Medicine in Drug Discovery最新文献_第10页

Comparing monopharmacotherapy of antiarrhythmic and anticoagulant drugs with other drugs for atrial fibrillation: A complete review of clinical trials 比较抗心律失常和抗凝药物单药治疗与其他药物治疗心房颤动:临床试验的完整回顾

Medicine in Drug Discovery Pub Date : 2023-06-01 Epub Date: 2023-03-31 DOI: 10.1016/j.medidd.2023.100154

Akshat D. Modi , Yajan N. Pancholi , Dharmeshkumar M. Modi

{"title":"Comparing monopharmacotherapy of antiarrhythmic and anticoagulant drugs with other drugs for atrial fibrillation: A complete review of clinical trials","authors":"Akshat D. Modi , Yajan N. Pancholi , Dharmeshkumar M. Modi","doi":"10.1016/j.medidd.2023.100154","DOIUrl":"10.1016/j.medidd.2023.100154","url":null,"abstract":"<div><p>Atrial fibrillation (AF) is a life-changing and life-threatening cardiac electropathological condition, especially in patients with prior history of cardiovascular diseases. This multifaceted condition is one of the top 5 leading causes of cardiovascular death with a rapidly increasing prevalence and death rate. From inception till now, numerous clinical trials have been conducted to explore novel therapeutic targets and strategies along with pre-existing treatments for patients suffering from atrial fibrillation. The pharmacotherapy approach to treat AF (acute, chronic, persistent, paroxysmal, non-valvular, nonrheumatic, and rapid) comprises mainly antiarrhythmic drugs (AAD) and anticoagulant drugs (ACD) for rate and rhythm control along with the prevention of strokes. This narrative review aims to discuss monotherapeutic clinical trials that compared AADs (class II: carvedilol and xamoterol; class III: amiodarone; class IV: verapamil, diltiazem, and nifedipine) and ACDs (vitamin K antagonist: warfarin; factor Xa inhibitor: apixaban; factor IIa and Xa inhibitor: heparin) with cardiac glycoside (digoxin), angiotensin II receptor antagonist (telmisartan), platelet inhibitor (indobufen), anti-convulsant (magnesium sulfate), anti-inflammatory (aspirin), and antipyretic drugs (aspirin) to treat various types of AF in patients with a diverse history of cardiovascular diseases. This study provides a review of all clinical trials on this topic and provides a comparative chart for healthcare professionals to determine the best-suited treatment for their patients.</p></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"18 ","pages":"Article 100154"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47900437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Potent anti-Toxoplasma gondii activity of 4-chlorophenylthioacetone-derived thiosemicarbazones: Involvement of CCR2 and CCR5 receptors and 5-lipoxygenase in the mode of action 4-氯苯基硫代丙酮衍生的硫代氨基脲类抗刚地弓形虫活性:CCR2和CCR5受体和5-脂氧合酶参与作用模式

Medicine in Drug Discovery Pub Date : 2023-06-01 Epub Date: 2023-04-24 DOI: 10.1016/j.medidd.2023.100157

Rayane Aparecida Nonato Rabelo , Diego Rodney Rodrigues de Assis , Alexandre Almeida Oliveira , César Luís Nascimento Barbosa , Rafaela das Dores Pereira , Ricardo Wagner de Almeida Vitor , Wiliam César Bento Régis , Mauro Martins Teixeira , Heloísa Beraldo , Fabiana Simão Machado

