immunosuppressive properties. These compounds induce immunosuppression by inhibiting the activation of pathogenic T cells, suppressing B cell activation and antibody production, and enhancing the differentiation of regulatory T cells. This review summarized the mechanisms by which artemisinin and its analogs modulate excessive inflammation and immune responses in rheumatic and skeletal diseases, autoimmune inflammatory diseases, and autoimmune disorders, through pathways including TNF, Toll-like receptors, IL-6, RANKL, MAPK, PI3K/AKT/mTOR, JAK/STAT, and NRF2/GPX4. Notably, in the context of the NF-κB pathway, artemisinin not only inhibits NF-κB expression by disrupting upstream cascades and/or directly binding to NF-κB but also downregulates multiple downstream genes controlled by NF-κB, including inflammatory chemokines and their receptors. These downstream targets regulate various immune cell functions, apoptosis, proliferation, signal transduction, and antioxidant responses, ultimately intervening in systemic autoimmune diseases and autoimmune responses in organs such as the kidneys, nervous system, skin, liver, and biliary system by modulating immune dysregulation and inflammatory responses. Ongoing multicenter randomized clinical trials are investigating the effects of these compounds on rheumatic, inflammatory, and autoimmune diseases, with the aim of translating promising preclinical data into clinical applications.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1432625/fullartemisininautoimmune diseasesautoimmune disordersartememisinin derivativesNF-κB pathwayimmune modulation |
| spellingShingle | Zhiyong Long Wang Xiang Wei Xiao Yu Min Fei Qu Bolin Zhang Liuting Zeng Advances in the study of artemisinin and its derivatives for the treatment of rheumatic skeletal disorders, autoimmune inflammatory diseases, and autoimmune disorders: a comprehensive review Frontiers in Immunology artemisinin autoimmune diseases autoimmune disorders artememisinin derivatives NF-κB pathway immune modulation |
| title | Advances in the study of artemisinin and its derivatives for the treatment of rheumatic skeletal disorders, autoimmune inflammatory diseases, and autoimmune disorders: a comprehensive review |
| title_full | Advances in the study of artemisinin and its derivatives for the treatment of rheumatic skeletal disorders, autoimmune inflammatory diseases, and autoimmune disorders: a comprehensive review |
| title_fullStr | Advances in the study of artemisinin and its derivatives for the treatment of rheumatic skeletal disorders, autoimmune inflammatory diseases, and autoimmune disorders: a comprehensive review |
| title_full_unstemmed | Advances in the study of artemisinin and its derivatives for the treatment of rheumatic skeletal disorders, autoimmune inflammatory diseases, and autoimmune disorders: a comprehensive review |
| title_short | Advances in the study of artemisinin and its derivatives for the treatment of rheumatic skeletal disorders, autoimmune inflammatory diseases, and autoimmune disorders: a comprehensive review |
| title_sort | advances in the study of artemisinin and its derivatives for the treatment of rheumatic skeletal disorders autoimmune inflammatory diseases and autoimmune disorders a comprehensive review |
| topic | artemisinin autoimmune diseases autoimmune disorders artememisinin derivatives NF-κB pathway immune modulation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1432625/full |
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