Pharmacological Research - Reports最新文献

{"title":"Curcumin as a modulator of drug metabolism and gene expression: Implications for pharmacogenomics","authors":"Igbayilola Yusuff Dimeji ,&nbsp;Hamidu Lawan Jabba ,&nbsp;Ngabea Murtala ,&nbsp;Adekola Saheed Ayodeji","doi":"10.1016/j.prerep.2025.100067","DOIUrl":"10.1016/j.prerep.2025.100067","url":null,"abstract":"<div><div>Curcumin, a polyphenolic chemical derived from <em>Curcuma longa</em>, has long been used as a culinary ingredient and in traditional medicine because of its unique orange--yellow color. Anti-inflammatory, antioxidant, antibacterial, and chemopreventive qualities are only a few of its many pharmacological activities. The increasing relevance of curcumin in pharmacogenomics is examined in this review, with particular attention given to how it affects gene expression and drug metabolism. Curcumin alters important enzymes and pathways, including drug transporters and cytochrome P450s, which impacts how the body breaks down medications. Additionally, it controls transcription factors such as Nrf2 and NF-κB, which affect genes related to inflammation and detoxification. Curcumin is a promising adjuvant in personalized medicine since it can improve therapeutic efficacy and decrease adverse drug reactions through these mechanisms. Its potential application in precision treatment procedures is supported by its capacity to fine-tune metabolic and signalling pathways. This review aims to investigate the possible function of curcumin in pharmacogenomics, namely, in modifying individual reactions to medications depending on genetic variants, as well as how it affects drug metabolism and gene expression.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100067"},"PeriodicalIF":0.0,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145227093","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":"Ibuprofen: A review on its synthesis, mechanism of action, pharmacological properties, and environmental impact","authors":"Irene Ebosereme Ainyanbhor ,&nbsp;Great Iruoghene Edo ,&nbsp;Ali B.M. Ali ,&nbsp;Patrick Othuke Akpoghelie ,&nbsp;Morenike Olufunmilayo Akpo ,&nbsp;Emad Yousif ,&nbsp;Joseph Oghenewogaga Owheruo ,&nbsp;Ufuoma Augustina Igbuku ,&nbsp;Oluwatobi Victoria Obayomi ,&nbsp;Arthur Efeoghene Athan Essaghah ,&nbsp;Dilber Uzun Ozsahin ,&nbsp;Huzaifa Umar ,&nbsp;Dina S. Ahmed ,&nbsp;Ahmed A. Alamiery","doi":"10.1016/j.prerep.2025.100066","DOIUrl":"10.1016/j.prerep.2025.100066","url":null,"abstract":"<div><h3>Background</h3><div>Ibuprofen, the third most frequently prescribed over-the-counter drug globally, is used for treatment of inflammation, pain and pyrexia.</div></div><div><h3>Objective</h3><div>This review discusses its synthesis, mechanism of action, pharmacokinetics, pharmacodynamics, derivatives, prospect as well as its environmental impact as an emerging contaminant.</div></div><div><h3>Findings</h3><div>Its anti-inflammatory property stems from its reduction in synthesis of prostaglandins in inflammatory processes through the inhibition of COX-1 and COX-2 enzyme. However, adverse effect such as gastrointestinal ulceration, myocardial infarction and renal failure has been associated with the use of this drug especially during prolonged usage. Hence, the need for structural modification of this drug reduce or eliminate its adverse effect and also improved efficacy. Research report indicates derivative of ibuprofen from its structural modification results in novel drugs for relief of pain and inflammation with little or no side effects associated with the parent drug. Research also propose the prodrug Ibu-GLVL as a prospective drug for the treatment and management of Alzheimer disease. Despite the classical uses and prospect of this drug, its adverse environmental impact due to observed toxicity in organisms as well as possible contamination of food chain needs to be properly addressed.</div></div><div><h3>Conclusion</h3><div>This review emphasizes the need to develop more sophisticated methods for effective removal of emerging contaminant including ibuprofen in WWTP since most traditional WWTP are ineffective in removal of such contaminant. This will reduce and may eliminate the adverse environmental effect posed by this emerging contaminant due its wide usage across the globe.