Wu-Mei-Wan Ameliorates Murine Ulcerative Colitis by Regulating Macrophage Polarization

Abstract

An increasing body of evidence shows that macrophages play an important role in the pathogenesis of ulcerative colitis (UC). Macrophage polarization and changes in related signaling pathways are reported to have a protective effect on intestinal inflammation. The well-known Chinese medicine Wumeiwan (WMW) has been used to treat diarrhea, one of the main symptoms of colitis, for more than 2,000 years. Increasing evidence shows that WMW can inhibit intestinal inflammation and repair damaged intestinal mucosa, but its effector mechanisms are unknown. Therefore, we studied the prophylactic effects of WMW in dextran sulfate sodium (DSS)-induced UC and its effects on macrophage mechanisms and polarization. The results show that colitis was significantly alleviated in mice in the WMW group, and the secretion and expression of pro-inflammatory factors TNF-α, IL-1, and IL-6 were inhibited in the serum and colonic tissues of mice with WMW-treated colitis, whereas anti-inflammatory factors IL-10, Arg-1, and TGF-β1 were increased. Subsequent studies found that WMW could inhibit M1 polarization and promote M2 polarization in colonic macrophages in DSS-induced colitis mice. Network pharmacology was used to predict potential targets and pathways, and further studies confirmed the related targets The results showed that WMW gradually inhibits the activation of the P38MAPK and NF-κB signaling pathways and further activates the STAT6 signaling pathway. In summary, WMW interferes with the p38MAPK, NF-κB and STAT6 signaling pathways to regulate M1/M2 polarization in macrophages, thereby protecting mice against DSS-induced colitis.

New Insights into Baicalein’s Effect on Chlorpyrifos-Induced Liver Injury in Carp: Involving Macrophage Polarization and Pyropto sis

“…52 In addition, it was found that an increased polarization of colonic macrophages from MO to M1 and a decreased M2 polarization caused by activation of the NF-κB pathway are potential causes of DSS-induced colitis, which is the mechanism by which the herbal Wu-Mei-Wan exerts its protective effect. 53 We found that the macrophage M1/M2 polarization imbalance occurred in the liver tissue of carp exposed to CPF, which was manifested by a significant upregulation of the M1-type marker expression and significant downregulation of the M2-type marker and that the imbalance could be reversed by Bai. The above results suggest that M1/M2 polarization of macrophages is a downstream effector process of the CPF-induced NF-κB pathway activation.…”

“…It was shown that miR-224-5p and PTX3 constitute a regulatory axis that promotes M1 macrophage polarization and, thus, bone and joint injury through activation of the p65/NF-κB pathway . In addition, it was found that an increased polarization of colonic macrophages from MO to M1 and a decreased M2 polarization caused by activation of the NF-κB pathway are potential causes of DSS-induced colitis, which is the mechanism by which the herbal Wu-Mei-Wan exerts its protective effect . We found that the macrophage M1/M2 polarization imbalance occurred in the liver tissue of carp exposed to CPF, which was manifested by a significant upregulation of the M1-type marker expression and significant downregulation of the M2-type marker and that the imbalance could be reversed by Bai.…”

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

“…Du et al ( Du et al, 2021 ) reported that Wumeiwan could reduce DAI and histopathological scores in the UC rats by inhibiting the inflammatory reaction. In DSS-induced acute colitis mice, Wumeiwan could increase the percentage of M2 macrophages and decrease the percentage of M1 macrophages, and significantly reduce the secretion of pro-inflammatory factors, including TNF-α, IL-1β, and IL-6, by inhibiting M1 macrophage polarization and increase the secretion of anti-inflammatory factors, including IL-10, Arg-1, and TGF-β1, in colon tissues by promoting M1 macrophage polarization ( Yan et al, 2022 ).…”

“…Xiong et al ( Xiong et al, 2021 ) reported that berberine could inhibit M1 polarization and promote M2 polarization in colonic macrophages, improve the intestinal inflammatory environment, and relieve colitis by inhibiting the NF-κB signaling pathway. Yan et al ( Yan et al, 2022 ) study found that Wumeiwan could inhibit M1 macrophage polarization and promote M2 macrophage polarization by inhibiting the activation of the NF-κB signaling pathway, thereby inhibiting inflammatory responses and alleviating colonic tissue damage in DSS-induced colitis.…”

“…The results of in vivo and in vitro experiments ( Xu et al, 2021 ) showed that baicalin reduced the levels of IL-12, TNF-α, and iNOS, inhibited the expression levels of iNOS, CCL-5, and p-STAT1 proteins, and increased the levels of IL-4 and IL-10, improved the expression levels of Arg1, MRC1, p-JAK1, and p-STAT6 proteins, and promote M2 macrophage polarization by activating JAK1/STAT6 pathway. In DSS-induced colitis mice, Wumeiwan regulated macrophage M1/M2 polarization in colonic macrophages to ameliorate colitis by activating the STAT6 signaling pathway ( Yan et al, 2022 ). Astragaloside IV alleviated clinical disease activity, reduced the levels of the pro-inflammatory cytokine, increased the levels of the anti-inflammatory cytokine, and reduced the percentages of macrophages by suppressing M1 macrophage polarization partially by remodeling the STAT1 signaling pathway ( Tian et al, 2021 ).…”