scholarly journals Treatment with a Zinc Metalloprotease Purified from Bothrops moojeni Snake Venom (BmooMP-Alpha-I) Reduces the Inflammation in an Experimental Model of Dextran Sulfate Sodium-Induced Colitis

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Maraisa Cristina Silva ◽  
Helioswilton Sales-Campos ◽  
Carlo José Freire Oliveira ◽  
Tamires Lopes Silva ◽  
Flávia Batista Ferreira França ◽  
...  

It has been described that the metalloprotease BmooMP-alpha-I purified from Bothrops moojeni snake venom is able to hydrolyze the TNF molecule. However, this observation has been based mainly on in vitro investigation, in addition to molecular modeling and docking approaches. Considering that there is no in vivo study to demonstrate the biological effects of this enzyme, the major aim to the present work was to investigate whether the BmooMP-alpha-I has any anti-inflammatory efficacy by setting up a murine experimental design of colitis induced by dextran sulfate sodium (DSS). For this purpose, C57BL/6 mice were divided into six groups, as follows: (i) animals without intestinal inflammation, (ii) animals without intestinal inflammation treated with BmooMP-alpha-I (50 μg/animal/day), and (iii) animals with intestinal inflammation induced by 3% of DSS, (iv) mice with intestinal inflammation induced by DSS and treated with BmooMP-alpha-I enzyme at the 50, 25, or 12.5 μg/animal/day dosages by intraperitoneal route. Clinical signs of colitis were observed daily for calculating the morbidity scores, cytokine measurements, and histological features. We observed that the animals treated with different doses of the enzyme presented a remarkable improvement of colitis signs, as confirmed by a significant increase of the intestine length in comparison to the DSS group. Also, no difference was observed between the groups treated with the enzyme or vehicle, as the colon length of these animals was slightly lower than that of the group of healthy animals, without induction of intestinal inflammation. The cytokine quantification in supernatants of intestinal tissue homogenates showed a significant reduction of 38% in IFN-gamma levels, when the animals were treated with 50 μg of the BmooMP-alpha-I compared to the animals receiving DSS only. A significant reduction of 39% in TNF levels was also observed in all doses of treatment with BmooMP-alpha-I, in addition to a significant reduction of 35% in the amount of IL-12p40. Histological examinations revealed that the BmooMP-alpha-I 50 μg treated group preserved colon architecture and goblet cells and reduced the ulcer area, when compared with DSS mice, which showed typical inflammatory changes in tissue architecture, such as ulceration, crypt dilation, loss of tissue architecture, and goblet cell depletion, accompanied by a significant cell infiltration. In conclusion, our results suggest that the improvement of clinical scores and histological findings related to BmooMP-alpha-I treatment in this experimental model could be attributed to the metalloprotease ability to modulate cytokine production locally at the inflamed intestine. These findings highlight the potential anti-inflammatory role and effectiveness of this enzyme as a therapeutic alternative in this type of immunopathological condition.

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2630
Author(s):  
Jiah Yeom ◽  
Seongho Ma ◽  
Jeong-Keun Kim ◽  
Young-Hee Lim

Colitis causes destruction of the intestinal mucus layer and increases intestinal inflammation. The use of antioxidants and anti-inflammatory agents derived from natural sources has been recently highlighted as a new approach for the treatment of colitis. Oxyresveratrol (OXY) is an antioxidant known to have various beneficial effects on human health, such as anti-inflammatory, antibacterial activity, and antiviral activity. The aim of this study was to investigate the therapeutic effect of OXY in rats with dextran sulfate sodium (DSS)-induced acute colitis. OXY ameliorated DSS-induced colitis and repaired damaged intestinal mucosa. OXY downregulated the expression of pro-inflammatory cytokine genes (TNF-α, IL-6, and IL-1β) and chemokine gene MCP-1, while promoting the production of anti-inflammatory cytokine IL-10. OXY treatment also suppressed inflammation via inhibiting cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression in the colon, as well as the activity of myeloperoxidase (MPO). OXY exhibited anti-apoptotic effects, shifting the Bax/Bcl-2 balance. In conclusion, OXY might improve DSS-induced colitis by restoring the intestinal mucus layer and reducing inflammation within the intestine.