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100066"},"PeriodicalIF":0.0,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145121125","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":"Veterinary bacteriostatic and ionophore antibiotics in aquatic organisms: A systematic review and scientometric analysis of biomarker and exposure concentrations","authors":"Thaís Pereira Nascimento ,&nbsp;Andrea Carina Crupkin ,&nbsp;Mirta Luján Menone","doi":"10.1016/j.prerep.2025.100065","DOIUrl":"10.1016/j.prerep.2025.100065","url":null,"abstract":"<div><div>The intensive use of veterinary antibiotics, particularly bacteriostatic agents and ionophores, represents an increasing ecotoxicological concern for aquatic ecosystems. This study integrates scientometric analysis with a systematic literature review specifically aimed at identifying gaps in experimental research addressing the effects of these pharmaceuticals on aquatic organisms through biomarker-based assessments. A total of 648 publications published between 1968 and 2024 were screened; however, only 20 in vivo studies involving 10 aquatic species (7 vertebrates and 3 invertebrates) met the inclusion criteria, of which 17 investigated bacteriostatic antibiotics and 3 ionophores. Acute exposure designs predominated (35 %), followed by subchronic (30 %), chronic (15 %), and combined acute–chronic (20 %) assays. Reported environmental concentrations ranged from nanograms to hundreds of micrograms per liter, whereas experimental exposures frequently reached milligram-per-liter levels — in some cases exceeding environmental concentrations by several orders of magnitude. Observed effects included oxidative stress, immunological alterations, reproductive impairment, embryotoxicity, and histopathological damage. The findings demonstrate a disproportionate reliance on standard model organisms, particularly <em>Danio rerio</em>, and a notable scarcity of studies involving native or ecologically relevant species. This review highlights a critical need for future research to adopt chronic exposure scenarios, incorporate native species, environmentally relevant concentrations, and apply standardized- sensitive biomarkers. Addressing these gaps is essential to advance the environmental risk assessment of veterinary antibiotics and to support more effective and evidence-based environmental policymaking.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100065"},"PeriodicalIF":0.0,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145104675","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":"Dieckol from brown algae targeting the Hepatocellular Carcinoma pathway: A computational pharmacology study","authors":"Hamad Hasan ,&nbsp;Alzamka M.A. Almabruk ,&nbsp;Mustapha Belaidi ,&nbsp;Saleh Bufarwa","doi":"10.1016/j.prerep.2025.100064","DOIUrl":"10.1016/j.prerep.2025.100064","url":null,"abstract":"<div><div><em>Hepatocellular carcinoma</em> (<strong>HCC</strong>) is a leading cause of cancer mortality worldwide, underscoring the urgent need for novel, multi-target therapeutics. This study systematically evaluates Dieckol, a phlorotannin from brown algae, using a dry-lab pipeline integrating quantum chemical calculations, transcriptomic data mining, network pharmacology, molecular docking, molecular dynamics (<strong>MD</strong>), and ADMET-toxicity prediction. Density Functional Theory (<strong>DFT</strong>) analysis revealed favorable electronic properties for selective bio-interactions, including a narrow HOMO–LUMO gap (0.119 eV) and high electron-accepting capacity. From 313 predicted targets and 7325 HCC-associated genes, 33 overlapping genes were identified, enriched in cell cycle, apoptosis, and oncogenic signaling pathways, particularly hsa05225 (HCC pathway). Protein–protein interaction and drug–target–pathway networks highlighted CDKN1A, TP53, DNMT1, AURKA, and MAPK1 as central targets. Molecular docking demonstrated strong binding affinities with key HCC-related proteins (CDKN1A: −10.3 kcal/mol; TP53: −9.5 kcal/mol), supported by stable MD simulations and favorable MMGBSA binding energies (e.g., DNMT1: −362.9 kcal/mol). Dieckol also modulated immune-infiltration signatures of key genes (e.g., PIK3R1, NRAS, CDKN2A), suggesting immunomodulatory potential. Gene and protein expression analyses validated differential upregulation of hub targets in tumor vs. normal liver tissues. In silico ADME profiling revealed low oral bioavailability, poor GI absorption, and selective CYP2C9 inhibition, while toxicity predictions showed no carcinogenicity or genotoxicity but flagged moderate renal and dermal risks. Collectively, our findings position Dieckol as a promising multi-target agent for HCC intervention, warranting further in <em>vitro</em> and in <em>vivo</em> validation.