Gut Microbiota-Mediated Transformation of Coptisine Into a Novel Metabolite 8-Oxocoptisine: Insight Into Its Superior Anti-Colitis Effect

Coptisine (COP) is a bioactive isoquinoline alkaloid derived from Coptis Chinemsis Franch, which is traditionally applied for the management of colitis. However, the blood concentration of COP was extremely low, and its gut microbiota-mediated metabolites were thought to contribute to its prominent bioactivities. To comparatively elucidate the protective effect and underlying mechanism of COP and its novel gut microbiota metabolite (8-oxocoptisine, OCOP) against colitis, we used dextran sulfate sodium (DSS) to induce colitis in mice. Clinical symptoms, microscopic alternation, immune-inflammatory parameters for colitis were estimated. The results indicated that OCOP dramatically ameliorated disease activity index (DAI), the shortening of colon length and colonic histopathological deteriorations. OCOP treatment also suppressed the mRNA expression and release of inflammatory mediators (TGF-β, TNF-α, IL-6, IL-18, IL-1β and IFN-γ) and elevated the transcriptional and translational levels of anti-inflammatory cytokine (IL-10) as well as the mRNA expression levels of adhesion molecules (ICAM-1 and VCAM-1). Besides, the activation of NF-κB pathway and NLRP3 inflammasome was markedly inhibited by OCOP. Furthermore, OCOP displayed superior anti-colitis effect to COP, and was similar to MSZ with much smaller dosage. Taken together, the protective effect of OCOP against DSS-induced colitis might be intimately related to inhibition of NF-κB pathway and NLRP3 inflammasome. And the findings indicated that OCOP might have greater potential than COP to be further exploited as a promising candidate in the treatment of colitis.

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Protective Effect of Cicer arietinum L. (Chickpea) Ethanol Extract in the Dextran Sulfate Sodium-Induced Mouse Model of Ulcerative Colitis

Nutrients ◽

10.3390/nu12020456 ◽

2020 ◽

Vol 12 (2) ◽

pp. 456 ◽

Cited By ~ 2

Author(s):

Mia Kim ◽

Kyung-Sook Chung ◽

Se-Jung Hwang ◽

Ye Seul Yoon ◽

Young Pyo Jang ◽

...

Keyword(s):

Mouse Model ◽

Mrna Expression ◽

Cicer Arietinum ◽

Inflammatory Mediators ◽

Clinical Symptoms ◽

Activity Index ◽

Disease Activity Index ◽

Ethanol Extract ◽

Spleen Weight ◽

Protective Effects

Inflammatory bowel disease (IBD) is a major risk factor of colorectal cancer. Drugs currently used for IBD exhibit adverse effects including vomiting, nausea, and diarrhea. Naturally derived novel alternative therapies are required to overcome these limitations. In this study, we investigated the protective effects of ethanol extract of Cicer arietinum (CEE) in a dextran sodium sulfate (DSS)-induced mouse model of colitis. CEE markedly improved DSS-induced clinical symptoms and histological status, such as the disease activity index, spleen weight, and colon length. Moreover, CEE-treated mice showed significant recovery of DSS-induced crypt damage and cell death. CEE suppressed myeloperoxidase (MPO) activity and macrophage marker F4/80 mRNA expression in colonic tissue of mice with DSS-induced colitis, indicating neutrophil infiltration and macrophage accumulation, respectively. Although DSS upregulated pro-inflammatory mediators and activated transcription factors, CEE downregulated the mRNA expression of cytokines including interleukin-6, interleukin-1β, and tumor necrosis factor-α, protein expression of cyclooxygenase-2 and inducible nitric oxide synthase, as well as activation of nuclear factor-kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT3). Hence, our findings reveal that the anti-inflammatory properties of CEE, involving the downregulation of the expression of pro-inflammatory mediators by inactivating NF-κB and STAT3 in DSS-induced colitis mice.

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Protective Effect of Probiotics Isolated from Traditional Fermented Tea Leaves (Miang) from Northern Thailand and Role of Synbiotics in Ameliorating Experimental Ulcerative Colitis in Mice

Nutrients ◽

10.3390/nu14010227 ◽

2022 ◽

Vol 14 (1) ◽

pp. 227

Author(s):

Napapan Kangwan ◽

Sarawut Kongkarnka ◽

Nitsara Boonkerd ◽

Kridsada Unban ◽

Kalidas Shetty ◽

...

