Pharmacological Research - Reports最新文献

{"title":"Insights into the antibacterial activity of Limosilactobacillus fermentum curd isolate against gram-positive and gram-negative pathogenic bacteria","authors":"Suchhanda Nandi ,&nbsp;Shyamapada Mandal","doi":"10.1016/j.prerep.2025.100034","DOIUrl":"10.1016/j.prerep.2025.100034","url":null,"abstract":"<div><div>It is widely known that lactic acid bacteria (LAB), commonly found in fermented products like curd, extends health benefits and antibacterial properties, particularly in traditional Chinese medicine (TCM). In spite of the growing demand for sweet curd contained in earthen pots in our region, no research has specifically explored its unique properties. This study aims to address this gap by examining the probiotic characteristics, antibacterial activity and consumer appeal of sweet curd in earthen pots. A sweet curd sample containing in an earthen pot was microbiologically cultured to isolate LAB applying conventional methods and 16S rRNA gene sequencing. The strain thus isolated was identified to be <em>Limosilactobacillus fermentum</em> 406B, showed broad-spectrum antibacterial activity against gram-positive: <em>Staphylococcus aureus</em>, <em>Bacillus cereus</em>, <em>Streptococcus pneumoniae</em> and <em>Listeria monocytogenes</em> and gram-negative: <em>Escherichia coli</em>, <em>Pseudomonas aeruginosa</em>, <em>Acinetobacter baumannii</em> and <em>Proteus vulgaris</em> bacterial pathogens. Antimicrobial property and minimum inhibitory concentration (MIC) were assessed by agar well diffusion and broth dilution method, respectively. Initial tests based on colony morphology, gram staining and biochemical assays confirmed it as a <em>Lactobacillus</em> species, with sequencing confirming its identity as <em>Limosilactobacillus fermentum</em> 406B. The strain demonstrated excellent physiological tolerance to NaCl, bile, low pH and varying temperatures, confirming its suitability as a probiotic. Additionally, safety tests showed that it was non-pathogenic, as it tested negative for gelatinase and DNase production and displayed an acceptable antibiotic susceptibility profile. With a cumulative probiotic potential (CPP) of 100 %, <em>L. fermentum</em> 406B holds significant promise as a probiotic strain. These results underscore the strain’s potential not just in TCM but also as a prospective biotherapeutic agent, considering its extensive antibacterial activity and robust safety profile.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"3 ","pages":"Article 100034"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143686034","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":"The protective potential of Blighia sapida on the behavioural and hematobiochemical disruption in kerosene-exposed Clarias gariepinus: In Vivo and In Silico evaluation","authors":"M.B. Adekola ,&nbsp;O.C. Ojelade ,&nbsp;S.A. Olurode ,&nbsp;T.O. Adebowale ,&nbsp;A.O. Akinde ,&nbsp;J.T. Apata ,&nbsp;A.F. Adesina ,&nbsp;P. Oyeyemi ,&nbsp;C.U. Alichi ,&nbsp;O.T. Ajala","doi":"10.1016/j.prerep.2025.100036","DOIUrl":"10.1016/j.prerep.2025.100036","url":null,"abstract":"<div><h3>Introduction</h3><div>The discharge of petroleum products poses significant toxicological risks to aquatic life and the environment, undermining Sustainable Development Goals (SDG 14). Members of the Sapindaceae family, to which <em>Blighia sapida</em> belongs, have been utilized for the treatment of blood, heart, urinary and mental disorders. The study investigated the protective effects of ethanol extract (EE) from <em>Blighia sapida</em> stem-bark on <em>Clarias gariepinus</em> sub-adults using their behavioral, biochemical, hematological parameters, as well as <em>in silico</em> evaluation.</div></div><div><h3>Methods</h3><div>The study randomly divided 189 <em>Clarias gariepinus</em> into nine groups (G) in triplicates with seven fish to make 27 treatment tanks. The groups were G1: control, G2: 100 mL kerosene, G3: 200 mL kerosene, G4: 100 mL kerosene + 50 mg/kg bwt.EE, G5: 100 mL kerosene + 100 mg/kg bwt.EE, G6: 100 mL kerosene + 150 mg/kg bwt.EE, G7: 200 mL kerosene + 50 mg/kg bwt.EE, G8: 200 mL kerosene + 100 mg/kg bwt.EE, G9: 200 mL kerosene + 150 mg/kg bwt.EE. The experimental setup was repeated every other day for 28 days in a 30 L plastic aquaria. Behavioral parameters such as active swimming, aggression, jumping, air gulping, slothful movement, and feed response were recorded before and during the treatment using the focal sampling technique. Gas chromatography- mass spectrometry (GC-MS) of the ethanol extract was analyzed. <em>In silico</em> molecular docking studies were used to analyze the binding interactions with CYP₄₅₀ 2E1.</div></div><div><h3>Results</h3><div>The observed behavioral alterations were normalized in a dose-dependent manner at the end of the experiment, the extract mitigated kerosene-induced biochemical disruptions, reducing ALT, AST, and creatinine levels. The levels of disruptions in hematology at 100- and 200-mL kerosene exposure was restored close to control values. However, the EE displayed amelioration on the effects of kerosene. <em>In silico</em> analysis revealed high negative binding interactions between compounds identified in the extract and CYP 450 2E1. Better docking scores further validate the protective potential of the top three compounds [9-Octadecenoic acid (-7.9 kCal/mol.), (<em>E</em>)-, Hexadecanamide (-7.5 kCal/mol.), 9-Octadecenamide, (<em>Z</em>)- (-7.8 kCal/mol.)] identified in <em>B. sapida</em> ethanol extract against the molecular protein target compared with ademethionine, the standard drug (-6.6 kCal/mol.). The study concluded that <em>Blighia sapida</em> extract shows promises as a sustainable intervention against kerosene-induced toxicity in aquatic organisms. Also, the top three compounds fingerprinted from the extract of this plant, unlike the standard compound, exhibited adequate drug-like properties.