Iranian Journal of Pharmaceutical Research最新文献

{"title":"Modulating the Biliverdin Reductase (BVR)/ERK1/2 Axis to Attenuate Oxidative Stress in Rat Arterial Rings.","authors":"Kuldeepak Sharma, Mateja Skufca Sterle, Hugon Mozina","doi":"10.5812/ijpr-156828","DOIUrl":"10.5812/ijpr-156828","url":null,"abstract":"<p><strong>Background: </strong>Biliverdin reductase (BVR) plays a central role in bile pigment metabolism by reducing biliverdin (BV) to bilirubin (BR), a potent antioxidant that scavenges reactive oxygen species (ROS) under normal and pathological conditions. Elevated oxidative stress activates extracellular signal-regulated protein kinases 1/2 (ERK1/2) signaling, which strongly interacts with BVR's C and D motifs, forming the BVR/ERK1/2 axis. In pathological states, increased ERK1/2 activity inhibits BVR's ability to convert BV to BR, exacerbating oxidative damage and contributing to cardiovascular disease. Therefore, the interaction between BVR and ERK1/2 is critical in modulating oxidative stress.</p><p><strong>Objectives: </strong>This study aimed to evaluate the effects of BR and the ERK1/2 inhibitor PD-98059, both individually and in combination, on ROS levels, ERK1/2 activity, and vascular responses under normoxic and hypoxia-reoxygenation (H-R) injury conditions.</p><p><strong>Methods: </strong>Aortic rings from rats were subjected to equal distending pressure after oxidative stress induction using 22'-Azobis (2-amidinopropane) dihydrochloride (ABAP) in an organ bath. Different doses of BR were administered in combination with the ERK1/2 inhibitor PD-98059 to assess their impact on ROS depletion, vascular relaxation, and maximal effect (Emax).</p><p><strong>Results: </strong>The combination of BR and PD-98059 significantly enhanced aortic relaxation and Emax under both normoxic and H/R conditions compared to either treatment alone. Inhibiting ERK1/2 with PD-98059 appeared to upregulate BVR activity, increasing BR synthesis and reducing oxidative damage in aortic rings.</p><p><strong>Conclusions: </strong>Biliverdin reductase plays a vital role in defending against oxidative stress and endothelial dysfunction through its dual-specificity kinase activity and interaction with ERK1/2. ERK1/2 inhibition further enhances BR's ROS-scavenging ability and vascular protective effects. Targeting the interaction between BVR and ERK1/2 holds potential as an effective therapeutic strategy for conditions characterized by excessive ROS levels, such as cardiovascular diseases.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"23 1","pages":"e156828"},"PeriodicalIF":1.8,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Application of Machine Learning in Predicting the Permeability of Drugs Across the Blood Brain Barrier.","authors":"Sogand Jafarpour, Maryam Asefzadeh, Ehsan Aboutaleb","doi":"10.5812/ijpr-149367","DOIUrl":"10.5812/ijpr-149367","url":null,"abstract":"<p><p>The inefficiency of some medications to cross the blood-brain barrier (BBB) is often attributed to their poor physicochemical or pharmacokinetic properties. Recent studies have demonstrated promising outcomes using machine learning algorithms to predict drug permeability across the BBB. In light of these findings, our study was conducted to explore the potential of machine learning in predicting the permeability of drugs across the BBB. We utilized the B3DB dataset, a comprehensive BBB permeability molecular database, to build machine learning models. The dataset comprises 7,807 molecules, including information on their permeability, stereochemistry, and physicochemical properties. After preprocessing and cleaning, various machine learning algorithms were implemented using the Python library Pycaret to predict permeability. The extra trees classifier model outperformed others when using Morgan fingerprints and Mordred chemical descriptors (MCDs), achieving an area under the curve (AUC) of 0.93 and 0.95 on the test dataset. Additionally, we conducted an experiment to train a voting classifier combining the top three performing models. The best-blended model, trained on MCDs, achieved an AUC of 0.96. Furthermore, Shapley additive exPlanations (SHAP) analysis was applied to our best-performing single model, the extra trees classifier trained on MCDs, identifying the Lipinski rule of five as the most significant feature in predicting BBB permeability. In conclusion, our combined model trained on MCDs achieved an AUC of 0.96, an F1 Score of 0.91, and an MCC of 0.74. These results are consistent with prior studies on CNS drug permeability, highlighting the potential of machine learning in this domain.