Pharmacological Research - Reports最新文献

{"title":"Cognitive and functional effects of Ginkgo biloba in neurodegenerative disorders: Systematic review and meta analysis","authors":"Syed Haris Omar ,&nbsp;Md Ahsan Ghani","doi":"10.1016/j.prerep.2026.100077","DOIUrl":"10.1016/j.prerep.2026.100077","url":null,"abstract":"<div><h3>Background</h3><div>The incidence of neurodegenerative disorders is increasing globally, and although treatments exist, few are effective in slowing the rate of cognitive/functional decline associated with these conditions. The standardised <em>Ginkgo biloba</em> extract EGb-761 has been studied for possible neuroprotection, however the findings have varied significantly.</div></div><div><h3>Aim and Objective</h3><div>This systematic review and meta-analysis examined the cognitive, functional and behavioural effects of EGb-761 in adults suffering from Alzheimer's disease, vascular dementia or mild cognitive impairment and evaluated the strength of evidence.</div></div><div><h3>Methods</h3><div>PRISMA 2020 guidelines were followed for the preparation of this systematic review. The study was also registered at PROSPERO (CRD420251207465). Randomised and quasi-randomised controlled trials published between 2000 and 2025 were identified via a search of 5 major databases. A variety of cognitive, behavioural, and functional measures were analysed using standardised mean differences or mean differences with 95 % confidence intervals. The <em>I²</em> statistic was used to determine the level of heterogeneity between studies. All statistical analyses were completed using Review Manager 5.4.</div></div><div><h3>Results</h3><div>Eighteen studies representing 7558 participants were included in the final analysis, 10 of which provided sufficient data for inclusion in a meta-analysis. While there were statistically insignificant changes in cognitive function, the pooled SMD of ADAS Cog was 0.03 with a 95 % CI of −0.27–0.33, with high levels of heterogeneity (<em>I²</em> = 80 %). Similarly, the pooled MD of behavioural outcomes as measured by GERRI was 0.06 with a 95 % CI of −0.07–0.20, showing no statistically significant difference. The pooled SMD of functional outcomes as measured by ADL was 0.02 with a 95 % CI of −0.17–0.21, again showing no statistically significant difference, with low levels of heterogeneity (<em>I²</em> = 7 %).</div></div><div><h3>Conclusion</h3><div><em>Ginkgo biloba</em> extract had small and clinically meaningless effects on cognition, behaviour and functional ability. The quality of the evidence ranged from low to moderate, suggesting further large-scale, well-controlled studies are required to establish whether it may be useful in the treatment of neurodegenerative disorders.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"5 ","pages":"Article 100077"},"PeriodicalIF":0.0,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146037760","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":"Nanocarrier-assisted phytochemical drug delivery in cancer therapy: A bibliometric analysis and integrative review of challenges, innovations, and translational potential","authors":"Simran Gajanan Amonkar ,&nbsp;Aditi Venkatesh Naik","doi":"10.1016/j.prerep.2026.100075","DOIUrl":"10.1016/j.prerep.2026.100075","url":null,"abstract":"<div><div>Phytochemicals demonstrate broad anticancer potential and favourable safety profiles, yet their therapeutic value is limited by poor solubility, rapid metabolism, and low bioavailability. Nanocarrier-assisted delivery addresses these challenges by enhancing stability, prolonging circulation, and enabling tumour-selective release. Developments across polymeric, lipid-based, inorganic, protein-derived, and exosome-like systems have strengthened delivery performance through ligand-directed targeting, surface engineering, and stimuli-responsive designs. A bibliometric assessment of 117 peer-reviewed studies published between 2010 and 2025 reveals increasing research activity in encapsulation strategies, targeted delivery approaches, and translational nanomedicine, with major contributions from India, China, and the United States. Emerging innovations including AI-guided formulation methods, hybrid nanosystems, and multi-omics-based optimisation are advancing phytochemical therapeutics toward greater precision and clinical feasibility. The growing body of evidence supports the translational promise of phytochemical-loaded nanocarriers. Continued progress in scalable synthesis, regulatory alignment, and rigorous in vivo evaluation will be essential for establishing these platforms as next-generation cancer therapeutics.