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Wang H, Zhou F, Shen M, Ma R, Yu Q. Classification of Nanomaterial Drug Delivery Systems for Inflammatory Bowel Disease. Int J Nanomedicine 2025; 20:1383-1399. [PMID: 39925683 PMCID: PMC11804237 DOI: 10.2147/ijn.s502546] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Accepted: 01/16/2025] [Indexed: 02/11/2025] Open
Abstract
Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, primarily arises from defects in the colonic barrier, imbalances of the gut microbiota, and immune response issues. These complex causes make it difficult to achieve a complete cure. Patients with IBD frequently experience recurrent abdominal pain and bloody diarrhea, while severe cases may result in intestinal obstruction, perforation, and cancer. Lifelong maintenance therapy may thus be needed to manage these symptoms; however, traditional IBD drugs, such as 5-aminosalicylic acid, glucocorticoids, immunosuppressants, and biological agents, are often associated with problems including poor solubility, instability, and ineffective targeting, as well as causing serious side effects in non-target tissues. Nanomaterial drug delivery systems (NDDS) have recently shown great promise in optimizing drug distribution, solubility through biocompatible coatings, enhancing bioavailability via PEGylation and reducing side effects. These formulations can enhance a drug's pharmacokinetics by modifying its properties, improve its ability to cross barriers, and boost bioavailability. In addition, NDDS can enable targeted delivery, increase local drug concentrations, improve efficacy, and reduce side effects, as well as protecting active drug molecules from immune recognition and protease degradation. The clinical use of these systems for treating IBD, however, requires further research. This review summarizes the classification of NDDS for IBD, and concludes that, despite ongoing challenges, NDDS may represent an effective treatment approach for IBD. In summary, NDDS enhance the targeted delivery of therapeutic agents to specific cells or tissues, thereby improving drug bioavailability and therapeutic efficacy. These systems effectively surmount biological barriers, facilitating efficient drug delivery to targeted sites, which is crucial for attaining optimal therapeutic outcomes. This review contributes to a deeper understanding of how the physicochemical properties of NDDS influence pharmacological behavior in vivo and can expedite their clinical translation.
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Affiliation(s)
- Haichen Wang
- Department of Gastroenterology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, 215002, People’s Republic of China
| | - Feifei Zhou
- Department of Gastroenterology, Suzhou City Wuzhong District Chengnan Street Community Health Service Center, Suzhou, Jiangsu, 215002, People’s Republic of China
| | - Mengdan Shen
- Department of Gastroenterology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, 215002, People’s Republic of China
| | - Ronglin Ma
- Department of Gastroenterology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, 215002, People’s Republic of China
| | - Qiang Yu
- Department of Gastroenterology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, 215002, People’s Republic of China
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Ioannidis O, Cheva A, Varnalidis I, Koutelidakis I, Papaziogas V, Christidis P, Anestiadou E, Aggelopoulos K, Mantzoros I, Pramateftakis MG, Kotidis E, Driagka B, Aggelopoulos S, Giamarellos-Bourboulis EJ. The Combined Administration of Eicosapentaenoic Acid (EPA) and Gamma-Linolenic Acid (GLA) in Experimentally Induced Colitis: An Experimental Study in Rats. J Clin Med 2024; 13:6661. [PMID: 39597805 PMCID: PMC11594508 DOI: 10.3390/jcm13226661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Revised: 10/11/2024] [Accepted: 10/18/2024] [Indexed: 11/29/2024] Open
Abstract
Background/Objectives: Ulcerative colitis (UC) is a chronic inflammatory bowel disease with limited effective treatments, prompting the need for investigation of novel therapeutic approaches. Eicosapentaenoic acid (EPA) and gamma-linolenic acid (GLA) have demonstrated potential anti-inflammatory properties, but their combined effects on UC have not been thoroughly investigated. This study aimed to evaluate the effect of the combined administration of EPA and GLA on clinical and histopathologic features of experimental UC models. Methods: Thirty-six male Wistar rats were randomized in three groups (DSS group, Ensure Plus group, and Oxepa group), with twelve rats in each group. Experimental colitis was induced by administrating dextran sulfate sodium (DSS) 8%. The DSS group received tap water, the Ensure Plus group was given a high caloric diet, and the Oxepa group received a special diet containing high levels of EPA and GLA. Disease activity index (DAI) and microscopic activity index (MAI) were measured. Inflammatory markers were calculated both in blood and large intestine, liver, spleen, and lung tissue samples. Neutrophil and macrophage populations were assessed with immunohistochemistry. Results: No significant differences in the DAI index were found between the groups, but the MAI revealed statistically significant differences (p < 0.001). While no significant differences were observed in tumor necrosis factor-alpha (TNF-α) levels, interleukin-17 (IL-17) levels in the large intestine showed statistically significant differences (p = 0.05), with the Ensure Plus and Oxepa groups displaying lower levels compared to the DSS group (p = 0.021 and p = 0.043, respectively). Significant differences in neutrophil infiltration were found in both the large intestine (p < 0.001) and lungs (p = 0.002), with the Oxepa group showing fewer cells. Similarly, significant differences in macrophage infiltration were observed in the large intestine (p = 0.038) and spleen (p < 0.001), with the Oxepa group having lower macrophage counts. Conclusions: In conclusion, the combination of EPA and GLA demonstrates local anti-inflammatory effects and improves the histopathological outcomes in UC.
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Affiliation(s)
- Orestis Ioannidis
- 4th Department of Surgery, General Hospital “George Papanikolaou”, Aristotle University of Thessaloniki, 57010 Exochi, Greece; (I.V.); (P.C.); (E.A.); (K.A.); (I.M.); (M.G.P.); (E.K.); (B.D.); (S.A.)
| | - Angeliki Cheva
- Pathology Department, Faculty of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece;
| | - Ioannis Varnalidis
- 4th Department of Surgery, General Hospital “George Papanikolaou”, Aristotle University of Thessaloniki, 57010 Exochi, Greece; (I.V.); (P.C.); (E.A.); (K.A.); (I.M.); (M.G.P.); (E.K.); (B.D.); (S.A.)
| | - Ioannis Koutelidakis
- 2nd Department of Surgery, G.Gennimatas General Hospital, Aristotle University of Thessaloniki, 54635 Thessaloniki, Greece; (I.K.); (V.P.)
| | - Vasileios Papaziogas
- 2nd Department of Surgery, G.Gennimatas General Hospital, Aristotle University of Thessaloniki, 54635 Thessaloniki, Greece; (I.K.); (V.P.)
| | - Panagiotis Christidis
- 4th Department of Surgery, General Hospital “George Papanikolaou”, Aristotle University of Thessaloniki, 57010 Exochi, Greece; (I.V.); (P.C.); (E.A.); (K.A.); (I.M.); (M.G.P.); (E.K.); (B.D.); (S.A.)
| | - Elissavet Anestiadou
- 4th Department of Surgery, General Hospital “George Papanikolaou”, Aristotle University of Thessaloniki, 57010 Exochi, Greece; (I.V.); (P.C.); (E.A.); (K.A.); (I.M.); (M.G.P.); (E.K.); (B.D.); (S.A.)
| | - Konstantinos Aggelopoulos
- 4th Department of Surgery, General Hospital “George Papanikolaou”, Aristotle University of Thessaloniki, 57010 Exochi, Greece; (I.V.); (P.C.); (E.A.); (K.A.); (I.M.); (M.G.P.); (E.K.); (B.D.); (S.A.)
| | - Ioannis Mantzoros
- 4th Department of Surgery, General Hospital “George Papanikolaou”, Aristotle University of Thessaloniki, 57010 Exochi, Greece; (I.V.); (P.C.); (E.A.); (K.A.); (I.M.); (M.G.P.); (E.K.); (B.D.); (S.A.)