Keyword(s):

Protective Effect ◽

Clinical Symptoms ◽

Activity Index ◽

Intestinal Barrier ◽

Body Weight Loss ◽

Disease Activity Index ◽

Experimental Period ◽

Tea Leaves ◽

Barrier Integrity ◽

Intestinal Barrier Integrity

This study aimed to investigate the protective effect of probiotics and synbiotics from traditional Thai fermented tea leaves (Miang) on dextran sulfate sodium (DSS)-induced colitis in mice, in comparison to sulfasalazine. C57BL/6 mice were treated with probiotics L. pentosus A14-6, CMY46 and synbiotics, L. pentosus A14-6 combined with XOS, and L. pentosus CMY46 combined with GOS for 21 days. Colitis was induced with 2% DSS administration for seven days during the last seven days of the experimental period. The positive group was treated with sulfasalazine. At the end of the experiment, clinical symptoms, pathohistological changes, intestinal barrier integrity, and inflammatory markers were analyzed. The probiotics and synbiotics from Miang ameliorated DSS-induced colitis by protecting body weight loss, decreasing disease activity index, restoring the colon length, and reducing pathohistological damages. Furthermore, treatment with probiotics and synbiotics improved intestinal barrier integrity, accompanied by lowing colonic and systemic inflammation. In addition, synbiotics CMY46 combined with GOS remarkedly elevated the expression of IL-10. These results suggested that synbiotics isolated from Miang had more effectiveness than sulfasalazine. Thereby, they could represent a novel potential natural agent against colonic inflammation.

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l-Isoleucine Administration Alleviates DSS-Induced Colitis by Regulating TLR4/MyD88/NF-κB Pathway in Rats

Frontiers in Immunology ◽

10.3389/fimmu.2021.817583 ◽

2022 ◽

Vol 12 ◽

Author(s):

Xiangbing Mao ◽

Rui Sun ◽

Qingxiang Wang ◽

Daiwen Chen ◽

Bing Yu ◽

...

Keyword(s):

Mrna Expression ◽

Activity Index ◽

Control Diet ◽

Average Daily Gain ◽

Disease Activity Index ◽

Inflammatory Cells ◽

Feed Conversion ◽

Enterocyte Apoptosis

Inflammatory bowel disease (namely, colitis) severely impairs human health. Isoleucine is reported to regulate immune function (such as the production of immunoreactive substances). The aim of this study was to investigate whether l-isoleucine administration might alleviate dextran sulfate sodium (DSS)-induced colitis in rats. In the in vitro trial, IEC-18 cells were treated by 4 mmol/L l-isoleucine for 12 h, which relieved the decrease of cell viability that was induced by TNF-α (10 ng/ml) challenge for 24 h (P <0.05). Then, in the in vivo experiment, a total of 44 Wistar rats were allotted into 2 groups that were fed l-isoleucine-supplemented diet and control diet for 35 d. From 15 to 35 d, half of the rats in the 2 groups drank the 4% DSS-adding water. Average daily gain, average daily feed intake and feed conversion of rats were impaired by DSS challenge (P <0.05). Drinking the DSS-supplementing water also increased disease activity index (DAI) and serum urea nitrogen level (P <0.05), shortened colonic length (P <0.05), impaired colonic enterocyte apoptosis, cell cycle, and the ZO-1 mRNA expression (P <0.05), increased the ratio of CD11c-, CD64-, and CD169-positive cells in colon (P <0.05), and induced extensive ulcer, infiltration of inflammatory cells, and collagenous fiber hyperplasia in colon. However, dietary l-isoleucine supplementation attenuated the negative effect of DSS challenge on growth performance (P <0.05), DAI (P <0.05), colonic length and enterocyte apoptosis (P <0.05), and dysfunction of colonic histology, and downregulated the ratio of CD11c-, CD64-, and CD169-positive cells, pro-inflammation cytokines and the mRNA expression of TLR4, MyD88, and NF-κB in the colon of rats (P <0.05). These results suggest that supplementing l-isoleucine in diet improved the DSS-induced growth stunting and colonic damage in rats, which could be associated with the downregulation of inflammation via regulating TLR4/MyD88/NF-κB pathway in colon.

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Bacillus licheniformis Zhengchangsheng® attenuates DSS-induced colitis and modulates the gut microbiota in mice

Beneficial Microbes ◽

10.3920/bm2018.0122 ◽

2019 ◽

Vol 10 (5) ◽

pp. 543-553 ◽

Cited By ~ 3

Author(s):

Y. Li ◽

M. Liu ◽

J. Zhou ◽

B. Hou ◽

X. Su ◽

...