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100064"},"PeriodicalIF":0.0,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145104676","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":"Long term monitoring of serum valproate assays using patient median values show stable test results over a period of more than 20 years","authors":"Anders Larsson,&nbsp;Anna-Karin Hamberg,&nbsp;Jonathan Cedernaes,&nbsp;Mathias Karlsson","doi":"10.1016/j.prerep.2025.100063","DOIUrl":"10.1016/j.prerep.2025.100063","url":null,"abstract":"<div><div>Monitoring assay performance using traditional internal quality control (IQC), and external quality assurance (EQA) methods has limitations, particularly regarding sample commutability. This study investigates the use of patient-derived valproate data, specifically median and quartile values, as a complementary approach to quality control in a clinical laboratory setting. A retrospective analysis was performed on 13,336 routine serum valproate results collected between January 2004 and December 2024 at Akademiska Hospital, Uppsala. Valproate was analyzed using immunoassays on the Architect ci8200 platform until 2020, after which testing was transferred to the Roche Cobas Pro c503. Annual patient medians and quartiles were calculated, and seasonal patterns were evaluated. Method transfer and performance were assessed using internal controls and patient data. The number of annual test requests declined modestly over the study period. Median valproate concentrations remained stable across the 21-year period, with minimal variability in interquartile ranges. The 0.10 and 0.90 percentiles showed slightly higher fluctuation, likely due to sample timing variation rather than analytical drift. Seasonal analysis revealed no clinically relevant variation. The method transfer in 2021 did not introduce observable shifts in patient medians, supporting good method comparability. Longitudinal monitoring of patient median and quartile valproate concentrations provides a robust, clinically meaningful tool for supplementary assay performance surveillance. This approach is particularly suitable for therapeutic drug monitoring, where treatment protocols and target ranges are stable over time.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100063"},"PeriodicalIF":0.0,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145048817","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":"Theories of drug action, 100 years of progress: From occupation to biased signaling contributions","authors":"M. Verónica Donoso,&nbsp;Isidora Rubilar,&nbsp;J. Pablo Huidobro-Toro","doi":"10.1016/j.prerep.2025.100062","DOIUrl":"10.1016/j.prerep.2025.100062","url":null,"abstract":"<div><div>A.J. Clark applied the law of mass action to explain how drugs work, a formulation known as the occupation theory. This hypothesis advanced that drugs occupy receptors through the formation of a [drug-receptor] complex intimately linked to the generation of a pharmacologic response. Full agonists were distinguished from antagonists based on the nature of the complex formed and concentration-response curves. Stephenson introduced the notion of drug efficacy and intrinsic activity to modify Clark’s proposal, explaining why antagonists, which occupy receptors, do not elicit a direct receptor-mediated response. According to this modification, partial agonists do not achieve full efficacy due to low intrinsic activity based on dose-response curves, while antagonists dramatically lack all intrinsic activity. Detailed structural biology findings of GPCRs provided new insights into possible conformational changes through the multiple forms of [drug-receptor] complexes, which ultimately cause clinical responses. Moreover, the recognition that several β-arrestins produce GPCRs' intracellular signaling through the activation of various protein kinases accounts for the novel idea that drugs that interact preferentially through this intracellular pathway, such as receptor antagonists, also elicit cellular responses. The evolution of these ideas proposed that drugs interact with the multiple receptor conformations, eliciting interactions that consequently elicits varying states of receptor activity, followed by ensuing intracellular responses. This new proposal changed the nomenclature from full agonists to selective G protein ligands and antagonists as preferential β-arrestins ligands. Agonists and antagonists are all now referred to as receptor ligands, independent of the nature of the [drug-receptor] complex formed.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100062"},"PeriodicalIF":0.0,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145026987","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":"Single-nucleotide polymorphisms in CYP27B1 and VDR genes associated with treatment outcomes in hepatitis B and C: A minireview","authors":"Alessandra Ramalho Correia ,&nbsp;Victor Cavicchioli ,&nbsp;Lara Cândida de Sousa Machado ,&nbsp;Rahisa Scussel ,&nbsp;Ricardo Andrez Machado-de-Ávila ,&nbsp;Iane de Oliveira Pires Porto ,&nbsp;Iara Barreto Neves Oliveira","doi":"10.1016/j.prerep.2025.100061","DOIUrl":"10.1016/j.prerep.2025.100061","url":null,"abstract":"<div><div>Vitamin D, essential for immune modulation, is metabolized by enzymes encoded by the <em>CYP27B1</em> gene and exerts its effects through the vitamin D receptor (VDR). Genetic variations in these genes may influence antiviral response, particularly to treatments with pegylated interferon