Unexpected mechanism of colitis amelioration by artesunate, a natural product from Artemisia annua L.
Abstract
Background Artemisinin and its derivatives are known to exert immunosuppressive effects through modulating adaptive immunity. We investigated a novel role of artesunate in regulating innate immunity, including both macrophages (MΦ) and dendritic cells (DCs), which are known to involve in DSS-induced colitis.Methods Effects of artesunate on innate immunity were extensively evaluated, both in vivo using DSS-colitis model with WT and T cell-deficient RAG mice (RAG-/-) and in vitro using cell culture models, including in-depth analyses of MΦ/DC apoptosis and cytokine expression by flow cytometry, Western blot, or immunohistology.Results Unexpectedly, artesunate significantly ameliorated the DSS colitis of both WT and RAG1-/- mice with similar potency, suggesting a mechanism that involves primarily innate rather than adaptive immunity. In vivo mechanistic studies revealed that artesunate markedly induced apoptosis of lamina propria MΦs and DCs and suppressed mucosal TNF-α and IL-12p70 in DSS-colitis. In vitro, artesunate potently induced a dose- and time-dependent apoptosis of murine bone marrow-derived DCs and human THP-1 MΦs, through the caspases-9-mediated intrinsic pathway. Artesunate significantly decreased the secretion of IL-12p40/70 by DCs and TNF-α by MΦs. Furthermore, a combination of artesunate with an immunomodulator (methotrexate/triptolide/azathioprine) exhibited superior potency in promoting apoptosis of MΦs than any individual drug alone.Conclusions The immunomodulatory mechanism of artesunate in colitis involves a novel and potent induction of the intrinsic apoptosis pathway of proliferating MΦs and DCs and suppression of IL-12 and TNF-α. Artemisinin and its derivatives are promising new therapeutic alternatives for IBD, either alone or in combination with other immunomodulators.
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Artemisinin is efficacious against chronic conditions including fibrosis, colitis, and inflammation.
“Besides infectious diseases, artemisinin is also efficacious against a number of chronic conditions including fibrosis (Zeng et al. 2015; Dolivo et al. 2020), colitis (Sun et al. 2019) and inflammation (Shi et al. 2015).”
From Enhancing artemisinin content in and delivery from Artemisia annua: a review of alternative, classical, and transgenic approaches (2021) · cites this paper as Sun et al. 2019
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Wani, K. I., Choudhary, S., Zehra, A., Naeem, M., Weathers, P., & Aftab, T. (2021) · Planta · doi:10.1007/s00425-021-03676-3 · Cited by 74 · see citing works
- Authors
- Sun, W., Han, X., Wu, S., Wu, J., Yang, C., & Li, X.
- Affiliations
- Shanghai Jiao Tong University (CN)
- Johns Hopkins University (US)
- Corresponding author
- Li, Xuhang
- Venue
- Inflammopharmacology
- Published
- 2019-12-21
- Volume
- 28
- Issue
- 4
- Pages
- 851-868
- ISSN
- 0925-4692 (ISSN-L)
- 1568-5608
- OpenAlex
- W2995147881
- Cited by
- 31
- References
- 40
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 8 · 2023: 4 · 2022: 3 · 2021: 8 · 2020: 1
- FWCI
- 1.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Inflammopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81370509)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Health Sciences › Medicine › Complementary and alternative medicine › Natural Compounds in Disease Treatment
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Keywords
- artesunate, DSS-induced colitis, inflammatory bowel disease, innate immunity, macrophage apoptosis, dendritic cell apoptosis, caspase-9, IL-12, TNF-α, immunomodulation, methotrexate, triptolide, azathioprine, Artemisia annua, artemisinin derivatives
- MeSH terms
- THP-1 Cells, Artesunate, Animals, Biological Products, Cells, Cultured, Colitis, Dendritic Cells, Disease Models, Animal, Humans, Immunity, Innate, Immunologic Factors, Intestinal Mucosa, Macrophages, Mice, Inbred C57BL, Tumor Necrosis Factor-alpha, Dextran Sulfate, Apoptosis, Interleukin-12, Artemisia annua, Mice, Adaptive Immunity
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