Curcumin Alleviated Dextran Sulfate Sodium-Induced Colitis by Regulating M1/M2 Macrophage Polarization and TLRs Signaling Pathway.

Zeng-Ping Kang,You-Bao Zhong,You-Bao Zhong,You-Bao Zhong,Jian Long,Meng-Xue Wang,Duan-Yong Liu,Tian-Tian Wu,Hai-Mei Zhao,Hai-Yan Wang,Angelica Oliveira Gomes

doi:10.1155/2021/3334994

Abstract

Curcumin has shown good efficacy in mice with experimental colitis and in patients with ulcerative colitis, but the mechanism of action through the regulation of M1/M2 macrophage polarization has not been elaborated. The ulcerative colitis was modeled by dextran sulfate sodium; colitis mice were orally administrated with curcumin (10 mg/kg/day) or 5-ASA (300 mg/kg/day) for 14 consecutive days. After curcumin treatment, the body weight, colon weight and length, colonic weight index, and histopathological damage in colitis mice were effectively improved. The concentrations of proinflammatory cytokines IL-1β, IL-6, and CCL-2 in the colonic tissues of colitis mice decreased significantly, while anti-inflammatory cytokines IL-33 and IL-10 increased significantly. Importantly, macrophage activation was suppressed and M1/M2 macrophage polarization was regulated in colitis mice, and the percentage of CD11b+F4/80+ and CD11b+F4/80+TIM-1+ and CD11b+F4/80+iNOS+ decreased significantly and CD11b+F4/80+CD206+ and CD11b+F4/80+CD163+ increased significantly. Additionally, curcumin significantly downregulated CD11b+F4/80+TLR4+ macrophages and the protein levels of TLR2, TLR4, MyD88, NF-κBp65, p38MAPK, and AP-1 in colitis mice. Our study suggested that curcumin exerted therapeutic effects in colitis mice by regulating the balance of M1/M2 macrophage polarization and TLRs signaling pathway.

Highlights

Inflammatory bowel disease (IBD) is a chronic, relapsing, autoimmune disease of the colon and small intestine mainly comprising Crohn’s disease (CD) and ulcerative colitis (UC) [1, 2]
M1 macrophages are typical inflammatory cells and secreting proinflammatory cytokines IL-1β and IL-6, Evidence-Based Complementary and Alternative Medicine which directly lead to intestinal mucosal injury and aggravate IBD [8]. e number of M1 macrophages is significantly increased in the intestinal mucosa of DSS-induced colitis mice and active IBD patients [8]
We found a significant increase in the percentage of CD11b+F4/80+TIM-1+ macrophages (Figure 3(e)) in colitis mice, whereas curcumin administration treatment resulted in a significant decrease in the percentage of CD11b+F4/80+TIM-1+ macrophages (Figure 3(e))

Summary

Introduction

Inflammatory bowel disease (IBD) is a chronic, relapsing, autoimmune disease of the colon and small intestine mainly comprising Crohn’s disease (CD) and ulcerative colitis (UC) [1, 2]. A growing body of evidence suggests that macrophage polarization is closely associated with the onset, activation, and remission of IBD [4,5,6], accompanied by a shift in macrophage phenotype. M1 macrophages are typical inflammatory cells and secreting proinflammatory cytokines IL-1β and IL-6, Evidence-Based Complementary and Alternative Medicine which directly lead to intestinal mucosal injury and aggravate IBD [8]. E number of M1 macrophages is significantly increased in the intestinal mucosa of DSS-induced colitis mice and active IBD patients [8]. M2 macrophages secrete anti-inflammatory cytokines (e.g., IL10) and are involved in tissue repair and inflammation remission to alleviate IBD [9]. Erefore, targeted induction of M1/M2 macrophage polarization may be a potential strategy for IBD treatment Mitochondrial reactive oxygen protects the intestine from inflammation through functional M2 macrophage polarization [10]. erefore, targeted induction of M1/M2 macrophage polarization may be a potential strategy for IBD treatment

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Conclusion