| | - Manousos George Pramateftakis
- 4th Department of Surgery, General Hospital “George Papanikolaou”, Aristotle University of Thessaloniki, 57010 Exochi, Greece; (I.V.); (P.C.); (E.A.); (K.A.); (I.M.); (M.G.P.); (E.K.); (B.D.); (S.A.)
| | - Efstathios Kotidis
- 4th Department of Surgery, General Hospital “George Papanikolaou”, Aristotle University of Thessaloniki, 57010 Exochi, Greece; (I.V.); (P.C.); (E.A.); (K.A.); (I.M.); (M.G.P.); (E.K.); (B.D.); (S.A.)
| | - Barbara Driagka
- 4th Department of Surgery, General Hospital “George Papanikolaou”, Aristotle University of Thessaloniki, 57010 Exochi, Greece; (I.V.); (P.C.); (E.A.); (K.A.); (I.M.); (M.G.P.); (E.K.); (B.D.); (S.A.)
| | - Stamatios Aggelopoulos
- 4th Department of Surgery, General Hospital “George Papanikolaou”, Aristotle University of Thessaloniki, 57010 Exochi, Greece; (I.V.); (P.C.); (E.A.); (K.A.); (I.M.); (M.G.P.); (E.K.); (B.D.); (S.A.)
| | - Evangelos J. Giamarellos-Bourboulis
- 4th Department of Internal Medicine, National and Kapodistrian University of Athens Medical School, “Attikon” Hospital, 12462 Athens, Greece;
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Zou X, Lu RL, Liao B, Liu SJ, Dai SX. Causal relationship between asthma and ulcerative colitis and the mediating role of interleukin-18: a bidirectional Mendelian study and mediation analysis. Front Immunol 2023; 14:1293511. [PMID: 38162651 PMCID: PMC10757619 DOI: 10.3389/fimmu.2023.1293511] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2023] [Accepted: 11/30/2023] [Indexed: 01/03/2024] Open
Abstract
Objective Numerous observational investigations have documented a correlation between asthma and ulcerative colitis(UC). In this Mendelian Randomization (MR) study, we utilized extensive summary data from Genome-Wide Association Studies (GWAS) to further estimate the association between adult-onset asthma and the risk of UC, and to investigate the role of Interleukin-18 (IL-18) as a potential mediator. Materials and methods A two-step, two-sample MR study was conducted through mediation analysis. For this study, we employed a two-sample MR analysis using the inverse variance-weighted (IVW), weighted median, weighted mode, and MR-Egger regression techniques. We utilized publicly accessible summary statistics from a GWAS meta-analysis of adult-onset asthma in the UK Biobank (n=327,253; cases=26,582; controls=300,671) as the exposure factor. The outcomes were derived from GWAS data of individuals with European ancestry (n=26,405; cases=6,687; controls=19,718). GWAS data for IL-18 were obtained from individuals of European ancestry (n=9,785,222; cases=3,636; controls=9,781,586). Results The MR analysis indicates that adult-onset asthma is associated with an increased risk of UC, with an odds ratio (OR) of 1.019 (95% CI 1.001-1.045, P=0.006). However, there is no strong evidence to suggest that UC significantly impacts the risk of adult-onset asthma. IL-18 may act as a potential mediator in the causal relationship between adult-onset asthma and UC, with a mediation proportion of 3.9% (95% CI, 0.6%-6.9%). Conclusion In summary, our study established a causal relationship between asthma and UC, in which IL-18 contributes to a small extent. However, the primary factors underlying the influence of asthma on UC remain unclear. Future research should focus on identifying other potential mediators. In clinical practice, it is important to pay greater attention to intestinal lesions in patients with asthma.
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Affiliation(s)
- Xin Zou
- Department of Gastroenterology, Ganzhou Municipal Hospital(Guangdong Provincial People’s Hospital Ganzhou Hospital), Ganzhou, Jiangxi, China
| | - Rui-Ling Lu
- Department of Gastroenterology, Ganzhou Municipal Hospital(Guangdong Provincial People’s Hospital Ganzhou Hospital), Ganzhou, Jiangxi, China
- Department of Rheumatology and Immunology, The Second Clinical Medical College, Jinan University (Shenzhen People’s Hospital), Shenzhen, Guangdong, China
| | - Bin Liao
- Department of Gastroenterology, Ganzhou Municipal Hospital(Guangdong Provincial People’s Hospital Ganzhou Hospital), Ganzhou, Jiangxi, China
| | - Shi-Jie Liu
- Department of Gastroenterology, Geriatric Center, National Regional Medical Center, Guangdong Provincial People’s Hospital Ganzhou Hospital, Ganzhou, Jiangxi, China
| | - Shi-Xue Dai
- Department of Gastroenterology, Geriatric Center, National Regional Medical Center, Guangdong Provincial People’s Hospital Ganzhou Hospital, Ganzhou, Jiangxi, China
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Choi SI, Shin YC, Lee JS, Yoon YC, Kim JM, Sung MK. N-Acetylglucosamine and its dimer ameliorate inflammation in murine colitis by strengthening the gut barrier function. Food Funct 2023; 14:8533-8544. [PMID: 37655824 DOI: 10.1039/d3fo00282a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/02/2023]
Abstract
Ulcerative colitis (UC) is a chronic gastrointestinal disease whose incidence is increasing rapidly worldwide. Anti-inflammatory medications, including 5-aminosalicylic acid (5-ASA), corticosteroids, and immunosuppressants, are used for its treatment; however, new alternatives would be required due to the serious side effects of some of these medications. N-Acetylglucosamine (NAG) is an amino sugar composed of mucin that is secreted by intestinal epithelial cells. It is also used to promote the growth of intestinal bacteria. The current study aimed to determine the efficacy of NAG against dextran sulfate sodium (DSS)-induced chronic colitis and elucidate its mechanism of action. Mice were randomly divided into control, DSS, 0.1% sulfasalazine, 0.1% NAG, 0.3% NAG, and 0.3% NAG-dimer (NAG-D) groups, and results showed that colitis-induced body weight loss, disease activity, colonic tissue damage, colon length shortening, and the loss of mucin-secreting area were significantly improved in the NAG-D group. The intestinal permeability indicator, serum CD 14 level, and expression of the tight junction protein, occludin, were both improved in the 0.3% NAG group. Inflammatory biomarkers, including GATA3, IFN-γ, p-IκBα, COX2, TGF-β1, and Smad7, were significantly lower in the 0.3% NAG and NAG-D groups than in the DSS group. The intestinal microbial composition was most significantly altered in the 0.3% NAG group, showing decreased ratios of pathogenic bacteria, such as Betaproteobacteria, especially Burkholderiales. The results overall suggested that NAG or NAG-D supplementation can alleviate inflammation by strengthening the intestinal barrier function and maintaining gut microbiota homeostasis in a DSS-induced colitis mouse model.
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Affiliation(s)
- Sung-In Choi
- Department of Food and Nutrition, College of Human Ecology, Sookmyung Women's University, Chungpa-ro 47-gil 100, Yongsan-gu, Seoul 04310, Republic of Korea.
| | | | - Joong Su Lee
- Amicogen Inc., Jinju-si 52621, Republic of Korea
| | - Yeo Cho Yoon
- Amicogen Inc., Jinju-si 52621, Republic of Korea
| | - Ju Myung Kim
- Amicogen Inc., Jinju-si 52621, Republic of Korea
| | - Mi-Kyung Sung
- Department of Food and Nutrition, College of Human Ecology, Sookmyung Women's University, Chungpa-ro 47-gil 100, Yongsan-gu, Seoul 04310, Republic of Korea.
