Drug Research最新文献

{"title":"The Effects of Quercetin on Apoptosis and Antioxidant Activity in a Renal Ischemia/Reperfusion Injury Animal Model.","authors":"Amin Bagheri,&nbsp;Ghazal Radman,&nbsp;Negar Aria,&nbsp;Fatemeh Rezaei,&nbsp;Mohammad Khajenouri,&nbsp;Shamim Ghiabi,&nbsp;Yasin Bagheri","doi":"10.1055/a-1999-7600","DOIUrl":"https://doi.org/10.1055/a-1999-7600","url":null,"abstract":"<p><p>Renal ischemia-reperfusion injury (IRI) is considered as one of the most prevalent causes of acute kidney injury (AKI), which can happen in various clinical situations including hypovolemic shock, injury, thrombo-embolism, and after a kidney transplant. This paper aims to evaluate the reno-protective effects of Quercetin in induced ischemia/reperfusion injury by regulating apoptosis-related proteins, inflammatory cytokines, MMP-2, MMP-9, and nuclear factor kappa-light-chain-enhancer inactivated B cells (NF-kB) in rats. The male Wistar rats (n=32) were randomly divided into Sham, untreated IR, and Quercetin-treated IR (gavage and intraperitoneal). Quercetin was given orally and intraperitoneally one hour before inducing ischemia-reperfusion injury . After reperfusion, blood samples and kidneys were collected to assess renal function and inflammatory cytokines, apoptotic signaling proteins, and antioxidants. Urea, creatinine, and MDA levels improved in Quercetin-treated groups with different administration methods. In addition, the activities of other antioxidant in Quercetin-treated rats were higher than those in the IR group. Further, Quercetin inhibited NF-kB signaling, apoptosis-associated factors and produced matrix metalloproteinase protein in the kidneys of rats. Based on the findings, the antioxidant, anti-inflammatory, and anti-apoptotic effects of the Quercetin diminished renal ischemia-reperfusion injury in the rats significantly. It is suggested that a single dosage of Quercetin have a reno-protective impact in the case of renal I/R injury.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":"73 5","pages":"255-262"},"PeriodicalIF":2.2,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9582745","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}

{"title":"Prazosin Protects the Liver Against Renal Ischemia/Reperfusion Injury in Rats.","authors":"Fatemeh Khajepour,&nbsp;Fariba Mahmoodpoor,&nbsp;Elmira Jafari,&nbsp;Farzad Kakaei,&nbsp;Farina Bahraminia,&nbsp;Shadi Aghajani,&nbsp;Sepideh Zununi Vahed,&nbsp;Yasin Bagheri","doi":"10.1055/a-2015-7976","DOIUrl":"https://doi.org/10.1055/a-2015-7976","url":null,"abstract":"<p><p>Acute kidney injury (AKI) is a common subsequent problem after many medical conditions. AKI is associated with distant organ dysfunction where systemic inflammation and oxidative stress play major roles. In this study, the effect of Prazosin, an α1-Adrenergic receptor antagonist, was investigated on the liver injury induced by kidney ischemia-reperfusion (I/R) in rats. Male adult Wistar rats (n=21) were divided into three groups: sham, kidney I/R, and kidney I/R pre-treated with Prazosin (1 mg/kg). Kidney I/R was induced by vascular clamping of the left kidney for 45 min to reduce the blood flow. Oxidative and antioxidant factors along with apoptotic (Bax, Bcl-2, caspase3), and inflammatory (NF-κβ, IL-1β, and IL-6) factors were measured in the liver at protein levels. Prazosin could reserve liver function (p<0.01) and increase glutathione level (p<0.05) after kidney I/R significantly. Malonil dialdehyde (MDA), a lipid peroxidation marker, was diminished more significantly in Prazosin-treated rats compared to the kidney I/R group (p<0.001). Inflammatory and apoptotic factors were diminished by Prazosin pre-treatment in the liver tissue (p<0.05). Pre-administration of Prazosin could preserve liver function and decrease its inflammatory and apoptotic factors under kidney I/R conditions.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":"73 5","pages":"289-295"},"PeriodicalIF":2.2,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9580075","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}