2011 ◽  
Vol 39 (05) ◽  
pp. 957-969 ◽  
Author(s):  
Su-Jin Kim ◽  
Yang-Gui Kim ◽  
Dae-Seung Kim ◽  
Yong-Deok Jeon ◽  
Min-Cheol Kim ◽  
...  

Ulcerative colitis (UC) is an inflammatory bowel disease, which is a chronic gastrointestinal disorder. Oldenlandia diffusa (OD) has been used as a traditional oriental medicine for inflammation. However, the regulatory effect and molecular mechanism of OD in intestinal inflammation are not yet understood. This study investigated the protective effect of OD in dextran sulfate sodium (DSS)-induced colitis. Mice treated with DSS showed remarkable clinical signs, including weight loss, and reduced colon length. Administration of OD attenuated these signs and significantly suppressed levels of interleukin (IL)-6, IL-1β and expression of cyclooxygenase-2 in DSS-treated colon tissues. OD also reduced the activation of transcription nuclear factor-κB p65 in DSS-treated colon tissues. Hentriacontane, a constituent of OD, attenuated weight loss, colon shortening, and levels of IL-6 caused by DSS. Taken together, the results provide experimental evidence that OD might be a useful therapeutic medicine for patients with UC.


2019 ◽  
Vol 20 (6) ◽  
pp. 1473 ◽  
Author(s):  
Rogatien Charlet ◽  
Boualem Sendid ◽  
Srini Kaveri ◽  
Daniel Poulain ◽  
Jagadeesh Bayry ◽  
...  

Intravenous immunoglobulin (IVIg) therapy has diverse anti-inflammatory and immunomodulatory effects and has been employed successfully in autoimmune and inflammatory diseases. The role of IVIg therapy in the modulation of intestinal inflammation and fungal elimination has not been yet investigated. We studied IVIg therapy in a murine model of dextran sulfate sodium (DSS)-induced colitis. Mice received a single oral inoculum of Candida albicans and were exposed to DSS treatment for 2 weeks to induce colitis. All mice received daily IVIg therapy starting on day 1 for 7 days. IVIg therapy not only prevented a loss of body weight caused by the development of colitis but also reduced the severity of intestinal inflammation, as determined by clinical and histological scores. IVIg treatment significantly reduced the Escherichia coli, Enterococcus faecalis, and C. albicans populations in mice. The beneficial effects of IVIg were associated with the suppression of inflammatory cytokine interleukin (IL)-6 and enhancement of IL-10 in the gut. IVIg therapy also led to an increased expression of peroxisome proliferator-activated receptor gamma (PPARγ), while toll-like receptor 4 (TLR-4) expression was reduced. IVIg treatment reduces intestinal inflammation in mice and eliminates C. albicans overgrowth from the gut in association with down-regulation of pro-inflammatory mediators combined with up-regulation of anti-inflammatory cytokines.


Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1895
Author(s):  
Azra Memon ◽  
Bae Yong Kim ◽  
Se-eun Kim ◽  
Yuliya Pyao ◽  
Yeong-Geun Lee ◽  
...  

Background: Phytoncide is known to have antimicrobial and anti-inflammatory properties. Purpose: This study was carried out to confirm the anti-inflammatory activity of two types of phytoncide extracts from pinecone waste. Methods: We made two types of animal models to evaluate the efficacy, an indomethacin-induced gastroenteritis rat model and a dextran sulfate sodium-induced colitis mouse model. Result: In the gastroenteritis experiment, the expression of induced-nitric oxide synthase (iNOS), a marker for inflammation, decreased in the phytoncide-supplemented groups, and gastric ulcer development was significantly inhibited (p < 0.05). In the colitis experiment, the shortening of the colon length and the iNOS expression were significantly suppressed in the phytoncide-supplemented group (p < 0.05). Conclusions: Through this study, we confirmed that phytoncide can directly inhibit inflammation in digestive organs. Although further research is needed, we conclude that phytoncide has potential anti-inflammatory properties in the digestive tract and can be developed as a functional agent.


