Pharmacological Research - Reports最新文献

{"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":"2025-12-01","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 supplementation improves impairment in cognitive function in type 2 diabetes-induced rats","authors":"Azubuike Raphael Nwaji ,&nbsp;Kenneth Chiedozie Oparaji ,&nbsp;Chima Igwe ,&nbsp;Esther Onyinyechi Igwe ,&nbsp;Miracle Princess Okechukwu ,&nbsp;Joyful Idimmachi Esinulo ,&nbsp;Toochukwu Simon ,&nbsp;Kingsley Godspower Ogbonna","doi":"10.1016/j.prerep.2025.100055","DOIUrl":"10.1016/j.prerep.2025.100055","url":null,"abstract":"<div><h3>Background</h3><div>Diabetes mellitus (DM) is a metabolic disorder facilitated by defective regulation of glucose and lipid metabolism. This glycemic fluctuation may be responsible for the alterations associated with diabetic brain.</div></div><div><h3>Aim</h3><div>The study aimed to investigate the impact of melatonin treatment on brain of alloxan-fructose-induced type 2 diabetic rat model.</div></div><div><h3>Materials and methods</h3><div>A single dose of alloxan (150 mg/kg, i.p.) was given to 14-day fructose solution (20 % w/v) pre-treated rats in drinking water. Rats with glucose levels above 200 mg/dL were classified as diabetic after three days post-induction. 20 rats were randomly assigned to four groups and treated as control, melatonin, diabetic untreated, and diabetic treated groups, respectively. Melatonin (10 mg/kg, p.o.) was given daily for 15 days after diabetic induction.</div></div><div><h3>Results</h3><div>Supplementation of diabetic rats with melatonin had an effect on the lipid profile by significantly decreasing TG and VLDL-c while no changes were observed in the TC, HDL-c and LDL-c. Melatonin also impacted neuroinflammatory markers by significantly (p &lt; 0.05) decreasing the brain level of TNF-α and decreasing NO with no changes observed in the CRP levels of the treated rats. There was a significant (p &lt; 0.05) increase in dopamine with no effect on serotonin levels. A protective effect against cognitive dysfunction is also shown by significantly increasing % alternation.</div></div><div><h3>Conclusion</h3><div>This study affirms the beneficial effects of melatonin in alloxan-fructose-induced type 2 diabetes by reducing lipid peroxidation, neuroinflammation, and improving cognitive functions. Thus, suggests that melatonin may be essential for defending the brain against cognitive alterations linked to DM.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100055"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144654774","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":"Effect of paraquat-induced toxicity and the therapeutic potentials of Moringa oleifera and Moringa stenopetala leaf alkaloid extracts","authors":"Stephen Adeniyi Adefegha ,&nbsp;Opeyemi Babatunde Ogunsuyi ,&nbsp;Olayemi Philemon Aro ,&nbsp;Ganiyu Oboh","doi":"10.1016/j.prerep.2025.100049","DOIUrl":"10.1016/j.prerep.2025.100049","url":null,"abstract":"<div><div>Paraquat (PQ) exposure is a risk factor for Parkinson's disease (PD), motivating treatment investigations. The efficacy of Ayurveda moringa leaf alkaloids in treating Paraquat toxicity was investigated in <em>Drosophila</em> models. The study included 10 fruit fly groups, four groups of which received moringa leaf alkaloid samples alone, one group was Paraquat-induced, and others received both. The experiment was terminated on day 3, after which fly heads and bodies were homogenized. <em>Moringa oleifera</em> and <em>Moringa stenopetala</em> alkaloid extracts were tested on Paraquat-induced flies' survival, biochemical, and genetic markers of PQ-toxicity. Alkaloid extracts significantly improved paraquat-induced fly survivability. Both <em>Moringa</em> species exhibited a stronger inhibition of monoamine oxidase and acetylcholinesterase at 50 mg/ml. Both <em>Moringa</em> species increased tyrosine hydroxylase activity, with PQ+MSL (50 mg/ml) displaying a more pronounced ameliorative effect. In comparison with the Paraquat-induced group, <em>Moringa stenopetala</em> significantly increased both catalase and total thiol levels. At the genetic level, catalase and tyrosine hydroxylase mRNA levels were downregulated in paraquat-induced flies. <em>Moringa stenopetala</em> exhibited a higher upregulation of tyrosine hydroxylase mRNA expression compared to <em>Moringa oleifera</em>, while <em>Moringa oleifera</em> upregulated catalase mRNA expression more than <em>Moringa stenopetala</em>. In conclusion, alkaloid extracts from moringa leaves demonstrated neuroprotective effects against paraquat-induced neurotoxicity in fruit flies. However, <em>Moringa stenopetala</em> exhibited superior medicinal properties compared to <em>Moringa oleifera</em>, as observed from this study. These findings support the antioxidant potential of Moringa extracts in counteracting environmental toxicant-induced stress. Future studies using non-lethal, neurodegeneration-focused Paraquat exposure models may further elucidate their neuroprotective potential.