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Zhou Y, Ji G, Yang X, Chen Z, Zhou L. Behavioral abnormalities in C57BL/6 mice with chronic ulcerative colitis induced by DSS. BMC Gastroenterol 2023; 23:84. [PMID: 36959628 PMCID: PMC10037843 DOI: 10.1186/s12876-023-02718-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2022] [Accepted: 03/13/2023] [Indexed: 03/25/2023] Open
Abstract
BACKGROUND Clinical epidemiological studies have found that some patients with ulcerative colitis (UC) are prone to mental disorders. DSS-induced acute and chronic UC models are often used to evaluate the efficacy of anti-UC drugs. However, whether DSS has an effect on mouse behavior has not been reported. METHODS Acute and chronic UC models were induced by 3% DSS and 1.5% DSS, respectively. The bloody stool, the changes in the colon length, and histopathological changes in the colon were used to evaluate the success of the animal model. The behavior of mice was evaluated by open field experiment, tail suspension experiment and Sucrose preference test. RESULTS The weight of mice in 3% DSS group decreased significantly, the DAI score increased significantly, the colon length of mice was significantly shortened, and the structure of colonic crypts was abnormal, which showed inflammatory cell infiltration and shrinkage of crypts. Compared with the control group, the immobility time of 3%DSS group mice in the tail suspension test and forced swimming test had no effect, the number of running and grooming times was significantly reduced, and there was no significant difference in the number of standing times. No abnormality was observed in HE staining of the hippocampus. However, in 1.5% DSS-induced chronic UC model, behavioral and hippocampal abnormalities were observed not only UC symptoms. CONCLUSIONS The acute UC model induced by 3% DSS has certain influence on the behavior of mice, but the mental state of mice is normal, which may be the abnormal behavior caused by UC symptoms; However, the chronic UC model induced by 1.5% DSS has a significant effect on the behavior of mice, and the mice have mental disorders, which are caused by mental disorders.
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Affiliation(s)
- Yuxin Zhou
- School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang, 330013, PR China
| | - Gang Ji
- School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang, 330013, PR China
| | - Xiaoyi Yang
- School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang, 330013, PR China
| | - Zhenhua Chen
- School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang, 330013, PR China.
| | - Liangliang Zhou
- School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang, 330013, PR China.
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Elgalil Mohamed Ahmed A, Attia MA, Abd-Elaziz MEE, Abd Ellatif R. Histological study of the effect of quercetin on experimentally induced ulcerative colitis in adult male albino rats. TANTA MEDICAL JOURNAL 2022; 50:285. [DOI: 10.4103/tmj.tmj_101_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/01/2023]
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Ding S, Yan W, Fang J, Jiang H, Liu G. Potential role of Lactobacillus plantarum in colitis induced by dextran sulfate sodium through altering gut microbiota and host metabolism in murine model. SCIENCE CHINA-LIFE SCIENCES 2021; 64:1906-1916. [DOI: 10.1007/s11427-020-1835-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Accepted: 09/28/2020] [Indexed: 02/06/2023]
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Li X, Lu C, Yang Y, Yu C, Rao Y. Site-specific targeted drug delivery systems for the treatment of inflammatory bowel disease. Biomed Pharmacother 2020; 129:110486. [PMID: 32768972 DOI: 10.1016/j.biopha.2020.110486] [Citation(s) in RCA: 64] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Revised: 06/30/2020] [Accepted: 06/30/2020] [Indexed: 12/14/2022] Open
Abstract
Inflammatory bowel disease (IBD) includes Crohn's disease and ulcerative colitis and manifests as a complex and dysregulated immune response. To date, there is no cure for IBD; thus, lifelong administration of maintenance drugs is often necessary. Since conventional IBD treatment strategies do not target the sites of inflammation, only limited efficacy is observed with their use. Moreover, the possibility of severe side effects resulting from systemic drug redistribution is high when conventional drug treatments are used. Therefore, a straightforward disease-targeted drug delivery system is desirable. Based on the pathophysiological changes associated with IBD, novel site-specific targeted drug delivery strategies that deliver drugs directly to the inflammation sites can enhance drug accumulation and decrease side effects. This review summarizes novel inflammation targeted delivery systems in the management of IBD. It also discusses the challenges and new perspectives in this field.
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Affiliation(s)
- Xin Li
- Department of Pharmacology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Chao Lu
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Yanyan Yang
- Department of Pharmacology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Chaohui Yu
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.
| | - Yuefeng Rao
- Department of Pharmacology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.
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Xu X, Lin S, Yang Y, Gong X, Tong J, Li K, Li Y. Histological and ultrastructural changes of the colon in dextran sodium sulfate-induced mouse colitis. Exp Ther Med 2020; 20:1987-1994. [PMID: 32782508 PMCID: PMC7401218 DOI: 10.3892/etm.2020.8946] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2019] [Accepted: 04/24/2020] [Indexed: 12/13/2022] Open
Abstract
Ulcerative colitis (UC) is a complex disease that results from a dysregulated immune response in the gastrointestinal tract. A mouse model orally administered with dextran sodium sulfate (DSS) is the most widely used experimental animal model of UC. However, the ultrastructure of the colon in mouse colitis is poorly understood. In the present study, colonic specimens from DSS-induced UC mice underwent hematoxylin and eosin staining, Masson's trichrome staining and Verhoeff's elastic staining. In addition, the ultrastructure of samples was examined by transmission electron microscopy. UC was successfully induced by 7 consecutive days of DSS oral administration. The goblet cell architecture of the UC tissue was damaged in the mucosa. Additionally, a significant number of inflammatory cells infiltrated into the stroma and the structure of the intestinal gland was destroyed. The tissue in the submucosa showed significant edema. Hyperplasia was also identified in the submucosa, promoting a disorganized microstructure within the colon wall. Numerous collagen fibers in the muscular layer were disrupted, and the fiber bundles were thinner compared with those in the normal control group. Furthermore, in the DSS-induced UC group, the smooth muscle cell showed edema, the cell membrane structure was unclear and the shape of the nucleus was irregular. In conclusion, the present study revealed important histological and ultrastructural changes in the colon of DSS-induced UC mice. These features may contribute to improved understanding of the pathogenesis and mechanism of UC.
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Affiliation(s)
- Xiaojuan Xu
- Department of Pathology and Pathophysiology, Tongji University School of Medicine, Shanghai 200092, P.R. China.,Key Laboratory of Arrhythmias of the Ministry of Education of China, Shanghai East Hospital, Shanghai 200120, P.R. China
| | - Sisi Lin
- Department of Pathology and Pathophysiology, Tongji University School of Medicine, Shanghai 200092, P.R. China
| | - Yanhua Yang
- Department of Pathology, Qingdao Municipal Hospital, Qingdao, Shandong 266011, P.R. China
| | - Xiaohui Gong
- Key Laboratory of Arrhythmias of the Ministry of Education of China, Shanghai East Hospital, Shanghai 200120, P.R. China
| | - Jianhua Tong
- Shanghai East Hospital, Institute for Biomedical Engineering and Nano Science, Tongji University School of Medicine, Shanghai 200092, P.R. China
| | - Kun Li
- Department of Pathology and Pathophysiology, Tongji University School of Medicine, Shanghai 200092, P.R. China
| | - Yongyu Li
- Department of Pathology and Pathophysiology, Tongji University School of Medicine, Shanghai 200092, P.R. China
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Lenti MV, Cococcia S, Ghorayeb J, Di Sabatino A, Selinger CP. Stigmatisation and resilience in inflammatory bowel disease. Intern Emerg Med 2020; 15:211-223. [PMID: 31893346 PMCID: PMC7054377 DOI: 10.1007/s11739-019-02268-0] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2019] [Accepted: 12/18/2019] [Indexed: 12/16/2022]
Abstract
Inflammatory bowel disease, which includes Crohn's disease and ulcerative colitis, is an immune-mediated, chronic relapsing disorder characterised by severe gastrointestinal symptoms that dramatically impair patients' quality of life, affecting psychological, physical, sexual, and social functions. As a consequence, patients suffering from this condition may perceive social stigmatisation, which is the identification of negative attributes that distinguish a person as different and worthy of separation from the group. Stigmatisation has been widely studied in different chronic conditions, especially in mental illnesses and HIV-infected patients. There is a growing interest also for patients with inflammatory bowel disease, in which the possibility of disease flare and surgery-related issues seem to be the most important factors determining stigmatisation. Conversely, resilience represents the quality that allows one to adopt a positive attitude and good adjustments despite adverse life events. Likewise, resilience has been studied in different populations, age groups, and chronic conditions, especially mental illnesses and cancer, but little is known about this issue in patients with inflammatory bowel disease, even if this could be an interesting area of research. Resilience can be strengthened through dedicated interventions that could potentially improve the ability to cope with the disease. In this paper, we focus on the current knowledge of stigmatisation and resilience in patients with inflammatory bowel disease.