{"title":"Regulation of Adipose Tissue Insulin Resistance and Diabetic Parameters in Drug Naïve Subjects with Type 2 Diabetes Treated with Canagliflozin Monotherapy.","authors":"Eiji Kutoh,&nbsp;Alexandra N Kuto,&nbsp;Eri Ozawa,&nbsp;Rumi Kurihara,&nbsp;Midori Akiyama","doi":"10.1055/a-2007-1893","DOIUrl":"https://doi.org/10.1055/a-2007-1893","url":null,"abstract":"<p><p>The objective of this study is to investigate the link between the baseline/changes of body weight and those of diabetic parameters during treatment with an SGLT-2 inhibitor. Drug naïve subjects with T2DM received canagliflozin monotherapy for 3 months. Adipo-IR was selected as the significant factor responsible for the changes of (Δ)BMI with this drug. While no correlations were noted between ΔBMI and ΔFBG, ΔHbA1c, ΔHOMA-R or ΔQUICKI, significant negative correlations were observed between ΔBMI and Δadipo-IR (R=-0.308). The subjects were divided into two groups with baseline BMI<25 (n=31, group alpha) or≥25 (n=39, group beta). Baseline levels of FBG, HbA1c, T-C, TG, non-HDL-C, LDL-C showed no differences between group alpha and beta. The subjects were also divided into two equal numbers of subjects (n=35 each) based on the changes of weight: the lower half (-3.6%, p<0.00001, group A) and the upper half (0.1%, n.s., group B) of ∆BMI. FBG, HbA1c or HOMA-R significantly, similarly decreased, while QUICKI increased in group A and B. TG significantly decreased, while HDL-C increased in group A. HOMA-B significantly increased, while adipo-IR insignificantly decreased in group B. Collectively, these results suggest that 1) adipose tissue insulin resistance is responsible for the weight changes with canagliflozin. 2) baseline levels of glycemic and some lipid parameters were similar between obese and non-obese populations. 3) weight changes with canagliflozin were not associated with its glycemic or insulin sensitizing efficacies but were linked to adipose-tissue insulin resistance, some lipids, and beta-cell function.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":"73 5","pages":"279-288"},"PeriodicalIF":2.2,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9937209","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}

{"title":"AGEs RAGE Pathways: Alzheimer's Disease.","authors":"Shubhrat Maheshwari","doi":"10.1055/a-2008-7948","DOIUrl":"https://doi.org/10.1055/a-2008-7948","url":null,"abstract":"<p><p>Neurofibrillary tangles and plaques containing tau serve as the biological markers for Alzheimer disease (AD) and pathogenesis is widely believed to be driven by the production and deposition of the β-amyloid peptide (Aβ). The β-amyloid peptide (Aβ) that results from the modification of the amyloid precursor protein (APP) by builds up as amyloid deposits in neuronal cells. Thus, a protein misfolding process is involved in the production of amyloid. In a native, aqueous buffer, amyloid fibrils are usually exceedingly stable and nearly insoluble. Although amyloid is essentially a foreign substance made of self-proteins, the immune system has difficulty identifying and eliminating it as such for unknown reasons. While the amyloidal deposit may have a direct role in the disease mechanism in some disease states involving amyloidal deposition, this is not always the case. Current research has shown that PS1 (presenilin 1) and BACE (beta-site APP-cleaving enzyme) have - and -secretase activity that increases β-amyloid peptide (Aβ). Wealth of data has shown that oxidative stress and AD are closely connected that causes the death of neuronal cells by producing reactive oxygen species (ROS). Additionally, it has been demonstrated that advanced glycation end products (AGEs) and β-amyloidal peptide (Aβ) together increase neurotoxicity. The objective of this review is to compile the most recent and intriguing data of AGEs and receptor for advanced glycation end products (RAGE) pathways which are responsible for AD.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":"73 5","pages":"251-254"},"PeriodicalIF":2.2,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9580073","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}

{"title":"A preliminary study to identify existing drugs for potential repurposing in breast cancer based on side effect profile.","authors":"Emdormi Rymbai,&nbsp;Deepa Sugumar,&nbsp;Praveen Thaggikuppe Krishnamurthy,&nbsp;Divakar Selvaraj,&nbsp;Soumya Vasu,&nbsp;Shiva Priya,&nbsp;Saravanan Jayaram","doi":"10.1055/a-2011-5662","DOIUrl":"https://doi.org/10.1055/a-2011-5662","url":null,"abstract":"<p><p>Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer-related death in women after lung cancer. The present study aims to identify potential drug candidates using the PROMISCUOUS database for breast cancer based on side effect profile and then proceed with <i>in silico</i> and <i>in vitro</i> studies. PROMISCUOUS database was used to construct a group of drugs that share maximum side effects with letrozole. Based on the existing literature, ropinirole, risperidone, pregabalin, and gabapentin were selected for <i>in silico</i> and <i>in vitro</i> studies. The molecular docking was carried out using AUTODOCK 4.2.6. MCF-7 cell line was used to evaluate the anti-cancer activity of the selected drugs. PROMISCUOUS database revealed that as many as 23 existing drugs shared between 62 and 79 side-effects with letrozole. From docking result, we found that, ropinirole showed a good binding affinity (-7.7 kcal/mol) against aromatase compared to letrozole (-7.1 kcal/mol) which was followed by gabapentin (-6.4 kcal/mol), pregabalin (-5.7 kcal/mol) and risperidone (-5.1 kcal/mol). From the in vitro results, ropinirole and risperidone showed good anti-cancer activity of IC₅₀ with 40.85±11.02 μg/ml and 43.10±9.58 μg/ml cell viability. Based on this study results and existing literature we conclude that risperidone, pregabalin, and gabapentin are not ideal candidates for repurposing in breast cancer but ropinirole could be an excellent choice for repurposing in breast cancer after further studies.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":"73 5","pages":"296-303"},"PeriodicalIF":2.2,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9581498","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}