{"title":"Potent anti-Toxoplasma gondii activity of 4-chlorophenylthioacetone-derived thiosemicarbazones: Involvement of CCR2 and CCR5 receptors and 5-lipoxygenase in the mode of action","authors":"Rayane Aparecida Nonato Rabelo , Diego Rodney Rodrigues de Assis , Alexandre Almeida Oliveira , César Luís Nascimento Barbosa , Rafaela das Dores Pereira , Ricardo Wagner de Almeida Vitor , Wiliam César Bento Régis , Mauro Martins Teixeira , Heloísa Beraldo , Fabiana Simão Machado","doi":"10.1016/j.medidd.2023.100157","DOIUrl":"10.1016/j.medidd.2023.100157","url":null,"abstract":"<div><p>Toxoplasmosis is a disease requiring therapeutic innovation, and thiosemicarbazones with antimicrobial activity are candidates to control <em>Toxoplasma gondii</em> infection. Here, the anti-<em>T. gondii</em> activities of (<em>E</em>)-2-(1-(4-chlorophenylthio)propan-2-ylidene)-hydrazinecarbothioamides (<strong>Ca</strong> and <strong>Cb</strong>) were investigated. <em>T. gondii</em>-infected macrophages (MOs) or glial cells treated with <strong>Ca</strong> or <strong>Cb</strong> showed a decrease in the number of intracellular parasites. A deficiency in the chemokine receptor CCR2, but not CCR5, partially reduced anti-<em>T. gondii</em> activity induced by <strong>Ca</strong> or <strong>Cb</strong>. In contrast, a deficiency in 5-lipoxygenase (5-LO) activity potentiated anti-<em>T. gondii</em> activities induced by these compounds. <em>In vivo</em> treatment with <strong>Ca</strong> increased the survival of <em>T. gondii</em>-infected wild-type mice, and this was associated with increased IFN-γ and IL-12 production. A deficiency in CCR5 or CCR2 abolished the protective effect of <strong>Ca</strong> treatment <em>in vivo</em>, while a deficiency in 5-LO increased <strong>Cb</strong> anti-<em>T. gondii</em> effects. Collectively, our data suggest that <strong>Ca</strong> and <strong>Cb</strong> are potential therapeutic candidates for the treatment of toxoplasmosis.</p></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"18 ","pages":"Article 100157"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44032970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mechanism-based approaches of 1,3,4 thiadiazole scaffolds as potent enzyme inhibitors for cytotoxicity and antiviral activity 1,3,4-噻二唑支架作为细胞毒性和抗病毒活性的强效酶抑制剂的机制研究

Medicine in Drug Discovery Pub Date : 2023-02-01 Epub Date: 2022-12-15 DOI: 10.1016/j.medidd.2022.100150

Davinder Kumar , Harsh Kumar , Virender Kumar , Aakash Deep , Aastha Sharma , Minakshi Gupta Marwaha , Rakesh Kumar Marwaha

{"title":"Mechanism-based approaches of 1,3,4 thiadiazole scaffolds as potent enzyme inhibitors for cytotoxicity and antiviral activity","authors":"Davinder Kumar , Harsh Kumar , Virender Kumar , Aakash Deep , Aastha Sharma , Minakshi Gupta Marwaha , Rakesh Kumar Marwaha","doi":"10.1016/j.medidd.2022.100150","DOIUrl":"10.1016/j.medidd.2022.100150","url":null,"abstract":"<div><p>Significant progress in understanding cancer pathogenesis, it remains one of the leading causes of death after cardiovascular diseases. Similarly viral infections have emerged from wildlife or re-emerged, generating serious threats to the global health. As a result, there is an urgent need for the development of novel, more effective anticancer and antiviral therapeutics. Scientists, medicinal chemists and researchers are continuously finding novel targets, mechanisms and molecules against theses severe and dangerous infections. Therefore, ongoing extensively study and research emphasizes 1,3,4 thiadiazole pharmacophore have versatile pharmacological actions. Due to mesoionic behaviour of 1,3,4 thiadiazole pharmacophore allows to enter and easily cross biological membrane which allow to interact various biological proteins. In this review study an attempt has been made of various mechanisms involved in cancer and viral prevalence with updated studies done so far. This review study also findings the role of 1,3,4 thiadiazole motif in the management of various cancers and viral infection. This study also highlighting research statics on clinical trials and various patents containing 1,3,4 thiadiazole derivatives.</p></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"17 ","pages":"Article 100150"},"PeriodicalIF":0.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48081400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Improved prediction of drug-drug interactions using ensemble deep neural networks 利用集成深度神经网络改进药物相互作用预测

Medicine in Drug Discovery Pub Date : 2023-02-01 Epub Date: 2022-11-26 DOI: 10.1016/j.medidd.2022.100149