2021 ◽  
Vol 37 (1) ◽  
Author(s):  
Sou Hyun Kim ◽  
Doyoung Kwon ◽  
Seung Won Son ◽  
Tae Bin Jeong ◽  
Seunghyun Lee ◽  
...  

Abstract Background Inflammatory bowel disease (IBD), including both Crohn’s disease and ulcerative colitis, are chronic human diseases that are challenging to cure and are often unable to be resolved. The inbred mouse strain C57BL/6 N has been used in investigations of IBD as an experimental animal model. The purpose of the current study was to compare the inflammatory responsiveness of C57BL/6NKorl mice, a sub-strain recently established by the National Institute of Food and Drug Safety Evaluation (NIFDS), with those of C57BL/6 N mice from two different sources using a dextran sulfate sodium (DSS)-induced colitis model. Results Male mice (8 weeks old) were administered DSS (0, 1, 2, or 3%) in drinking water for 7 days. DSS significantly decreased body weight and colon length and increased the colon weight-to-length ratio. Moreover, severe colitis-related clinical signs including diarrhea and rectal bleeding were observed beginning on day 4 in mice administered DSS at a concentration of 3%. DSS led to edema, epithelial layer disruption, inflammatory cell infiltration, and cytokine induction (tumor necrosis factor-α, interleukin-6, and interleukin-1β) in the colon tissues. However, no significant differences in DSS-promoted abnormal symptoms or their severity were found between the three sub-strains. Conclusions These results indicate that C57BL/6NKorl mice responded to DSS-induced colitis similar to the generally used C57BL6/N mice, thus this newly developed mouse sub-strain provides a useful animal model of IBD.


2018 ◽  
Vol 99 ◽  
pp. 697-703 ◽  
Author(s):  
Thaise Boeing ◽  
Priscila de Souza ◽  
Tiago José Bonomini ◽  
Luísa Nathália Bolda Mariano ◽  
Lincon Bordignon Somensi ◽  
...  

2006 ◽  
Vol 0 (0) ◽  
pp. 060606032707040-??? ◽  
Author(s):  
Ashlesh K Murthy ◽  
Candice N Dubose ◽  
Jeffrey A Banas ◽  
Jacqueline J Coalson ◽  
Bernard P Arulanandam

Planta Medica ◽  
2021 ◽  
Author(s):  
Jiaqi Wu ◽  
Yuzheng Wu ◽  
Yue Chen ◽  
Mengyang Liu ◽  
Haiyang Yu ◽  
...  

AbstractUlcerative colitis has been recognized as a chronic inflammatory disease predominantly disturbing the colon and rectum. Clinically, the aminosalicylates, steroids, immunosuppressants, and biological drugs are generally used for the treatment of ulcerative colitis at different stages of disease progression. However, the therapeutic efficacy of these drugs does not satisfy the patients due to the frequent drug resistance. Herein, we reported the anti-ulcerative colitis activity of desmethylbellidifolin, a xanthone isolated from Gentianella acuta, in dextran sulfate sodium-induced colitis in mice. C57BL/6 mice were treated with 2% dextran sulfate sodium in drinking water to induce acute colitis. Desmethylbellidifolin or balsalazide sodium was orally administrated once a day. Biological samples were collected for immunohistological analysis, intestinal barrier function evaluation, cytokine measurement, and gut microbiota analysis. The results revealed that desmethylbellidifolin alleviated colon shortening and body weight loss in dextran sulfate sodium-induced mice. The disease activity index was also lowered by desmethylbellidifolin after 9 days of treatment. Furthermore, desmethylbellidifolin remarkably ameliorated colonic inflammation through suppressing the expression of interleukin-6 and tumor necrosis factor-α. The intestinal epithelial barrier was strengthened by desmethylbellidifolin through increasing levels of occludin, ZO-1, and claudins. In addition, desmethylbellidifolin modulated the gut dysbiosis induced by dextran sulfate sodium. These findings suggested that desmethylbellidifolin effectively improved experimental ulcerative colitis, at least partly, through maintaining intestinal barrier integrity, inhibiting proinflammatory cytokines, and modulating dysregulated gut microbiota.


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