Keyword(s):

Gut Microbiota ◽

Bacillus Licheniformis ◽

Activity Index ◽

Intestinal Barrier ◽

Disease Activity Index ◽

Experimental Colitis ◽

Valuable Insight ◽

Microbial Composition ◽

Gastrointestinal Health ◽

Human Inflammatory Bowel Disease

Human inflammatory bowel disease (IBD) and experimental colitis models in mice are associated with shifts in gut microbiota composition, and several probiotics are widely used to improve gastrointestinal health. Here, we investigated whether the probiotic Bacillus licheniformis Zhengchangsheng® (BL) ameliorates dextran sulphate sodium (DSS)-induced colitis through alteration of the gut microbiota. Experimental colitis was induced in BALB/C mice by dissolving 3% DSS in their drinking water for 7 days, which were gavaged with 0.2 ml phosphate-buffered saline or BL (3×107 cfu/ml) once a day. Administration of BL attenuated several effects of DSS-induced colitis, including weight loss, increased disease activity index, and disrupted intestinal barrier integrity. In addition, BL mitigated the reduction in faecal microbiota richness in DSS treated mice. Interestingly, BL was found to reduce the elevated circulating endotoxin level in mice with colitis by modulating the microbial composition of the microbiota, and this was highly associated with a proportional decrease in gut Bacteroidetes. Our results demonstrate that BL can attenuate DSS-induced colitis and provide valuable insight into microbiota interactions during IBD.

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Genetic variation of rs7958311 in P2X7R gene is associated with the susceptibility and disease activity of ankylosing spondylitis

Postgraduate Medical Journal ◽

10.1136/postgradmedj-2018-136036 ◽

2019 ◽

Vol 95 (1123) ◽

pp. 251-257

Author(s):

Zhipeng Pan ◽

Xu Zhang ◽

Yubo Ma ◽

Shengqian Xu ◽

Zongwen Shuai ◽

...

Keyword(s):

Genetic Variation ◽

Ankylosing Spondylitis ◽

Protective Effect ◽

Disease Activity ◽

Allelic Variation ◽

Activity Index ◽

Disease Activity Index ◽

Nucleotide Polymorphisms ◽

Genotype Frequencies ◽

Male Patients

ObjectivesTo describe association between the genetic variation of inflammation-associated gene, P2X7R, and ankylosing spondylitis (AS) susceptibility.MethodsFour single nucleotide polymorphisms (SNPs) of P2X7R gene were genotyped in 673 patients with AS and 687 healthy controls. Allele and genotype frequencies and different genetic models were performed to calculate ORs and 95% CIs, the demographic and clinical characteristics of patients were recorded. The data analyses were also conducted by sex.ResultsCompared with controls, genetic variation in rs7958311 but not the other three SNPs was statistically significant in female patients (χ2=6.907, p=0.032). Specifically, the P2X7R gene rs7958311 polymorphism A allele showed a protective effect in AS susceptibility (OR=0.704, p=0.049, pFDR=0.061). In addition, female individuals with GA and/or AA genotypes had a lower risk of having AS compared with those with GG genotype (GA vs GG: OR=0.446, p=0.012, pFDR=0.030; AA vs GG: OR=0.440, p=0.039, pFDR=0.061; GA/AA vs GG: OR=0.445, p=0.009, pFDR=0.030). Furthermore, individuals with A allele (ie, GA/AA vs GG) had a higher disease activity, including Bath Ankylosing Spondylitis Disease Activity Index (overall: Z=− 2.630, p=0.014; male: Z=− 2.243, p=0.025), Schober test (overall: Z=− 3.041, p<0.001; male: Z=− 2.243, p=0.025) and chest expansion (overall: Z=− 3.895, p=0.004; male: Z=− 2.403, p=0.016).ConclusionThe allelic variation of rs7958311 SNP in P2X7R gene may have a protective effect on AS susceptibility in females and is associated with disease activity in male patients.

