Pharmacological Reports最新文献

{"title":"Carvacrol in asthma management: a comprehensive review of its therapeutic potential and mechanisms of action.","authors":"Deepa Neopane, Poonam Kushwaha","doi":"10.1007/s43440-025-00709-6","DOIUrl":"https://doi.org/10.1007/s43440-025-00709-6","url":null,"abstract":"<p><p>Asthma, a chronic inflammatory disorder of the airways, remains a significant global health concern. Current treatments focus on symptom management and inflammation control, but the search for more effective and safer therapies continues. Carvacrol, a naturally occurring monoterpenoid phenol found in essential oils of various plants, has emerged as a promising bioactive compound with potent anti-inflammatory, antioxidant, and bronchodilatory properties. This review explores the potential of carvacrol as a novel therapeutic agent for asthma management. We discuss its mechanisms of action, including modulation of inflammatory pathways, inhibition of oxidative stress, and relaxation of bronchial muscles. Additionally, preclinical and clinical studies evaluating the efficacy and safety of carvacrol in asthma treatment are analyzed. The integration of carvacrol into existing treatment regimens could offer a multifaceted approach to asthma management, enhancing therapeutic outcomes and improving patients' quality of life.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Compound PZ-1262, a 4-isoquinoline-sulfonamide analog of Brexpiprazole, produces potential antidepressant, anxiolytic and procognitive effects in rodent models.","authors":"Anna Partyka, Joanna Gołębiowska, Krzysztof Marciniec, Vittorio Canale, Wojciech Trybała, Grzegorza Satała, Katarzyna Grychowska, Magdalena Jastrzębska-Więsek, Andrzej J Bojarski, Agnieszka Nikiforuk, Władysława A Daniel, Anna Wesołowska, Paweł Zajdel, Piotr Popik","doi":"10.1007/s43440-025-00713-w","DOIUrl":"https://doi.org/10.1007/s43440-025-00713-w","url":null,"abstract":"<p><strong>Background: </strong>Novel antipsychotics are characterized by multitarget profile of action, affecting among others, dopamine and serotonin receptors. In a series of experiments, we designed, synthesized and examined two new isoquinoline-sulfonamide analogs of the modern multitarget antipsychotics aripiprazole and brexpiprazole, compounds PZ-1262 and PZ-1264. We hypothesized that the 4-isoquinolinesulfonamide moiety, derived from the structure of 5-HT₆ receptor antagonists, would provide compounds with enhanced activity at 5-HT₆ receptors, along with partial agonistic activity at 5-HT_1A and D₂ receptors.</p><p><strong>Methods: </strong>The receptor binding profile, functional activity, and metabolic stability of PZ-1262 and PZ-1264 were evaluated through in vitro assays. Potential antipsychotic, antidepressant, anxiolytic, and pro-cognitive effects were assessed using in vivo behavioral tests in rodents.</p><p><strong>Results: </strong>In vitro, PZ compounds demonstrated partial agonistic activity at 5-HT_1A receptor, antagonistic activity at D₂ and D₃ as well as 5-HT_2A, 5-HT₆ and 5-HT₇ receptors and metabolic stability. In vivo, both compounds enhanced phencyclidine-induced hyperactivity in rats and decreased immobility time in the forced swim test in mice, without influencing spontaneous locomotor activity. In the novel object recognition test in rats, they demonstrated pro-cognitive effects in phencyclidine disturbed conditions. PZ-1262 potentiated D-amphetamine-induced hyperactivity, exhibited anxiolytic-like effects in the four plates test in mice, and demonstrated significant brain penetration.</p><p><strong>Conclusions: </strong>The complex pharmacodynamic profile translated into the useful psychotropic effects. While the compounds potentiated D-amphetamine- and phencyclidine-induced hyperactivity, this action could be regarded as a desired activating effect rather than evidence against antipsychotic-like efficacy. Present findings point to PZ-1262 as a more promising lead compound for further research.