Pharmacological Research - Reports最新文献

{"title":"Corrigendum to “Oxidative imbalance induced by dithiocarbamate fungicide, Mancozeb aborts Nrf2 anti-oxidant signaling pathway protection in Vero cell line” [Pharmacol. Res. – Rep., Vol. 3 (2025) 100041]","authors":"Shilpa T, Vaishnavi A, Aswati Ravindranathan Nair","doi":"10.1016/j.prerep.2025.100044","DOIUrl":"10.1016/j.prerep.2025.100044","url":null,"abstract":"","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"3 ","pages":"Article 100044"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144279196","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":"Designing of potential siRNA molecules for African norovirus gene silencing: A computational approach","authors":"Oluwakemi Ebenezer ,&nbsp;Abel Kolawole Oyebamiji ,&nbsp;Adesoji Alani Olanrewaju ,&nbsp;Omowumi Temitayo Akinola ,&nbsp;Samson Olusegun Afolabi ,&nbsp;Ayodeji Arnold Olaseinde ,&nbsp;Jack Tuszynski","doi":"10.1016/j.prerep.2024.100021","DOIUrl":"10.1016/j.prerep.2024.100021","url":null,"abstract":"<div><div>Introducing siRNAs into cells could degrade specific messenger RNA (mRNA) molecules, reducing the expression of the corresponding protein encoded by those mRNA molecules. Norovirus is the leading cause of both epidemic and pandemic acute gastroenteritis, which is inflammation of the stomach and intestine worldwide, and, as of present, no efficient vaccine is available to combat this norovirus disease. Since siRNA, therapeutics have gained significant attention for their potential to target and silence disease-causing genes. Our study utilizes different computational tools to design siRNA agents against the polyprotein of norovirus without causing off-target effects. According to the results of GC (guanine-cytosine) content, fold-free energy, binding energy, melting temperature, efficacy predictions, and molecular docking against human argonaute 2 protein (AGO2), two siRNA molecules are expected to exert the most effective action. The effectiveness and efficiency of siRNAs against norovirus need to be further examined in vivo before their use as alternative and practical molecular therapeutic agents.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"3 ","pages":"Article 100021"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144279195","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 potentials of trihydroxylflavonone-7-rhamnoglucoside against hepatocellular Lesch-Nyhan Syndrome induced by mixture of caffeine and KBrO3 via NOS/cAMP/PKA and DARPP-32, BDNF/TrkB signaling cascades","authors":"J.K. Akintunde ,&nbsp;P. Adeyemi ,&nbsp;O.H. Alonge ,&nbsp;S.O. Salami ,&nbsp;A.D. Ate ,&nbsp;T.E. Oladele ,&nbsp;O.A. Akinbode ,&nbsp;D.A. Fadare","doi":"10.1016/j.prerep.2025.100040","DOIUrl":"10.1016/j.prerep.2025.100040","url":null,"abstract":"<div><div>The management of Lesch-Nyhan Syndrome (LNS) associated with hepatocellular toxicosis has remained in the speculative phase. Also, due to numerous pharmacological capacities of 4,5,7-Trihydroxylflavonone-7-rhamnoglucoside popularly known as naringin, it may be a potent therapeutic flavonoid against hepatic LNS. We therefore studied the effect of 4,5,7-Trihydroxylflavonone-7-rhamnoglucoside on rats’ hepatic cells exhibiting LNS through NOS/cAMP/PKA/DARPP-32 and BDNF/TrkB signaling pathways. Sixty-seven male rats were divided into nine (n = 7) groups. Group I received distilled water only. Group II and III were exposed to 100 mg/kg KBrO₃ and 250 mg/kg caffeine, respectively. Group IV was co-exposed to 100 mg/kg KBrO₃ and 250 mg/Kg caffeine. Group V and VI were exposed to 100 mg/kg KBrO₃ each plus 100 mg/kg haloperidol and 50 mg/kg naringin, respectively. Group VII received 250 mg/kg caffeine + 50 mg/kg naringin. Group VIII received 100 mg/kg KBrO₃ + 250 mg/kg caffeine + 50 mg/kg naringin. Group IX received 50 mg/kg naringin. Exposure to KBrO₃ and/or caffeine for 21 days induced hepatocellular damage with alterations of ATP hydrolytic enzymes, neurotransmitter enzymes, arginase, PDE-5¹, MDA and NO levels. Also, genes associated with hepatic LNS were up-regulated and characterized by periportal inflammation and vascular congestion. Post-treatment with 4,5,7-Trihydroxylflavonone-7-rhamnoglucoside for 14 days reverted the hepatic LNS in an <em>in vivo</em> model. We therefore concluded that bio-stimulation of TrKB/BDNF and DARPP-32 levels by 4,5,7-Trihydroxylflavonone-7-rhamnoglucoside may prolong the functionality of liver among individuals suffering from LNS.