Thanh Hoa Vo , Ngan Thi Kim Nguyen , Nguyen Quoc Khanh Le

{"title":"Improved prediction of drug-drug interactions using ensemble deep neural networks","authors":"Thanh Hoa Vo , Ngan Thi Kim Nguyen , Nguyen Quoc Khanh Le","doi":"10.1016/j.medidd.2022.100149","DOIUrl":"https://doi.org/10.1016/j.medidd.2022.100149","url":null,"abstract":"<div><p>Nowadays, combining multiple drugs is the optimal therapy to decelerate the pathologic process, which contains various underlying adverse effects due to drug-drug interactions (DDIs). Artificial intelligence (AI) has the potential to evaluate the interaction, pharmacodynamics, and possible side effects between drugs. Over the past years, many AI-based DDI prediction techniques, including both machine learning and deep learning, that harness available big data have been presented. Although significant progressives have been gained through previous methods, improvements are still crucial. In this work, we introduce an ensemble deep neural network that can help to improve the predictive performance of DDIs. As a result, our prediction model could predict 86 types of DDIs on a benchmark dataset with an average accuracy of 93.80%. Our ensemble classifier produces better performance when compared with the existing proposed methods on the same dataset. Our model's high performance places it among the top list of those well-built pharmacovigilance-assisted tools that facilitate the detection of DDIs to support medical decisions and drug development. We released our source codes and models at https://github.com/khanhlee/edn-ddi.</p></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"17 ","pages":"Article 100149"},"PeriodicalIF":0.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50170838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A review of the pharmacodynamic effect of chemo-herbal drug combinations therapy for cancer treatment 化疗-中草药联合治疗癌症的药效学效应综述

Medicine in Drug Discovery Pub Date : 2023-02-01 Epub Date: 2022-11-24 DOI: 10.1016/j.medidd.2022.100147

Ambrose Okem , Charlotte Henstra , Maarten Lambert , Rose Hayeshi

{"title":"A review of the pharmacodynamic effect of chemo-herbal drug combinations therapy for cancer treatment","authors":"Ambrose Okem , Charlotte Henstra , Maarten Lambert , Rose Hayeshi","doi":"10.1016/j.medidd.2022.100147","DOIUrl":"10.1016/j.medidd.2022.100147","url":null,"abstract":"<div><p>There is mounting evidence that cancer patients co-administer herbal drugs with chemotherapy, however, information on the pharmacodynamic (PD) effects of such combination therapy is scarce. Natural products including crude extracts, herbal formulas, and bioactive compounds from plants hold great potential to prevent and treat cancers. More importantly, some herbal drugs can reduce the incidence of chemotherapy-induced toxicity including oral mucositis, gastrointestinal toxicity, hepatotoxicity etc. This review focuses on the effectiveness of some herbal products as adjuvant therapy and describes the possible mechanisms of chemo-herbal drug PD interactions in enhancing the efficacy/ or reducing the side effects of chemotherapy. We also highlighted recent advances in preclinical <em>in vitro</em> and <em>in vivo</em> studies to establish the effectiveness of herbal medicine to enhance efficacy or counteract chemotherapy-induced side effects. In addition, we draw particular attention to the synergistic effects of chemo-herbal drug combination therapy to prevent and treat cancers using evidence from clinical trials. We concluded that herbal drugs hold great potential as adjuvant therapy for the prevention and treatment of chemotherapy-induced side effects. It is important to also highlight that the clinical evidence on chemo-herbal drug combination therapy is limited. There is an urgent need for an in-depth PD evaluation including the safety pharmacology of chemo-herbal drug combination therapy as well as reliable evidence from multicentre clinical trials to establish the beneficial or negative effects of chemo-herbal drug combination therapy in the ongoing fight against cancer.</p></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"17 ","pages":"Article 100147"},"PeriodicalIF":0.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46726044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 12

Repurposing of drugs for combined treatment of COVID-19 cytokine storm using machine learning 利用机器学习重新利用药物联合治疗新冠肺炎细胞因子风暴

Medicine in Drug Discovery Pub Date : 2023-02-01 Epub Date: 2022-11-29 DOI: 10.1016/j.medidd.2022.100148