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The metabolism of big endothelin-1 axis and lipids affects carotid atherosclerotic plaque stability - the possible opposite effects of treatment with statins and aspirin.","authors":"Adam Płoński, Anna Krupa, Dariusz Pawlak, Katarzyna Sokołowska, Beata Sieklucka, Marcin Gabriel, Adam Filip Płoński, Jerzy Głowiński, Krystyna Pawlak","doi":"10.1007/s43440-025-00714-9","DOIUrl":"https://doi.org/10.1007/s43440-025-00714-9","url":null,"abstract":"<p><strong>Background: </strong>The understanding of endothelin's role in carotid plaque instability is limited. We have studied the big endothelin-1 (ET-1) axis and its role in carotid plaque stability in patients undergoing carotid endarterectomy (CEA). The interactions of endothelins with known CVD risk factors were also evaluated.</p><p><strong>Methods: </strong>We studied 77 patients, who were divided into subgroups based on the optimal cut-off for grey-scale median (GSM), a marker of plaque instability. GSM values < 46.87 were designated as unstable carotid plaque, while GSM ≥ 46.87 were assigned to stable plaque. Twelve people without carotid atherosclerosis served as controls. Big ET-1, ET-1 and ET-1 (1-31) were measured and the endothelin-converting enzyme-1 (ECE-1) and chymase activity were calculated. Clinical and laboratory parameters were also evaluated.</p><p><strong>Results: </strong>ET-1 levels and ECE-1 activity were increased in all patient groups compared to controls (all P < 0.001) - and were higher in patients with unstable plaque than in those with stable plaque (P < 0.01). ET-1 (1-31) did not differ between the groups. ET-1 levels and ECE-1 activity inversely correlated with total cholesterol, LDL-cholesterol, and GSM values, whereas GSM was positively associated with total cholesterol and LDL fractions. Detailed analysis of patients according to the pharmacotherapy used revealed that statins favored ET-1 formation independently of cholesterol-lowering properties, whereas aspirin reduced this effect.</p><p><strong>Conclusions: </strong>ET-1 formation is the main pathway of big ET-1 metabolism in patients with carotid atherosclerosis, especially in those with plaque instability. Statins and aspirin appear to have opposing effects on ET-1 formation, suggesting the greater benefit related to plaque stability in patients taking both drugs concomitantly.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Juvenile fluoxetine treatment affects the maturation of the medial prefrontal cortex and behavior of adolescent female rats.","authors":"Joanna Kryst, Agnieszka Chocyk, Anna Solarz-Andrzejewska, Iwona Majcher-Maślanka","doi":"10.1007/s43440-025-00712-x","DOIUrl":"https://doi.org/10.1007/s43440-025-00712-x","url":null,"abstract":"<p><strong>Background: </strong>Serotonin is strongly involved in the regulation of brain development, including the proper formation of neuronal circuits and synaptic plasticity. One of the factors that can affect brain serotonin levels is exposure to fluoxetine (FLX), a selective serotonin reuptake inhibitor, the first-line pharmacological treatment for depression and anxiety in the pediatric population. The safety of early-life FLX treatment is still questionable. Women are more prone to anxiety and depression from a young age. We hypothesized that juvenile FLX treatment influences the brain maturation and behavior of adolescent females.</p><p><strong>Methods: </strong>On postnatal days 20 to 28, juvenile female rats were injected once daily with FLX. Five days later, anxiety- and fear-related behaviors and amphetamine-induced locomotor activity were assessed. On postnatal day 40, the numbers of neurons and glial cells in the medial prefrontal cortex (mPFC) and hippocampus were estimated via stereological methods. Additionally, the mRNA expression of cell survival/apoptosis and synaptic plasticity markers was evaluated via RT‒qPCR.