Current Research in Pharmacology and Drug Discovery最新文献_第8页

Therapeutics for COVID-19 and post COVID-19 complications: An update COVID-19和COVID-19后并发症的治疗方法:最新进展

Current Research in Pharmacology and Drug Discovery Pub Date : 2022-01-01 DOI: 10.1016/j.crphar.2022.100086

Debdoot Basu , Vivek P. Chavda , Anita A. Mehta

{"title":"Therapeutics for COVID-19 and post COVID-19 complications: An update","authors":"Debdoot Basu , Vivek P. Chavda , Anita A. Mehta","doi":"10.1016/j.crphar.2022.100086","DOIUrl":"10.1016/j.crphar.2022.100086","url":null,"abstract":"<div><p>Since its inception in late December 2020 in China, novel coronavirus has affected the global socio-economic aspect. Currently, the world is seeking safe and effective treatment measures against COVID-19 to eradicate it. Many established drug molecules are tested against SARS-CoV-2 as a part of drug repurposing where some are proved effective for symptomatic relief while some are ineffective. Drug repurposing is a practical strategy for rapidly developing antiviral agents. Many drugs are presently being repurposed utilizing basic understanding of disease pathogenesis and drug pharmacodynamics, as well as computational methods. In the present situation, drug repurposing could be viewed as a new treatment option for COVID-19. Several new drug molecules and biologics are engineered against SARS-CoV-2 and are under different stages of clinical development. A few biologics drug products are approved by USFDA for emergency use in the covid management. Due to continuous mutation, many of the approved vaccines are not much efficacious to render the individual immune against opportunistic infection of SARS-CoV-2 mutants. Hence, there is a strong need for the cogent therapeutic agent for covid management. In this review, a consolidated summary of the therapeutic developments against SARS-CoV-2 are depicted along with an overview of effective management of post COVID-19 complications.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100086"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/16/44/main.PMC8813675.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39763964","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: 49

microRNAs: An opportunity to overcome significant challenges in malaria detection and control microRNAs:一个克服疟疾检测和控制方面重大挑战的机会

Current Research in Pharmacology and Drug Discovery Pub Date : 2022-01-01 DOI: 10.1016/j.crphar.2022.100115

Ruhi Sikka , Praveen Kumar Bharti , Himanshu Gupta

{"title":"microRNAs: An opportunity to overcome significant challenges in malaria detection and control","authors":"Ruhi Sikka , Praveen Kumar Bharti , Himanshu Gupta","doi":"10.1016/j.crphar.2022.100115","DOIUrl":"10.1016/j.crphar.2022.100115","url":null,"abstract":"<div><p>Organ damage and pathological disease states lead to the rapid release of microRNAs (miRNAs), a class of endogenous small non-coding RNAs, into the blood circulation. Because secreted miRNAs can be detected in biologic fluids such as plasma, they are currently being explored as promising non-invasive biomarkers of infectious and non-infectious diseases. Malaria remains a major global health challenge but still the potential of miRNAs has not been explored extensively in the context of malaria compared to other diseases. Here, we highlight important miRNAs found during different phases of the malaria life cycle in the anopheline vector and the human host. We have also put forward our opinion on how malaria parasite-stage-specific miRNAs can be incorporated into new diagnostic and prognostic tools to detect carrier mosquitoes and infected patients. In addition, we have emphasised the potential of miRNAs to be used as new therapeutics to treat severe malaria patients, an unresearched area of malaria control.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100115"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d0/0f/main.PMC9253159.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40572091","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: 3

Metabolic and clinical effect of alpha-lipoic acid administration in schizophrenic subjects stabilized with atypical antipsychotics: A 12-week, open-label, uncontrolled study 非典型抗精神病药物稳定的精神分裂症患者服用α -硫辛酸的代谢和临床效果:一项为期12周的开放对照研究

Current Research in Pharmacology and Drug Discovery Pub Date : 2022-01-01 DOI: 10.1016/j.crphar.2022.100116

Fiammetta Iannuzzo , Gianpaolo Antonio Basile , Domenica Campolo , Giovanni Genovese , Gianluca Pandolfo , Loretta Giunta , Domenica Ruggeri , Antonino Di Benedetto , Antonio Bruno