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100049"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144330606","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":"2025-12-01","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":"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":"2025-12-01","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":"Doxorubicin-mediated nephrotoxicity is associated with tubuloglomerular dysfunction accompanied with oxido-inflammatory stress: Implication of lutein, a natural carotenoid","authors":"Monalisa Oghenemarho Ataikiru ,&nbsp;Jerome Ndudi Asiwe ,&nbsp;John Chukwuka Igweh ,&nbsp;Alexander Obidike Naiho","doi":"10.1016/j.prerep.2025.100051","DOIUrl":"10.1016/j.prerep.2025.100051","url":null,"abstract":"<div><div>Renal toxicity is one of the pathological consequences of doxorubicin therapy in cancer patients. Meanwhile the renoprotective impact of lutein, a natural carotenoid widely known for its health benefits has not been fully studied. Hence, this study was designed to investigate the renal protective potential of lutein on doxorubicin induced renal toxicity. Animals were pretreated with lutein (40 mg/kg i.p) 25 days prior to doxorubicin (15 mg/kg i.p) exposure for 3 consecutive days. Following 28 days experimentation, animals were euthanized and kidney and blood samples were collected, processed for biochemical assay as well as histological evaluation. Our results showed that exposure to doxorubicin significantly increased serum creatinine, urea and elicited electrolyte imbalance accompanied with oxidative stress, inflammation, apoptosis and dysregulated autophagic process as well as distorted histoarchitecture. Interestingly, pretreatment with lutein offered renal protection by reversing these aberrant pathological changes caused by doxorubicin. Conclusively, lutein protects against doxorubicin-mediated nephrotoxicity via inhibition of oxidative stress, inflammation, apoptosis as well as suppression of tubuloglomerular dysfunction.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100051"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144502356","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":"2025-12-01","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":"Anti-inflammatory and antioxidant activities of a dibenzoylmethane derivative in experimental models of inflammation and pain","authors":"Matheus Brum Felício ,&nbsp;Caio de Castro Mello ,&nbsp;Marcela de Sá Hauck ,&nbsp;Tiago Antônio de Oliveira Mendes ,&nbsp;Virginia Ramos Pizziolo ,&nbsp;Maria do Carmo Pelusio ,&nbsp;Gaspar Diaz-Muñoz ,&nbsp;Leandro Licursi de Oliveira ,&nbsp;Marisa Alves Nogueira Diaz","doi":"10.1016/j.prerep.2025.100052","DOIUrl":"10.1016/j.prerep.2025.100052","url":null,"abstract":"<div><div>This study evaluated the anti-inflammatory, antinociceptive, and antioxidant activities of the synthetic compound 2-benzyl-1,3-diphenyl-1,3-propanedione (DPBP) in paw edema and inflammatory bowel disease models. Additionally, the pharmacokinetics of the compound were assessed following intraperitoneal and transdermal administration. The anti-inflammatory activity was evaluated through formalin-induced paw edema and by measuring levels of anti-inflammatory cytokines (IL-4, IL-10) and pro-inflammatory cytokines (IFN-γ). Antinociceptive activity was determined by assessing the reduction in time animals spent licking, shaking, or biting the injected paw, as well as by the reduction in abdominal writhing induced by intraperitoneal injection of acetic acid. Antioxidant activity was assessed by measuring the activities of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST), along with tissue concentrations of malondialdehyde (MDA) and nitric oxide (NO). DPBP was detected in serum for up to 12 h following both transdermal and intraperitoneal administration. Transdermal administration of DPBP demonstrated significant antioxidant activity, reducing nitric oxide levels in the colon and small intestine of animals with inflammatory bowel disease. These results show that the transdermal route is a viable alternative for this disease, especially considering the growing interest in alternative and innovative therapies for inflammatory bowel disease, with transdermal delivery emerging as a promising approach. Intraperitoneal administration reduced paw edema, decreased nociceptive behavior following formalin-induced pain, and reduced abdominal writhing caused by acetic acid. Furthermore, intraperitoneal administration increased the production of anti-inflammatory cytokines such as IL-4 and IL-10 and enhanced the activity of antioxidant enzymes (SOD and GST). These findings suggest that DPBP exhibits strong anti-inflammatory, antinociceptive, and antioxidant activities, making it a promising candidate for the treatment of inflammation and its associated symptoms.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100052"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144516954","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":"2025-12-01","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":"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":"2025-12-01","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}