and ribavirin. This work consists of a descriptive literature review analyzing the influence of single-nucleotide polymorphisms (SNPs) in the <em>CYP27B1</em> and <em>VDR</em> genes on the antiviral treatment response for HBV and HCV. The results indicate that specific SNPs, such as rs4646536 and rs10877012 in the <em>CYP27B1</em> gene and rs7975232/<em>Apa</em>I, rs1544410/<em>Bsm</em>I, rs731236/<em>Taq</em>I, and rs10735810—rs2228570/<em>Fok</em>I in the <em>VDR</em> gene, may be associated with variable therapeutic responses, including higher rates of sustained virological response (SVR) and reduced viral load. Given the limited efficacy of current antiviral therapies, identifying relevant SNPs in genes related to the vitamin D pathway may help select responsive patients, personalize hepatitis B and C therapy approaches, and minimize side effects.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100061"},"PeriodicalIF":0.0,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144916374","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":"Safety and efficacy of adjuvant fecal microbiota transplantation therapy in patients with diabetes mellitus: A systematic review and meta-analysis","authors":"Yunzhen Lei ,&nbsp;Jiaying Diao ,&nbsp;Yiyue Tang ,&nbsp;Shanshan Yao ,&nbsp;Nanqu Huang ,&nbsp;Min Xu ,&nbsp;Xingli Hu ,&nbsp;Qianfeng Jiang","doi":"10.1016/j.prerep.2025.100059","DOIUrl":"10.1016/j.prerep.2025.100059","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;Exploring the Safety and Efficacy of Fecal Microbiota Transplantation in Treating Diabetes Mellitus&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;A systematic search was conducted across four databases (PubMed, Cochrane Library, Web of Science, and Embase) for relevant studies published up to March 2025. The primary outcomes of interest included glycemic parameters, such as glycated hemoglobin (HbA1c), fasting blood glucose (FBG), Postprandial 2-Hour Blood Glucose (2H-PBG), fasting C-peptide (FCP), and postprandial 2-Hour C-peptide (2H-FCP). Secondary outcomes included lipid profiles, blood pressure, and uric acid levels. Heterogeneity was assessed using Cochran’s &lt;em&gt;Q&lt;/em&gt; test and the &lt;em&gt;I²&lt;/em&gt; statistic. A fixed-effects model was employed when no significant heterogeneity was observed (&lt;em&gt;I²&lt;/em&gt; &lt; 50 % or &lt;em&gt;P&lt;/em&gt; ≥ 0.10 for the &lt;em&gt;Q&lt;/em&gt; test); otherwise, a random-effects model was applied. For outcomes reported in consistent units, weighted mean difference (WMD) were calculated, while standardized mean difference (SMD) were used for outcomes measured in different units. Subgroup analyses were performed to assess the effects of fecal microbiota transplantation (FMT) on different types of diabetes mellitus and various intervention protocols. Meta-regression was conducted to explore potential factors influencing the effects of FMT on glucose metabolism. Publication bias was evaluated using Begg’s and Egger’s tests, with &lt;em&gt;P&lt;/em&gt; &lt; 0.05 indicating potential bias. The quality of evidence for all outcomes was assessed using the GRADE framework.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;This meta-analysis included 6 studies to investigate the effects of adjunctive FMT on glycemic and metabolic parameters in patients receiving conventional treatment. The results demonstrated that FMT supplementation significantly reduced 2H-PBG [SMD −2.74, 95 % CI: −3.78 to −0.63], TG [WMD −0.32, 95 % CI: −0.57 to −0.08], and ALT [WMD −2.67, 95 % CI: −4.56 to −0.78]. Subgroup analysis by diabetes type revealed that FMT exhibited a favorable trend in lowering 2H-PBG in both type 1 diabetes (T1D) and type 2 diabetes (T2D) patients. Notably, FMT significantly decreased FCP and 2H-FCP in T1D patients but increased these parameters in T2D patients. Additionally, FMT was found to reduce homeostasis model assessment of β-cell function (HOMA-β) in T2D patients, while showing no significant impact on T1D patients. Subgroup analysis by intervention modality indicated that both oral capsule administration and feeding tube delivery exhibited trends toward reducing 2H-FCP. Meta-regression identified that patients with lower baseline levels of TC and LDL derived greater glycemic benefits from FMT. No significant adverse events were reported across all included studies. Evidence quality assessment classified DBP, TC, TG, LDL, and uric acid as low-quality evidence; weight, BMI, HbA1c, FBG, 2H-PBG, FCP, 2H-FCP, HOMA-β, SBP, HDL, alanine aminotransferase","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100059"},"PeriodicalIF":0.0,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863599","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":"Co-administration of modafinil, atomoxetine, and citalopram increases exploratory behavior, produces withdrawal