Abstract
Shikonin is a natural product with antioxidant and anti-inflammatory activities. The biological activity of shikonin is still not fully understood, as well as its association with innate immunity and immune and inflammatory bowel disease (IBD) in humans. In this study, the toxicity of shikonin on Raw264.7 cells was assayed by MTT, and polarization of inflammatory macrophages was determined by flow cytometry. The results showed that shikonin can inhibit the polarization of macrophages towards M1 type and significantly inhibited the production of NO in the concentration range of 0.5–1 μM. In addition, after treatment with shikonin, the production of IL-1β and TNF-α was significantly decreased. After shikonin administration, the body weight loss and decrease of colon length were significantly suppressed in DSS-treated colitis C57BL/6 mice. The pro-inflammatory cytokines TNF-α and IL-1β in colonic homogenate were significantly decreased. Shikonin treatment resulted in a notable improvement in the histopathological manifestations in DSS-treated animals at 25/50 mg/kg. Meanwhile, we found that shikonin can regulate differentiation of T helper 17 cell (Th17)/regulatory T cell (Treg), thereby regulating the balance of Th17/Treg cells and exerting an anti-inflammatory effect in IBD animal models. In conclusion, we found that shikonin protects against DSS-induced acute colitis by, among other things, reducing immune cell infiltration, polarizing macrophages, and regulating Th17/Treg differentiation, as well as by downregulating the release of inflammatory cytokines. These findings showed that shikonin can improve inflammation by affecting macrophage polarization. Our experimental data provide experimental evidence and theory basis for research on anti-inflammatory effects for the shikonin as health or functional food.
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Data availability
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Change history
20 June 2023
A Correction to this paper has been published: https://doi.org/10.1007/s00210-023-02583-6
15 May 2024
This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1007/s00210-024-03160-1
Abbreviations
- IBD:
-
Inflammatory bowel disease
- MTT:
-
3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
- IL-1β:
-
Interleukin-1β
- TNF-α:
-
Tumor necrosis factor-α
- DSS:
-
Dextran sulfate sodium
- Treg:
-
Regulatory T cell
- Th17:
-
T helper 17 cell
- CD:
-
Crohn’s disease
- UC:
-
Ulcerative colitis
- SAIDs:
-
Steroidal anti-inflammatory drugs
- NSAIDS:
-
Non-steroidal anti-inflammatory drugs
- IFN-γ:
-
Interferon γ
- FBS:
-
Fetal bovine serum
- EDTA:
-
Ethylenediaminetetraacetic acid
- LPS:
-
Lipopolysaccharides
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Funding
This project was supported by the Science and Technology Program of Xiamen, China (3502Z20214ZD3008) and Fujian provincial health technology project (2019D024).
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Miersalijiang Yasen and Xiaohui Chen contributed to the conception and design of the present study, analyzed and interpreted the data, and critically revised the manuscript for important intellectual content. Shengrong Lin,Yunbang Liang and Xiaomin Xue contributed to analyzed the data, and drafted and revised the manuscript. Miersalijiang Yasen, Xiaohui Chen confirm the authenticity of all the raw data. All authors read and approved the final manuscript. The authors declare that all data were generated in-house and that no paper mill was used.
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Our protocol conforms with the guide for the care and use of laboratory animals published by the US National Institutes of Health (NIH Publication No. 85–23, revised 1996) and was approved by the Ethics Committee of Xiamen University Laboratory Animal Center.
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Chen, X., Lin, S., Liang, Y. et al. RETRACTED ARTICLE: Experimental evidence of shikonin as a novel intervention for anti-inflammatory effects. Naunyn-Schmiedeberg's Arch Pharmacol 396, 3547–3557 (2023). https://doi.org/10.1007/s00210-023-02542-1
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DOI: https://doi.org/10.1007/s00210-023-02542-1