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"23 1","pages":"e149367"},"PeriodicalIF":1.8,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Malleatin A and B: New Premyrsine-Type Diterpenes from <i>Euphorbia malleata</i> with Cytotoxic Effects Against A2780 Wild and A2780 R-CIS Ovarian Cancer Cell Lines in Mono or Combination Treatment with Cisplatin.","authors":"Behzad Zolfaghari, Forough Akbari, Sajad Esmaeili, Mahmoud Aghaei, Fatemeh Mosaffa, Seyedeh Sara Ghorbanhosseini, Mustafa Ghanadian","doi":"10.5812/ijpr-147396","DOIUrl":"10.5812/ijpr-147396","url":null,"abstract":"<p><strong>Background: </strong>This study focused on macrocyclic diterpenes derived from Euphorbia, particularly myrsinanes, and their potential in cytotoxic and combination treatments for resistant cancer cells. We examine premyrsinanes isolated from <i>Euphorbia malleata</i> and explore their cytotoxic properties.</p><p><strong>Methods: </strong><i>Euphorbia malleata</i> was collected from Taragh-Roud, Natanz, Iran. The semi-polar chloroform/acetone extract was chromatographed and fractionated using a large silica column. Fractions containing diterpene resonances were selected based on ¹H-NMR spectra and were further subjected to smaller silica or Sephadex columns, followed by a recycling HPLC system. The isolated compounds were identified through 1D and 2D-NMR experiments and mass spectrometry. The cytotoxicity of the isolated compounds was assessed using the MTT assay against A2780 wild and A2780 cisplatin-resistant (R-CIS) cells, both in mono and combination treatments with cisplatin.</p><p><strong>Results and conclusions: </strong>Using a Waters 616 HPLC pump and a YMC prep silica column, we successfully isolated two new premyrsinane diterpenes (Malleatin A and Malleatin B) alongside two known compounds (beta-sitosterol and loliolide). Malleatin A exhibited cytotoxicity against A2780 wild and A2780 R-CIS cells, with an IC₅₀ range of 50 - 65 μM in the MTT assay. While cisplatin demonstrated significant cytotoxic effects on the A2780 wild cell line, it was ineffective against the A2780 R-CIS cells due to their resistance. However, the combination therapy of Malleatin A and cisplatin exhibited a synergistic effect, significantly increasing the mortality rate of the resistant cells compared to monotherapy. The Combination Index (CI) of 0.58 indicates effective synergy, and the Dose Reduction Index (DRI) of 3.65 suggests a favorable reduction in the dosage of cisplatin needed, potentially reducing its associated side effects.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"23 1","pages":"e147396"},"PeriodicalIF":1.8,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of Apoptosis, Autophagy, and Metastasis by Luteolin in Human Bladder Cancer EJ138 Cells: An Experimental Study.","authors":"Mohammad Amin Vatankhah, Alireza Ziyabakhsh, Mohammad Vakili Ojarood","doi":"10.5812/ijpr-153408","DOIUrl":"10.5812/ijpr-153408","url":null,"abstract":"<p><strong>Background: </strong>Chemotherapy remains a primary approach to cancer treatment, widely applied in bladder cancer (BC). However, the various side effects and resistance associated with chemotherapeutic drugs pose significant challenges in BC therapy, prompting interest in natural compounds like luteolin. Studies focus on its effects on key biological processes involved in BC, including metastasis, apoptosis, and autophagy.