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Affiliation(s)
- Marco Vincenzo Lenti
- First Department of Internal Medicine, San Matteo Hospital Foundation, University of Pavia, Pavia, Italy
| | - Sara Cococcia
- First Department of Internal Medicine, San Matteo Hospital Foundation, University of Pavia, Pavia, Italy
| | | | - Antonio Di Sabatino
- First Department of Internal Medicine, San Matteo Hospital Foundation, University of Pavia, Pavia, Italy
| | - Christian P Selinger
- Leeds Gastroenterology Institute, Leeds Teaching Hospitals NHS Trust, Beckett Lane, Leeds, LS9 7TF, UK.
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Ma Q, Ouyang Y, Meng F, Noolvi MN, Avvaru SP, More UA, Aminabhavi TM, Du M, Liu H, Zhuang Y, Pang M, Cai T, Cai Y. A review of pharmacological and clinical studies on the application of Shenling Baizhu San in treatment of Ulcerative colitis. JOURNAL OF ETHNOPHARMACOLOGY 2019; 244:112105. [PMID: 31344480 DOI: 10.1016/j.jep.2019.112105] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/08/2019] [Revised: 07/18/2019] [Accepted: 07/20/2019] [Indexed: 06/10/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE The prescription of Shenling Baizhu San (SLBZS) was derived from the Song Dynasty "Taiping Huimin Heji Ju Fang", which was a representative prescription for treating spleen asthenic diarrhea. The prescription comprised of 10 herbs for treating weak spleen and stomach. It describes symptoms like eating less, loose stools, cough, shortness of breath and tired limbs. SLBZS has been reported to be capable of eliminating discomfort when it is administered for treating irritable bowel syndrome and diarrhea. This traditional Chinese medicine (TCM) formula has been widely used for improving gastrointestinal dysfunction and modifying the immune response to inflammation. AIM OF THE STUDY This review is aimed to provide the up-to-date information on the pharmacology and clinical research of SLBZS in the treatment of ulcerative colitis (UC), and to discuss the research findings and possible deficiencies, hoping to better guide the clinical application and scientific research of SLBZS in the treatment of UC. MATERIALS AND METHODS Relevant studies from 2004 to 2018 on SLBZS in the treatment of UC mechanism and curative effect were collected from ancient books, pharmacopoeia, reports, thesis via library and Digital databases (PubMed, CNKI, Google Scholar, Web of Science, SciFinder, Springer, Elsevier, etc). RESULTS SLBZS could regulate inflammatory factors and intestinal flora, and ERK/p38 MAPK signaling pathway may be one of its targets. In addition, clinical research results show that SLBZS has a good therapeutic effect on UC, and the adverse reactions are small. CONCLUSION Although SLBZS has achieved some success in the treatment of UC, there are still some scientific gaps. There is a lack of uniform standards for constructing UC animal models, and some methods of modeling through environmental and dietary interventions are not reproducible, and there is a lack of uniform dosing regimen standards. SLBZS doses follow the tradition and lack toxicological validation. Therefore, more specific toxicological research models are essential. The clinical application of SLBZS requires reassessment and standardization. Although all clinical research reports randomly assigned patients to different groups, most did not describe a detailed method of randomization and no description of the analysis data. In addition, extensive in vitro studies and further in-depth molecular studies are essential for the determination of mechanisms that have been performed in all in vivo experiments on animal models and patients.
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Affiliation(s)
- Qianqian Ma
- College of Pharmacy, Jinan University, Guangzhou, 510632, China
| | - Yong Ouyang
- Guangzhou Hospital of Integrated Traditional Chinese and Western Medicine, Guangzhou, 510800, China
| | - Fansu Meng
- Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of TCM, Zhongshan, Guangdong, 528400, China
| | | | - Stephen Paul Avvaru
- Gujarat Technological University, Chandkheda, Ahmedabad, Gujarat, 382424, India
| | - Uttam A More
- Shree Dhanvantary Pharmacy College, Kim, Surat, Gujarat, 394110, India
| | | | - Manling Du
- College of Pharmacy, Jinan University, Guangzhou, 510632, China
| | - Hui Liu
- College of Pharmacy, Jinan University, Guangzhou, 510632, China
| | - Yong Zhuang
- College of Pharmacy, Jinan University, Guangzhou, 510632, China
| | - Mujuan Pang
- College of Pharmacy, Jinan University, Guangzhou, 510632, China
| | - Tiange Cai
- College of Life Sciences, Liaoning University, Shenyangm, 110036, China.
| | - Yu Cai
- College of Pharmacy, Jinan University, Guangzhou, 510632, China; Cancer Research Institute of Jinan University, Guangzhou, 510632, China; International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), School of Pharmacy, Jinan University, Guangzhou, 510632, China.
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Busti F, Marchi G, Girelli D. Iron replacement in inflammatory bowel diseases: an evolving scenario. Intern Emerg Med 2019; 14:349-351. [PMID: 30721398 DOI: 10.1007/s11739-019-02043-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2019] [Accepted: 01/29/2019] [Indexed: 12/23/2022]
Affiliation(s)
- Fabiana Busti
- Department of Medicine, Section of Internal Medicine, University of Verona, EuroBloodNet Referral Center for Iron Metabolism Disorders, Azienda Ospedaliera Universitaria Integrata Verona, 37138, Verona, Italy
| | - Giacomo Marchi
- Department of Medicine, Section of Internal Medicine, University of Verona, EuroBloodNet Referral Center for Iron Metabolism Disorders, Azienda Ospedaliera Universitaria Integrata Verona, 37138, Verona, Italy
| | - Domenico Girelli
- Department of Medicine, Section of Internal Medicine, University of Verona, EuroBloodNet Referral Center for Iron Metabolism Disorders, Azienda Ospedaliera Universitaria Integrata Verona, 37138, Verona, Italy.
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13
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Chen Y, Zhang M, Ren F. A Role of Exopolysaccharide Produced by Streptococcus thermophilus in the Intestinal Inflammation and Mucosal Barrier in Caco-2 Monolayer and Dextran Sulphate Sodium-Induced Experimental Murine Colitis. Molecules 2019; 24:molecules24030513. [PMID: 30708992 PMCID: PMC6384629 DOI: 10.3390/molecules24030513] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2018] [Revised: 01/29/2019] [Accepted: 01/30/2019] [Indexed: 12/17/2022] Open
Abstract
Exopolysaccharide (EPS) produced by probiotics may play an important role in gastrointestinal disease prevention, including ulcerative colitis. However, there is no literature reporting on the intervention effects of purified EPS. The aim of this study was to investigate the alleviating effect of the purified EPS produced by Streptococcus thermophilus MN-BM-A01 on murine model of colitis induced by dextran sulphate sodium (DSS). A water-soluble heteropolysaccharide (EPS-1) isolated from MN-BM-A01 was composed of rhamnose, glucose, galactose, and mannose in a molar ratio of 12.9:26.0:60.9:0.25, with molecular weight of 4.23 × 105 Da. After EPS-1 administration, the disease severity of mouse colitis was significantly alleviated, mainly manifesting as the decrease of disease activity index and mitigated colonic epithelial cell injury. Meanwhile, pro-inflammatory cytokines levels (tumor necrosis factor-α, interleukin-6, and interferon-γ) were significantly suppressed, the reduced expressions of tight junction protein (claudin-1, occludin, and E-canherin) were counteracted. In addition, the results in vitro showed that EPS-1 protected intestinal barrier integrity from the disruption by lipopolysaccharide in Caco-2 monolayer, increased expression of tight junction and alleviated pro-inflammatory response. Collectively, our study confirmed the protective effects of purified EPS produced by Streptococcus thermophilus on acute colitis via alleviating intestinal inflammation and improving mucosal barrier function.
