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

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.

Curcumin regulates the homeostasis of Th17/Treg and improves the composition of gut microbiota in type 2 diabetic mice with colitis

“…When the blood glucose concentration of the mice exceeded 16.7 mmol/L on both occasions (Liang et al, 2018), they were considered diabetic for inclusion in subsequent experiments. In conjunction with our previous studies (Kang et al, 2021) and with appropriate adjustments, DB mice were given 1.5% (w/v) DSS solution ad libitum to induce experimental colitis. Detailed experimental treatments are shown in Figure 1.…”

A potential therapeutic target in traditional Chinese medicine for ulcerative colitis: Macrophage polarization

“…et al, 2019 ; Lertnimitphun et al, 2019 ; Liu et al, 2020 ; Mai et al, 2020 ; Chen Y. et al, 2021 ; Wu MM. et al, 2021 ; Kang et al, 2021b ; Guo et al, 2021 ; Lv et al, 2021 ; Tian et al, 2021 ; Xie et al, 2021 ; Xiong et al, 2021 ; Zhuang et al, 2021 ; Long et al, 2022 ).…”

“…In LPS-Induced RAW264.7 cells, safranal ( Lertnimitphun et al, 2019 ) reduced NO, IL-6, and TNF-α production and suppressed the expression of iNOS and COX-2 via inhibiting the phosphorylation of JNK, ERK, p38, and IκBα, suggesting that safranal suppressed macrophage-mediated inflammatory responses via inhibition of M1 macrophage polarization by inhibiting MAPK and NF-κB signaling pathways. In the colitis mice model, curcumin alleviated experimental colitis by decreasing the percentage of M1 macrophages and increasing the percentage of M2 macrophages via inhibition of the TLRs/NF-κB-MAPK signaling pathway ( Kang et al, 2021a ).…”

“…Currently, many modern studies have shown that TCM can regulate intestinal macrophage polarization to improve the inflammatory microenvironment of the intestine and thus play a therapeutic role in UC. In regulating macrophage polarization, heat-clearing prescriptions have outstanding effects, such as Baitouweng decoction ( Xuan-Qing et al, 2021 ), Gegen Qinlian decoction ( Xu 2021 ), Scutellariae Radix ( Zhu W. et al, 2016 ), Coptidis Rhizoma ( Xiong et al, 2021 ), Prunella vulgaris ( Mai et al, 2020 ) and so on, In addition, some prescriptions for activating blood and resolving stasis, such as Curcumin ( Kang et al, 2021b ), Ligusticum chuanxiong ( Tian et al, 2021 ), and tonifying prescriptions, such as Panax ginseng ( Long et al, 2022 ), Shenling Baizhu San ( Yu et al, 2022 ) can also improve intestinal inflammation by regulating macrophage polarization in the treatment of UC.…”

“…Curcumin could effectively inhibit the occurrence and development of DSS-induced UC and alleviate the disease. In DSS-induced colitis models, curcumin significantly increased the body weight and colon length, decreased the colon weight, colon mass index, and DAI score, and effectively improved histopathological damage in colitis mice (Zhang et al, 2019;Kang et al, 2021b;Xiao et al, 2022). Additionally, curcumin significantly reduced the levels of proinflammatory cytokines, including TNF-α, IL-1β, IL-6, CCL-2, and IL-17A, and significantly increased the levels of anti-inflammatory cytokines, including IL-33 and IL-10 (Zhang et al, 2019;Kang et al, 2021b;Xiao et al, 2022).…”