</p><p><strong>Objectives: </strong>This study investigated the regulation of mRNA expression of genes associated with apoptosis (BCL2, P53), autophagy (ULK1, ATG12), and metastasis (MMP2, MMP9) in malignant BC cells treated with luteolin.</p><p><strong>Methods: </strong>This was an in vitro experimental study. EJ138 BC cells were treated with various concentrations of luteolin, and its impact on cell viability, proliferation, and gene expression was assessed.The cytotoxic effect of luteolin on EJ138 BC cells was evaluated using the MTT assay after 24- and 48-hour treatments with different luteolin concentrations. Flow cytometry was performed to examine luteolin's anti-proliferative effect, and RT-PCR was used to analyze mRNA expression of BCL2, P53, ULK1, ATG12, MMP2, and MMP9 genes.</p><p><strong>Results: </strong>MTT assay results confirmed that luteolin reduced the proliferation rate of BC cells. Flow cytometry indicated increased cell death in EJ138 BC cells following luteolin treatment. RT-PCR findings demonstrated that luteolin upregulated P53, ULK1, and ATG12 expression while downregulating BCL2 mRNA expression. However, luteolin treatment in EJ138 cells did not significantly alter MMP2 and MMP9 expression levels.</p><p><strong>Conclusions: </strong>These findings indicate that luteolin exerts cytotoxic effects on EJ138 BC cells by dysregulating mRNA expression of genes involved in apoptosis and autophagy. Therefore, luteolin shows potential as an effective anti-cancer agent for BC therapy.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"23 1","pages":"e153408"},"PeriodicalIF":1.8,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Glucagon-Like Peptide-1 (GLP-1) Receptor Agonist Liraglutide Regulates Sirtuin-1-Mediated Neutrophil Extracellular Traps to Improve Diabetes-Induced Bone Metabolism Imbalance.","authors":"Shuai Zhong, Liangzhi Huang, Tingting Lin, Yanyan Li, Bin Deng, Dezhi Kong, Zhanlin Liao, Zugui Huang","doi":"10.5812/ijpr-148139","DOIUrl":"10.5812/ijpr-148139","url":null,"abstract":"<p><strong>Background: </strong>Diabetes mellitus (DM) is a chronic metabolic disorder that disrupts normal bone remodeling.</p><p><strong>Objectives: </strong>This study aimed to investigate how the glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide (LIR) addresses bone metabolism imbalances induced by type-II diabetes.</p><p><strong>Methods: </strong>Type-II diabetic rat models were established through a single intraperitoneal injection of streptozotocin (STZ). Blood glucose levels were measured using a blood glucose meter, and insulin levels were assessed using an assay kit. Bone formation markers [alkaline phosphatase (ALP), osteocalcin (OCN), and procollagen I N-terminal propeptide (PINP)] and bone resorption markers [tartrate-resistant acid phosphatase (TRACP) and CTX-1] were monitored using assay kits. Bone marrow mesenchymal stem cells (BMSCs) were cultured in vitro under high-fat and high-glucose (HFHS) conditions to mimic diabetic bone metabolism dysregulation. Neutrophil extracellular traps (NETs) formation was examined through immunofluorescent staining and Western blot analysis.</p><p><strong>Results: </strong>Liraglutide was found to reduce STZ-induced NETs formation, as indicated by decreased expression of cit-H3 by 36.90% - 53.57%, myeloperoxidase (MPO) by 55.81% - 65.12%, NE by 53.95% - 65.17%, and PAD4 by 46.81% - 63.83%, alongside increased Sirtuin-1 (SIRT1) expression in femur tissue (70.71% - 91.19%). In vitro, LIR enhanced osteogenesis and inhibited apoptosis, effects that were partially reversed by SIRT1 knockdown. Additionally, SIRT1 knockdown partially restored LIR-induced reductions in oxidative stress, inflammation, and NETs formation.</p><p><strong>Conclusions: </strong>LIR mitigates diabetes-induced bone metabolism imbalance by inhibiting NETs formation through SIRT1 mediation.