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Affiliation(s)
- Yun Chen
- Key Laboratory of Functional Dairy, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China.
| | - Ming Zhang
- School of Food and Chemical Engineering, Beijing Technology and Business University, Beijing 100048, China.
| | - Fazheng Ren
- Key Laboratory of Functional Dairy, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China.
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Advances in Pharmaceutical Strategies Enhancing the Efficiencies of Oral Colon-Targeted Delivery Systems in Inflammatory Bowel Disease. Molecules 2018; 23:molecules23071622. [PMID: 29973488 PMCID: PMC6099616 DOI: 10.3390/molecules23071622] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2018] [Revised: 06/25/2018] [Accepted: 06/28/2018] [Indexed: 12/15/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a common disease characterized by chronic inflammation in gastrointestinal tracts, which is primarily treated by administering anti-inflammatory and immunosuppressive drugs that inhibit the burden of intestinal inflammation and improve disease-related symptoms. However, the established therapeutic strategy has limited therapeutic efficacy and adverse drug reactions. Therefore, new disease-targeting drug-delivery strategies to develop more effective treatments are urgent. This review provides an overview of the drug-targeting strategies that can be used to treat IBD, and our recent attempts on the colon-specific delivery system (Pae-SME-CSC) with a paeonol-loaded self-microemulsion (Pae-SMEDDS) are introduced.
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15
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Gong X, Xu X, Lin S, Cheng Y, Tong J, Li Y. Alterations in biomechanical properties and microstructure of colon wall in early-stage experimental colitis. Exp Ther Med 2017; 14:995-1000. [PMID: 28810551 PMCID: PMC5526050 DOI: 10.3892/etm.2017.4607] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2016] [Accepted: 04/07/2017] [Indexed: 12/18/2022] Open
Abstract
The aim of the current study was to investigate the effects of early-stage dextran sodium sulfate (DSS)-induced mouse colitis on the biomechanical properties and microstructure of colon walls. In the present study, colitis was induced in 8-week-old mice by the oral administration of DSS, and then 10 control and 10 experimental colitis samples were harvested. Uniaxial tensile tests were performed to measure the ultimate tensile strength and ultimate stretches of colon tissues. In addition, histological investigations were performed to characterize changes in the microstructure of the colon wall following treatment. The results revealed that the ultimate tensile stresses were 232±33 and 183±25 kPa for the control and DSS groups, respectively (P=0.001). Ultimate stretches at rupture for the control and DSS groups were 1.43±0.04 and 1.51±0.06, respectively (P=0.006). However, there was no statistically significant difference in tissue stiffness between the two groups. Histological analysis demonstrated high numbers of inflammatory cells infiltrated into the stroma in the DSS group, leading to significant submucosa edema. Hyperplasia was also identified in the DSS-treated submucosa, causing a disorganized microstructure within the colon wall. Furthermore, a large number of collagen fibers in the DSS-treated muscular layer were disrupted, and fiber bundles were thinner when compared with the control group. In conclusion, early-stage experimental colitis alters the mechanical properties and microstructural characteristics of the colon walls, further contributing to tissue remodeling in the pathological process.
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Affiliation(s)
- Xiaohui Gong
- Key Laboratory of Arrhythmias of the Ministry of Education of China, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200092, P.R. China.,Department of PathoPhysiology, Institute of Digestive Disease, Tongji University School of Medicine, Shanghai 200092, P.R. China
| | - Xiaojuan Xu
- Key Laboratory of Arrhythmias of the Ministry of Education of China, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200092, P.R. China.,Department of PathoPhysiology, Institute of Digestive Disease, Tongji University School of Medicine, Shanghai 200092, P.R. China
| | - Sisi Lin
- Department of PathoPhysiology, Institute of Digestive Disease, Tongji University School of Medicine, Shanghai 200092, P.R. China
| | - Yu Cheng
- Shanghai East Hospital, Institute for Biomedical Engineering and Nano Science, Tongji University School of Medicine, Shanghai 200092, P.R. China
| | - Jianhua Tong
- Shanghai East Hospital, Institute for Biomedical Engineering and Nano Science, Tongji University School of Medicine, Shanghai 200092, P.R. China
| | - Yongyu Li
- Department of PathoPhysiology, Institute of Digestive Disease, Tongji University School of Medicine, Shanghai 200092, P.R. China
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Zong SY, Pu YQ, Xu BL, Zhang T, Wang B. Study on the physicochemical properties and anti-inflammatory effects of paeonol in rats with TNBS-induced ulcerative colitis. Int Immunopharmacol 2016; 42:32-38. [PMID: 27863299 DOI: 10.1016/j.intimp.2016.11.010] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2016] [Revised: 10/18/2016] [Accepted: 11/11/2016] [Indexed: 12/13/2022]
Abstract
Paeonol, an active component from Paeonia suffruticosa Andr., has a variety of biological activities, such as vascular endothelial cell protection, anti-oxidation, and anti-inflammation. The aim of this study was to investigate the basic physicochemical properties of paeonol, including solubility, oil-water partition coefficient, and permeability. Then evaluated the anti-inflammatory effects of paeonol were evaluated on 2,4,6-trinitrobenzenesulfonic acid-induced ulcerative colitis in rats. The rats were divided randomly into 6 groups, namely, normal, model, paeonol-treated (100, 200, and 400mg/kg), and positive. Each group had 10 rats. Inhibition effects were evaluated by the disease activity index (DAI), colon weight/length ratio, as well as macroscopical and histological evaluations. Serum interleukin (IL)-17, IL-6 and transforming growth factor beta 1 (TGF-β1) levels were determined by enzyme-linked immunosorbent assay. The solubility and oil-water partition coefficient of paeonol in different phosphate buffer solutions were 284.06-598.23 and 461.97-981.17μg/mL, respectively. The effective passive permeability value Pe was 23.49×10-6cm/s. In terms of anti-inflammatory results, compared with the model group, treatment with 200 and 400mg/kg doses of paeonol had significantly decreased DAI, colon weight/length ratio, and macroscopic and histopathological scores. Furthermore, the serum levels of IL-17 and IL-6 were significantly reduced, whereas the TGF-β1 level was increased in the two paeonol-treated groups (medium- and high-dose group). Therefore, paeonol had poor water solubility, but oral absorption was good. In addition, paeonol had therapeutic effects on ulcerative colitis, and the therapeutic efficacy was dose dependent. The results presented in this study provide evidence for the development of a novel therapeutic agent in the treatment of UC. However, whether this agent could have therapeutic benefit or adverse effects in human IBD remains to be fully explored.