{"title":"Metabolic and clinical effect of alpha-lipoic acid administration in schizophrenic subjects stabilized with atypical antipsychotics: A 12-week, open-label, uncontrolled study","authors":"Fiammetta Iannuzzo , Gianpaolo Antonio Basile , Domenica Campolo , Giovanni Genovese , Gianluca Pandolfo , Loretta Giunta , Domenica Ruggeri , Antonino Di Benedetto , Antonio Bruno","doi":"10.1016/j.crphar.2022.100116","DOIUrl":"10.1016/j.crphar.2022.100116","url":null,"abstract":"<div><h3>Background</h3><p>Many of the atypical antipsychotics induce metabolic side effects, limiting their use in clinical practice. Alpha-lipoic acid (ALA) was proposed as a new approach in schizophrenia to improve metabolic effects of atypical antipsychotics. The aim of the study is to evaluate the effect of ALA on metabolic and clinical parameters among schizophrenic subjects.</p></div><div><h3>Methods</h3><p>15 schizophrenic subjects, in stable atypical antipsychotic monotherapy were included in the study. ALA was administrated at the oral daily dose of 600 mg/d in addition to antipsychotic therapy. Metabolic, clinical, and psychopathological parameters were measured at typical antipsychotics. e initial screening, and after 12 weeks.</p></div><div><h3>Results</h3><p>ALA produced a statistically significant reduction in QTc (<em>p</em> = <em>0.012</em>), blood glucose (<em>p</em> = <em>0.005</em>), AST (<em>p</em> = <em>0.021</em>), γGT (<em>p</em> = <em>0.035</em>), CPK (<em>p</em> = <em>0.005</em>) and prolactinaemia (<em>p</em> = <em>0.026</em>). In contrast, there was a significant increase in HbA1c (<em>p</em> = <em>0.026</em>). No effects on body weight and blood lipid levels (triglycerides, total cholesterol, HDL, LDL) emerged.</p></div><div><h3>Conclusions</h3><p>ALA treatment appeared to be effective for reducing diabetes risk, liver functionality parameters, hyperprolactinaemia and QTC interval. ALA appears to be safe as adjunctive components in schizophrenia.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100116"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9389248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40433142","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: 2

When disease extent is not always a key parameter: Management of refractory ulcerative proctitis 当疾病程度不总是一个关键参数:难治性溃疡性直肠炎的处理

Current Research in Pharmacology and Drug Discovery Pub Date : 2022-01-01 DOI: 10.1016/j.crphar.2021.100071

Georgios Michalopoulos , Konstantinos Karmiris

{"title":"When disease extent is not always a key parameter: Management of refractory ulcerative proctitis","authors":"Georgios Michalopoulos , Konstantinos Karmiris","doi":"10.1016/j.crphar.2021.100071","DOIUrl":"10.1016/j.crphar.2021.100071","url":null,"abstract":"<div><h3>Background</h3><p>Patients with ulcerative proctitis represent a sub-group of ulcerative colitis patients with specific characteristics. Disease-related symptoms, endoscopic findings and patient's personality perspectives create a difficult-to-assess condition in certain cases.</p></div><div><h3>Objectives</h3><p>To summarize available evidence on the management of refractory ulcerative proctitis and provide insights in treatment options.</p></div><div><h3>Results</h3><p>/Conclusion: Topical therapy plays a central role due to the location of the disease. However, well-established treatment options may become exhausted in a considerable proportion of ulcerative proctitis patients, indicating the need to advance to more potent therapies in order to induce and maintain clinical response and remission in these refractory cases. Systemic corticosteroids, thiopurines, calcineurin inhibitors, biologic agents and small molecules have all been tested with variable success rates. Investigational interventions as well as surgical procedures are kept as the ultimate resort in multi-treatment resistant cases. Identifying early prognostic factors that herald a disabling disease progression will help in optimizing treatment and avoiding surgery.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100071"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0b/ee/main.PMC8695253.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39789122","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

Examination of central nervous system by functional observation battery after massive intravenous infusion of carbon monoxide-bound and oxygen-bound hemoglobin vesicles in rats 大鼠大量静脉输注一氧化碳和氧结合血红蛋白囊泡后中枢神经系统功能观察电池的观察

Current Research in Pharmacology and Drug Discovery Pub Date : 2022-01-01 DOI: 10.1016/j.crphar.2022.100135

Hiromi Sakai , Shunichi Yasuda , Chie Okuda , Tetsuya Yamada , Keita Owaki , Yoji Miwa

