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Pharmaceuticals
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Drug Treatments for Inflammatory Bowel Diseases
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Drug Treatments for Inflammatory Bowel Diseases

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: closed (29 August 2023) | Viewed by 25035

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

Prof. Dr. Anderson Luiz-Ferreira

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Guest Editor
Inflammatory Bowel Disease Research Laboratory, Federal University of Catalão, Catalão, Brazil
Interests: experimental colitis; inflammation; ulcerative colitis; oxidative stress; colorectal cancer; Crohn’s disease
Dr. Carmine Stolfi

E-Mail Website
Guest Editor
Department of Systems Medicine, University of Rome “Tor Vergata”, 00133 Rome, Italy
Interests: colorectal cancer; immunotherapy; inflammatory bowel diseases; anti-cancer drugs
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are idiopathic, relapsing, and remitting chronic inflammatory diseases that affect the gastrointestinal tract, bringing significant morbidity and loss of quality of life for the affected individuals. In UC, the inflammation is mostly restricted to the mucosa and involves only the colon, although the extent of colonic involvement may vary among patients and over time. In CD, the inflammatory process is transmural, affecting any portion of the gastrointestinal tract from the mouth to the anus, and may be associated with penetrating phenomena such as intraperitoneal abscesses or fistulas. Although the etiology is unknown, the interaction of environmental factors with the gut microbiota of a genetically susceptible host is believed to lead to the abnormal colonic mucosal immune response seen in these diseases.

Current pharmacological strategies for the management of IBD include the use of aminosalicylates, corticosteroids, thiopurines, cyclosporine, and biological therapies. These drugs aim to silence both active and chronic inflammation and prevent the progression of the disease, with the ultimate goal to induce clinical, biochemical, and endoscopic remission. However, a high percentage of individuals do not respond or lose response to treatments over time, and a prolonged use of such therapeutics can even result in side effects that, other than the disease itself, contribute to reducing the patients' quality of life. For these reasons, the search for new therapeutic targets/approaches to better manage the symptoms of these serious diseases as well as therapy-related potential side effects is worth pursuing.

This Special Issue of Pharmaceuticals, entitled “Drug Treatments for Inflammatory Bowel Diseases”, focuses on the most recent and relevant advances in new/potential drugs and therapies, which have shown promising results in preclinical studies and may represent effective future strategies for the management of these serious diseases. In this regard, the Special Issue welcomes original research articles, short communications, basic science reviews, as well as case studies and clinical trials.

Prof. Dr. Anderson Luiz-Ferreira
Dr. Carmine Stolfi
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • inflammatory bowel diseases
  • ulcerative colitis
  • Crohn’s disease
  • biologic therapy
  • gut inflammation
  • clinical trials
  • cytokines
  • gut microbiota
  • gut dysbiosis
  • innate and adoptive immunity

Published Papers (12 papers)

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Editorial

Jump to: Research, Review

5 pages, 187 KiB  
Editorial
Special Issue “Drug Treatments for Inflammatory Bowel Diseases”
by Anderson Luiz-Ferreira and Carmine Stolfi
Pharmaceuticals 2024, 17(1), 59; https://doi.org/10.3390/ph17010059 - 29 Dec 2023
Viewed by 773
Abstract
Inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are chronic idiopathic, relapsing and remitting inflammatory diseases that affect the gastrointestinal tract, causing significant morbidity and loss of quality of life in affected individuals [...] Full article
(This article belongs to the Special Issue Drug Treatments for Inflammatory Bowel Diseases)