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"5 ","pages":"Article 100075"},"PeriodicalIF":0.0,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145978280","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":"Five proposals to increase translational value of animal models of neuropsychiatry disorders","authors":"Roberto Andreatini ,&nbsp;José Carlos Fernandes Galduróz","doi":"10.1016/j.prerep.2026.100076","DOIUrl":"10.1016/j.prerep.2026.100076","url":null,"abstract":"<div><div>Currently, there is growing concern about the translational value of data originating from preclinical studies and some very interesting proposals to overcome this gap have been made (e.g., ARRIVE). However, some relevant differences between methodologies used in clinical and preclinical studies are still not addressed, such the limited use of behavioural scales, the clear definition of case and non-case, and the consideration the individual response in preclinical studies. In this article, five strategies are proposed to reduce this gap.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"5 ","pages":"Article 100076"},"PeriodicalIF":0.0,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145978279","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":"Evaluation of food effects on two anticancer drugs in humans: Application of physiologically based pharmacokinetic modeling as a surrogate strategy to minimize In-Vivo studies in drug development","authors":"Gobardhan Bal ,&nbsp;Lakshmi Kanakaraj ,&nbsp;Bibhash Chandra Mohanta","doi":"10.1016/j.prerep.2026.100074","DOIUrl":"10.1016/j.prerep.2026.100074","url":null,"abstract":"<div><h3>Purpose</h3><div>In oral drug delivery system, food may influence the effectiveness of the drug by modulating its bioavailability. Understanding these interactions between food and drugs is crucial during drug development. However, the conventional approaches used to identify them are expensive and time-consuming clinical trials, which are often impractical. The objective of this study is to address these challenges by leveraging physiologically based pharmacokinetic(PBPK) models as efficient <em>in-silico</em> tools to predict food effects using significantly less time and resources.</div></div><div><h3>Methods</h3><div>This work focused on developing and validating PBPK models of two low solubility anticancer drugs, Alectinib and Acalabrutinib, utilizing minimal <em>in-vitro</em> characterization data available at the early stage of drug development to demonstrate successful prediction of food effect. The models were developed for healthy humans incorporating drug-specific physicochemical properties, <em>in-vitro</em> characterization data, and physiological parameters of the gastrointestinal tract under both fasted and fed conditions.</div></div><div><h3>Results</h3><div>The prediction accuracy of the developed models was validated against the observed clinical data and further used for virtual population simulation to predict the food effect. The model validation parameters met the 2-fold error limit criteria. The predicted food effect data revealed that, despite low solubility, Alectinib exhibited a significant positive food effect, while Acalabrutinib showed no clinically relevant impact, consistent with the observed clinical data.</div></div><div><h3>Conclusion</h3><div>This work underscores the significance of the <em>in-silico</em> modeling and simulation approach in predicting the food effect of orally administered drugs, which could be used to minimize or optimize time-extensive and cost-expensive clinical trials in drug development.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"5 ","pages":"Article 100074"},"PeriodicalIF":0.0,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145978278","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":"Protective effects of Ziziphus lotus Lam. leaf extract against paracetamol-induced nephrotoxicity in rats: Phytochemical profiling, antioxidant activity, and molecular docking analysis","authors":"Cletus Anes Ukwubile ,&nbsp;Nnamdi David Menkiti ,&nbsp;Ahamefula Anslem Ahuchaogu ,&nbsp;Nathan Isaac Dibal ,&nbsp;Blessing Ogechukwu Umeokoli","doi":"10.1016/j.prerep.2025.100073","DOIUrl":"10.1016/j.prerep.2025.100073","url":null,"abstract":"<div><div><em>Ziziphus lotus</em> (L.) Lam. is traditionally used in Nigeria for the treatment of renal and inflammatory disorders. Despite its ethnomedicinal importance, scientific evidence supporting its nephroprotective