Maanaskumar R. Gantla , Igor F. Tsigelny , Valentina L. Kouznetsova

{"title":"Repurposing of drugs for combined treatment of COVID-19 cytokine storm using machine learning","authors":"Maanaskumar R. Gantla , Igor F. Tsigelny , Valentina L. Kouznetsova","doi":"10.1016/j.medidd.2022.100148","DOIUrl":"10.1016/j.medidd.2022.100148","url":null,"abstract":"<div><p>Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) induced cytokine storm is the major cause of COVID-19 related deaths. Patients have been treated with drugs that work by inhibiting a specific protein partly responsible for the cytokines production. This approach provided very limited success, since there are multiple proteins involved in the complex cell signaling disease mechanisms. We targeted five proteins: Angiotensin II receptor type 1 (AT1R), A disintegrin and metalloprotease 17 (ADAM17), Nuclear Factor‑Kappa B (NF‑κB), Janus kinase 1 (JAK1) and Signal Transducer and Activator of Transcription 3 (STAT3), which are involved in the SARS‑CoV‑2 induced cytokine storm pathway. We developed machine-learning (ML) models for these five proteins, using known active inhibitors. After developing the model for each of these proteins, FDA-approved drugs were screened to find novel therapeutics for COVID‑19. We identified twenty drugs that are active for four proteins with predicted scores greater than 0.8 and eight drugs active for all five proteins with predicted scores over 0.85. Mitomycin C is the most active drug across all five proteins with an average prediction score of 0.886. For further validation of these results, we used the PyRx software to conduct protein–ligand docking experiments and calculated the binding affinity. The docking results support findings by the ML model. This research study predicted that several drugs can target multiple proteins simultaneously in cytokine storm-related pathway. These may be useful drugs to treat patients because these therapies can fight cytokine storm caused by the virus at multiple points of inhibition, leading to synergistically effective treatments.</p></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"17 ","pages":"Article 100148"},"PeriodicalIF":0.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9706997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10779789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Exploring the potential of phytochemicals and nanomaterial: A boon to antimicrobial treatment 探索植物化学物质和纳米材料的潜力:抗菌治疗的福音

Medicine in Drug Discovery Pub Date : 2023-02-01 Epub Date: 2023-01-23 DOI: 10.1016/j.medidd.2023.100151

Homesh Yadav , Anand Mahalvar , Madhulika Pradhan , Krishna Yadav , Kantrol Kumar Sahu , Rahul Yadav

{"title":"Exploring the potential of phytochemicals and nanomaterial: A boon to antimicrobial treatment","authors":"Homesh Yadav , Anand Mahalvar , Madhulika Pradhan , Krishna Yadav , Kantrol Kumar Sahu , Rahul Yadav","doi":"10.1016/j.medidd.2023.100151","DOIUrl":"10.1016/j.medidd.2023.100151","url":null,"abstract":"<div><p>Controlling microorganism outbreaks is a critical challenge in preventing the spread of infectious diseases. In addition, an increase in drug-resistant bacterial strains came from cross-contamination and medication overuse, making the problem much more difficult to control. One of the most humongous obstacles to the efficient treatment of a wide range of common infections is antimicrobial resistance (AML-R). Currently, antibiotics are being used hugely to treat such infectious conditions. However, because of their synthetic nature, the development of resistance to them when used over a long period of time or in low doses prompts us to seek alternative treatments. Phytoactives or bioactives from plant sources are the natural solutions to these conditions, as Mother Nature has already provided the answer to every ailment that mankind has faced. The most effective therapies for AML-R have been derived from natural Phytoactives. Because of the abundance of biologically active molecules found in nature, it is by far the best alternative to treat any infections. However, the bioavailability, pharmacokinetic characteristics, low solubility, poor gastrointestinal absorption, low hydrophilicity, and delayed intrinsic dissolution are the major physicochemical barriers that hinder the utilization of these natural actives as AML treatments. These problems can be overcome through the application of novel drug-delivery technologies. This review provides a comprehensive study of AML Phytoactives-based drug delivery, leveraging the potential of nanotechnology to address and overcome the delivery problems associated with them, resulting in a successful approach toward antimicrobial therapy.</p></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"17 ","pages":"Article 100151"},"PeriodicalIF":0.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45908359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Metabolic profiling of serum and urine in preeclampsia and gestational diabetes in early pregnancy 妊娠早期子痫前期和妊娠糖尿病患者血清和尿液代谢特征分析

Medicine in Drug Discovery Pub Date : 2022-12-01 Epub Date: 2022-08-28 DOI: 10.1016/j.medidd.2022.100143

Nupur Rani Agarwal , Garima Kachhawa , Bolaji Fatai Oyeyemi , Neel Sarovar Bhavesh

