scholarly journals Black Lentil Aqueous Extract Attenuates Colitis-Associated Colon Carcinogenesis in Mice (OR04-06-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Elvira Gonzalez de Mejia ◽  
Candice Mazewski ◽  
Diego Luna-Vital ◽  
Mark Berhow

Abstract Objectives The objective was to compare the efficacy of a black lentil aqueous extract (BL) and a semi-purified anthocyanin (ANC) extract to prevent tumor development and inflammatory processes and impact on immune response in an azoxymethane (AOM)/dextran sodium sulfate (DSS) mouse model. Methods BL was obtained from an overnight soak of organic beluga black lentils (1:2 w/v) in water, filtered, frozen, and freeze-dried. The major ANC identified was delphinidin 3-O-(2-O-β-d-glucopyranosyl-α-l-arabinopyranoside (D3G). Seven and a half week old C57BL/6 mice were randomly separated into four groups: healthy control (n = 6), disease control (n = 14), BL (n = 12), and D3G (n = 12). After a one week acclimation, the mice were given treatments for 11 weeks, either placebo or BL: 600 or D3G: 41 mg/kg body weight (equivalent to D3G in a BL extract) using a voluntary jelly administration every morning throughout the study. Following the first week of treatments, mice received an AOM injection of 10 mg/kg body weight. Three cycles of DSS in water started one week later. The first cycle had 2% DSS for one week; the second and third cycles had 1%. Each cycle had two weeks of regular water post-DSS. Inflammation, progression, and immune markers were analyzed in the colon, spleen, and plasma by histology, gene expression, ELISA, and protein arrays. Results BL had total ANC concentration of 21.3 mg D3G equivalent/g dry extract and total polyphenol concentration of 264.9 mg gallic acid equivalent/g dry extract. BL group had a lower disease activity index (DAI), throughout and at the end, of 2.4 compared to 6.3 of the disease control and 4.0 of D3G group (P < 0.05). Mice in the BL group had an average of 7.8 neoplasms while the disease control had 12.8 and D3G had 12.1 (P < 0.05). BL group had a lower relative spleen weight and colon weight to length at 5 and 59 mg/cm compared to 10 and 82 mg/cm and 10 and 83 mg/cm of the disease control and D3G groups, respectively (P < 0.05). Based on colon cancer cell results, BL lowered expression of inhibitory immune markers, like PD-L1 (P < 0.05). Conclusions BL attenuated the DAI and helped mice maintain their weight throughout the AOM/DSS treatment. BL also resulted in a lower total and lower large neoplasm number, relative lower spleen weight, and colon weight to length ratio compared to the disease control. BL showed anti-carcinogenic anti-inflammatory properties. Funding Sources USDA-NIFA-HATCH project 1014457.

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 317-317
Author(s):  
Elvira Gonzalez de Mejia ◽  
Candice Mazewski ◽  
Diego Luna ◽  
Mark Berhow

Abstract Objectives The objective was to compare the impact of black lentil water extract (BL) and delphinidin 3-O-(2-O-β-d-glucopyranosyl-α-l-arabinopyranoside) (D3G)-rich lentil extract on tumor development and inflammation in an azoxymethane (AOM)/dextran sodium sulfate (DSS) model. Methods C57BL/6 mice were randomly separated into four groups: healthy control (n = 6), AOM/DSS control (n = 14), AOM/DSS + BL (600 mg/kg body weight, n = 12), and AOM/DSS + D3G (41 mg/kg body weight, equivalent to D3G concentration in BL, n = 12). Mice were given treatments for 11 weeks using a voluntary oral jelly administration. Fecal samples were collected three times: after one week of treatments prior to the first AOM injection, after the first (of three) DSS cycle, and at the time of euthanasia. Secretory leukoprotease inhibitor (SLPI) expression was evaluated by qPCR, calprotectin by ELISA and fecal metabolite profiles by Agilent GC-MS system. Results AOM/DSS + BL presented a lower (p &lt; 0.05) disease activity index, throughout and at the end (2.4) compared to AOM/DSS control (6.3). AOM/DSS + BL mice had an average of 7.8 neoplasms/mouse vs. 12.8 for the AOM/DSS (p &lt; 0.05). Pro-inflammatory cytokines were downregulated in the colon mucosa in AOM/DSS + BL and AOM/DSS + D3G: interleukin 1β (−77.5%, −70.7%), interleukin 6 (−44.4%, −44.9%), respectively, compared to the AOM/DSS control. In non-polyp tissue,  SLPI expression was higher compared to the healthy (1.0) and AOM/DSS control (5.0), AOM/DSS + BL (14.6) and AOM/DSS + D3G (10.3) groups. In polyp tissue,  SLPI expression was highest in the AOM/DSS + BL group (24.3) versus the AOM/DSS control (9.3) and AOM/DSS + D3G (10.0). At the time of euthanasia, fecal calprotectin concentration was low for the healthy control (1.6 µg/g), AOM/DSS + BL (1.8 µg/g), and AOM/DSS + D3G (2.4 µg/g), but increased dramatically for the AOM/DSS control (4.1 µg/g) (p &lt; 0.05). Gallic and protocatechuic acids and epicatechin were found in feces; the concentration of amino acids such as alanine, isoleucine, and leucine was lower, and unsaturated fatty acids were higher for AOM/DSS + BL and AOM/DSS + D3G versus the AOM/DSS control. Conclusions BL and D3G-rich extracts showed anti-inflammatory effects and modified fecal metabolites while BL additionally prevented growth of neoplasia. Funding Sources US Department of Agriculture Hatch 1,014,457.