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"23 1","pages":"e148139"},"PeriodicalIF":1.8,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Apoptotic Impact of Heliox Cold Plasma on a Cervical Cell Line Using Gold Nanoparticle-Doped Graphene Oxide Nanosheets.","authors":"Mahsa Vatani, Simzar Hosseinzadeh, Amirhossein Sari, Hamidreza Ghomi Marzdashti, Azam Rahimpour, Roya Fattahi","doi":"10.5812/ijpr-150385","DOIUrl":"10.5812/ijpr-150385","url":null,"abstract":"<p><strong>Background: </strong>Invasive cervical cancer is recognized as the second most common malignancy in women after breast cancer.</p><p><strong>Objectives: </strong>This study investigates, for the first time, the effect of gold nanoparticle-doped graphene oxide (GO) nanosheets on the human epithelial carcinoma (HeLa) cell line in the presence of heliox cold plasma.</p><p><strong>Methods: </strong>Graphene oxide nanosheets were synthesized using the Hummer method and then doped with gold nanoparticles. The nanoparticles were characterized by transmission electron microscopy (TEM), and the diffraction peaks of GO and gold nanoparticles were confirmed through X-ray diffraction (XRD) analysis. Additionally, the optical absorbance of the nanoparticles was measured in the range of 200 - 900 nm using UV-Visible spectroscopy. A plasma generator was fabricated to produce cold plasma using helium (He) and oxygen (O₂) gases at a 99:1 ratio. The radicals generated by the cold plasma were analyzed via optical emission spectroscopy (OES). Cell treatment was conducted by applying various concentrations of GO and GO/Au nanoparticles. Cellular phenotype was monitored through optical microscopy, and biocompatible concentrations of both nanoparticles were determined using the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. Subsequently, cold plasma at varying distances and durations was applied to the nanoparticle-treated cells. The generated radicals and the expression of apoptotic genes in treated cells were assessed using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and real-time PCR, respectively.</p><p><strong>Results: </strong>The width of the bacillus-like gold nanoparticles was 15.13 ± 0.96 nm. The cold plasma generated radicals such as N2I2⁺, N2II1⁻, He•, and O⁻•. XRD analysis confirmed the successful coupling of gold onto the GO nanosheets. The biocompatible concentrations of GO and GO/Au nanoparticles were found to be 30 µg/100 µL and 20 µg/100 µL, respectively, as determined by the MTT assay. Radical formation increased as incubation time was extended from 30 to 60 seconds. Furthermore, real-time PCR analysis demonstrated the highest levels of p53, Bax, and caspase 3/8 expression at a plasma exposure time of 60 seconds in the composite-treated group, while Bcl2 expression was significantly reduced.</p><p><strong>Conclusions: </strong>The findings suggest that the parameters of heliox cold plasma and the concentrations of GO/Au nanoparticles must be optimized to effectively induce apoptosis in cervical cancer cells.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"23 1","pages":"e150385"},"PeriodicalIF":1.8,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"C-Phycocyanin and Phycocyanobilin as a Novel Adjuvant in Hepatitis B Vaccine.","authors":"Nargess Abdali, Reza Tabaripour, Solaleh Javadi, Mehrab Nasirikenari, Mehdi Birjandi, Vahid Siavashi, Mohammad Reza Naghavi, Zahra Hasani, Ali Ahmari, Hossein Hanifi","doi":"10.5812/ijpr-147060","DOIUrl":"https://doi.org/10.5812/ijpr-147060","url":null,"abstract":"<p><strong>Background: </strong>Vaccine adjuvants are components that enhance immune responses to an antigen. Given the importance of adjuvants, research on novel adjuvants with higher efficacy and fewer adverse effects remains crucial. <i>Spirulina</i> (<i>Arthrospira</i> sp.), an aqueous, photosynthetic, filamentous, spiral, multicellular microalga also classified as a cyanobacterium, is well known for its high protein content, vitamins, essential fatty acids, and amino acids. C-phycocyanin (C-PC) is one of the most significant proteins in <i>Spirulina</i>.</p><p><strong>Objectives: </strong>This study aimed to investigate the adjuvant capabilities of three <i>Spirulina</i>-derived substances-<i>Spirulina</i> extract, C-phycocyanin (C-PC), and phycocyanobilin (PCB)-in conjunction with the Hepatitis B surface antigen (HBsAg).