Berberine inhibits macrophage M1 polarization via AKT1/SOCS1/NF-κB signaling pathway to protect against DSS-induced colitis

Liu, Yunxin; Liu, Xiang; Hua, Weiwei; Wei, Qingyan; Fang, Xianjun; Zhao, Zheng; Ge, Chun; Liu, Chao; Chen, Chen; Tao, Yifu; Zhu, Yubing

doi:10.1016/j.intimp.2018.01.049

Cited by 84 publications

(59 citation statements)

References 42 publications

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“…UC manifested as an idiopathic, relapsing and etiologically complicated inflammatory disorder, involving the interaction between environment factors, genetic emotivity, perturbation of immune homeostasis, and dysfunction of intestinal mucosal barrier 5,6,18 . Over the past decades, oral administration of berberine has been demonstrated to exert protective capacity on DSSinduced experimental acute UC, which dominantly attributed to the critical role of berberine in modulating the inflammatory responses from immune cell and epithelial cells, maintaining the intestinal barrier function, and regulating gut microbiota 24,41,42 . Besides, berberine could also attenuate colonic macromorphological and histopathological inflammation through suppressing the expansion and overaction of Th17 cells in DSS-induced murine chronic UC 43,44 .…”

Section: Discussionmentioning

confidence: 99%

Intervention of oncostatin M-driven mucosal inflammation by berberine exerts therapeutic property in chronic ulcerative colitis

Feng

Chen

et al. 2020

Cell Death Dis

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Ulcerative colitis (UC) is a chronic and etiologically refractory inflammatory gut disorder. Although berberine, an isoquinoline alkaloid, has been revealed to exert protective effects on experimental colitis, the underlying molecular mechanism in chronic intestinal inflammation remains ill-defined. This study was designed to uncover the therapeutic efficacy and immunomodulatory role of berberine in chronic UC. Therapeutic effects of oral administration of berberine were investigated in dextran sodium sulfate (DSS)-induced murine chronic UC and the underlying mechanisms were further identified by si-OSMR transfection in human intestinal stromal cells. Berberine significantly attenuated the experimental symptoms and gut inflammation of chronic UC. Berberine treatment could also maintain the intestinal barrier function and rectify tissue fibrosis. In accordance with infiltrations of antigen-presenting cells (APCs), innate lymphoid cells (ILCs), and activated NK cells in colonic lamina propria, increased expression of OSM and OSMR were observed in the inflamed tissue of chronic UC, which were decreased following berberine treatment. Moreover, berberine inhibited the overactivation of human intestinal stromal cells through OSM-mediated JAK-STAT pathway, which was obviously blocked upon siRNA targeting OSMR. The research provided an infusive mechanism of berberine and illustrated that OSM and OSMR intervention might function as the potential target in chronic UC.

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Section: Discussionmentioning

confidence: 99%

Intervention of oncostatin M-driven mucosal inflammation by berberine exerts therapeutic property in chronic ulcerative colitis

Feng

Chen

et al. 2020

Cell Death Dis

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“…In fact, considerable studies have reported that modulating macrophage polarization, especially inhibiting M1 macrophage polarization, shows protective effects in inflammatory diseases such as ulcerative colitis. 42 Regarding IRF5, various reports have shown that Irf5 ablation, especially in myeloid cells, inhibits M1 macrophage polarization and suppresses the progression of inflammatory diseases such as sepsis 31 and systemic lupus erythematosus. 35 Moreover, a recent study reported that the silencing of Irf5 by nanoparticle-delivered siRNA improved Fig.…”

Section: Discussionmentioning

confidence: 99%

Irf5 deficiency in myeloid cells prevents necrotizing enterocolitis by inhibiting M1 macrophage polarization