signs, and enhances self-administration of this drug mixture","authors":"Jorge Juárez,&nbsp;Amanda C. Hernandez De la Torre,&nbsp;Jesús E. Yepez","doi":"10.1016/j.prerep.2025.100060","DOIUrl":"10.1016/j.prerep.2025.100060","url":null,"abstract":"<div><div>The monoaminergic systems are necessary for the motor and reinforcing effects of addictive psychostimulants such as cocaine and amphetamines. The participation of the dopaminergic system (DA) in relation to these properties has been studied extensively, but the role of the noradrenergic (NA) and serotoninergic (5-HT) systems has not been clarified. Clinical psychostimulants like modafinil have not shown clear evidence of addictive effects, perhaps due to differential activity in the latter two systems. The aim of this study was to determine the effect of monotherapies with modafinil (MOD, a drug with main activity in the inhibition of dopamine reuptake), atomoxetine (ATX, a selective norepinephrine reuptake inhibitor), and citalopram (CIT, a selective serotonin reuptake inhibitor), and coadministration (MOD+ATX+CIT), on locomotor activity, signs of anhedonia after drug withdrawal and self-administration of MOD and the mixture of these substances. Male Wistar rats were treated chronically (16 days) via the endogastric route with ATX at 2 mg/kg, CIT at 3 mg/kg, MOD at 60 mg/kg, or a combination (2ATX+3CIT+60MOD). The co-administered rats (COAD) increased exploratory behavior and showed signs of anhedonia post-withdrawal. The MOD and COAD groups showed higher MOD intake after being water-deprived for 12 h, while a sensitization of exploratory behavior was observed in the COAD group after consuming the ATX+CIT+MOD mixture. Higher seeking self-administration of the mixture was noted only in the COAD group. Results suggest that early simultaneous activation of the DA, NA, and 5-HT systems produces plastic changes that favor the posterior self-administration and rewarding effects of drugs that activate these three neurotransmission systems.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100060"},"PeriodicalIF":0.0,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144841797","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":"Antiproliferative effects of phytocompounds from Ichnocarpus frutescens (L.) W.T. Aiton against breast cancer cell line MDA MB-231 by in vitro and in silico analysis","authors":"Roshna Kattilaparambil ,&nbsp;Vinoth Sathasivam ,&nbsp;Saradhadevi Muthukrishnan ,&nbsp;Hemamalini Vedagiri ,&nbsp;Ashok Iyaswamy ,&nbsp;Arun Muthukrishnan ,&nbsp;Alagupandi Raman ,&nbsp;Gayathiri Gunasangkaran ,&nbsp;Janaranjani Murugesan ,&nbsp;Gurusaravanan Packiaraj","doi":"10.1016/j.prerep.2025.100058","DOIUrl":"10.1016/j.prerep.2025.100058","url":null,"abstract":"<div><div>Breast cancer is an invasive disease in women and could be a major concern due to its serious health risk. This study explores the bioactive compounds from <em>Ichnocarpus frutescens</em> root extract against breast cancer cell (MDA MB-231). The bioactive compounds from the root were extracted using various solvents. The total phenol, flavonoids, alkaloid and tannin quantified and <em>in vitro</em> antioxidant activity were also evaluated using standard methods. GCMS analysis and the binding affinity of the active components were investigated against EGFR, CHD 1, HER-2 and BRCA 1protein. The most promising active ligand was subjected to 100 ns molecular dynamics (MD) simulations. Further, cell proliferation was examined in MDA MB-231 by MTT, wound healing and staining assays. The <em>I. frutescens</em> root extract exhibited high levels secondary metabolites. Additionally, ethyl acetate (EA) extract shows highest antioxidant activity with lowest IC₅₀ values in DPPH (55.22 μg/mL) and ABTS (36.31 μg/mL) radical scavenging assay. The fourteen bioactive compounds were identified by GCMS analysis. However, it has been the first report the compound Estra-1,3,5(10)-trien-6-one, 3,17-bis(acetyloxy), 6-(O-methyloxime), (17.beta.)- exhibiting high binding affinity (-9.5) against HER-2 receptor protein. The results of the molecular dynamics indicate that the ligand forms a stronger complex with the breast cancer protein BRCA1. Furthermore, MTT assay demonstrated a significant anti-proliferative effect against MDA MB-231 breast cancer cells with IC₅₀ value of 84 μg mL⁻¹. Nuclear damage in these cells was examined using AO/EtBr and DAPI staining. <em>In vitro</em> studies confirmed the anti-proliferative activity of the extract against MDA MB-231 breast cancer cells. These findings suggest that this plant extract could be a promising source for the development of novel anti-cancer agents.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100058"},"PeriodicalIF":0.0,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144831429","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}