activity and underlying molecular mechanisms remains limited. This study aims to investigate the phytochemical composition, antioxidant potential, and nephroprotective effects of <em>Z. lotus</em> leaf extract against paracetamol-induced nephrotoxicity in rats, supported by molecular docking analysis. The methanol leaf extract of <em>Z. lotus</em> was fractionated by solvent partitioning, and the bioactive ethyl acetate fraction (EF) was analyzed using GC–MS NMR, and FTIR. Total phenolic and flavonoid contents were determined by colorimetric methods, while antioxidant activity was assessed by DPPH and ABTS assays. Nephroprotective effects were evaluated in rats by measuring serum urea, creatinine, uric acid, renal MDA, SOD, CAT, and GSH levels. Molecular docking predicted interactions between the identified compounds and protein targets associated with oxidative stress and renal injury. Phytochemical screening revealed alkaloids, flavonoids, tannins, triterpenoids, cardiac glycosides, and phytosterols. GC–MS identified 18 major constituents, and NMR elucidated five key compounds: phthalic acid monoethyl ester, methyl α-<span>D</span>-glucopyranoside, styracitol, pentadecanoic acid 14-methyl ester, and n-hexadecanoic acid. The extract exhibited strong antioxidant activity (DPPH IC₅₀ = 8.22 µg/mL; ABTS IC₅₀ = 12.08 µg/mL) and high phenolic content (408.12 mg GAE/g). Treatment with <em>Z. lotus</em> significantly restored renal biomarkers levels to normal, improved antioxidant enzyme levels, and provided histological evidence of renal protection. Molecular docking revealed that the five compounds showed high binding affinities (−7.2 to −9.1 kcal/mol) with key nephroprotective proteins. The polyphenolic and fatty acid constituents of <em>Z. lotus</em> contribute to its potent antioxidant and nephroprotective properties, providing scientific validation for its traditional use and potential for developing novel nephroprotective therapies.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"5 ","pages":"Article 100073"},"PeriodicalIF":0.0,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145765940","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":"Doxycycline attenuates cognitive impairment, neuroinflammation and oxidative stress in a mouse model of sepsis-associated encephalopathy","authors":"Maria Laura da Cruz Castro ,&nbsp;Flávia Monteiro Ferreira ,&nbsp;Camila Francieli Chagas ,&nbsp;Sttefany Viana Gomes ,&nbsp;Renata Rebeca Pereira ,&nbsp;Aline Meireles Coelho ,&nbsp;Saulo Fehelberg Pinto Braga ,&nbsp;Gabrielly Guimarães Coutinho ,&nbsp;Vitória Louise Teixeira e Silva ,&nbsp;Sirlaine Pio Gomes da Silva ,&nbsp;André Talvani ,&nbsp;Allan Jefferson Cruz Calsavara ,&nbsp;Daniela Caldeira Costa","doi":"10.1016/j.prerep.2025.100072","DOIUrl":"10.1016/j.prerep.2025.100072","url":null,"abstract":"<div><div>Sepsis-associated encephalopathy (SAE), affecting up to 70 % of patients with sepsis, is a diffuse cerebral dysfunction that correlates with higher mortality rates and long-term cognitive impairments such as memory deficits. The pathophysiology of SAE includes neuroinflammation, oxidative stress, apoptosis, microglial activation, blood-brain barrier (BBB) dysfunction, and metabolic disturbances. The compromised BBB during sepsis allows inflammatory mediators to infiltrate, increasing oxidative stress. Studies highlight the role of BBB disruption in SAE, with matrix metalloproteinase 9 (MMP-9) activity increasing BBB permeability. The antibiotic doxycycline inhibits MMP activity and shows promise in protecting BBB integrity by reducing neuroinflammation and oxidative stress. This study evaluates the impact and mechanisms underlying doxycycline treatment on cognitive function in mice with polymicrobial sepsis. Doxycycline treatment improves cognition in the animals and increases brain-derived neurotrophic factor (BDNF) levels in the hippocampus. Doxycycline also inhibits MMP-9, reduces neuroinflammation and attenuates oxidative stress in the brain. In addition, molecular modeling suggests that doxycycline effectively binds to MMP-9. These findings suggest that doxycycline attenuates cognitive deficits, reduces neuroinflammation and oxidative stress, and inhibits MMP-9 in a mouse model of sepsis-associated encephalopathy.