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Affiliation(s)
- Shi-Yu Zong
- Experiment Center for Teaching and Learning, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Pudong New District, Shanghai 201203, China; School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Pudong New District, Shanghai 201203, China.
| | - Yi-Qiong Pu
- Experiment Center for Teaching and Learning, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Pudong New District, Shanghai 201203, China.
| | - Ben-Liang Xu
- Experiment Center for Teaching and Learning, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Pudong New District, Shanghai 201203, China.
| | - Tong Zhang
- Experiment Center for Teaching and Learning, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Pudong New District, Shanghai 201203, China; School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Pudong New District, Shanghai 201203, China.
| | - Bing Wang
- Experiment Center for Teaching and Learning, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Pudong New District, Shanghai 201203, China; School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Pudong New District, Shanghai 201203, China.
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Hydroalcoholic Extract from Inflorescences of Achyrocline satureioides (Compositae) Ameliorates Dextran Sulphate Sodium-Induced Colitis in Mice by Attenuation in the Production of Inflammatory Cytokines and Oxidative Mediators. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2016; 2016:3475356. [PMID: 27847525 PMCID: PMC5099481 DOI: 10.1155/2016/3475356] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/15/2016] [Accepted: 09/21/2016] [Indexed: 12/29/2022]
Abstract
Achyrocline satureioides is a South American herb used to treat inflammatory and gastrointestinal diseases. This study evaluated intestinal anti-inflammatory effects of the hydroalcoholic extract of inflorescences of satureioides (HEAS) in dextran sulfate sodium (DSS) induced colitis in mice. Mice were orally treated with vehicle, 5-aminosalicylic acid (100 mg/kg), or HEAS (1–100 mg/kg). Clinical signs of colitis and colonic histopathological parameters were evaluated, along with the determination of levels of reduced glutathione and lipid hydroperoxide (LOOH), the superoxide dismutase (SOD), and myeloperoxidase (MPO) activity in colon. The colonic content of cytokines (TNF, IL-4, IL-6, and IL-10) was measured. Additionally, the effects of the extract on nitric oxide (NO) release by lipopolysaccharide (LPS) stimulated macrophages and diphenylpicrylhydrazyl levels were determined. Mucin levels and SOD activity, as well as the LOOH, MPO, TNF, and IL-6 accumulation in colon tissues, were normalized by the HEAS administration. In addition, the extract elicited an increase in IL-4 and IL-10 levels in colon. NO release by macrophages was inhibited by HEAS and its scavenger activity was confirmed. Together these results suggest that preparations obtained from inflorescences from A. satureioides could be used in treatment for IBD. Besides, this work corroborates the popular use of A. satureioides in inflammatory disorders.
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Liu WX, Wang Y, Sang LX, Zhang S, Wang T, Zhou F, Gu SZ. Chymase inhibitor TY-51469 in therapy of inflammatory bowel disease. World J Gastroenterol 2016; 22:1826-1833. [PMID: 26855541 PMCID: PMC4724613 DOI: 10.3748/wjg.v22.i5.1826] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2015] [Revised: 06/10/2015] [Accepted: 08/25/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the effect of chymase inhibitor TY-51469 in the therapy of inflammatory bowel disease and the underlying mechanism.
METHODS: Seventy-five healthy Sprague-Dawley rats were randomly assigned to one of the three groups (control group, model group and TY-51469 experiment group) and each group had twenty-five rats. The rats of the model group and experiment group were subjected to treatment with 3.5% dextran sulfate sodium (DSS) 10 mg/kg to induce colitis. The control group and model group were subjected to intraperitoneal injection of saline, while the experiment group was subjected to intraperitoneal injection of 10 mg/kg TY-51469 each day. Five rats of each group were sacrificed on 0, 7, 14, 21 and 28 d, respectively. The degree of inflammation was assessed by histopathological scoring; flow cytometry was performed to detect the proportion of CD4+CD25+ Tregs in peripheral blood; colon tissues of rats were collected to measure mRNA and protein expression by PCR, Western blot and immunohistochemistry; serum levels of interleukin (IL)-10, transforming growth factor (TGF)-β1 and IL-17A were detected by ELISA.
RESULTS: The rats in the experiment group and model group had significantly more severe colitis than the ones in the control group (P < 0.05) before treatment on day 0; no significant difference was observed between the experiment group and model group (P > 0.05). After treatment with TY-51469, the rats in the experiment group had significantly less severe colitis compared with the model group on 7, 14, 21 and 28 d (P < 0.05). The proportion of CD4+CD25+ Tregs was lower in the model group and experiment group than in the control group; the experiment group had a significantly higher proportion of CD4+CD25+ Tregs than that in the model group (P < 0.05). The model group and experiment group demonstrated lower expression of Foxp3 than the control group; the experiment group had higher Foxp3 expression than the model group (P < 0.05). Cytokines IL-10, TGF-β1 and IL-17A were lower in the model group and experiment group than in the control group; the experiment group had higher expression than the model group (P < 0.05).
CONCLUSION: After treatment with chymase inhibitor TY-51469, the experiment group demonstrated more significantly reduced intestinal inflammation and higher expression of immune tolerance related cytokines (IL-10, TGF-β1, IL-17A) and Foxp3 which is specifically expressed in Tregs compared with the model group. Therefore, chymase inhibitor TY-51469 might ameliorate the progression of DSS-induced colitis possibly by increasing the expression of Tregs and cytokines.
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New insights into immune mechanisms underlying autoimmune diseases of the gastrointestinal tract. Autoimmun Rev 2015; 14:1161-9. [PMID: 26275585 DOI: 10.1016/j.autrev.2015.08.004] [Citation(s) in RCA: 88] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2015] [Accepted: 08/05/2015] [Indexed: 02/07/2023]
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Prudhviraj G, Vaidya Y, Singh SK, Yadav AK, Kaur P, Gulati M, Gowthamarajan K. Effect of co-administration of probiotics with polysaccharide based colon targeted delivery systems to optimize site specific drug release. Eur J Pharm Biopharm 2015; 97:164-72. [DOI: 10.1016/j.ejpb.2015.09.012] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2015] [Revised: 09/17/2015] [Accepted: 09/22/2015] [Indexed: 12/21/2022]
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Abstract
OBJECTIVES Ulcerative colitis is an inflammatory bowel disease that rarely exists in isolation in affected patients. We examined the association of ulcerative colitis and International Classification of Diseases mental disorder, as well as the temporal comorbidity of three broad International Classification of Diseases groupings of mental disorders in patients with ulcerative colitis to determine if mental disorder is more likely to occur before or after ulcerative colitis. METHODS We used physician diagnoses from the regional health zone of Calgary, Alberta, for patient visits from fiscal years 1994 to 2009 for treatment of any presenting concern in that Calgary health zone (763,449 patients) to identify 5113 patients age younger than 1 year to age 92 years (2120 males, average age = 47 years; 2993 females, average age = 48 years) with a diagnosis of ulcerative colitis. RESULTS The 16-year cumulative prevalence of ulcerative colitis was 0.0058%, or 58 cases per 10,000 persons (95% confidence interval = 56-60 per 10,000). Although the cumulative prevalence of mental disorder in the overall sample was 5390 per 10,000 (53.9%), we found that 4192 patients with ulcerative colitis (82%) also had a diagnosis of a mental disorder. By annual rate of ulcerative colitis, patients with mental disorder had a significantly higher annual prevalence. The mental disorder grouping neuroses/depressive disorders was most likely to arise before ulcerative colitis (odds ratio = 1.87 for males; 2.24 for females). CONCLUSIONS A temporal association was observed between specific groups of International Classification of Diseases mental disorder and ulcerative colitis, indicating a possible etiologic relationship between the disorders or their treatments, or both.
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Affiliation(s)
- David Cawthorpe
- Research and Evaluation Coordinator in the Department of Psychiatry and Community Health Services at the University of Calgary in Alberta, Canada.
| | - Marta Davidson
- Internal Medicine Resident at the University of Calgary in Alberta, Canada.