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"3 ","pages":"Article 100040"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143922084","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":"Oxidative imbalance induced by dithiocarbamate fungicide, Mancozeb aborts Nrf2 anti-oxidant signaling pathway protection in Vero cell line","authors":"Shilpa T,&nbsp;Vaishnavi A,&nbsp;Aswati Ravindranathan Nair","doi":"10.1016/j.prerep.2025.100041","DOIUrl":"10.1016/j.prerep.2025.100041","url":null,"abstract":"<div><div>Indiscriminate use of the dithiocarbamate fungicide mancozeb (MZB) presents serious risks to both human health and environment. These risks are exacerbated during xenobiotic detoxification in kidneys, where glomerular filtration and excretion can lead to the accumulatation of degradation products in renal cells, rendering them more susceptible to toxic effects. Present study examined cytotoxicity of MZB (1–14 μM) in Vero cells, a sensitive model for nephrotoxicity assessment, over different time periods (6–48 h) and detected EC₅₀ of 11 μM. MZB cytotoxicity was dose- and time-dependent, as shown by a 29 ± 0.02 % cell viability at 14 μM and an EC₅₀ of 9 ± 1 μM at 48 hours. DNA damage at 11 μM MZB (EC₅₀) was evidenced as increased tail length (89 ± 9 μm), tail moment (62 ± 10 a.u.), and tail DNA content (60 ± 6 %). Cytotoxic effects of MZB were associated with the generation of reactive oxygen species (13 ± 0.1 RFU), upregulation of the pro-apoptotic <em>Bax</em> gene, activation of <em>Caspase</em>-3, and downregulation of the anti-apoptotic <em>Bcl</em>-2 gene. The study identified MZB induced redox imbalance and oxidative stress in Vero cells through the disruption of <em>Nrf</em>2-mediated antioxidant signaling pathways.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"3 ","pages":"Article 100041"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144116853","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":"Levetiracetam produces anxiolytic-like effects and attenuates the adverse consequences of stress exposure in mice","authors":"Victor Hadera,&nbsp;Matheus S. Braga,&nbsp;Leonardo B.M. Resstel,&nbsp;Francisco S. Guimarães,&nbsp;Felipe V. Gomes","doi":"10.1016/j.prerep.2025.100046","DOIUrl":"10.1016/j.prerep.2025.100046","url":null,"abstract":"<div><div>Levetiracetam, a second-generation antiepileptic drug, is proposed to regulate neurotransmitter release, including glutamate, by inhibiting the synaptic protein SV2A, as well as modulating voltage-gated calcium channels and reducing excessive synaptic vesicle exocytosis. It may also influence the activity of Kv3.1 channels, which play a critical role in maintaining the fast-spiking activity of parvalbumin-expressing GABAergic interneurons. Through these mechanisms, levetiracetam may help restore the excitatory/inhibitory (E/I) balance, which is often disrupted in psychiatric disorders. Here, we investigated whether acute levetiracetam (50, 100, and 150 mg/kg) produces anxiolytic- and antidepressant-like effects and attenuates the expression and extinction of contextual fear conditioning, as well as cognitive deficits induced by a single footshock exposure in male C57BL/6 mice. Levetiracetam produced an anxiolytic-like effect in the elevated plus-maze, reduced fear expression, and mitigated cognitive impairments in the object recognition test following single footshock exposure. These results suggest that, in addition to its antiepileptic properties, levetiracetam may have therapeutic potential for treating stress-related abnormalities in emotional regulation and cognitive processing.