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Protective effect and mechanism of Monascus-fermented red yeast rice against colitis caused by Salmonella enterica serotype Typhimurium ATCC 14028

Food & Function ◽

10.1039/d0fo01017k ◽

2020 ◽

Vol 11 (7) ◽

pp. 6363-6375

Author(s):

Ya-ping Huang ◽

Ping Li ◽

Ting Du ◽

Xin-jun Du ◽

Shuo Wang

Keyword(s):

Gut Microbiota ◽

Protective Effect ◽

Salmonella Enterica ◽

Intestinal Inflammation ◽

Underlying Mechanism ◽

Red Yeast Rice ◽

Red Yeast ◽

Gut Microbiota Dysbiosis

The effect of red yeast rice on Salmonella enterica-induced intestinal inflammation and gut microbiota dysbiosis in mice as well as the underlying mechanism.

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Treatment of inflammatory bowel disease (IBD) in dogs and cats

Polish Journal of Veterinary Sciences ◽

10.2478/v10181-011-0026-7 ◽

2011 ◽

Vol 14 (1) ◽

pp. 165-171 ◽

Cited By ~ 9

Author(s):

K. Malewska ◽

A. Rychlik ◽

R. Nieradka ◽

M. Kander

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Clinical Symptoms ◽

Activity Index ◽

Disease Activity Index ◽

Immunosuppressive Drugs ◽

Clinical Activity ◽

Aminosalicylic Acid ◽

Probiotic Treatment ◽

Inflammatory Bowel

Treatment of inflammatory bowel disease (IBD) in dogs and catsThe treatment of inflammatory bowel disease (IBD) possesses numerous difficulties owing to the unclear etiology of the disease. This article overviews the drugs used in the treatment of IBD depending on the intensity of clinical symptoms (Canine Inflammatory Bowel Disease Activity Index and Canine Chronic Enterophaty Clinical Activity Index). Patients demonstrating mild symptoms of the disease are usually placed on an appropriate diet which may be combined with immunomodulative or probiotic treatment. In moderate progression of IBD, 5-aminosalicylic acid (mesalazine or olsalazine) derivatives may be administered. Patients showing severe symptoms of the disease are usually treated with immunosuppressive drugs, antibiotics and elimination diet. Since the immune system plays an important role in the pathogenesis of the disease, the advancements in biological therapy research will contribute to the progress in the treatment of canine and feline IBD in the coming years.

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Study on the mechanism of Indigo naturalis and its two main compounds (indigo and indirubin) in the treatment of ulcerative colitis based on TLR4/MyD88/NF-κB pathway and intestinal microorganisms

10.21203/rs.3.rs-31454/v1 ◽

2020 ◽

Author(s):

Qi-yue Yang ◽

Ya-nan He ◽

Le-le Ma ◽

Run-chun Xu ◽

Nan Li ◽

...

Keyword(s):

Ulcerative Colitis ◽

Gut Microbiota ◽

Intestinal Inflammation ◽

Activity Index ◽

Disease Activity Index ◽

Pathological Section ◽

Inflammatory Cytokine Production ◽

Tnf Α ◽

Indigo Naturalis ◽

Inflammation Cytokines

Abstract Background: Indigo naturalis is a natural dye extracted from plants and has a good anti-inflammatory effect. Clinical studies have shown that it can improve ulcerative colitis (UC), but the active constituents and the mechanism are unclear. Methods: The anti-UC activity of Indigo naturalis and its two main compounds (indigo and indirubin) were investigated in dextran sulfate sodium (DSS)-induced UC mice. Indigo naturalis, indigo and indirubin were administrated to DSS-induced UC rats by oral gavage for 1 weeks. The anti-UC effect was evaluated by pathological section, inflammatory cytokine production, western blotting, and gut microbiota analysis via 16S rRNA sequencing. Results: Indigo naturalis, indigo and indirubin can improve the UC induced by DSS. Their effect intensity is Indigo naturalis > indirubin > indigo based on disease activity index, body weight, colon length and pathological section. Indigo naturalis, indigo and indirubin also decrease the expression of NF-κB，TLR4 and MYD88 proteins, thus reducing the level of related inflammation cytokines (IL-1β, IL-6 and TNF-α) both in serum and tissue. In addition, Indigo naturalis and indigo improved symptoms of gut microbial disturbance, and decreased Firmicutes/Bacteroidetes ratio and the significantly increased probiotics such as Lactobacillus. Indirubin has little effect on the regulation of gut microbial. Conclusions: Indigo naturalis could attenuate the DSS-induced UC in mice, by means of ameliorating intestinal inflammation, improving intestinal mucosa, and regulating the disturbed gut microbiota. Indigo and indirubin could also attenuate the DSS-induced UC in mice, but their comprehensive effect is not as good as Indigo naturalis.