Research

Jump to: Editorial, Review

28 pages, 5654 KiB  
Article
(R,R)-BD-AcAc2 Mitigates Chronic Colitis in Rats: A Promising Multi-Pronged Approach Modulating Inflammasome Activity, Autophagy, and Pyroptosis
by Sameh Saber, Mohannad Mohammad S. Alamri, Jaber Alfaifi, Lobna A. Saleh, Sameh Abdel-Ghany, Adel Mohamed Aboregela, Alshaimaa A. Farrag, Abdulrahman H. Almaeen, Masoud I. E. Adam, AbdulElah Al Jarallah AlQahtani, Ali M. S. Eleragi, Mustafa Ahmed Abdel-Reheim, Heba A. Ramadan and Osama A. Mohammed
Pharmaceuticals 2023, 16(7), 953; https://doi.org/10.3390/ph16070953 - 03 Jul 2023
Cited by 2 | Viewed by 1702
Abstract
Ulcerative colitis is a chronic and incurable form of inflammatory bowel disease that can increase the risk of colitis-associated cancer and mortality. Limited treatment options are available for this condition, and the existing ones often come with non-tolerable adverse effects. This study is [...] Read more.
Ulcerative colitis is a chronic and incurable form of inflammatory bowel disease that can increase the risk of colitis-associated cancer and mortality. Limited treatment options are available for this condition, and the existing ones often come with non-tolerable adverse effects. This study is the first to examine the potential benefits of consuming (R,R)-BD-AcAc2, a type of ketone ester (KE), and intermittent fasting in treating chronic colitis induced by dextran sodium sulfate (DSS) in rats. We selected both protocols to enhance the levels of β-hydroxybutyrate, mimicking a state of nutritional ketosis and early ketosis, respectively. Our findings revealed that only the former protocol, consuming the KE, improved disease activity and the macroscopic and microscopic features of the colon while reducing inflammation scores. Additionally, the KE counteracted the DSS-induced decrease in the percentage of weight change, reduced the colonic weight-to-length ratio, and increased the survival rate of DSS-insulted rats. KE also showed potential antioxidant activities and improved the gut microbiome composition. Moreover, consuming KE increased the levels of tight junction proteins that protect against leaky gut and exhibited anti-inflammatory properties by reducing proinflammatory cytokine production. These effects were attributed to inhibiting NFκB and NLRP3 inflammasome activation and restraining pyroptosis and apoptosis while enhancing autophagy as revealed by reduced p62 and increased BECN1. Furthermore, the KE may have a positive impact on maintaining a healthy microbiome. To conclude, the potential clinical implications of our findings are promising, as (R,R)-BD-AcAc2 has a greater safety profile and can be easily translated to human subjects. Full article
(This article belongs to the Special Issue Drug Treatments for Inflammatory Bowel Diseases)
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16 pages, 596 KiB  
Article
Rosiglitazone Does Not Affect the Risk of Inflammatory Bowel Disease: A Retrospective Cohort Study in Taiwanese Type 2 Diabetes Patients
by Chin-Hsiao Tseng
Pharmaceuticals 2023, 16(5), 679; https://doi.org/10.3390/ph16050679 - 01 May 2023
Cited by 1 | Viewed by 2295
Abstract
Human studies on the effect of rosiglitazone on inflammatory bowel disease (IBD) are still lacking. We investigated whether rosiglitazone might affect IBD risk by using the reimbursement database of Taiwan’s National Health Insurance to enroll a propensity-score-matched cohort of ever users and never [...] Read more.