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Pan T, Guo HY, Zhang H, Liu AP, Wang XX, Ren FZ. Oral administration of Lactobacillus paracasei alleviates clinical symptoms of colitis induced by dextran sulphate sodium salt in BALB/c mice. Benef Microbes 2015; 5:315-22. [PMID: 24889889 DOI: 10.3920/bm2013.0041] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The aim of this study was to investigate the alleviating effect of Lactobacillus paracasei subsp. paracasei LC-01 (LC-01) on the murine model of colitis induced by dextran sulphate sodium (DSS). 50 pathogen-free, 6-week-old male BALB/c mice were divided randomly into 5 groups, including a control group and four DSS-LC-01-treated groups (DSS, DSS-106, DSS-108, and DSS-1010 with 0, 1×106, 1×108 and 1×1010 cfu/ml LC-01, respectively). To test the effectiveness of LC-01 as a prophylactic it was administered for 7 days before the onset of the disease in DSS-LC-01-treated mice. After 7 days, colitis was induced by administration of 2.5% (w/v) DSS in drinking water for a further 7 days. The disease activity index (DAI), histological score, myeloperoxidase (MPO) activity and the level of the pro-inflammatory cytokines interleukin-1β (IL-1β) and tumour necrosis factor α (TNF-α) were measured. DAI, histological scores and MPO activity of mice treated with a medium or high dose of LC-01 were significantly lower compared to a low-dose of LC-01 and DSS treatment alone (P<0.05). Colon length shortening could be prevented with increasing dose of LC-01. In addition, the levels of IL-1β and TNF-α were suppressed significantly by treatment with a medium and high dose of LC-01. However, no significant difference in the indices mentioned above were observed between a low dose of LC-01 and treatment with DSS alone (P≯0.05). An appropriate dose of LC-01 can prevent intestinal damage in mice with DSS-induced colitis. The expression of inflammatory cytokines related to pathogenesis of DSS-induced colitis decreased following treatment with LC-01.
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Affiliation(s)
- T Pan
- Beijing Laboratory for Food Quality and Safety, and Key Laboratory of Functional Dairy, College of Food Science and Nutritional Engineering, China Agricultural University, P.O. Box 303, No. 17 Tsinghua East Road, Beijing 100083, China P.R
| | - H Y Guo
- Beijing Higher Institution Engineering Research Center of Animal Product, China Agricultural University, No. 17 Tsinghua East Road, Beijing 100083, China P.R
| | - H Zhang
- Beijing Laboratory for Food Quality and Safety, and Key Laboratory of Functional Dairy, College of Food Science and Nutritional Engineering, China Agricultural University, P.O. Box 303, No. 17 Tsinghua East Road, Beijing 100083, China P.R
| | - A P Liu
- Mengniu Dairy (Beijing) Company, Beijing 011500, China P.R
| | - X X Wang
- College of Food Science and Technology Engineering, Gansu Agricultural University, Lanzhou 730070, China P.R
| | - F Z Ren
- Beijing Laboratory for Food Quality and Safety, and Key Laboratory of Functional Dairy, College of Food Science and Nutritional Engineering, China Agricultural University, P.O. Box 303, No. 17 Tsinghua East Road, Beijing 100083, China P.R. Beijing Higher Institution Engineering Research Center of Animal Product, China Agricultural University, No. 17 Tsinghua East Road, Beijing 100083, China P.R
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Yang K, Tang ZP. Suppositories for treatment of ulcerative colitis. Shijie Huaren Xiaohua Zazhi 2014; 22:5648-5652. [DOI: 10.11569/wcjd.v22.i36.5648] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
In recent decades, the incidence of ulcerative colitis (UC) presents a gradually upward trend. The combination of topical and oral therapy is more widely adopted in current management of UC in comparison with traditional oral therapy. As a typical topical therapy, suppository treatment has received increasing attention due to its convenience, high tolerance and good curative effect. Aminosalicylic acid preparations are the major Western medicine suppositories, consisting of sulfasalazine suppository and mesalazine suppository, with the latter considered the first choice for mild-to-moderate UC due to better efficacy and fewer side effects. For traditional Chinese medicine (TCM), several drugs have been applied as suppositories. Qingchang suppository is a representative of TCM suppositories whose therapeutic principle is based on heat-clearing and detoxicating effects. This article reviews the recent progress in suppository treatment of UC.
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Hartavi M, Nak SG, Oral B, Deligönül A. No association between the SOCS-1 −1478CA/del polymorphism and ulcerative colitis in Turkish subjects. Mol Biol Rep 2014; 41:6505-8. [DOI: 10.1007/s11033-014-3533-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2013] [Accepted: 06/19/2014] [Indexed: 01/01/2023]
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Yoshikawa A, Yoshida S, Takeuchi T, Fujiki Y, Makino S, Hanafusa T. Gastrointestinal involvement at the onset of granulomatosis with polyangiitis: A case report. Mod Rheumatol 2014; 27:162-164. [PMID: 25221912 DOI: 10.3109/14397595.2014.954742] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
A 30-year-old man had developed fever, bloody stools, and oral aphtha. Proteinase 3-antineutrophil cytoplasmic antibody level was 31 EU. Lower intestinal endoscopy revealed edematous mucosa with hemorrhage in the transverse colon. Biopsies of oral aphtha showed necrotizing angiitis with granuloma. Based on these findings, he was diagnosed with granulomatosis with polyangiitis (GPA). Digestive symptoms were remitted by treatment with prednisolone and azathioprine. GPA with digestive symptoms as the initial development is rare.
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Affiliation(s)
- Ayaka Yoshikawa
- a Department of Internal Medicine (I) , Osaka Medical College , Takatsuki City, Osaka , Japan
| | - Shuzo Yoshida
- a Department of Internal Medicine (I) , Osaka Medical College , Takatsuki City, Osaka , Japan
| | - Tohru Takeuchi
- a Department of Internal Medicine (I) , Osaka Medical College , Takatsuki City, Osaka , Japan
| | - Yohei Fujiki
- a Department of Internal Medicine (I) , Osaka Medical College , Takatsuki City, Osaka , Japan
| | - Shigeki Makino
- a Department of Internal Medicine (I) , Osaka Medical College , Takatsuki City, Osaka , Japan
| | - Toshiaki Hanafusa
- a Department of Internal Medicine (I) , Osaka Medical College , Takatsuki City, Osaka , Japan
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Gut microbiota imbalance and chaperoning system malfunction are central to ulcerative colitis pathogenesis and can be counteracted with specifically designed probiotics: a working hypothesis. Med Microbiol Immunol 2013; 202:393-406. [PMID: 23864544 DOI: 10.1007/s00430-013-0305-2] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2013] [Accepted: 06/29/2013] [Indexed: 12/19/2022]
Abstract
In this work, we propose that for further studies of the physiopathology and treatment for inflammatory bowel diseases, an integral view of the conditions, including the triad of microbiota-heat shock proteins (HSPs)-probiotics, ought to be considered. Microbiota is the complex microbial flora that resides in the gut, affecting not only gut functions but also the health status of the whole body. Alteration in the microbiota's composition has been implicated in a variety of pathological conditions (e.g., ulcerative colitis, UC), involving both gut and extra-intestinal tissues and organs. Some of these pathologies are also associated with an altered expression of HSPs (chaperones) and this is the reason why they may be considered chaperonopathies. Probiotics, which are live microorganisms able to restore the correct, healthy equilibrium of microbiota composition, can ameliorate symptoms in patients suffering from UC and modulate expression levels of HSPs. However, currently probiotic therapy follows ex-adiuvantibus criteria, i.e., treatments with beneficial effects but whose mechanism of action is unknown, which should be changed so the probiotics needed in each case are predetermined on the basis of the patient's microbiota. Consequently, efforts are necessary to develop diagnostic tools for elucidating levels and distribution of HSPs and the microbiota composition (microbiota fingerprint) of each subject and, thus, guide specific probiotic therapy, tailored to meet the needs of the patient. Microbiota fingerprinting ought to include molecular biology techniques for sequencing highly conserved DNA, e.g., genes encoding 16S RNA, for species identification and, in addition, quantification of each relevant microbe.
