Phloretin ameliorates dextran sulfate sodium-induced ulcerative colitis in mice by regulating the gut microbiota

Wu, Minna; Li, Puze; An, Yunying; Ren, Jie; Yan, Dong; Cui, Jiazeng; Duan, Li; Li, Min; Wang, Mingyong; Zhong, Genshen

doi:10.1016/j.phrs.2019.104489

Cited by 191 publications

(148 citation statements)

References 61 publications

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“…is is consistent with the notion that Lactobacillaceae are a well-known anti-inflammatory microbial family that can restore the protective gut microbiome in DSS mice and cause downregulation of 17 cells and differentiation of Treg cells in intestinal epithelial cells, thereby preventing cytokineinduced inflammation and ameliorating the severity of colitis symptoms in experimental models [52][53][54]. Akkermansia, a key species of Verrucomicrobiaceae, was found to exacerbate colonic damage due to its enzymatic capacity to degrade the mucus layer [40,55].…”

Section: Discussionsupporting

confidence: 87%

Integrating Pharmacology and Microbial Network Analysis with Experimental Validation to Reveal the Mechanism of Composite Sophora Colon‐Soluble Capsule against Ulcerative Colitis

Ding

Chen

Wang

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Ulcerative colitis (UC) has multifactorial pathogenesis that acts synergistically, such as immune system dysregulation and expansion of infectious gut microbiota. Therefore, a multicomponent treatment derived from Chinese herbal medicine that interacts with multiple targets synergistically is needed. Composite sophora colon-soluble capsule (CSCC) is a Chinese herbal formula that has shown therapeutic efficacy against UC in randomized clinical trials. However, its bioactive components and potential target genes against UC remain unclear. Here, we used a network pharmacology approach to detect component-target-pathway interactions of CSCC against UC. A total of 29 gene targets, 91 bioactive components, and 20 enriched pathways of CSCC were identified. The IL-17 signaling pathway activated by infectious gastrointestinal microbes and predicted by the network analysis to be a major pathway modulated by CSCC against UC was studied in a dextran sulfate sodium-induced colitis model. CSCC showed remarkable efficacy against UC with respect to the attenuation of colon length, body weight loss, and disease activity index through gut microbiota recovery and intestinal immune homeostasis. The rectal administration of CSCC reduced the numbers of Th17 cells isolated from both mesenteric lymph nodes and lamina propria mononuclear cells and the levels of IL-17A, IL-6, IL-1β, and TNF-α. Additionally, the percentage of Treg cells and the levels of their hallmark cytokines were upregulated. Rectal administration of CSCC led to microbiota regulation with a significant correlation between suppression of Verrucomicrobiaceae and Ruminococcaceae, as well as the elevation of Lactobacillaceae, and CSCC administration via microbiome correlation heatmaps and cooccurrence network analysis at multiple time points. Thus, our study presents an effective herbal formula, CSCC, for UC treatment and explores its components and mechanisms of efficacy through the examination of gut microbiota and hallmark cytokines in the IL-17 pathway.

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Section: Discussionsupporting

confidence: 87%

Integrating Pharmacology and Microbial Network Analysis with Experimental Validation to Reveal the Mechanism of Composite Sophora Colon‐Soluble Capsule against Ulcerative Colitis

Ding

Chen

Wang

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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“…The gut microbiota has been suggested to be both one of the underlying causes of IBDs, when dysfunctional (gut dysbiosis) ( Manichanh et al, 2012 ; Khan et al, 2019 ; Alam et al, 2020 ), and a mediator of the anti-inflammatory and therapeutic effects of several different types of pharmacological, nutraceutical and nutritional interventions that proved beneficial against these disorders when investigated in preclinical models (and in the DSS model, in particular) ( Wu M. et al, 2019 ; Fernandez et al, 2020 ; Gu et al, 2020 ). Gut dysbiosis is also known to accompany, and possibly underlie, some behavioral disturbances, such as those that are observed in DSS-treated mice, i.e., anxiety and cognitive deficits ( Reichmann et al, 2015 ; Emge et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

Fish Oil, Cannabidiol and the Gut Microbiota: An Investigation in a Murine Model of Colitis

Silvestri

Pagano

Lacroix³

et al. 2020

Front. Pharmacol.