Human studies on the effect of rosiglitazone on inflammatory bowel disease (IBD) are still lacking. We investigated whether rosiglitazone might affect IBD risk by using the reimbursement database of Taiwan’s National Health Insurance to enroll a propensity-score-matched cohort of ever users and never users of rosiglitazone. The patients should have been newly diagnosed with diabetes mellitus between 1999 and 2006 and should have been alive on 1 January 2007. We then started to follow the patients from 1 January 2007 until 31 December 2011 for a new diagnosis of IBD. Propensity-score-weighted hazard ratios were estimated with regards to rosiglitazone exposure in terms of ever users versus never users and in terms of cumulative duration and cumulative dose of rosiglitazone therapy for dose–response analyses. The joint effects and interactions between rosiglitazone and risk factors of psoriasis/arthropathies, dorsopathies, and chronic obstructive pulmonary disease/tobacco abuse and the use of metformin were estimated by Cox regression after adjustment for all covariates. A total of 6226 ever users and 6226 never users were identified and the respective numbers of incident IBD were 95 and 111. When we compared the risk of IBD in ever users to that of the never users, the estimated hazard ratio (0.870, 95% confidence interval: 0.661–1.144) was not statistically significant. When cumulative duration and cumulative dose of rosiglitazone therapy were categorized by tertiles and hazard ratios were estimated by comparing the tertiles of rosiglitazone exposure to the never users, none of the hazard ratios reached statistical significance. In secondary analyses, rosiglitazone has a null association with Crohn’s disease, but a potential benefit on ulcerative colitis (UC) could not be excluded. However, because of the low incidence of UC, we were not able to perform detailed dose–response analyses for UC. In the joint effect analyses, only the subgroup of psoriasis/arthropathies (-)/rosiglitazone (-) showed a significantly lower risk in comparison to the subgroup of psoriasis/arthropathies (+)/rosiglitazone (-). No interactions between rosiglitazone and the major risk factors or metformin use were observed. We concluded that rosiglitazone has a null effect on the risk of IBD, but the potential benefit on UC awaits further investigation. Full article
(This article belongs to the Special Issue Drug Treatments for Inflammatory Bowel Diseases)
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19 pages, 2706 KiB  
Article
Super Carbonate Apatite-miR-497a-5p Complex Is a Promising Therapeutic Option against Inflammatory Bowel Disease
by Naoto Tsujimura, Takayuki Ogino, Masayuki Hiraki, Taisei Kai, Hiroyuki Yamamoto, Haruka Hirose, Yuhki Yokoyama, Yuki Sekido, Tsuyoshi Hata, Norikatsu Miyoshi, Hidekazu Takahashi, Mamoru Uemura, Tsunekazu Mizushima, Yuichiro Doki, Hidetoshi Eguchi and Hirofumi Yamamoto
Pharmaceuticals 2023, 16(4), 618; https://doi.org/10.3390/ph16040618 - 19 Apr 2023
Viewed by 1810
Abstract
The incidence of inflammatory bowel disease (IBD) is increasing worldwide. It is reported that TGF-β/Smad signal pathway is inactivated in patients with Crohn’s disease by overexpression of Smad 7. With expectation of multiple molecular targeting by microRNAs (miRNAs), we currently attempted to identify [...] Read more.
The incidence of inflammatory bowel disease (IBD) is increasing worldwide. It is reported that TGF-β/Smad signal pathway is inactivated in patients with Crohn’s disease by overexpression of Smad 7. With expectation of multiple molecular targeting by microRNAs (miRNAs), we currently attempted to identify certain miRNAs that activate TGF-β/Smad signal pathway and aimed to prove in vivo therapeutic efficacy in mouse model. Through Smad binding element (SBE) reporter assays, we focused on miR-497a-5p. This miRNA is common between mouse and human species and enhanced the activity of TGF-β/Smad signal pathway, decreased Smad 7 and/or increased phosphorylated Smad 3 expression in non-tumor cell line HEK293, colorectal cancer cell line HCT116 and mouse macrophage J774a.1 cells. MiR-497a-5p also suppressed the production of inflammatory cytokines TNF-α, IL-12p40, a subunit of IL-23, and IL-6 when J774a.1 cells were stimulated by lipopolysaccharides (LPS). In a long-term therapeutic model for mouse dextran sodium sulfate (DSS)-induced colitis, systemic delivery of miR-497a-5p load on super carbonate apatite (sCA) nanoparticle as a vehicle restored epithelial structure of the colonic mucosa and suppressed bowel inflammation compared with negative control miRNA treatment. Our data suggest that sCA-miR-497a-5p may potentially have a therapeutic ability against IBD although further investigation is essential. Full article