{"title":"Examination of central nervous system by functional observation battery after massive intravenous infusion of carbon monoxide-bound and oxygen-bound hemoglobin vesicles in rats","authors":"Hiromi Sakai , Shunichi Yasuda , Chie Okuda , Tetsuya Yamada , Keita Owaki , Yoji Miwa","doi":"10.1016/j.crphar.2022.100135","DOIUrl":"10.1016/j.crphar.2022.100135","url":null,"abstract":"<div><p>Carbon monoxide (CO) is known as a toxic gas inducing “CO poisoning”, which acutely affects the central nervous system (CNS) and which persistently affects brain functions depending on the exposure time and CO concentration. By contrast, in pathological rodent models, intravenous infusion of CO-bound hemoglobin vesicles (CO-HbV) has shown various beneficial effects such as anti-oxidative and anti-inflammatory reactions. This study assessed effects of CO-HbV infusion on CNS using a functional observation battery, sensory reflexes, grip strength, and landing foot splay measurements. The test fluids were CO-HbV and O<sub>2</sub>-bound HbV (O<sub>2</sub>-HbV) suspended in saline ([Hb] = 10 g/dL), and saline alone for comparison. The rats received either 16 or 32 mL/kg of fluid intravenously at 1.5 mL/min/kg. Observations were made before infusion, and at 5 min, 4, 8, 24, 48 and 72 h after infusion. Massive doses of 16 and 32 mL/kg respectively corresponded to about 29 and 57% of the whole circulating blood volume (56 mL/kg). No toxicological effect was observed in any measurement item for any group in comparison to the control saline infusion group. Histopathological examination of hippocampal tissue at 14 days after infusion showed the number of necrotic cells to be minimal. Results obtained from rats in this experiment suggest that the massive intravenous infusion of CO-HbV yields beneficial anti-oxidative and anti-inflammatory effects without showing CO-poisoning-related symptoms of CNS damage.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100135"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/be/be/main.PMC9780079.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10437354","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: 2

Plant metabolite diosmin as the therapeutic agent in human diseases 植物代谢物薯蓣皂苷作为人类疾病的治疗剂

Current Research in Pharmacology and Drug Discovery Pub Date : 2022-01-01 DOI: 10.1016/j.crphar.2022.100122

Saad Mustafa , Mahmood Akbar , Mohammad Aasif Khan , Kumari Sunita , Shabana Parveen , Jogendra Singh Pawar , Sheersh Massey , Nupur Rani Agarwal , Syed Akhtar Husain

{"title":"Plant metabolite diosmin as the therapeutic agent in human diseases","authors":"Saad Mustafa , Mahmood Akbar , Mohammad Aasif Khan , Kumari Sunita , Shabana Parveen , Jogendra Singh Pawar , Sheersh Massey , Nupur Rani Agarwal , Syed Akhtar Husain","doi":"10.1016/j.crphar.2022.100122","DOIUrl":"10.1016/j.crphar.2022.100122","url":null,"abstract":"<div><p>Plant-derived flavonoids have been the focus of research for many years mainly in the last decade owing to their therapeutic properties. So far, about 4000 flavonoids have been identified from plants and diosmin (a flavone glycoside) is one of them. Online databases, previous studies, and reviews have been used to gather information on anti-oxidant, immunomodulatory, anti-cancer, anti-parasitic, and anti-microbialproperties of diosmin. Effects of diosmin in combination with other flavonoids have been reviewed thoroughly and its administrative routes are also summarized. Additionally, we studied the effect of diosmin on critical protein networks. It exhibits therapeutic effects in diabetes and its associated complications such as neuropathy and dyslipidemia. Combination of diosmin with hesperidin is found to be very effective in the treatment of chronic venous insufficiency and haemorrhoids. Diosmin is an exquisite therapeutic agent alone as well as in combination with other flavonoids.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100122"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/81/5d/main.PMC9780066.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10803442","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: 10

Regulatory role of miRNAs in Wnt signaling pathway linked with cardiovascular diseases mirna在心血管疾病相关Wnt信号通路中的调节作用

Current Research in Pharmacology and Drug Discovery Pub Date : 2022-01-01 DOI: 10.1016/j.crphar.2022.100133

Jiban Kumar Behera , Manojit Bhattacharya , Pabitra Mishra , Akansha Mishra , Adya Anindita Dash , Niladri Bhusan Kar , Bhaskar Behera , Bidhan Chandra Patra