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"3 ","pages":"Article 100046"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144241313","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":"S-adenosyl-L-methionine modulates hippocampal DNA methylation, exerting fast and long-lasting anti-stress effects independent of alterations in TrkB-mTOR expression","authors":"Amanda J. Sales,&nbsp;Izaque S. Maciel,&nbsp;Francisco S. Guimarães","doi":"10.1016/j.prerep.2025.100032","DOIUrl":"10.1016/j.prerep.2025.100032","url":null,"abstract":"<div><div>Emerging evidence suggests that targeting DNA methylation, a key epigenetic mechanism, may represent a promising therapeutic approach for the treatment of stress-related disorders, including depression. Preclinical studies indicate that the inhibition of DNA methylation induces rapid and sustained antidepressant-like effects through the increased BDNF-TrkB-mTOR signaling in the prefrontal cortex, a brain region associated to the neurobiology of depression and neuroplasticity. S-adenosyl-l-methionine (SAMe), a methyl donor, has been shown to reverse depressive-like behaviors by modulating DNA methylation. However, the molecular mechanisms underlying the SAMe antidepressant effects are not yet fully understood. Therefore, this study evaluated whether SAMe induces rapid and long-lasting behavioral effects by modulating DNA methylation and mTOR-TrkB expression in mice. For this purpose, male Swiss mice received intraperitoneal (i.p.) injections of SAMe (25, 50, and 100 mg/kg) or vehicle (10 mL/kg), 30 minutes, 7 days, or 14 days prior to the forced swimming test (FST) or tail suspension test (TST), two predictive tests of antidepressant action. Global DNA methylation and mTOR-TrkB levels were measured in the hippocampus and prefrontal cortex. SAMe (50 mg/kg) induced a rapid and sustained decrease in immobility time in both the FST and TST, and prevented the stress-induced effects in hippocampal DNA methylation without changing the analyzed protein expression. These findings suggest that the rapid and sustained anti-stress effects observed in mice, resulting from the modulation of hippocampal DNA methylation due to acute SAMe treatment, are not related with TrkB-mTOR signaling.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"3 ","pages":"Article 100032"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143152930","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":"Spinal Muscular Atrophy (SMA): Treatment strategies, challenges and future prospects","authors":"Nikunja Kishor Mishra,&nbsp;Amiyakanta Mishra","doi":"10.1016/j.prerep.2025.100031","DOIUrl":"10.1016/j.prerep.2025.100031","url":null,"abstract":"<div><h3>Introduction</h3><div>Spinal muscular atrophy (SMA) is a pediatric neuromuscular disorder that is distinguished by a defect or mutation in the survival motor neuron1 (SMN1) gene. It is a profoundly impactful childhood motor neuron disorder. In its most severe instances and in the absence of treatment, it tragically results in death within the initial two years of life. The disease is identified by muscle weakness and atrophy, predominating in proximal limb muscles. The most common mutation causing SMA is a homozygous deletion of exon 7 of SMN1. Recent therapeutic breakthroughs provide hope to families and patients by tackling the deficiency in SMN protein using gene therapy or alternative genetic manipulation techniques. It is becoming increasingly clear that none of these therapies alone will provide a cure for SMA. Therefore, the objective of the study is to review the correlation between SMN protein levels in tissues and the pathology of SMA. It also aims to provide a comprehensive review of the three currently licensed therapies for SMA, offering a brief overview of their preclinical and clinical studies that led to marketing authorization, coupled with real-world data analysis. Additionally, the study delves into discussions surrounding combined therapy, supplementary therapeutic approaches, challenges in clinical care, and future prospects for the treatment of SMA.</div></div><div><h3>Materials and methods</h3><div>The data for this study were gathered from a range of scholarly sources, including PubMed, Scopus, Springer and other relevant search engines. These sources were selected to ensure access to the latest and most comprehensive literature on SMA management, reflecting current treatment paradigms and advancements in the field.