(This article belongs to the Special Issue Drug Treatments for Inflammatory Bowel Diseases)
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13 pages, 2563 KiB  
Article
Mucosal Genes Expression in Inflammatory Bowel Disease Patients: New Insights
by Sumaiah J. Alarfaj, Sally Abdallah Mostafa, Walaa A. Negm, Thanaa A. El-Masry, Marwa Kamal, Mohamed Elsaeed and Ahmed Mohamed El Nakib
Pharmaceuticals 2023, 16(2), 324; https://doi.org/10.3390/ph16020324 - 20 Feb 2023
Cited by 1 | Viewed by 1737
Abstract
Individual differences in IBD illness severity, behavior, progression, and therapy response are evident. Since a break in the intestinal epithelial barrier causes IBD to begin, mucosal gene expression in IBD is crucial. Due to its high sensitivity and dynamic nature, molecular analysis of [...] Read more.
Individual differences in IBD illness severity, behavior, progression, and therapy response are evident. Since a break in the intestinal epithelial barrier causes IBD to begin, mucosal gene expression in IBD is crucial. Due to its high sensitivity and dynamic nature, molecular analysis of biomarkers in intestinal biopsies is feasible and provides a reliable means of evaluating localized inflammation. The goal of this investigation was to discover alterations in gene expression in the inflamed mucosa of IBD patients undergoing treatment with 5-amino salicylic acid (5ASA) (N = 39) or anti-TNF drugs (N = 22). The mucosal expression of numerous IBD-related genes was evaluated using qPCR. We discovered that the levels of the proteins Lipocalin-2 (LCN2), Nitric Oxide Synthase 2 (NOS2), Mucin 2 (MUC2), Mucin 5AC (MUC5AC), and Trefoil factor 1 (TFF1), which are overexpressed in untreated IBD patients compared to non-IBD subjects, are decreased by both therapy regimens. On the other hand, anti-TNF medicine helped the levels of ABCB1 and E-cadherin return to normal in IBD patients who were not receiving treatment. Full article
(This article belongs to the Special Issue Drug Treatments for Inflammatory Bowel Diseases)
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10 pages, 936 KiB  
Article
Real-World Study on Vedolizumab Serum Concentration, Efficacy, and Safety after the Transition from Intravenous to Subcutaneous Vedolizumab in Inflammatory Bowel Disease Patients: Single-Center Experience
by Vlasta Oršić Frič, Vladimir Borzan, Ines Šahinović, Andrej Borzan and Sven Kurbel
Pharmaceuticals 2023, 16(2), 239; https://doi.org/10.3390/ph16020239 - 05 Feb 2023
Cited by 1 | Viewed by 1895
Abstract
Little is known about how the change from intravenous to subcutaneous vedolizumab in a real-life setting in inflammatory bowel disease patients on stable maintenance therapy affects clinical outcomes. We compared the data on vedolizumab serum trough concentration, efficacy, and safety prior to and [...] Read more.
Little is known about how the change from intravenous to subcutaneous vedolizumab in a real-life setting in inflammatory bowel disease patients on stable maintenance therapy affects clinical outcomes. We compared the data on vedolizumab serum trough concentration, efficacy, and safety prior to and six months after the switch from intravenous to subcutaneous vedolizumab. In total, 24 patients, 13 with ulcerative colitis (UC) and 11 with Crohn’s disease (CD), were included. Mean serum trough concentration of intravenous vedolizumab was significantly lower than mean serum trough concentration of subcutaneous vedolizumab (p = 0.002). There was no significant difference between C-reactive protein levels, fecal calprotectin levels or clinical scores (Harvey–Bradshaw index or Partial Mayo score) prior to transition to subcutaneous vedolizumab and after 6 months. In four (16.7%) patients, two CD and two UC, therapy was discontinued during the follow-up period with a median of 5 months (minimum–maximum: 4–6). In all patients, therapy was discontinued due to loss of response. In total, 13 adverse events were reported by 11 patients, and the most common adverse event was COVID-19. No serious adverse events were reported. In conclusion, subcutaneous vedolizumab has shown to be effective and safe in patients on previously established maintenance therapy with intravenous vedolizumab. Full article