{"title":"Interferon-γ-Treated Mesenchymal Stem Cells Modulate the T Cell-Related Chemokines and Chemokine Receptors in an Animal Model of Experimental Autoimmune Encephalomyelitis.","authors":"Reza Ahmadifard,&nbsp;Abdollah Jafarzadeh,&nbsp;Merat Mahmoodi,&nbsp;Maryam Nemati,&nbsp;Mehdi Rahmani,&nbsp;Hossein Khorramdelazad,&nbsp;Fatemeh Ayoobi","doi":"10.1055/a-1995-6365","DOIUrl":"https://doi.org/10.1055/a-1995-6365","url":null,"abstract":"<p><strong>Background: </strong>Mesenchymal stem cells (MSCs) modulate immune responses, and their immunomodulatory potential can be enhanced using inflammatory cytokines. Here, the modulatory effects of IFN-γ-licensed MSCs on expression of T cell-related chemokines and chemokine receptors were evaluated using an experimental autoimmune encephalomyelitis (EAE) model.</p><p><strong>Material and methods: </strong>EAE was induced in 3 groups of C57bl/6 mice and then treated with PBS, MSCs and IFN-γ-treated MSCs. The EAE manifestations were registered daily and finally, the brain and spinal cords were isolated for histopathological and gene expression studies.</p><p><strong>Results: </strong>The clinical scores were lowered in MSCs and IFN-γ-licensed MSCs groups, however, mice treated with IFN-γ-licensed MSCs exhibited lower clinical scores than MSCs-treated mice. Leukocyte infiltration into the brain was reduced after treatment with MSCs or IFN-γ-licensed MSCs compared to untreated group (P<0.05 and P<0.01, respectively). In comparison with untreated EAE mice, treatment with MSCs reduced CCL20 expression (P<0.001) and decreased CXCR3 and CCR6 expression (P<0.02 and P<0.04, respectively). In comparison with untreated EAE mice, treatment with IFN-γ-licensed MSCs reduced CXCL10, CCL17 and CCL20 expression (P<0.05, P<0.05, and P<0.001, respectively) as well as decreased CXCR3 and CCR6 expression (P<0.002 and P<0.02, respectively), whilst promoting expression of CCL22 and its receptor CCR4 (P<0.0001 and P<0.02, respectively). In comparison with MSC-treated group, mice treated with IFN-γ-licensed MSCs exhibited lower CXCL10 and CCR6 expression (P<0.002 and P<0.01, respectively), whereas greater expression of CCL22 and CCR4 (P<0.0001 and P<0.01, respectively).</p><p><strong>Conclusion: </strong>Priming the MSC with IFN-γ can be an efficient approach to enhance the immunomodulatory potential of MSCs.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":"73 4","pages":"213-223"},"PeriodicalIF":2.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9614826","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}

{"title":"Transethosomes: A Promising Challenge for Topical Delivery Short Title: Transethosomes for Topical Delivery.","authors":"Mohammad Adnan,&nbsp;Md Faheem Haider,&nbsp;Nazish Naseem,&nbsp;Tanweer Haider","doi":"10.1055/a-1974-9078","DOIUrl":"https://doi.org/10.1055/a-1974-9078","url":null,"abstract":"<p><p>Skin provides an excellent barrier to molecular transport, as the stratum corneum is the most formidable barrier to the passage of most pharmaceuticals. Various attempts have been made to improve drug administration into the body through intact skin. Though very few routes are as attractive as the topical route, drug transport through the skin is challenging. To overcome the challenges, researchers have found a system in which the drug is encapsulated into the vesicle, penetrating deeper into the skin to hit the target site. Vesicular systems like transethosome, an ultra- deformable vesicle (UDV), tend to accumulate in the skin layers. Since transethosomes have small particle size and can easily alter the shape of vesicles compared to other vesicular systems, they can penetrate through the layers of skin. Hence, the drug encapsulated into transethosomes can easily reach the target site. Transethosomes consist of ethanol and phospholipids along with an edge activator. Ethanol and edge activator help to enhance the skin permeation of transethosomes. Various methods of preparation of transethosomes, comparison of transethosomes with other lipid vesicles, characterization of transethosomes, and application of transethosomes have been covered in this review. Transethosomes can deliver a different variety of drugs, such as anticancer, corticosteroids, proteins and peptides, analgesics.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":"73 4","pages":"200-212"},"PeriodicalIF":2.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9614812","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}