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"3 ","pages":"Article 100036"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143768675","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":"Synthesis, characterization and evaluation of antioxidant and antibacterial activities of novel isatin-derived hydrazone derivatives of N-amino-11-azaartemisinin","authors":"Komal Rathi ,&nbsp;Priyanka Yadav ,&nbsp;Varun Rawat ,&nbsp;Aditi Pandey ,&nbsp;Achal Mukhija ,&nbsp;Biswajit Saha ,&nbsp;Ram Awatar Maurya ,&nbsp;Ved Prakash Verma","doi":"10.1016/j.prerep.2025.100033","DOIUrl":"10.1016/j.prerep.2025.100033","url":null,"abstract":"<div><div>The rise of antibiotic-resistant bacterial infections and the associated oxidative stress highlight the urgent need for new therapeutic agents. Artemisinin <strong>1</strong> and isatins are both pharmacologically active compounds with significant antibacterial, antimalarial, anticancer, and antioxidant properties respectively. In this study, we synthesized and biologically evaluated a series of isatin-derived hydrazones <strong>14a-z</strong> of <em>N</em>-amino-11-azaartemisinin, aiming to address gaps in the development of effective drugs for oxidative stress and bacterial infections. The antioxidant activity was assessed through the DPPH radical scavenging assay, revealing compound <strong>14a</strong> (IC₅₀ = 1.54 ± 0.53 μg mL⁻¹) as highly potent, comparable to L-ascorbic acid (IC₅₀ = 1.60 ± 0.62 μg mL⁻¹). Notably, antibacterial tests highlighted compound <strong>14o</strong> as having superior efficacy (MIC = 0.25 μg mL⁻¹) against <em>E. coli</em>, while <strong>14l</strong> exhibited excellent activity (MIC = 0.5 μg mL⁻¹) against <em>Bacillus subtilis</em>. In addition to these biological evaluations, we explored the thermodynamic properties of synthesised compounds using isothermal titration calorimetry (ITC) and studied the thermal stability and degradation patterns through thermogravimetric analysis (TGA). These findings underscore the potential of isatin-derived hydrazones as novel drug candidates for combating bacterial infections and free-radical associated conditions, contributing to the ongoing search for innovative therapies in the face of growing resistance and global health challenges.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"3 ","pages":"Article 100033"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143552297","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":"Therapeutic potential and bioactive compounds of Apium graveolens: A phytopharmacological review","authors":"Ghadi Daoud ,&nbsp;Farogh Ahsan ,&nbsp;Tarique Mahmood ,&nbsp;Shahzadi Bano ,&nbsp;Vaseem Ahamad Ansari ,&nbsp;Syed Mehdi Hasan Zaidi ,&nbsp;Jamal Akhtar Ansari","doi":"10.1016/j.prerep.2025.100039","DOIUrl":"10.1016/j.prerep.2025.100039","url":null,"abstract":"<div><div><em>Apium graveolens</em> (<em>A. graveolens</em>), often referred to as celery, is a widely consumed vegetable with a long history of use in traditional medicine. It offers numerous health advantages, such as anti-inflammatory, antioxidant, and antihypertensive properties. Celery is used in both traditional medicine and modern pharmacology for its therapeutic effects. This review is justified to consolidate recent research on its medicinal properties. Emphasizing its therapeutic potential can steer future research and practical applications in pharmaceuticals, enhancing comprehension of its health benefits and encouraging its use in various treatments. Phytochemical studies have discovered numerous bioactive compounds in <em>A. graveolens</em>, such as flavonoids, phenolic acids, coumarins, and essential oils, all of which play a role in its extensive pharmacological effects. Studies have demonstrated that <em>A. graveolens</em> exhibits antioxidant, anti-inflammatory, antimicrobial, antihypertensive, antidiabetic, hepatoprotective, and other pharmacological effects. The presence of compounds such as apigenin, luteolin, and phthalides plays a pivotal role in these therapeutic effects by modulating various biological pathways, including oxidative stress, inflammatory cascades, and lipid metabolism. These compounds also exhibit diuretic effects, promoting urine production and aiding in toxin removal, thereby alleviating stress on the kidneys. The clinical evidence supporting the efficacy of <em>A. graveolens</em> in humans is still limited; its abundant phytochemical profile and new preclinical findings indicate its promise as an adjunctive therapeutic agent. This review provides a scientific basis for the continued exploration and use of <em>A. graveolens</em> in modern medicine, highlighting its role in promoting its pharmacological aspects through its diverse bioactive components.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"3 ","pages":"Article 100039"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143898640","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":"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,&nbsp;Vaishnavi A,&nbsp;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}