(This article belongs to the Special Issue Drug Treatments for Inflammatory Bowel Diseases)
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11 pages, 508 KiB  
Article
Pioglitazone Has a Null Association with Inflammatory Bowel Disease in Patients with Type 2 Diabetes Mellitus
by Chin-Hsiao Tseng
Pharmaceuticals 2022, 15(12), 1538; https://doi.org/10.3390/ph15121538 - 11 Dec 2022
Cited by 5 | Viewed by 1475
Abstract
Pioglitazone shows potential benefits in inflammatory bowel disease (IBD) in preclinical studies, but its effect in humans has not been researched. We used a nationwide database of Taiwan’s National Health Insurance to investigate whether pioglitazone might affect IBD risk. We enrolled 12,763 ever [...] Read more.
Pioglitazone shows potential benefits in inflammatory bowel disease (IBD) in preclinical studies, but its effect in humans has not been researched. We used a nationwide database of Taiwan’s National Health Insurance to investigate whether pioglitazone might affect IBD risk. We enrolled 12,763 ever users and 12,763 never users matched on a propensity score from patients who had a new diagnosis of type 2 diabetes mellitus between 1999 and 2008. The patients were alive on 1 January 2009, and they were followed up for a new diagnosis of IBD until 31 December 2011. Propensity score-weighted hazard ratios were estimated, and the interactions between pioglitazone and major risk factors of IBD (i.e., psoriasis, arthropathies, dorsopathies, chronic obstructive pulmonary disease/tobacco abuse, and any of the above) and metformin were investigated. At the end of the follow-up, 113 ever users and 139 never users were diagnosed with IBD. When compared to never users, the hazard ratio for ever users was 0.809 (95% confidence interval: 0.631–1.037); and none of the hazard ratios for ever users categorized by tertiles of cumulative duration and cumulative dose reached statistical significance. No interactions with major risk factors or metformin were observed. Our findings suggested a null effect of pioglitazone on IBD. Full article
(This article belongs to the Special Issue Drug Treatments for Inflammatory Bowel Diseases)
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13 pages, 2344 KiB  
Article
MK2 Inhibitors as a Potential Crohn’s Disease Treatment Approach for Regulating MMP Expression, Cleavage of Checkpoint Molecules and T Cell Activity
by Eric J. Lebish, Natalie J. Morgan, John F. Valentine and Ellen J. Beswick
Pharmaceuticals 2022, 15(12), 1508; https://doi.org/10.3390/ph15121508 - 03 Dec 2022
Cited by 3 | Viewed by 1664
Abstract
Crohn’s Disease (CD) and Ulcerative Colitis (UC) are the two major forms of inflammatory bowel disease (IBD), which are incurable chronic immune-mediated diseases of the gastrointestinal tract. Both diseases present with chronic inflammation that leads to epithelial barrier dysfunction accompanied by loss of [...] Read more.