Author(s):  
P. Geetha ◽  
B. Lakshman Kumar ◽  
U. Indra ◽  
B. Pavithra Sheetal

Objective: Ulcerative colitis known as inflammatory bowel disease (IBD) of unknown etiology. We examined the antioxidant and myeloperoxidase status in a murine model of 7,12-dimethylbenz[a]anthracene induced colitis to elucidate the exact mechanism behind the inflammation.Methods: Male Wistar rats were exposed to ulcerative colitis using various concentration of DMBA (7,12-Dimethylbenz[A]anthracene) were periodically analysed on 4th, 8th, 12th, 24th and 32nd week from the date of induction. To determine the disease activity index changes in body weight, food consumption, the presence of gross blood in stool and consistency of feces and diarrhea were observed. Macroscopic characters were elucidated based on clinical features of the colon and rectum using scoring pattern. Tissue inflammation status was noted through myeloperoxidase (MPO) assay. The antioxidant status in tissue samples was analysed by superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and total reduced glutathione (GSH).Results: Gavage intubation of DMBA induced colitis showed significant changes from 4th week and severity on 32nd week. The body weight was gradually reduced. Macroscopic scoring showed severe scoring pattern the inflammation was significantly heavier by week 4; and by the end of 32 w, inflammation in rats was double that of the controls, tissue myeloperoxidase (MPO) activity showed the steady increase of neutrophil infiltration and inflammation rate every week. A significant change was noted in tissue antioxidant status and it showed the oxidation level. Statistically, significant change was recorded from 4th week till 32nd week.Conclusion: The conventional biochemical changes in colitis induced animal model revealed the association between the oxidative stress and ulcerative colitis.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Shashank Singh ◽  
Ruchika Bhatia ◽  
Pragyanshu Khare ◽  
Shikha Sharma ◽  
Sivasubramanian Rajarammohan ◽  
...  

Abstract Crohn’s and ulcerative colitis are common inflammatory conditions associated with Inflammatory bowel disease. Owing to the importance of diet based approaches for the prevention of inflammatory gut conditions, the present study was aimed to screen the human isolates of Bifidobacterium strains based on their ability to reduce LPS-induced inflammation in murine macrophage (RAW 264.7) cells and to evaluate prioritized strains for their preventive efficacy against ulcerative colitis in mice. Twelve out of 25 isolated strains reduced the production of LPS-induced nitric oxide and inflammatory cytokines. Furthermore, three strains, B. longum Bif10, B. breve Bif11, and B. longum Bif16 conferred protection against dextran sodium sulfate induced colitis in mice. The three strains prevented shortening of colon, spleen weight, percentage body weight change and disease activity index relative to colitis mice. Lower levels of Lipocalin-2, TNF-α, IL-1β and IL-6 and improved SCFA levels were observed in Bifidobacterium supplemented mice relative to DSS counterparts. Bacterial composition of B. longum Bif10 and B. breve Bif11 fed mice was partly similar to the normal mice, while DSS and B. longum Bif16 supplemented mice showed deleterious alterations. At the genus level, Bifidobacterium supplementation inhibited the abundances of pathobionts such as Haemophilus, Klebsiella and Lachnospira there by conferring protection.


2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Huixia Qiao ◽  
Yahui Huang ◽  
Xiaoyan Chen ◽  
Long Yang ◽  
Yue Wang ◽  
...  