{"title":"Metabolic profiling of serum and urine in preeclampsia and gestational diabetes in early pregnancy","authors":"Nupur Rani Agarwal , Garima Kachhawa , Bolaji Fatai Oyeyemi , Neel Sarovar Bhavesh","doi":"10.1016/j.medidd.2022.100143","DOIUrl":"10.1016/j.medidd.2022.100143","url":null,"abstract":"<div><p>PE and GDM are two major metabolic diseases affecting pregnancy. Individuals suffering from GDM are at an increased risk of developing PE in later gestational stages. Current study was done to evaluate first trimester serum and urine metabolome using nuclear magnetic resonance (NMR) spectroscopy to identify metabolites and pathways differentially regulated in both diseases. Serum metabolomics analysis revealed deregulation in larger group of metabolites and pathways as compared to urine between PE/GDM and NT groups. Few metabolites showed altered expression in both aliments. Perturbed metabolites have association with energy metabolism, protein metabolism, insulin sensitivity, gut microbiome and maintenance of redox balance. Deregulation in these metabolic pathways contributes to the pathology of GDM/PE. Our study revealed that serum metabolomic profile of PE and GDM shows overlap in 1st trimester of gestation. It also explored the potential of NMR metabolomics in identification of common biomolecules that could be developed into a clinical tool for early detection of both PE /GDM.</p><p>.</p></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"16 ","pages":"Article 100143"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590098622000240/pdfft?md5=88c790be9d228786a873a4ad38654104&pid=1-s2.0-S2590098622000240-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43694383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Screening technology of cyclic peptide library based on gene encoding 基于基因编码的环肽文库筛选技术

Medicine in Drug Discovery Pub Date : 2022-12-01 Epub Date: 2022-10-28 DOI: 10.1016/j.medidd.2022.100145

Yangqiang Chen , Chonggang Duan , Kai Chen , Shumeng Sun , Daizhou Zhang , Xiangjing Meng

引用次数: 0

Repurposing dimethyl fumarate for gastric ulcer and ulcerative colitis: Evidence of local efficacy without systemic side effect 富马酸二甲酯重新用于胃溃疡和溃疡性结肠炎:局部疗效无全身副作用的证据

Medicine in Drug Discovery Pub Date : 2022-12-01 Epub Date: 2022-08-03 DOI: 10.1016/j.medidd.2022.100142

Vishal Patel, Amit Joharapurkar, Samadhan Kshirsagar, Maulik Patel, Hardikkumar Savsani, Ashvinkumar Patel, Ramchandra Ranvir, Mukul Jain

{"title":"Repurposing dimethyl fumarate for gastric ulcer and ulcerative colitis: Evidence of local efficacy without systemic side effect","authors":"Vishal Patel, Amit Joharapurkar, Samadhan Kshirsagar, Maulik Patel, Hardikkumar Savsani, Ashvinkumar Patel, Ramchandra Ranvir, Mukul Jain","doi":"10.1016/j.medidd.2022.100142","DOIUrl":"10.1016/j.medidd.2022.100142","url":null,"abstract":"<div><p>Ulcerative colitis and gastric ulcer are ulcers of gastrointestinal track, especially associated with elevated oxidative stress and inflammation. Dimethyl fumarate (DMF) is used for the treatment of multiple sclerosis and psoriasis and is considered useful in a variety of conditions associated with inflammation. We have investigated the effect of oral DMF (1, 10, 25, 50, 100, 200 mg/kg) in ethanol-induced gastric ulcers in rats. The effect of oral (15, 30, and 60 mg/kg) and intracecal (15 mg/kg) DMF was also investigated in dextran sulfate sodium (DSS)-induced colitis in mice. Treatment of DMF by oral route prevented the development of ethanol-induced gastric ulcers by decreasing oxidative stress in a dose-related manner. Oral and intracecal administration of DMF attenuated body weight loss, increase in disease activity score, colon length shortening, colon weight loss, inflammation and fibrosis, and decreased myeloperoxidase activity. Oral and intracecal DMF prevented a decrease in hemoglobin and suppressed oxidative stress, and also decreased MCP-1, IL-1ß, and IL-6 levels in the inflamed colon. Unlike oral DMF, intracecal DMF treatment did not reduce spleen weight. The effect of intracecal DMF was similar to the highest tested dose of oral DMF (60 mg/kg). These results demonstrated that intracecal DMF suppresses inflammation and oxidative stress in ethanol and DSS-induced colitis without alteration of spleen weight. This suggests that the localized DMF administration could be beneficial approach of treating gastrointestinal ulcers.</p></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"16 ","pages":"Article 100142"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590098622000239/pdfft?md5=4e0f367da010b2257b00adad78d1a44c&pid=1-s2.0-S2590098622000239-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46009979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1