Crohn’s Disease (CD) and Ulcerative Colitis (UC) are the two major forms of inflammatory bowel disease (IBD), which are incurable chronic immune-mediated diseases of the gastrointestinal tract. Both diseases present with chronic inflammation that leads to epithelial barrier dysfunction accompanied by loss of immune tolerance and inflammatory damage to the mucosa of the GI tract. Despite extensive research in the field, some of the mechanisms associated with the pathology in IBD remain elusive. Here, we identified a mechanism by which the MAPK-activated protein kinase 2 (MK2) pathway contributes to disease pathology in CD by regulating the expression of matrix metalloproteinases (MMPs), which cleave checkpoint molecules on immune cells and enhance T cell activity. By utilizing pharmaceuticals targeting MMPs and MK2, we show that the cleavage of checkpoint molecules and enhanced T cell responses may be reduced. The data presented here suggest the potential for MK2 inhibitors as a therapeutic approach for the treatment of CD. Full article
(This article belongs to the Special Issue Drug Treatments for Inflammatory Bowel Diseases)
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18 pages, 8335 KiB  
Article
Exploring the Underlying Mechanism of Ren-Shen-Bai-Du Powder for Treating Inflammatory Bowel Disease Based on Network Pharmacology and Molecular Docking
by Ni Jin, Yao Liu, Peiyu Xiong, Yiyi Zhang, Jingwen Mo, Xiushen Huang and Yi Zhou
Pharmaceuticals 2022, 15(9), 1038; https://doi.org/10.3390/ph15091038 - 23 Aug 2022
Cited by 3 | Viewed by 2663
Abstract
Ren-Shen-Bai-Du Powder (RSBDP) is currently used for inflammatory bowel disease (IBD) therapy in China. However, its potential mechanism against IBD remains unknown. In this study, we initially identified potential targets of RSBDP against IBD through network pharmacology analysis and molecular docking. Afterwards, the [...] Read more.
Ren-Shen-Bai-Du Powder (RSBDP) is currently used for inflammatory bowel disease (IBD) therapy in China. However, its potential mechanism against IBD remains unknown. In this study, we initially identified potential targets of RSBDP against IBD through network pharmacology analysis and molecular docking. Afterwards, the DSS-induced colitis mice model was employed to assess the effects of RSBDP. The results of network pharmacology indicated that a total of 39 main active ingredients in RSBDP generated 309 pairs of drug-ingredient and ingredient-target correspondences through 115 highly relevant targets of IBD. The primary ingredients (quercetin, kaempferol, luteolin, naringenin, and sitosterol) exerted functions through multiple targets that include CYP1B1, CA4/7, and ESR1/2, etc. GO functional enrichment analysis revealed that the targets related to IBD were significantly enriched in the oxidation-reduction process, protein binding, and cytosol. Per the KEGG pathway analysis, pathways in cancer, adherens junction, and nitrogen metabolism were pivotal in the RSBDP’s treatment of IBD. Additionally, molecular docking demonstrated that a set of active ingredients and their targets displayed good bonding capabilities (e.g., kaempferol and AhR with combined energy < 5 kcal/mol). For the animal experiment, oral RSBDP promoted weight recovery, reduced intestinal inflammation, and decreased serum IL-1, IL-6, and IL-8 concentrations in the DSS + RSBDP group. Meanwhile, oral RSBDP significantly up-regulated the mRNA levels of CA7, CPY1B1, and PTPN11; in particular, the expression level of CYP1B1 in the DSS + RSBDP group was up-regulated by as high as 9-fold compared to the DSS group. Western blot results indicated that the protein levels of AKR1C1, PI3K, AKT, p-AKT, and Bcl-2 were significantly down-regulated, and Bax was significantly up-regulated in the DSS + RSBDP group. Compared to the DSS and control groups, the Bax/Bcl-2 value in the DSS + RSBDP group increased 4-fold and 8-fold, respectively, which suggested that oral RSBDP promotes apoptosis of intestinal epithelial cells. In short, this study established quercetin, kaempferol, luteolin, naringenin, and sitosterol as the primary key active ingredients of RSBDP that exert synergistic therapeutic effects against IBD through modulating the AhR/CYP1B1 and AKR1C1/PI3K/AKT pathways. Full article
(This article belongs to the Special Issue Drug Treatments for Inflammatory Bowel Diseases)
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Review