</div></div><div><h3>Results</h3><div>Both preclinical and clinical investigations of risdiplam, onasemnogene abeparvovec, and nusinersen have elucidated the restoration of functional SMN protein and its distribution in both peripheral tissues and central nervous system (CNS) motor neurons, representing a promising therapeutic benefit for the treatment of SMA.</div></div><div><h3>Discussion</h3><div>Clinical trials and real-world data provide robust support for the efficacy and safety profiles of the available drugs. Three therapies, nusinersen, onasemnogene abeparvovec, and risdiplam, aim to increase SMN levels in patients with SMA. Currently, an improvements in safety, efficacy, and motor function have been observed in combination therapies, such as the TOPAZ study (Nusinersen with Aptiegromab), the RESPOND study (Nusinersen with Onasemnogene abeparvovec) and the SAPPHIRE study (Aptiegromab alongside nusinersen or risdiplam).</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"3 ","pages":"Article 100031"},"PeriodicalIF":0.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143453118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, and evaluation of in-silico anti-cancer activity of novel gefitinib analogues against 21 target proteins","authors":"Supriti Khan Ushna ,&nbsp;Ananta Kumar Das","doi":"10.1016/j.prerep.2025.100030","DOIUrl":"10.1016/j.prerep.2025.100030","url":null,"abstract":"<div><div>Over time, evidence suggests that numerous drugs have been discovered, and computer modelling, or the \"In silico method\", to understand how anti-cancer proteins interacted. Gefitinib, a quinazoline, inhibits the EGFR tyrosine kinase by attaching to its ATP-binding site. In order to find out how effective new gefitinib analogues are at targeting cancer, this study used molecular docking and ADMET analysis. In this study, the 21 anti-cancer target proteins were utilized to perform docking by using autodock tools. Twenty new analogues were created using ligand-based design, and frontier molecular orbital analysis revealed that the designed molecules are more reactive and softer. The majority of the designed molecules have higher binding affinities than gefitinib, according to the docking studies. Additionally, the analysis revealed that the compounds C-4, C-5, C-7, C-9, C-11, C-12, and C-14 have superior affinity to more than two targets. Docking experiments of the mutated target proteins with designed molecules demonstrate that many target proteins exhibit binding properties comparable to those of the unmutated proteins. According to the literature review on targets, these molecules may be helpful in the treatment of many cancers, including tumour growth, chronic myelogenous leukemia, chronic lymphocytic leukemia, acute myeloid leukemia, acute lymphoid leukemia, thyroid cancers, and salivary gland cancers. It was shown by the binding affinity, drug similarity score, and other ADMET experiments that the designed molecules will have more significant anti-cancer activity.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"3 ","pages":"Article 100030"},"PeriodicalIF":0.0,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143152931","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 mitigates dichlorvos-initiated multi-organ dysfunction in rats by attenuating systemic oxidative stress and brain inflammatory mRNA transcripts","authors":"Adio Jamiu Akamo ,&nbsp;Boluwatife Adenike Olagunju ,&nbsp;Ofem Effiom Eteng ,&nbsp;Iyabode Adekemi Kehinde ,&nbsp;Adetutu Omolola Ojelabi ,&nbsp;Mushafau Adewale Akinsanya ,&nbsp;Adedayo Adebisi Adebisi ,&nbsp;Tobi Stephen Adekunbi ,&nbsp;Abiola Fatimoh Adenowo ,&nbsp;Flourence Anifowose ,&nbsp;Olufemi Mulkah Ajagun-Ogunleye ,&nbsp;Jacob Kehinde Akintunde","doi":"10.1016/j.prerep.2025.100029","DOIUrl":"10.1016/j.prerep.2025.100029","url":null,"abstract":"<div><div>Organophosphorus pesticides like dichlorvos (DDVP) are widely used for pest control, however their safety is a growing concern due to potential multi-factorial health risks. While curcumin (CUR) is known