Purpose. Jiaweishaoyao decoction (JWSYD) is a traditional prescription of Chinese medicine that is initially used for the treatment of diarrhea. This study is aimed at investigating the effects of JWSYD on DSS-induced ulcerative colitis (UC). Methods. DSS-induced UC mice and LPS-induced RAW264.7 cells were used as the UC model in vivo and in vitro. UC was assessed by body weight, disease activity index (DAI), colon length, spleen weight, and histopathological score (HE staining). The levels of TNF-α, IL-1β, and IL-6 were analyzed by ELISA and qRT-PCR. The levels of NLRP3 inflammasome- and NF-κB pathway-associated proteins were measured by western blot. Results. JWSYD alleviated DSS-induced UC in respect to body weight, DAI, colon length, spleen weight, and histopathological score. JWSYD reduced the levels of TNF-α, IL-1β, and IL-6 in DSS-induced UC mice and the supernatants of LPS-induced RAW264.7 cells. JWSYD suppressed the protein levels of inflammasome-associated proteins, including NLRP3, ASC1, Procaspase-1, Cleaved caspase-1, and Cleaved IL-1β in DSS-induced UC mice and LPS-induced RAW264.7 cells. In addition, JWSYD suppressed the NF-κB pathway in vitro and in vivo. Conclusion. JWSYD alleviated DSS-induced UC via inhibiting the NLRP3 inflammasome and NF-κB pathway.


2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Bing Wei ◽  
Ran Zhang ◽  
Jingbo Zhai ◽  
Junfeng Zhu ◽  
Fangli Yang ◽  
...  

Background. Ganoderma lucidum polysaccharides (GLP) has anti-inflammatory and immunomodulatory effects. Dysregulated immune responses are involved in the pathogenesis of dextran sulfate sodium (DSS)-induced colitis. The aim of this study was to assess the therapeutic potential of GLP to alleviate DSS-induced colitis. Methods. The mice were administered with GLP by intragastric gavage daily for two weeks prior to the DSS treatment. Mice were orally administered with 2.5% DSS dissolved in drinking water with GLP or water treatment for 6 days. The mice were killed on day 7 after induction of colitis. Survival rates, body weight loss, colon lengths, histological changes, and disease activity index scores (DAI) were evaluated. Results. GLP significantly improved survival rates, colon length shortening, body weight loss, histopathological score, and DAI scores in mice with DSS-induced colitis. GLP markedly suppressed the secretions of TNF-α, IL-1β, IL-6, IL-17A, and IL-4 and significantly affected populations of Th17 cells, B cells, NK cells, and NKT cells in the lamina propria lymphocytes. Conclusions. GLP prevented inflammation, maintained intestinal homeostasis, and regulated the intestinal immunological barrier functions in mice with DSS-induced colitis.


2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S147-S147
Author(s):  
S Rahman ◽  
A Elfiky ◽  
P H P van Hamersveld ◽  
C Verseijden ◽  
O Welting ◽  
...  

Abstract Background MiR-511 is embedded in intron region 5 of the CD206/MRC1 gene, expressed by macrophage and dendritic cell populations. In this study, we aimed to investigate the effect of MiR-511 deficiency on intestinal inflammation in a murine T cell transfer colitis model. Methods A double MiR-511- and Rag-1 (knockout) KO mouse was generated and a T cell transfer colitis was induced by intraperitoneal injection of naïve T cells from donor WT mice. Since these mice lack mature T and B cells, first signs of inflammation appeared at week 3 after T cell injection. An endoscopy score was obtained to determine inflammation at week 3 and 5, respectively. The experiment was terminated at week 5 and severity of inflammation was assessed on the basis of weight loss, colon weight/length ratio, histology score, spleen weight and disease activity index. In addition, flow cytometry was performed for analysing immune cell populations (monocyte, macrophages, dendritic cells, neutrophils) in the colons of both control and colitis groups and T cells in the spleens of colitis group, respectively. Results Following the induction of T cell transfer colitis, colon weight/length ratio, spleen weight and endoscopic score were significantly increased in the double KO mice compared to Rag-1 KO control mice. A higher histology score and disease activity index in the double KO with no change in weight loss compared to Rag-1 KO control mice was observed. A significant increase in monocyte population in the colons of double KO was seen and increased numbers of monocytes was also observed in the double KO control group with no inflammation. Also, a higher influx of T cells in the double KO mice with a significant increase in Foxp3 and IL4 population was observed in the group with colitis. Conclusion MiR-511 deficiency aggravates intestinal inflammation compared to Rag-1 KO control mice. Also, a higher presence of monocyte as well as T cell populations were observed in these mice. Together these data show that MiR-511 is involved in the regulation of intestinal health. Future research will focus on underlying mechanisms.


Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 456 ◽  
Author(s):  
Mia Kim ◽  
Kyung-Sook Chung ◽  
Se-Jung Hwang ◽  
Ye Seul Yoon ◽  
Young Pyo Jang ◽  
...  