{"title":"Regulatory role of miRNAs in Wnt signaling pathway linked with cardiovascular diseases","authors":"Jiban Kumar Behera , Manojit Bhattacharya , Pabitra Mishra , Akansha Mishra , Adya Anindita Dash , Niladri Bhusan Kar , Bhaskar Behera , Bidhan Chandra Patra","doi":"10.1016/j.crphar.2022.100133","DOIUrl":"10.1016/j.crphar.2022.100133","url":null,"abstract":"<div><p>MicroRNAs (miRNAs) are discovered in science about 23 years ago. These are short, a series of non-coding, single-stranded and evolutionary conserved RNA molecules found in eukaryotic cells. It involved post-transcriptional fine-tune protein expression and repressing the target of mRNA in different biological processes. These miRNAs binds with the 3′-UTR region of specific mRNAs to phosphorylate the mRNA degradation and inhibit the translation process in various tissues. Therefore, aberrant expression in miRNAs induces numerous cardiovascular diseases and developmental defects. Subsequently, the miRNAs and Wnt singling pathway are regulating a cellular process in cardiac development and regeneration, maintain the homeostasis and associated heart diseases. In Wnt signaling pathway majority of the signaling components are expressed and regulated by miRNAs, whereas the inhibition or dysfunction of the Wnt signaling pathway induces cardiovascular diseases. Moreover, inadequate studies about the important role of miRNAs in heart development and diseases through Wnt signaling pathway has been exist still now. For this reason in present review we summarize and update the involvement of miRNAs and the role of Wnt signaling in cardiovascular diseases. We have discussed the mechanism of miRNA functions which regulates the Wnt components in cellular signaling pathway. The fundamental understanding of Wnt signaling regulation and mechanisms of miRNAs is quite essential for study of heart development and related diseases. This approach definitely enlighten the future research to provide a new strategy for formulation of novel therapeutic approaches against cardiovascular diseases.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100133"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9c/e0/main.PMC9780067.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10428211","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

miRNA nanoencapsulation to regulate the programming of the blood-brain barrier permeability by hypoxia miRNA纳米包封调节缺氧对血脑屏障通透性的编程

Current Research in Pharmacology and Drug Discovery Pub Date : 2022-01-01 DOI: 10.1016/j.crphar.2022.100129

Esteban G. Figueroa , Aitor Caballero-Román , Josep R. Ticó , Montserrat Miñarro , Anna Nardi-Ricart , Alejandro González-Candia

{"title":"miRNA nanoencapsulation to regulate the programming of the blood-brain barrier permeability by hypoxia","authors":"Esteban G. Figueroa , Aitor Caballero-Román , Josep R. Ticó , Montserrat Miñarro , Anna Nardi-Ricart , Alejandro González-Candia","doi":"10.1016/j.crphar.2022.100129","DOIUrl":"10.1016/j.crphar.2022.100129","url":null,"abstract":"<div><p>Central nervous system (CNS)-related diseases are difficult to treat as most therapeutic agents they cannot reach the brain tissue, mainly due to the blood-brain barrier (BBB), arguably the tightest barrier between the human body and cerebral parenchyma, which routinely excludes most xenobiotic therapeutics compounds. The BBB is a multicellular complex that structurally forms the neurovascular unit (NVU) and is organized by neuro-endothelial and glial cells. BBB breakdown and dysfunction from the cerebrovascular cells lead to leakages of systemic components from the blood into the CNS, contributing to neurological deficits. Understanding the molecular mechanisms that regulate BBB permeability and disruption is essential for establishing future therapeutic strategies to restore permeability and improve cerebrovascular health. MicroRNAs (miRNAs), a type of small non-coding RNAs, are emerging as an important regulator of BBB integrity by modulating gene expression by targeting mRNA transcripts. miRNAs is implicated in the development and progression of various illnesses. Conversely, nanoparticle carriers offer unprecedented opportunities for cell-specific controlled delivery of miRNAs for therapeutic purposes. In this sense, we present in this graphical review critical evidence in the regulation of cell junction expression mediated by miRNAs induced by hypoxia and for the use of nanoparticles for the delivery of miRNA-based therapeutics in the treatment of BBB permeability.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100129"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9780061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10428212","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: 2

Promising effects of emoxypine and its succinate derivative in the management of various diseases-with insights on recent patent applications emoxypine及其琥珀酸盐衍生物在各种疾病治疗中的有希望的作用-对最近专利申请的见解

Current Research in Pharmacology and Drug Discovery Pub Date : 2022-01-01 DOI: 10.1016/j.crphar.2022.100121

