Berberine induces SOCS1 pathway to reprogram the M1 polarization of macrophages via miR-155–5p in colitis-associated colorectal cancer

Berberine is approved for the treatment of intestinal infections and diarrhea and has been shown to have anti-inflammatory and anti-tumor effects in pathological intestinal tissues. However, it is unclear whether the anti-inflammatory effect of berberine contributes to its anti-tumor effect on colit...

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Published in:European journal of pharmacology 2023-06, Vol.949, p.175724-175724, Article 175724
Main Authors: Ling, Qiaoyun, Fang, Jing, Zhai, Chi, Huang, Wan, Chen, Yu, Zhou, Ting, Liu, Yunxin, Fang, Xianjun
Format: Article
Language:English
Subjects:
Animals
Anti-Inflammatory Agents - metabolism
Anti-Inflammatory Agents - pharmacology
Anti-Inflammatory Agents - therapeutic use
Berberine
Berberine - pharmacology
Berberine - therapeutic use
Colitis-associated colorectal cancer
Colitis-Associated Neoplasms - drug therapy
Macrophage
Macrophages
Mice
MicroRNAs - genetics
MicroRNAs - metabolism
miR-155–5p
SOCS1
Suppressor of Cytokine Signaling 1 Protein - genetics
Suppressor of Cytokine Signaling 1 Protein - metabolism
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Summary:Berberine is approved for the treatment of intestinal infections and diarrhea and has been shown to have anti-inflammatory and anti-tumor effects in pathological intestinal tissues. However, it is unclear whether the anti-inflammatory effect of berberine contributes to its anti-tumor effect on colitis-associated colorectal cancer (CAC). In this study, we found that berberine effectively inhibited tumorigenesis and protected against colon shortening in CAC mouse model. Immunohistochemistry results showed a reduction in the number of macrophage infiltrations in the colon following berberine treatment. Further analysis revealed that most of the infiltrated macrophages were pro-inflammatory M1 type, which berberine effectively limited. However, in another CRC model without chronic colitis, berberine had no significant effect on tumor number or colon length. In vitro studies demonstrated that berberine treatment significantly reduced the percentage of M1 type and levels of Interleukin-1β (IL-1β), Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Additionally, miR-155–5p level was down-regulated, and suppressor of cytokine signaling 1 (SOCS1) expression was up-regulated in berberine-treated cells. Notably, the miR-155–5p inhibitor attenuated the regulatory effects of berberine on SOCS1 signaling and macrophage polarization. Altogether, our findings suggest that the inhibitory effect of berberine on CAC development is dependent on its anti-inflammatory activity. Moreover, miR-155–5p may be involved in the pathogenesis of CAC by regulating M1 macrophage polarization, and berberine could be a promising protective agent against miR-155-5p-mediated CAC. This study provides new insights into pharmacologic mechanisms of berberine and supports the possibility that other anti-miR-155–5p drugs may be beneficial in the treatment of CAC. •Berberine inhibited tumorigenesis in CAC mouse model but not in non-chronic colitis associated colorectal cancer.•Berberine effects on macrophages infiltration and polarization.•MiR-155/SOCS1 pathway is required for the modulation effect of berberine on.
ISSN:0014-2999
1879-0712
DOI:10.1016/j.ejphar.2023.175724