Berberine Chloride Suppresses the Development of Murine Acute Colitis due to the Enhancement of IL-10 Production in Macrophages

[Speaker] Shusaku Hayashi:1
[Co-author] Nonoka Wakabayashi:1, Ai Hertati:1, Makoto Kadowaki:1
1:Division of Gastrointestinal Pathophysiology, Institute of Natural Medicine, University of Toyama, Japan

Background/Aim: Abnormalities of intestinal innate immune functions have been regarded as key properties in immunogenetic profile of inflammatory bowel disease (IBD). Intestinal macrophages play pivotal roles in the regulation of immune homeostasis in the intestine. We have recently reported that the enhancement of IL-10 production in the intestinal macrophages has the potential to be a novel therapeutic mechanism against IBD (Scientific Reports, 2017; 7: 6187). Thus, to address the development of new therapeutic medicines for IBD, we have screened 96 compounds derived from medicinal herbs for the ability to enhance IL-10 production in the intestinal macrophages.
Methods: Male BALB/c mice were used. Bone marrow-derived macrophages (BMDMs) were prepared from the femurs and tibiae of mice and cultured with macrophage colony-stimulating factor (100 ng/ml) for 7 days. 96 compounds (10 µM) were applied to BMDMs (5x105) 1 h before LPS (100 ng/ml) stimulation for 24 h and IL-10 concentrations in culture supernatants. Colonic lamina propria (cLP) cells were isolated from the mouse colons and examined for cytokine mRNA expression. Experimental acute colitis in mice was induced by giving 3% dextran sulfate sodium (DSS) in drinking water for 7 days.
Results: Among the 96 compounds, we found that Alisol B and Berberine chloride significantly increased the LPS-stimulated IL-10 production in BMDMs. Alisol B and Berberine chloride (1-30 µM) significantly increased the LPS-stimulated IL-10 production of BMDMs in a concentration- dependent manner and the both compounds at 30 µM exhibited most potent enhancing effect. Furthermore, 30 µM Alisol B but not Berberine chloride increased the LPS-stimulated TNF-α production in BMDMs. Thus, we selected Berberine chloride for further studies. Berberine chloride (30 µM) increased the expression of IL-10 mRNA and inhibited the expression of proinflammatory cytokines such as TNF-α, IL-1β and IL-6 mRNA in the cLP cells. Importantly, the administration of Berberine chloride (100 mg/kg, po) markedly suppressed the development of DSS-induced colitis with a concomitant increment of IL-10 mRNA expression in the colons of colitis mice.
Conclusion: These results can lead to the hypothesis that enhancers of IL-10 production in intestinal macrophages suppress the development of colitis.
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