Dhruv Sanjay Gupta, Siddhi Bagwe Parab, Ginpreet Kaur

{"title":"Promising effects of emoxypine and its succinate derivative in the management of various diseases-with insights on recent patent applications","authors":"Dhruv Sanjay Gupta, Siddhi Bagwe Parab, Ginpreet Kaur","doi":"10.1016/j.crphar.2022.100121","DOIUrl":"10.1016/j.crphar.2022.100121","url":null,"abstract":"<div><p>Emoxypine and its succinate derivative share a common hydroxypridine structure, which is similar to pyridoxine. These compounds have been utilized therapeutically and industrially, owing to the wide range of properties offered. This includes antihypoxic, neuroprotective and cardioprotective effects, along with pharmacokinetic benefits such as the ability to cross the blood brain barrier (BBB), owing to its relatively small size and low molecular weight. It was observed that emoxypine exhibited iron chelating property in vitro, indicating its usage as a promising therapeutic strategy in the management of neurodegenerative conditions such as Alzheimer's disease (AD), as well as hematologic disorders like thalassemia and hemochromatosis. In addition to this, it has been observed to exert a potent antioxidant effect, therefore, it may be considered for the amelioration of disorders resulting from free radical injury. Studies on its mechanism of action and implications on cellular and molecular levels would help to further the understanding of its benefits, as well as prospects for filing patents for novel applications. The primary focus of this review is to shed light on the broad spectrum of pharmacological properties offered by emoxypine and its succinate derivative, and to highlight the scope for an increased number of pre-clinical and clinical trials to assess its safety and efficacy. In addition to this, the highlights of this article include the recent patents filed and scope for novel applications of these agents.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100121"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ee/28/main.PMC9389226.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40433136","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: 6

Prolyl hydroxylase inhibitor desidustat improves anemia in erythropoietin hyporesponsive state 脯氨酰羟化酶抑制剂去西杜司他改善红细胞生成素低反应状态下的贫血

Current Research in Pharmacology and Drug Discovery Pub Date : 2022-01-01 DOI: 10.1016/j.crphar.2022.100102

Amit A. Joharapurkar, Vishal J. Patel, Samadhan G. Kshirsagar, Maulik S. Patel, Hardikkumar H. Savsani, Chetan Kajavadara, Darshan Valani, Mukul R. Jain

{"title":"Prolyl hydroxylase inhibitor desidustat improves anemia in erythropoietin hyporesponsive state","authors":"Amit A. Joharapurkar, Vishal J. Patel, Samadhan G. Kshirsagar, Maulik S. Patel, Hardikkumar H. Savsani, Chetan Kajavadara, Darshan Valani, Mukul R. Jain","doi":"10.1016/j.crphar.2022.100102","DOIUrl":"10.1016/j.crphar.2022.100102","url":null,"abstract":"<div><p>Many anemic chronic kidney disease (CKD) patients are refractory to erythropoietin (EPO) effects due to inflammation, deranged iron utilization, and generation of EPO antibodies. This work assessed the effect of desidustat, an inhibitor of hypoxia inducible factor (HIF) prolyl hydroxylase (PHD), on EPO-refractory renal anemia. Sprague Dawley rats were made anemic by cisplatin (5 mg/kg, IP, single dose) and turpentine oil (5 mL/kg, SC, once a week). These rats were given recombinant human EPO (rhEPO, 1 μg/kg) and desidustat (15 or 30 mg/kg) for eight weeks. Separately, rhEPO (1–5 μg/kg) was given to anemic rats to sustain the normal hemoglobin levels and desidustat (15 mg/kg) for eight weeks. In another experiment, the anemic rats were treated rhEPO (5 μg/kg) for two weeks and then desidustat (15 mg/kg) for the next two weeks. Dosing of rhEPO was thrice a week, and for desidustat, it was on alternate days. Desidustat inhibited EPO-resistance caused by rhEPO treatment, decreased hepcidin, IL-6, IL-1β, and increased iron and liver ferroportin. Desidustat reduced EPO requirement and anti-EPO antibodies. Desidustat also maintained normal hemoglobin levels after cessation of rhEPO treatment. Thus, novel prolyl hydroxylase inhibitor desidustat can treat EPO resistance via improved iron utilization and decreased inflammation.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100102"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590257122000220/pdfft?md5=7ab92260618d2528e7ce75ad5d1111c5&pid=1-s2.0-S2590257122000220-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41974337","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: 2