N-Methylcytisine Ameliorates Dextran-Sulfate-Sodium-Induced Colitis in Mice by Inhibiting the Inflammatory Response

Jiao, Yan-Fang; Lü, Min; Zhao, Yuping; Liu, Ning; Niu, Ya-Ting; Niu, Yang; Zhou, Ran

doi:10.3390/molecules23030510

Cited by 29 publications

(9 citation statements)

References 46 publications

(45 reference statements)

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“…As shown in Figure 1, DSS evoked severe inflammation in mice such as a dramatic loss of body weight, colon length shortening from days three to seven compared to control mice, which were consistent with previous publications [19,20]. However, intraperitoneal injection of MMI-0100 (0.5 and 1 mg/kg, i.p.)…”

Section: Resultssupporting

confidence: 91%

MMI-0100 Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice through Targeting MK2 Pathway

et al. 2019

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Backgrounds: This study aimed to investigate the protective effects of MMI-0100, a cell-penetrating peptide inhibitor of MAPK-activated protein kinase II (MK2), on acute colitis induced by dextran sodium sulfate (DSS). Mice were injected intraperitoneally with different doses of MMI-0100 (0.5 and 1 mg/kg per day, six days). The physiological indexes, the parameters for colonic pathological injury and the intensity of inflammatory responses were evaluated by histological staining, quantitative PCR, western blotting, and immunostaining. MMI-0100 attenuated DSS-induced body weight loss, colon length shortening, and colonic pathological injury, including decreased myeloperoxidase (MPO) and inhibited inflammatory cell infiltration. MMI-0100 suppressed DSS-induced activation of CD11b+ and F4/80 positive cell, and dramatically decreased the expression of a series of pro-inflammatory cytokines such as TNF-α, IL-6, IL-1β, TGF- β, IFN-γ, IL-17A, COX-2 and iNOS. A TUNEL assay showed that MMI-0100 protected against DSS-induced apoptosis. This is consistent with the results of Western blotting assay in apoptosis-related proteins including Bcl-2, BAX, caspase-3. The anti-inflammatory effects of MMI-0100 on DSS-induced colitis were achieved by down-regulating the phosphorylation level of MK2, IκBα and p65 protein. The current study clearly demonstrates a protective role for MMI-0100 in experimental IBD.

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Section: Resultssupporting

confidence: 91%

MMI-0100 Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice through Targeting MK2 Pathway

et al. 2019

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“…At rest, IκB-α binds to the p50 and p65 subunits of NF-κB. Once microglia are activated, IκB-α is separated and transferred from the cytoplasm to the nucleus, resulting in transcription and expression of inflammatory factors [49]. NF-κB is expressed in nearly all cells and plays an important role in the activation of the M1 microglial phenotype [50].…”

Section: Discussionmentioning

confidence: 99%

Effects of Betaine on LPS-Stimulated Activation of Microglial M1/M2 Phenotypes by Suppressing TLR4/NF-κB Pathways in N9 Cells

et al. 2019

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Microglia mediate multiple facets of neuroinflammation. They can be phenotypically divided into a classical phenotype (pro-inflammatory, M1) or an alternative phenotype (anti-inflammatory, M2) with different physiological characteristics and biological functions in the inflammatory process. Betaine has been shown to exert anti-inflammatory effects. In this study, we aimed to verify the anti-inflammatory effects of betaine and elucidate its possible molecular mechanisms of action in vitro. Lipopolysaccharide (LPS)-activated microglial cells were used as an inflammatory model to study the anti-inflammatory efficacy of betaine and explore its mechanism of regulating microglial polarisation by investigating the morphological changes and associated inflammatory changes. Cytokine and inflammatory mediator expression was also measured by ELISA, flow cytometry, immunofluorescence, and western blot analysis. Toll-like receptor (TLR)-myeloid differentiation factor 88 (Myd88)-nuclear factor-kappa B (NF-κB) p65, p-NF-κB p65, IκB, p-IκB, IκB kinase (IKK), and p-IKK expression was determined by western blot analysis. Betaine significantly mitigated the production of pro-inflammatory cytokines and increased the release of anti-inflammatory cytokines. It promoted the conversion of the microglia from M1 to M2 phenotype by decreasing the expression of inducible nitric oxide synthase and CD16/32 and by increasing that of CD206 and arginase-1. Betaine treatment inhibited the TLR4/NF-κB pathways by attenuating the expression of TLR4-Myd88 and blocking the phosphorylation of IκB and IKK. In conclusion, betaine could significantly alleviate LPS-induced inflammation by regulating the polarisation of microglial phenotype; thus, it might be an effective therapeutic agent for neurological disorders.

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“…N -methylcytisine ( 6 ) is also a tricyclic quinolizidine alkaloid isolated from the seeds of traditional Chinese medicines Laburnum anagyroides and Sophora alopecuroides. It has been reported that oral administration of N -methylcytisine (4 and 16 mg/kg of body weight in mice) significantly attenuates the DSS-induced clinical symptoms and pathological damage which are associated with inhibiting colon proinflammatory cytokines through down-regulating NF-κB activation by inhibiting IκB and IKK phosphorylation (Jiao et al, 2018) (Figure 1).…”

Section: Plant-based Alkaloids Against Ibdmentioning

confidence: 99%

Plant-Derived Alkaloids: The Promising Disease-Modifying Agents for Inflammatory Bowel Disease

Jiao

Zheng

et al. 2019

Front. Pharmacol.

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Inflammatory bowel disease (IBD) represents a group of intestinal disorders with self-destructive and chronic inflammation in the digestive tract, requiring long-term medications. However, as many side effects and drug resistance are frequently encountered, safer and more effective agents for IBD treatment are urgently needed. Over the past few decades, a variety of natural alkaloids made of plants or medicinal herbs have attracted considerable interest because of the excellent antioxidant and anti-inflammatory properties; additionally, these alkaloids have been reported to reduce the colonic inflammation and damage in a range of colitic models. In this review paper, we summarize the recent findings regarding the anti-colitis activity of plant-derived alkaloids and emphasize their therapeutic potential for the treatment of IBD; obvious improvement of the colonic oxidative and pro-inflammatory status, significant preservation of the epithelial barrier function and positive modulation of the gut microbiota are the underlying mechanisms for the plant-derived alkaloids to treat IBD. Further clinical trials and preclinical studies to unravel the molecular mechanism are essential to promote the clinical translation of plant-derived alkaloids for IBD.

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N-Methylcytisine Ameliorates Dextran-Sulfate-Sodium-Induced Colitis in Mice by Inhibiting the Inflammatory Response

Cited by 29 publications

References 46 publications

MMI-0100 Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice through Targeting MK2 Pathway

MMI-0100 Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice through Targeting MK2 Pathway

Effects of Betaine on LPS-Stimulated Activation of Microglial M1/M2 Phenotypes by Suppressing TLR4/NF-κB Pathways in N9 Cells

Plant-Derived Alkaloids: The Promising Disease-Modifying Agents for Inflammatory Bowel Disease

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