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100072"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145624124","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":"Therapeutic potential of Abutilon indicum (L.) Sweet seed extract in PCOS: Insights from mass spectrometry, network pharmacology, and molecular docking","authors":"Rejuan Islam ,&nbsp;Subhajit Ghosh ,&nbsp;Subarna Thakur ,&nbsp;Tilak Saha","doi":"10.1016/j.prerep.2025.100071","DOIUrl":"10.1016/j.prerep.2025.100071","url":null,"abstract":"<div><h3>Background</h3><div>Polycystic ovary syndrome (PCOS) is a widespread endocrine disorder affecting women of reproductive age and is often associated with metabolic and inflammatory complications. <em>Abutilon indicum (L.)</em> Sweet, a small medicinal shrub widely used in traditional medicine systems, including Traditional Chinese Medicine (TCM), has been employed to manage a variety of health complications. Recent findings suggest that its seed extract may offer therapeutic potential against PCOS. This study aimed to investigate the bioactive constituents and underlying pharmacological mechanisms of the methanolic extract of <em>A. indicum</em> seeds (MEAS) in PCOS using a combination of GC-MS based profiling, network pharmacology, and molecular docking analyses.</div></div><div><h3>Methodology</h3><div>Phytochemical profiling of MEAS was performed using GC-MS, followed by ADMET-based screening to identify drug-like compounds. Target genes of MEAS phytochemicals were predicted via STP and SEA servers, while PCOS-related genes were retrieved from OMIM and DisGeNET databases. Common targets were intersected with differentially expressed genes (DEGs) derived from a publicly available PCOS-related gene expression dataset. These genes were further analyzed for protein–protein interaction (PPI), Gene Ontology (GO), and KEGG pathway enrichment. Molecular docking and MM/GBSA calculations were conducted to validate compound–target interactions.</div></div><div><h3>Results</h3><div>GC-MS analysis of MEAS revealed 19 phytochemical compounds, of which 13 satisfied drug-likeness criteria based on ADMET profiling. Database screening identified 110 targets associated with PCOS. Integration of these targets with DEGs resulted in the identification of 10 key PCOS-related genes, including ESR1, HMOX1, CYP17A1, PTAFR, and TLR2. Pathway enrichment analysis revealed a significant enrichment of inflammation-related pathways, oxidative stress, and insulin resistance. Furthermore, molecular docking and MMGBSA results confirmed that phytocompounds like thymidine, 9,12-octadecadienoic acid (<em>Z</em>, <em>Z</em>)-, methyl ester, 9,12-octadecadienoic acid (<em>Z</em>, <em>Z</em>)-, octadecanoic acid, and 9,12-octadecadienoic acid (<em>Z</em>, <em>Z</em>)-, 2-hydroxy-1-(hydroxymethyl) ethyl have strong binding efficacy with the PCOS-related target proteins.</div></div><div><h3>Conclusion</h3><div>This integrative study elucidates the multi-target pharmacological mechanisms of <em>A. indicum</em> seed constituents in modulating key pathways implicated in PCOS. The findings support the potential application of <em>A. indicum</em> within TCM-based approaches for managing PCOS and its complications.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100071"},"PeriodicalIF":0.0,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145473842","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":"Supplemental use of melatonin to protect against oxidative stress induced by intensive athletic training and competition","authors":"Yupeng Cui ,&nbsp;Xiaoyan Liu ,&nbsp;Russel J. Reiter","doi":"10.1016/j.prerep.2025.100069","DOIUrl":"10.1016/j.prerep.2025.100069","url":null,"abstract":"<div><div>Ample experimental evidence supports the protective effect of melatonin against oxidative damage and fatigue induced by overload athletic training. This article aims to review recent research on the protective effect and mechanisms of melatonin against oxidative stress induced by intensive training and competition, and to provide theoretical support for its application and future research directions. The mechanism of melatonin action involves around direct scavenger of reactive oxygen species, aggregation in mitochondria, and activating signal pathways by binding to receptors. Mitochondria may be one of the most important targets of melatonin in preventing oxidative stress, histiocytic damage and metabolic disorders induced by intensive training. Given the important role of redox signaling agents in activating different signal transduction systems to elicit adaptive changes to exercise stimuli, a phased short-term mode of melatonin supplementation tailored to athletes’ redox status and training load is recommended.