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27
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Pagliari D, Cianci R, Frosali S, Landolfi R, Cammarota G, Newton EE, Pandolfi F. The role of IL-15 in gastrointestinal diseases: a bridge between innate and adaptive immune response. Cytokine Growth Factor Rev 2013; 24:455-66. [PMID: 23791986 DOI: 10.1016/j.cytogfr.2013.05.004] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2013] [Revised: 05/09/2013] [Accepted: 05/21/2013] [Indexed: 12/27/2022]
Abstract
IL-15 is a member of the IL-2 family of cytokines whose signaling pathways are a bridge between innate and adaptive immune response. IL-15 is part of the intestinal mucosal barrier, and functions to modulate gut homeostasis. IL-15 has pivotal roles in the control of development, proliferation and survival of both innate and adaptive immune cells. IL-15 becomes up-regulated in the inflamed tissue of intestinal inflammatory disease, such as IBD, Celiac Disease and related complications. Indeed, several studies have reported that IL-15 may participate to the pathogenesis of these diseases. Furthermore, although IL-15 seems to be responsible for inflammation and autoimmunity, it also may increase the immune response against cancer. For these reasons, we decided to study the intestinal mucosa as an 'immunological niche', in which immune response, inflammation and local homeostasis are modulated. Understanding the role of the IL-15/IL-15R system will provide a scientific basis for the development of new approaches that use IL-15 for immunotherapy of autoimmune diseases and malignancies. Indeed, a better understanding of the complexity of the mucosal immune system will contribute to the general understanding of immuno-pathology, which could lead to new therapeutical tools for widespread immuno-mediated diseases.
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Affiliation(s)
- Danilo Pagliari
- Institute of Internal Medicine, Catholic University of the Sacred Heart, Rome, Italy
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28
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Di Sabatino A, Giuffrida P, Corazza GR. From impending toxic megacolon to multiple organ failure in severe ulcerative colitis. Intern Emerg Med 2013; 8:185-6. [PMID: 22923362 DOI: 10.1007/s11739-012-0849-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2012] [Accepted: 08/08/2012] [Indexed: 11/29/2022]
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29
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Sung MK, Park MY. Nutritional modulators of ulcerative colitis: Clinical efficacies and mechanistic view. World J Gastroenterol 2013; 19:994-1004. [PMID: 23467687 PMCID: PMC3582011 DOI: 10.3748/wjg.v19.i7.994] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2012] [Revised: 11/17/2012] [Accepted: 12/27/2012] [Indexed: 02/06/2023] Open
Abstract
Ulcerative colitis (UC) is an inflammation-associated disease of the colon and rectum. The onset and progress of the disease are directly influenced by the nature of the intestinal microflora, the intestinal barrier function, and the immunological responses of the host. The epithelial invasion of pathogenic bacteria due to excess contact and/or barrier dysfunction is related to inflammation mediated by intestinal immune responses. Although the etiology of UC is not clearly understood, recent studies have shown a rising incidence of UC worldwide, and this phenomenon is more prominent in Asian countries and in Asian immigrants in Western countries. The increased prevalence of UC also contributes to an increased risk of developing colorectal cancer. Environmental factors, including changes in dietary habits, have been suggested as major risk factors of UC. A systematic review showed a negative association between UC risk and vegetable intake, whereas total fat, omega-6 fatty acids and meat intake were positively associated with an increased risk of UC. Individual dietary factors and energy balance have been suggested as having important roles in inducing changes in the microbial population and intestinal barrier integrity and in regulating inflammatory immune responses, directly or indirectly. Excess energy intake is now known to increase pathogenic microbial populations. Likewise, the application of appropriate probiotics may reverse the pathogenic progression of the disease. In the meantime, dietary anti-inflammatory compounds, including omega-3 fatty acids and other phytochemicals, may directly suppress inflammatory responses in the course of UC development. In this review, the increased prevalence of UC and its management are interpreted from the standpoint of nutritional modulation to regulate the intestinal microflora population, intestinal epithelium permeability, and inflammatory responses.
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30
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Hokama A, Ohira T, Kishimoto K, Kinjo F, Fujita J. Impending megacolon: small bowel distension as a predictor of toxic megacolon in ulcerative colitis. Intern Emerg Med 2012; 7:487-8. [PMID: 22843318 DOI: 10.1007/s11739-012-0834-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2012] [Accepted: 07/14/2012] [Indexed: 12/17/2022]
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31
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Abstract
Diarrhea is defined as reduced stool consistency, increased water content and number of evacuations per day. A wide array of causes and pathophysiological mechanisms underlie acute and chronic forms of diarrhea. This review focuses on the major clinical aspects which should aid clinicians to diagnose chronic diarrhea. Clinical history, physical examination and stool evaluation and the predominant stool characteristic, i.e., bloody, watery, and fatty diarrhea, may narrow the differential diagnosis. Although mainly involved in acute diarrhea, many different infectious agents, including bacteria, viruses and protozoa, can be identified in chronic bloody/inflammatory diarrhea by appropriate microbiological tests and colonoscopic biopsy analysis. Osmotic diarrhea can be the result of malabsorption or maldigestion, with a subsequent passage of fat in the stool leading to steatorrhea. Secretory diarrhea is due to an increase of fluid secretion in the small bowel lumen, a mechanism often identified in gastroenteropancreatic neuroendocrine tumors. The evaluation of the fecal osmotic gap may help to characterize whether a chronic diarrhea is osmotic or secretory. Fatty diarrhea (steatorrhea) occurs if fecal fat output exceeds the absorptive/digestive capacity of the intestine. Steatorrhea results from malabsorption or maldigestion states and tests should differentiate between these two conditions. Individualized diagnostic work ups tailored on pathophysiological and clinical features are expected to reduce costs for patients with chronic diarrhea.
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Affiliation(s)
- Roberto Corinaldesi
- Department of Clinical Medicine, Digestive Diseases and Internal Medicine, University of Bologna, St. Orsola-Malpighi Hospital, Bldg #5, Nuove Patologie, Via Massarenti 9, 40138, Bologna, Italy.
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32
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Abstract
Serine proteases, cysteine proteases, aspartic proteases and matrix metalloproteinases play an essential role in extracellular matrix remodeling and turnover through their proteolytic action on collagens, proteoglycans, fibronectin, elastin and laminin. Proteases can also act on chemokines, receptors and anti-microbial peptides, often potentiating their activity. The intestinal mucosa is the largest interface between the external environment and the tissues of the human body and is constantly exposed to proteolytic enzymes from many sources, including bacteria in the intestinal lumen, fibroblasts and immune cells in the lamina propria and enterocytes. Controlled proteolytic activity is crucial for the maintenance of gut immune homeostasis, for normal tissue turnover and for the integrity of the gut barrier. However, in intestinal immune-mediated disorders, pro-inflammatory cytokines induce the up-regulation of proteases, which become the end-stage effectors of mucosal damage by destroying the epithelium and basement membrane integrity and degrading the extracellular matrix of the lamina propria to produce ulcers. Protease-mediated barrier disruption in turn results in increased amounts of antigen crossing into the lamina propria, driving further immune responses and sustaining the inflammatory process.
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Simão ÉM, Sinigaglia M, Bugs CA, Castro MAA, Librelotto GR, Alves R, Mombach JCM. Induced genome maintenance pathways in pre-cancer tissues describe an anti-cancer barrier in tumor development. MOLECULAR BIOSYSTEMS 2012; 8:3003-9. [DOI: 10.1039/c2mb25242b] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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