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Inflammatory bowel disorders can be associated with alterations in gut microbiota (dysbiosis) and behavioral disturbances. In experimental colitis, administration of fish oil (FO) or cannabinoids, such as cannabidiol (CBD), reduce inflammation. We investigated the effect of combined FO/CBD administration on inflammation and dysbiosis in the dextran sulphate sodium (DSS) model of mouse colitis, which also causes behavioral disturbances. Colitis was induced in CD1 mice by 4% w/v DSS in drinking water for five consecutive days followed by normal drinking water. FO (20–75 mg/mouse) was administered once a day starting two days after DSS, whereas CBD (0.3–30 mg/kg), alone or after FO administration, was administered once a day starting 3 days after DSS, until day 8 (d8) or day 14 (d14). Inflammation was assessed at d8 and d14 (resolution phase; RP) by measuring the Disease Activity Index (DAI) score, change in body weight, colon weight/length ratio, myeloperoxidase activity and colonic interleukin (IL)-1β (IL-1β), IL-10, and IL-6 concentrations. Intestinal permeability was measured with the fluorescein isothiocyanate-dextran. Behavioral tests (novel object recognition (NOR) and light/dark box test) were performed at d8. Fecal microbiota composition was determined by ribosomal 16S DNA sequencing of faecal pellets at d8 and d14. DSS-induced inflammation was stronger at d8 and accompanied by anxiety-like behavior and impaired recognition memory. FO (35, 50, 75 mg/mouse) alone reduced inflammation at d8, whereas CBD alone produced no effect at any of the doses tested; however, when CBD (3, 10 mg/kg) was co-administered with FO (75 mg/mouse) inflammation was attenuated. FO (20 mg/mouse) and CBD (1 mg/kg) were ineffective when given alone, but when co-administered reduced all inflammatory markers and the increased intestinal permeability at both d8 and d14, but not the behavioral impairments. FO, CBD, and their combination affected gut bacteria taxa that were not affected by DSS per se . Akkermansia muciniphila , a species suggested to afford anti-inflammatory action in colitis, was increased by DSS only at d14, but its levels were significantly elevated by all treatments at d8. FO and CBD co-administered at per se ineffective doses reduce colon inflammation, in a manner potentially strengthened by their independent elevation of Akkermansia muciniphila .

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“…[3] As the DSS-induced experimental UC model exhibits similar clinical manifestations, it has been regarded as one of the most successful and appropriate murine UC models. [21,22] Therefore, a murine model of UC induced by DSS was used in the present study.…”

Section: Discussionmentioning

confidence: 99%

Chlorogenic Acid Suppresses miR‐155 and Ameliorates Ulcerative Colitis through the NF‐κB/NLRP3 Inflammasome Pathway

Zeng

Zhang

Wang

et al. 2020

Molecular Nutrition Food Res

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Scope: The over-activation of the nucleotide-binding domain like receptor protein 3 (NLRP3) inflammasome plays an important role in the pathogenesis of ulcerative colitis (UC). Chlorogenic acid (CGA) exposure is identified as an effective strategy for repressing inflammatory responses. Methods and results: In this study, the NLRP3 inflammasome model with LPS/ATP-induced RAW264.7 cells in vitro and dextran-sulfate-sodium (DSS)-induced colitis in mice are used to evaluate the effect of CGA on NLRP3 inflammasome-related signaling. The results suggest that CGA suppressed the expression of NLRP3 inflammasome-related genes (apoptosis-associated speck-like protein containing CARD (ASC), cysteine-requiring aspartate protease (Caspase)-1 p45, Caspase-1 p20, pro-/cleaved-interleukin (IL)-1 , pro-/cleaved-IL-18), p-nuclear factor kappa B (NF-B) protein, and miR-155 in mice with colitis. Gain-and loss-of-function studies of miR-155 are performed to elucidate its role in inflammation. Moreover, activation of the NF-B/NLRP3 inflammasome pathway and miR-155 expression is investigated. CGA exposure in lipopolysaccharide (LPS)/adenosine triphosphate (ATP)-stimulated RAW264.7 cells leads to a decrease in p-NK-B and NLRP3 inflammasome-related proteins, which is dependent on the downregulation of miR-155 expression. Conclusions: These findings indicate that CGA prevented colitis by downregulating miR-155 expression and inactivating the NF-B/NLRP3 inflammasome pathway in macrophages. The current study has promising therapeutic implications in the treatment of UC.

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Phloretin ameliorates dextran sulfate sodium-induced ulcerative colitis in mice by regulating the gut microbiota

Cited by 191 publications

References 61 publications

Integrating Pharmacology and Microbial Network Analysis with Experimental Validation to Reveal the Mechanism of Composite Sophora Colon‐Soluble Capsule against Ulcerative Colitis

Integrating Pharmacology and Microbial Network Analysis with Experimental Validation to Reveal the Mechanism of Composite Sophora Colon‐Soluble Capsule against Ulcerative Colitis

Fish Oil, Cannabidiol and the Gut Microbiota: An Investigation in a Murine Model of Colitis

Chlorogenic Acid Suppresses miR‐155 and Ameliorates Ulcerative Colitis through the NF‐κB/NLRP3 Inflammasome Pathway

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