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100069"},"PeriodicalIF":0.0,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145473845","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":"Controlled release approaches in ocular drug delivery","authors":"Harshita Krishnatreyya ,&nbsp;Hemanga Hazarika","doi":"10.1016/j.prerep.2025.100070","DOIUrl":"10.1016/j.prerep.2025.100070","url":null,"abstract":"<div><div>Ocular drug delivery is significant as it delivers drugs to one of the most vital and intricate structures in the human body, the eye, which is currently the site for increased occurrences of diseases like dryness, glaucoma, age related macular degeneration, diabetic retinopathy etc. It is noticeable that drugs delivered at a controlled rate, over prolonged periods of time, are the most effective in treating ocular complications by improving drug therapeutic efficacy and ocular bioavailability. In this article, we provide a summary of the importance of controlled release (CR) systems in ocular delivery, its significance, and the most popular types of CR formulations. Factors to be considered while designing CR drug formulations and the essential mechanisms involved in CR of drugs have been briefed. The significance of diversely sourced biodegradable polymers and the impact of their physicochemical characteristics on drug release is discussed. Previously conducted research on CR formulations, few currently available and marketed ocular CR products and patents; the advantages, disadvantages and challenges of CR systems in ocular tissues are debated. With smarter developments arising to benefit people, there is no definitive endpoint to the progressing research that develops innovative and effective strategies to provide CR of ocular drugs with diminished side effects.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100070"},"PeriodicalIF":0.0,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145473841","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":"Melatonin alleviates streptozotocin-induced neuropathic pain in rat model: Involvement of noradrenergic receptor pathways","authors":"Ilhem Dallali ,&nbsp;Ahmed Hasan ,&nbsp;Feyza Alyu Altınok ,&nbsp;Nurcan Bektas Turkmen ,&nbsp;Yusuf Ozturk","doi":"10.1016/j.prerep.2025.100068","DOIUrl":"10.1016/j.prerep.2025.100068","url":null,"abstract":"<div><h3>Background</h3><div>Diabetic neuropathic pain is a persistent and debilitating complication of diabetes with limited treatments. Melatonin shows promise in pain modulation, though its underlying antinociceptive mechanisms remain unclear. This study investigated the analgesic efficacy of melatonin in alleviating streptozotocin-induced neuropathic pain in rats and explored the involvement of noradrenergic pathways.</div></div><div><h3>Methods</h3><div>Neuropathic pain was induced in male Sprague-Dawley rats via a single intravenous injection of streptozotocin (50 mg/kg). Melatonin (50 mg/kg, <em>i.p.</em>) was administered daily for two weeks. Gabapentin (50 mg/kg, <em>i.p.</em>) served as a positive control. Mechanical allodynia and thermal hyperalgesia were assessed using the e-Von Frey and Hargreaves tests, respectively, while locomotor activity was evaluated using an activity cage. To evaluate metabolic effects, blood glucose levels were monitored throughout the study. Adrenergic antagonists’ prazosin (α1, 10 mg/kg), yohimbine (α2, 4 mg/kg), and propranolol (β, 5 mg/kg) were administered prior to the final melatonin dose to assess noradrenergic involvement.</div></div><div><h3>Results</h3><div>Streptozotocin-induced diabetic rats exhibited pronounced mechanical and thermal hypersensitivity. Subacute melatonin treatment significantly reduced nociceptive responses and improved locomotor activity, showing efficacy comparable to gabapentin. It did not alter blood glucose levels, indicating a neutral metabolic effect. The analgesic effects of melatonin were attenuated by adrenergic antagonists, implicating noradrenergic signaling in its mechanism of action.</div></div><div><h3>Conclusions</h3><div>Melatonin exerts significant antiallodynic and antihyperalgesic effects in diabetic neuropathic rats, likely mediated via noradrenergic receptor pathways. Its neutral impact on glycemic control, combined with potential mood-regulating properties, supports its promise as a therapeutic candidate for managing diabetic neuropathic pain, pending clinical validation.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100068"},"PeriodicalIF":0.0,"publicationDate":"2025-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145361052","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}