</p><p><strong>Methods: </strong>Vaccine groups received the vaccine and adjuvants three times at two-week intervals, administered either orally or by injection in encapsulated or naked forms. To use the injectable form while preventing antigenic effects from the C-PC protein portion, the PCB portion was isolated and used as an injectable adjuvant.</p><p><strong>Results: </strong>The highest levels of interferon gamma (IFN-γ) and interleukin 4 (IL-4) stimulation were observed in the naked PCB form with the vaccine. In both oral and injectable forms of PCB and C-PC, results indicated an increased expression of Hepatitis B surface antibodies (HBsAb) in response to the antigen. The absence of a significant difference between C-PC and <i>Spirulina</i> extract in oral form suggested that the adjuvant effect of this microalga was primarily due to the C-PC compound. Additionally, the injectable form of PCB led to the highest HBsAb expression level. This enhancement of the humoral immune response indicated that these compounds have potential as adjuvants in both oral and injectable forms.</p><p><strong>Conclusions: </strong>These findings suggest the potential for improved Hepatitis B vaccine efficacy with this novel adjuvant, paving the way for further evaluation with other vaccines.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"23 1","pages":"e147060"},"PeriodicalIF":1.8,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The COVID-19 Pandemic and the Resilience of the Pharmaceutical Supply Chain: Lessons from Past Experiences and Strategies for the Future.","authors":"Mohamad Ali Aivazi, Hamid Reza Rasekh, Mohammad Peikanpour, Farzad Peiravian, Sajjad Esmaeili, Leila Zarei","doi":"10.5812/ijpr-152723","DOIUrl":"https://doi.org/10.5812/ijpr-152723","url":null,"abstract":"<p><strong>Background: </strong>The pharmaceutical supply chain (PSC) faced numerous challenges, particularly during the COVID-19 crisis. Due to the supply chain (SC) 's vulnerabilities, it requires enhanced capabilities to address these challenges. In Iran, specific economic and political issues have intensified the vulnerabilities of the PSC.</p><p><strong>Objectives: </strong>This study investigates the issues caused by the COVID-19 crisis in the PSC, identifies and characterizes these issues, and recommends appropriate courses of action to address future SC disruptions.</p><p><strong>Methods: </strong>This study is a qualitative-quantitative analysis conducted in Iran during the COVID-19 crisis. Qualitative thematic analysis was performed from July 2022 until May 2023. Semi-structured, in-depth, face-to-face interviews with 23 Iranian PSC specialists were conducted until saturation was reached. The qualitative phase was analyzed using MAXQDA 2021. The quantitative phase included a survey of 547 individuals working in pharmaceutical manufacturing in Iran, with the questionnaires analyzed using SPSS 26.</p><p><strong>Results: </strong>In the qualitative phase, the research identified two main themes: (1) vulnerabilities and (2) capabilities, along with 15 subthemes providing solutions to enhance the resilience of the PSC. In the quantitative phase, findings from 64 questionnaires highlighted major vulnerabilities and capabilities necessary to create a resilient SC. The median score for vulnerabilities was 5.12, while the median score for capabilities was 5.39.</p><p><strong>Conclusions: </strong>According to the questionnaire results, the quantitative findings indicate that capabilities received a higher score, suggesting that this sector of the PSC demonstrated better resilience against the pandemic. This study, with its contextual focus, mixed-method approach, comprehensive analysis of vulnerabilities and capabilities, and sector-specific insights, offers a novel contribution to the understanding of SC resilience within Iranian pharmaceutical manufacturing. It also has the potential to promote further research in other sectors of the PSC.