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.


Metabolites ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 44
Author(s):  
Genki Tanaka ◽  
Nozomi Hagihara ◽  
Ryota Hosomi ◽  
Takaki Shimono ◽  
Seiji Kanda ◽  
...  

Protein derived from fish has not only nutritional properties but also health-promoting properties. Few studies have examined the effect of dietary Alaska pollock protein (APP) on the anticolitis effect reported to be associated with metabolic syndrome (MetS). This study investigated the effect of APP intake on colitis symptoms, gut microbiota, and its metabolites in the experimental colitis mouse model induced by dextran sulfate sodium (DSS). Male C57BL/6J mice were divided into three groups: (1) DSS-untreated mice fed an American Institute of Nutrition (AIN) 93G diet (protein source is casein), (2) DSS-treated mice fed an AIN93G diet, and (3) DSS-treated mice fed an APP diet. After the mice were fed the diets for 21 days, experimental colitis was induced by three cycles of 2% DSS administration for 5 days followed by washouts over the course of 5 days. APP-reduced body weight loss increased the disease activity index, and elevated spleen weight and alleviated colon length shortening and colonic tissue damage. Furthermore, APP altered the structure and composition of the microbiota and short-chain fatty acids in feces. Since APP intake alleviates experimental colitis induced by DSS administration through alterations in the gut microbiota and its metabolites, we deduced that APP would inhibit MetS progression via colitis suppression.


Cancers ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 341 ◽  
Author(s):  
Sonia Leon-Cabrera ◽  
Armando Vázquez-Sandoval ◽  
Emmanuel Molina-Guzman ◽  
Yael Delgado-Ramirez ◽  
Norma Delgado-Buenrostro ◽  
...  

Signal transducer and activator of transcription 1 (STAT1) is part of the Janus kinase (JAK/STAT) signaling pathway that controls critical events in intestinal immune function related to innate and adaptive immunity. Recent studies have implicated STAT1 in tumor–stroma interactions, and its expression and activity are perturbed during colon cancer. However, the role of STAT1 during the initiation of inflammation-associated cancer is not clearly understood. To determine the role of STAT1 in colitis-associated colorectal cancer (CAC), we analyzed the tumor development and kinetics of cell recruitment in wild-type WT or STAT1−/− mice treated with azoxymethane (AOM) and dextran sodium sulfate (DSS). Following CAC induction, STAT1−/− mice displayed an accelerated appearance of inflammation and tumor formation, and increased damage and scores on the disease activity index (DAI) as early as 20 days after AOM-DSS exposure compared to their WT counterparts. STAT1−/− mice showed elevated colonic epithelial cell proliferation in early stages of injury-induced tumor formation and decreased apoptosis in advanced tumors with over-expression of the anti-apoptotic protein Bcl2 at the colon. STAT1−/− mice showed increased accumulation of Ly6G+Ly6C−CD11b+ cells in the spleen at 20 days of CAC development with concomitant increases in the production of IL-17A, IL-17F, and IL-22 cytokines compared to WT mice. Our findings suggest that STAT1 plays a role as a tumor suppressor molecule in inflammation-associated carcinogenesis, particularly during the very early stages of CAC initiation, modulating immune responses as well as controlling mechanisms such as apoptosis and cell proliferation.


2020 ◽  
Vol 21 (3) ◽  
pp. 857 ◽  
Author(s):  
Soonjae Hwang ◽  
Minjeong Jo ◽  
Ju Eun Hong ◽  
Chan Oh Park ◽  
Chang Gun Lee ◽  
...  

Chronic inflammation has been linked to colitis-associated colorectal cancer in humans. The human symbiont enterotoxigenic Bacteroides fragilis (ETBF), a pro-carcinogenic bacterium, has the potential to initiate and/or promote colorectal cancer. Antibiotic treatment of ETBF has shown promise in decreasing colonic polyp formation in murine models of colon cancer. However, there are no reported natural products that have shown efficacy in decreasing polyp burden. In this study, we investigated the chemopreventive effects of oral administration of zerumbone in ETBF-colonized mice with azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced tumorigenesis. Zerumbone significantly reduced the severity of disease activity index (DAI) scores as well as several parameters of colonic inflammation (i.e., colon weight, colon length, cecum weight and spleen weight). In addition, inflammation of the colon and cecum as well as hyperplasia was reduced. Zerumbone treatment significantly inhibited colonic polyp numbers and prevented macroadenoma progression. Taken together, these findings suggest that oral treatment with zerumbone inhibited ETBF-promoted colon carcinogenesis in mice indicating that zerumbone could be employed as a promising protective agent against ETBF-mediated colorectal cancer.


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