{"title":"Comparison of the efficacy of pioglitazone and metformin on ultrasound grade and liver enzymes level in patients with non-alcoholic fatty liver disease: A randomized controlled clinical trial.","authors":"Manouchehr Khoshbaten,&nbsp;Samineh Beheshtirouy,&nbsp;Shahrzad Shayanrad,&nbsp;Afshin Gharekhani,&nbsp;Haleh Rezaee","doi":"10.1055/a-1997-0401","DOIUrl":"https://doi.org/10.1055/a-1997-0401","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to evaluate the effectiveness of metformin and pioglitazone in combination with vitamin E on sonography grade and liver enzymes level in patients with non-alcoholic fatty liver disease.</p><p><strong>Methods: </strong>A randomized controlled clinical trial was designed with 68 patients diagnosed with non-alcoholic fatty liver disease by sonography and clinical examinations. Sixty-eight patients were randomly divided into two groups; 34 were assigned to receive 15 mg of pioglitazone per day and 34 were assigned to receive 1000 mg of metformin per day for 6 months. All of the patients received vitamin E at a dose of 800 IU daily for six months. The sonography grade of fatty liver and the levels of alanine aminotransferase and aspartate aminotransferase of patients were evaluated at baseline, and within three and six months after initiation of the intervention.</p><p><strong>Results: </strong>The use of metformin or pioglitazone in combination with vitamin E decreased the sonography grade of non-alcoholic fatty liver disease patients after 6 months of treatment (p-value<0.05); however, patients in metformin group benefit more compared to pioglitazone group. Patients who received metformin and vitamin E had a significant reduction in the levels of alanine aminotransferase and aspartate aminotransferase (p-value<0.05). There were no significant changes in the liver enzymes level of the patients who received pioglitazone and vitamin E (p-value>0.05).</p><p><strong>Major conclusion: </strong>The concomitant use of metformin and vitamin E significantly improves the sonography grade of fatty liver and the level of liver enzymes in patients with non-alcoholic fatty liver disease.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":"73 4","pages":"232-237"},"PeriodicalIF":2.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9688156","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}

{"title":"Development and Validation of HPLC Method for Quantification of Plumbagin in Plumbago Zeylanica L. Roots.","authors":"Babita Shukla,&nbsp;Poonam Kushwaha","doi":"10.1055/a-2019-4985","DOIUrl":"https://doi.org/10.1055/a-2019-4985","url":null,"abstract":"<p><strong>Background: </strong>An RP-HPLC (Reverse Phase-High-performance liquid chromatography) method for the quantitative estimation and validation of the plumbagin in the methanolic fraction of <i>Plumbago zeylanica</i> L<i>.</i> was developed.</p><p><strong>Method: </strong>For achieving good separation, the RP-HPLC method was carried out with reverse phase C18 column, using methanol and water as mobile phase in the ratio of 65:35 (v/v), at the flow rate of 1 mL/min. The detection wavelength was set at 265 nm.</p><p><strong>Results: </strong>The retention time of plumbagin was found at 7.5±0.2 min. The coefficient of determination of plumbagin was found to be (r²) 0.9985 and equation Y=23148x+4327. The LOD and LOQ were found to be 34.06 and 113 ng/mL, respectively.</p><p><strong>Conclusion: </strong>The developed method was accurate, specific, precise, and reproducible. This RP-HPLC may be useful for quantitative estimation of the chemical constituents present in the plant extract as well as the quality assessment of the herbal product.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":"73 4","pages":"238-242"},"PeriodicalIF":2.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9300655","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}

{"title":"Correction: Comparison of the efficacy of pioglitazone and metformin on ultrasound grade and liver enzymes level in patients with non-alcoholic fatty liver disease: A randomized controlled clinical trial.","authors":"Manouchehr Khoshbaten,&nbsp;Samineh Beheshtirouy,&nbsp;Shahrzad Shayanrad,&nbsp;Afshin Gharekhani,&nbsp;Haleh Rezaee","doi":"10.1055/a-2109-9465","DOIUrl":"https://doi.org/10.1055/a-2109-9465","url":null,"abstract":"","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":"73 4","pages":"e1"},"PeriodicalIF":2.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9692104","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}