</p><p><strong>Results: </strong>FLX-treated females showed decreased anxiety level, freezing behavior during fear conditioning and amphetamine-induced locomotor activity when compared to control females. Simultaneously, FLX-injected females presented greater regional volume and numbers of neurons and astrocytes in specific subregions of the mPFC when compared to the control group. Additionally, FLX-treated females showed increased expression of genes regulating cell survival and reduced mRNA levels of AMPA glutamate receptors in the mPFC.</p><p><strong>Conclusions: </strong>Juvenile FLX affects the maturation of the mPFC and attenuates anxiety-like behavior, fear memory and the locomotor response to amphetamine in adolescent females.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eribulin exerts multitarget antineoplastic activity in glioma cells.","authors":"Guilherme Augusto Sousa Alcântara, Mariane Cristina do Nascimento, Livia Bassani Lins de Miranda, Bruna Oliveira de Almeida, Keli Lima, Eduardo Magalhães Rego, Leticia Veras Costa-Lotufo, João Agostinho Machado-Neto","doi":"10.1007/s43440-025-00711-y","DOIUrl":"10.1007/s43440-025-00711-y","url":null,"abstract":"<p><strong>Background: </strong>Gliomas, particularly glioblastomas, are highly aggressive cancers with rapid proliferation and poor prognosis. Current treatments have limited efficacy, highlighting the need for new therapeutic strategies. Eribulin mesylate, a synthetic macrocyclic ketone, has shown potential as an anticancer agent in several malignancies. This study investigates the cellular and molecular effects of eribulin in glioma models, focusing on its impact on cell cycle progression, apoptosis, mitochondrial function, and migration.</p><p><strong>Methods: </strong>Glioma cell lines were treated with eribulin. Cell viability was measured by MTT assay, and the cell cycle was analyzed by flow cytometry. Apoptosis was assessed through morphological changes, PARP1 cleavage, and γH2AX expression. Mitochondrial integrity and reactive oxygen species levels were evaluated by flow cytometry. Cell migration was assessed using a spheroid-based assay, and protein expression changes were analyzed by Western blotting.</p><p><strong>Results: </strong>Eribulin reduced cell viability, with HOG cells exhibiting the highest sensitivity. Cell cycle analysis showed G₂/M phase arrest and morphological examination revealed polyploidy and apoptotic features. Mitochondrial dysfunction was observed, with decreased mitochondrial membrane potential and increased reactive oxygen species, particularly in HOG and T98G cells. Molecular analysis indicated activation of apoptotic pathways (PARP1 cleavage and γH2AX elevation) and reduced stathmin 1 expression. Eribulin also significantly reduced cell migration in HOG cells.</p><p><strong>Conclusion: </strong>Eribulin demonstrates potent anti-glioma effects through apoptosis, mitochondrial dysfunction, and cell cycle disruption. These findings support its potential as a therapeutic option for glioblastoma treatment, warranting further investigation into its mechanisms and clinical applicability.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of 3,5,4'-tri-[4-(nitrooxy)butanoyl]oxy resveratrol, a new nitric oxide-releasing derivative of resveratrol, on platelet activation.","authors":"Giuseppe Guglielmini, Emanuela Berardi, Federica Messina, Maria Carla Marcotullio, Paolo Gresele","doi":"10.1007/s43440-024-00691-5","DOIUrl":"https://doi.org/10.1007/s43440-024-00691-5","url":null,"abstract":"<p><strong>Background: </strong>Resveratrol is a polyphenol of red wine that is thought to contribute to the \"French paradox\" by protecting against atherosclerotic cardiovascular events. It has anti-inflammatory and antioxidant properties and enhances nitric oxide (NO) production. However, in conditions of severe endothelial dysfunction, its cardiovascular protective effects may be limited. Our study aimed to synthesize and characterize a new nitro derivative of resveratrol, trinitroresveratrol (TN-RSV), for its potential nitric oxide-donating and antiplatelet effects.