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"23 1","pages":"e152723"},"PeriodicalIF":1.8,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Curcumin-Etoposide Synergy: Unveiling the Molecular Mechanisms of Enhanced Apoptosis and Chemoresistance Attenuation in Breast Cancer.","authors":"Bahar Jaberian Asl, Reza Afarin, Mahdi Hatami, Amineh Dehghani Madiseh, Mohammadreza Roshanazadeh, Mojtaba Rashidi","doi":"10.5812/ijpr-150978","DOIUrl":"https://doi.org/10.5812/ijpr-150978","url":null,"abstract":"<p><strong>Background: </strong>Combining natural compounds with chemotherapeutic agents has emerged as a promising approach for cancer treatment. Curcumin (Cur), a natural polyphenol, is known for its anti-cancer properties, including the ability to induce apoptosis and arrest cell cycle progression.</p><p><strong>Objectives: </strong>This study aimed to evaluate the effects of Cur and etoposide (ETO), both individually and in combination, on the induction of apoptosis in breast cancer (BC) cell lines.</p><p><strong>Methods: </strong>The impact of Cur and ETO on cell proliferation was assessed using MTT viability assays. Apoptosis induction by these drugs was evaluated through Annexin V flow cytometry and caspase-3 and caspase-9 activity assays. Quantitative real-time PCR was employed to measure Bax and Bcl-2 gene expression levels. Western blotting was conducted to determine protein levels of p53, p21, Bax, and Bcl-2.</p><p><strong>Results: </strong>A non-significant dose of ETO was selected based on MTT assay results and combined with 75 µM of Cur. Curcumin enhanced ETO's pro-apoptotic effect by increasing caspase activities. The combination of Cur and ETO significantly reduced Bcl-2 gene expression while upregulating Bax expression. Furthermore, treatment with this combination elevated the protein levels of p53, p21, and Bax, compared to ETO or Cur alone, while significantly decreasing Bcl-2 protein levels.</p><p><strong>Conclusions: </strong>Cur has the potential to amplify ETO-induced apoptosis in BC cells. This combination may offer a promising therapeutic approach for BC.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"23 1","pages":"e150978"},"PeriodicalIF":1.8,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual COX-2/TNF-α Inhibitors as Promising Anti-inflammatory and Cancer Chemopreventive Agents: A Review.","authors":"Mobina Tajdari, Amirreza Peyrovinasab, Maryam Bayanati, Mohammad Ismail Mahboubi Rabbani, Amir Hossein Abdolghaffari, Afshin Zarghi","doi":"10.5812/ijpr-151312","DOIUrl":"10.5812/ijpr-151312","url":null,"abstract":"<p><p>Cyclooxygenases (COX) play a pivotal role in inflammation and are responsible for the production of prostaglandins (PGs). Two types of COXs have been identified as key biological targets for drug design: Constitutive COX-1 and inducible COX-2. Nonsteroidal anti-inflammatory drugs (NSAIDs) target COX-1, while selective COX-2 inhibitors are designed for COX-2. These COX isoforms are involved in multiple physiological and pathological pathways throughout the body. Overproduction of tumor necrosis factor-alpha (TNF-α) plays a role in COX-2's inflammatory activity. Tumor necrosis factor-alpha can contribute to cardiac fibrosis, heart failure, and various cancers by upregulating the COX-2/PGE2 axis. Therefore, suppressing COX activity has emerged as a potentially effective treatment for chronic inflammatory disorders and cancer. This review explores the mechanisms of TNF-α-induced COX-2/PGE2 expression, a significant pathophysiological feature of cancer development. Furthermore, we summarize chemical compounds with dual COX-2/TNF-α inhibitory actions, providing an overview of their structure-activity relationship. These insights may contribute to the development of new generations of dual-acting COX-2/TNF-α inhibitors with enhanced efficacy.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"23 1","pages":"e151312"},"PeriodicalIF":1.8,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}