for its antioxidant capacity, its influence on DDVP-incited multi-organ dysfunction and brain inflammation remain under-researched. This work assessed the ameliorative competence of CUR in a DDVP-mediated systemic intoxication rat model. Rats (42) were randomly appropriated into seven groups (6 rats/group): Control, DDVP only (20 mg.kg⁻¹day⁻¹), DDVP subjected with either CUR (50 and 100 mg.kg⁻¹day⁻¹) or the reference drug atropine (0.2 mg.kg⁻¹day⁻¹), and CUR only (50 and 10 mg.kg⁻¹day⁻¹) were investigated. Rats were afflicted with DDVP orally for seven days, followed by fourteen days of CUR intervention. We humanely killed the rats and harvested their blood and viscera (liver, kidney, heart, lung, and brain) for bioassays twenty-four hours following the final treatment. CUR significantly (p &lt; 0.05) abrogated DDVP-engendered elevations in H₂O₂, NO, and malondialdehyde contents, as well as GST activity; and reversed DDVP-elicited declines in GSH amounts, activities of SOD, catalase, and glutathione peroxidase in across all tissues. In the brain, CUR markedly (p &lt; 0.05) rescinded DDVP-occasioned upregulation of gene expression biomarkers for fibrosis (TGF-β-1), apoptosis regulator (nuclear factor-kB-p65), and pro-apoptosis (p53 and Bax); and markedly abated DDVP-provoked repression of anti-inflammatory cytokine (interleukin-10)]. Wholly CUR therapy mitigated DDVP-engendered multi-organ impairments in rats via rescinding oxidative stress and brain inflammation.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"3 ","pages":"Article 100029"},"PeriodicalIF":0.0,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143152929","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":"Vitamin D3 supplementation improve sexual behaviors of male wistar rats treated with flunitrazepam","authors":"David Tolulope Oluwole ,&nbsp;Oladipupo Samuel Ebiwonjumi ,&nbsp;Lydia Oluwatoyin Ajayi ,&nbsp;Ayodeji Folorunsho Ajayi","doi":"10.1016/j.prerep.2025.100028","DOIUrl":"10.1016/j.prerep.2025.100028","url":null,"abstract":"<div><div>Sexual function, a major component of male health and lifestyle, has been reported to be impaired by flunitrazepam abuse due to its central tranquilizing actions. Therefore, this study examined the role of vitamin D3 (Vit.D3) supplementation on the sexual behavior of flunitrazepam (Flu)-treated male rats. Thirty male Wistar rats, weighing 180–200 g, were allowed access to receptive female rats on three different occasions and screened for sexual proficiency; twenty male rats were selected and randomly allocated into four groups: Vehicle: receiving 0.5 ml of distilled water with 0.5 ml of olive oil;. Flu: receiving 0.35 mg/kg body weight (BW) of flunitrazepam in 0.5 ml of distilled water with 0.5 ml of olive oil; Vit. D3: receiving 0.1 μg/kg/day of vitamin D3 in 0.5 ml of olive oil with 0.5 ml distilled water; Flu + Vit. D3: receiving 0.35 mg/kg of flunitrazepam in 0.5 ml of distilled water with 0.1 μg/kg/day of Vitamin.D3 in 0.5 ml of olive oil. Treatments were administered orally for 56 days. Vitamin D3 supplementation significantly (p &lt; 0.05) reduced mount and intromission latencies, mount frequency and post-ejaculatory interval while increasing intromission frequencies, copulatory and inter-copulatory efficiencies with extended ejaculation latency in flunitrazepam-treated rats. Additionally, Vit.D3 supplementation significantly (p &lt; 0.05) increased serum concentrations of gonadotropin hormones, testosterone, and estradiol, while reducing prolactin concentration. Vitamin D3 supplementation optimized sexual performance and motivation by reducing mount and intromission latencies, improving sexual performance, and preventing premature ejaculation, thereby enhancing copulatory and inter-copulatory efficiencies. Vitamin D3 possibly optimized sexual performance by inhibiting prolactin sretion, which upregulates circulatory pituitary steroids and testicular androgens.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"3 ","pages":"Article 100028"},"PeriodicalIF":0.0,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143152932","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}