Wei

Tang

et al. 2019

Mucosal Immunology

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Necrotizing enterocolitis (NEC) is a severe inflammatory disease and is the most common cause of gastrointestinal mortality in newborns. However, the mechanisms remain unclear. Interferon regulatory factor 5 (IRF5) is a master regulator of macrophage function, which is essential for proinflammatory M1 macrophage polarization, and our previous data suggest the role of M1 macrophages promote NEC injury. Here, we investigated whether IRF5 is involved in the pathogenesis of NEC. We found that IRF5 was induced in infiltrated macrophages in neonates with NEC compared to the controls. We further confirmed IRF5 induction in macrophages in murine experimental NEC, and the infiltrated macrophages were predominantly polarized into M1 but not M2 phenotype in NEC. We generated the myeloid‐specific IRF5 defecient mice, and revealed that myeloid‐specific deficiency of IRF5 dramatically prevented experimental NEC, which was associated with reduced M1 macrophage polarization and systematic inflammation. Moreover, we found that ablation of IRF5 in myeloid cells markedly suppressed intestinal epithelial cells apoptosis and further prevented intestinal barrier dysfunction induced by experimental NEC. Overall, our study provides evidence that IRF5 in myeloid cells participates in the pathogenesis of NEC, while myeloid cell‐deletion of IRF5 prevents NEC via inhibiting M1 macrophage polarization. Support or Funding Information This study was supported by the National Natural Science Foundation of China (81501298, 81670390, and 81670259). This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

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“…Berberine is the major isoquinoline alkaloid in the stems and roots of Berberis species. Several studies have reported the therapeutic potential of berberine for IBD (Hong et al, 2012;Yan et al, 2012;Li et al, 2016;Liu et al, 2018). Among the numerous possible mechanisms involved in the efficacy of berberine in IBD (Habtemariam, 2016), recent reports have focused on berberine-mediated improvements in gut epithelial barrier dysfunction and the role of tight junction proteins zona occludens-1 and occludin (Gu et al, 2009;Yan et al, 2012;Tan et al, 2015;Li et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Berberine Upregulates P-Glycoprotein in Human Caco-2 Cells and in an Experimental Model of Colitis in the Rat via Activation of Nrf2-Dependent Mechanisms

Jing

Safarpour

Zhang

et al. 2018

J Pharmacol Exp Ther

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Downregulation of P-glycoprotein (P-gp) is implicated in the pathophysiology of inflammatory bowel disease (IBD). Berberine, a principal isoquinoline alkaloid extracted from species, has been reported to exhibit therapeutic potential in IBD. In this study, we used a dextran sulfate sodium (DSS)-induced colitis rat model to evaluate the effect of berberine on P-gp and explore its mechanism of action. Berberine treatment improved DSS-induced colitis symptoms, attenuated inflammatory markers (myeloperoxidase, tumor necrosis factor-, and interleukin-1 and -6), and enhanced P-gp expression in a dose-dependent manner. Although colonic expression of the P-gp-related nuclear receptor pregnane X receptor and transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) were downregulated in the colitis model, gene and protein expression analysis revealed that berberine treatment reversed only the downregulation of Nrf2. In vitro studies using Caco-2 cells showed that the multidrug resistance 1 () gene and P-gp protein were upregulated by berberine in a dose- and time-dependent manner. Significant upregulation of the gene by berberine was abrogated by Nrf2 silencing, indicating that the Nrf2-mediated pathway was responsible for this activation. Luciferase assays showed a dose-dependent increase in Nrf2 reporter gene activity after berberine treatment in Caco-2 cells, with a significant 2-fold elevation at 2.5M berberine, suggesting that berberine is a strong Nrf2 activator. These results indicate the possible involvement of Nrf2-mediated upregulation of P-gp in the therapeutic effect of berberine on colitis and highlight the potential of P-gp and/or Nrf2 as new therapeutic targets for IBD.

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Berberine inhibits macrophage M1 polarization via AKT1/SOCS1/NF-κB signaling pathway to protect against DSS-induced colitis

Cited by 84 publications

References 42 publications

Intervention of oncostatin M-driven mucosal inflammation by berberine exerts therapeutic property in chronic ulcerative colitis

Intervention of oncostatin M-driven mucosal inflammation by berberine exerts therapeutic property in chronic ulcerative colitis

Irf5 deficiency in myeloid cells prevents necrotizing enterocolitis by inhibiting M1 macrophage polarization

Berberine Upregulates P-Glycoprotein in Human Caco-2 Cells and in an Experimental Model of Colitis in the Rat via Activation of Nrf2-Dependent Mechanisms

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