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20 pages, 2316 KiB  
Review
Pharmacological Therapy in Inflammatory Bowel Diseases: A Narrative Review of the Past 90 Years
by Marcello Imbrizi, Fernando Magro and Claudio Saddy Rodrigues Coy
Pharmaceuticals 2023, 16(9), 1272; https://doi.org/10.3390/ph16091272 - 08 Sep 2023
Cited by 3 | Viewed by 1945
Abstract
Inflammatory Bowel Diseases had their first peak in incidence in countries in North America, Europe, and Oceania and are currently experiencing a new acceleration in incidence, especially in Latin America and Asia. Despite technological advances, 90 years after the development of the first [...] Read more.
Inflammatory Bowel Diseases had their first peak in incidence in countries in North America, Europe, and Oceania and are currently experiencing a new acceleration in incidence, especially in Latin America and Asia. Despite technological advances, 90 years after the development of the first molecule for the treatment of IBD, we still do not have drugs that promote disease remission in a generalized way. We carried out a narrative review on therapeutic advances in the treatment of IBD, the mechanisms of action, and the challenges facing the therapeutic goals in the treatment of IBD. Salicylates are still used in the treatment of Ulcerative Colitis. Corticosteroids have an indication restricted to the period of therapeutic induction due to frequent adverse events, while technologies with less systemic action have been developed. Most immunomodulators showed a late onset of action, requiring a differentiated initial strategy to control the disease. New therapeutic perspectives emerged with biological therapy, initially with anti-TNF, followed by anti-integrins and anti-interleukins. Despite the different mechanisms of action, there are similarities between the general rates of effectiveness. These similar results were also evidenced in JAK inhibitors and S1p modulators, the last therapeutic classes approved for the treatment of IBD. Full article
(This article belongs to the Special Issue Drug Treatments for Inflammatory Bowel Diseases)
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15 pages, 2132 KiB  
Review
Potential Use of Antioxidant Compounds for the Treatment of Inflammatory Bowel Disease
by Alexander V. Blagov, Varvara A. Orekhova, Vasily N. Sukhorukov, Alexandra A. Melnichenko and Alexander N. Orekhov
Pharmaceuticals 2023, 16(8), 1150; https://doi.org/10.3390/ph16081150 - 14 Aug 2023
Cited by 2 | Viewed by 1498
Abstract
Since inflammatory bowel diseases (IBDs) are chronic, the development of new effective therapeutics to combat them does not lose relevance. Oxidative stress is one of the main pathological processes that determines the progression of IBD. In this regard, antioxidant therapy seems to be [...] Read more.
Since inflammatory bowel diseases (IBDs) are chronic, the development of new effective therapeutics to combat them does not lose relevance. Oxidative stress is one of the main pathological processes that determines the progression of IBD. In this regard, antioxidant therapy seems to be a promising approach. The role of oxidative stress in the development and progression of IBD is considered in detail in this review. The main cause of oxidative stress in IBD is an inadequate response of leukocytes to dysbiosis and food components in the intestine. Passage of immune cells through the intestinal barrier leads to increased ROS concentration and the pathological consequences of exposure to oxidative stress based on the development of inflammation and impaired intestinal permeability. To combat oxidative stress in IBD, several promising natural (curcumin, resveratrol, quercetin, and melatonin) and artificial antioxidants (N-acetylcysteine (NAC) and artificial superoxide dismutase (aSOD)) that had been shown to be effective in a number of clinical trials have been proposed. Their mechanisms of action on pathological events in IBD and clinical manifestations from their impact have been determined. The prospects for the use of other antioxidants that have not yet been tested in the treatment of IBD, but have the properties of potential therapeutic candidates, have been also considered. Full article
(This article belongs to the Special Issue Drug Treatments for Inflammatory Bowel Diseases)
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22 pages, 1217 KiB  
Review
Tackling Inflammatory Bowel Diseases: Targeting Proinflammatory Cytokines and Lymphocyte Homing
by Yijie Song, Man Yuan, Yu Xu and Hongxi Xu
Pharmaceuticals 2022, 15(9), 1080; https://doi.org/10.3390/ph15091080 - 30 Aug 2022
Cited by 13 | Viewed by 4152
Abstract
Inflammatory bowel diseases (IBDs) are characterized by chronic inflammatory disorders that are a result of an abnormal immune response mediated by a cytokine storm and immune cell infiltration. Proinflammatory cytokine therapeutic agents, represented by TNF inhibitors, have developed rapidly over recent years and [...] Read more.
Inflammatory bowel diseases (IBDs) are characterized by chronic inflammatory disorders that are a result of an abnormal immune response mediated by a cytokine storm and immune cell infiltration. Proinflammatory cytokine therapeutic agents, represented by TNF inhibitors, have developed rapidly over recent years and are promising options for treating IBD. Antagonizing interleukins, interferons, and Janus kinases have demonstrated their respective advantages in clinical trials and are candidates for anti-TNF therapeutic failure. Furthermore, the blockade of lymphocyte homing contributes to the excessive immune response in colitis and ameliorates inflammation and tissue damage. Factors such as integrins, selectins, and chemokines jointly coordinate the accumulation of immune cells in inflammatory regions. This review assembles the major targets and agents currently targeting proinflammatory cytokines and lymphatic trafficking to facilitate subsequent drug development. Full article
(This article belongs to the Special Issue Drug Treatments for Inflammatory Bowel Diseases)
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