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Natural naphthoquinones isolated from Lithospermum erythrorhizon suppress dextran sulfate sodium-induced murine experimental colitis

10.1101/830224 ◽

2019 ◽

Author(s):

Wenxue Sun ◽

Hongwei Han ◽

Zhaoyue Wang ◽

Zhongling Wen ◽

Minkai Yang ◽

...

Keyword(s):

Nlrp3 Inflammasome ◽

Active Sites ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Activity Index ◽

Docking Simulation ◽

Disease Activity Index ◽

Experimental Colitis ◽

Intragastric Administration ◽

Underlying Mechanisms

AbstractThe purpose of this study was to explore the effects of natural shikonin and its derivatives on mice experimental colitis induced by dextran sulfate sodium, and to investigate the underlying mechanisms in vivo. Our results suggested that, intragastric administration of single compound like shikonin and its derivatives contributed to attenuating symptoms of malignant induced by DSS. Meanwhile, shikonin or its derivatives could also remarkably reduce the disease activity index and histopathological scores, suppress the levels of pro-inflammatory cytokines (including IL-6, IL-1β and TNF-α), while increase that of inflammatory cytokine IL-10 in serum. Additionally, both shikonin and alkanin were found to restrain the levels of COX-2, MPO and iNOS in serum and colonic tissues. Moreover, western blotting results demonstrated that shikonin and its derivatives could inhibit the activation of the NLRP3 inflammasome and the NF-κB signaling pathway, relieve the DSS-induced disruption of colonic epithelial tight junction (TJ) in colonic tissues. Further, docking simulation had been performed to prove that shikonin and its derivatives could bind to the active sites of NLRP3 inflammasome and the NF-κB to generate an effective inflammatory effect. Taken together, our experimental data can provide some evidence for the potential use of shikonin and its derivatives to treat the inflammatory bowel disease (IBD).

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135 FH and FGSH prepared from fish skin gelatin using ginger protease alleviates DSS-induced Colitis via Nrf2 pathway

Journal of Animal Science ◽

10.1093/jas/skz258.238 ◽

2019 ◽

Vol 97 (Supplement_3) ◽

pp. 115-116

Author(s):

Zhao Deng ◽

Jian Peng

Keyword(s):

Clinical Symptoms ◽

Activity Index ◽

Disease Activity Index ◽

Chronic Inflammatory Disease ◽

Fish Skin ◽

Important Indicator ◽

Nrf2 Pathway ◽

Gelatin Hydrolysate ◽

Fish Skin Gelatin ◽

Ginger Protease

Abstract Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic inﬂammatory disease aﬀecting the colon, and its incidence is rising worldwide. Hence, it is important to apply new strategies to cope with the IBD. We previously found that hydrolysate fractions (HF) and fish skin gelatin hydrolysate (FSGH), isolated from fish skin gelatin hydrolysate using ginger protease, could exert antioxidant effects in IPEC-J2 cells. Here, we aimed to evaluate the effects of FH and FGSH in a mouse model of dextran sodium sulfate (DSS)-induced colitis. Mouse were treated with 3% DSS in their drinking water for 7 days to induce acute colitis. FH (200 mg/kg) and FGSH (200 mg/kg) was administered for 7 days before and during DSS treatment via oral gavage once per day. Mouse were sacrificed at day 7 after colitis induction. The results showed that FH and FGSH significantly ameliorated the clinical symptoms of DSS-induced mice colitis, such as weight loss, disease activity index (DAI), colon shortening, spleen hypertrophy and histological scores. For MPO activity, an important indicator of neutrophil infiltration and acute inflammation in DSS-induced mouse colitis, FH and FGSH significantly reduced the level of DSS-induced hyperactivated MPO. Treatment with FH and FGSH also significantly inhibited the secretion proinflammatory cytokines TNF-α, IL-8 and IL-12 in DSS-induced mouse colitis. And FH and FGSH administration significantly increased expression of antioxidant enzymes GCLM, GCLC and GPX4 and maintained tight junction in colon tissues. Furthermore, we found that FH and FGSH significantly increased the level of Nrf2 in colon tissues, it indicated that FH and FGSH may alleviated colitis by Nrf2 pathway. Overall, these results suggested that FH and FGSH could be a potential promising candidate for the treatment of IBD.

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