</p><p><strong>Methods: </strong>3,5,4'-tri-[4-(nitrooxy)butanoyl]oxy resveratrol (TN-RSV) was synthetized starting from commercial resveratrol (RSV) through the intermediacy of 3,5,4'-tri-(4-bromo-butanoyl)oxy resveratrol. Platelet aggregation was assessed by light transmission aggregometry (LTA) using collagen as agonist. The release of nitric oxide (NO) from TN-RSV or from activated platelets was assessed as the concentration of the NO degradation products (nitrites plus nitrates, NOx) in the supernatant. Platelet adhesion to collagen under flow conditions was assessed using a parallel plate perfusion chamber. Reactive oxygen species (ROS) production from collagen-activated platelets was assessed by flow cytometry using the fluorescent probe H2DCFDA.</p><p><strong>Results: </strong>TN-RSV spontaneously released NO and significantly inhibited collagen-induced platelet aggregation in a dose-dependent manner. This effect was greater than that of resveratrol and it was not affected by the preincubation with L-NAME, a nitric-oxide synthase (NOS) inhibitor, indicating that TN-RSV directly inhibits platelet activation independently of NOS.</p><p><strong>Conclusions: </strong>Our findings suggest that TN-RSV has potential as an antiplatelet agent and that further research exploring its therapeutic applications for conditions associated with endothelial dysfunction and platelet hyperreactivity is warranted.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A single dose of haloperidol decanoate induces short-term hippocampal neuroinflammation: focus on the glial response.","authors":"Izaviany Schmitz, Larissa Daniele Bobermin, Amanda da Silva, Fernanda Becker Weber, Natalie K Thomaz, Felipe Schmitz, Morgana Brondani, Roselei Fachinetto, Guilhian Leipnitz, Angela T S Wyse, Carlos-Alberto Gonçalves, André Quincozes-Santos","doi":"10.1007/s43440-025-00706-9","DOIUrl":"https://doi.org/10.1007/s43440-025-00706-9","url":null,"abstract":"<p><strong>Background: </strong>Haloperidol is a widely used antipsychotic for the treatment of neuropsychiatric disorders, the pathophysiology of which may involve hippocampal alterations. Hippocampus is affected by long-term use of the drug, but the effects of acute doses on the hippocampus remain unclear. The present study investigated whether a single dose of haloperidol decanoate could induce short-term hippocampal neuroinflammation and changes in cholinergic, glutamatergic and redox homeostasis in adult rats, focusing on the glial response.</p><p><strong>Methods: </strong>Male Wistar rats (60 days old) received a single intramuscular injection of haloperidol decanoate (38 mg/kg) or vehicle. After 7 days, hippocampal tissue was used to assess gene expression of inflammatory mediators, glutamate transporters, and transcriptional factors that regulate neuroinflammation. The enzymatic activities of acetylcholinesterase (AChE), glutamine synthetase (GS), and glutathione peroxidase (GPx), and glutamate uptake and reduced glutathione (GSH) levels were also determined.</p><p><strong>Results: </strong>Haloperidol decanoate increased the gene expression of pro-inflammatory cytokines, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS). Moreover, downregulation of the transcriptional factor erythroid 2-related factor 2 (Nrf2) and the peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α) was observed. In contrast, nuclear factor κB (NFκB) transcriptional levels remained unchanged. Haloperidol also increased glutamate uptake, the glutamate transporter GLAST gene expression, and the AChE and GPx activities.</p><p><strong>Conclusions: </strong>Our findings show that a single dose of haloperidol decanoate induces short-term hippocampal neuroinflammation and changes in glial parameters, highlighting the need for future adjuvant glioprotective strategies that can attenuate these effects.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progress in the study of anti-tumor effects and mechanisms of vitexin.","authors":"Qiming Yang, Rui Huan, Defeng Meng, Junwei Qi, Lei Xia","doi":"10.1007/s43440-024-00664-8","DOIUrl":"10.1007/s43440-024-00664-8","url":null,"abstract":"<p><p>Vitexin (apigenin-8-C-beta-D-glucopyranoside) is a natural flavonoid derivative with anti-cancer, antioxidant, anti-inflammatory, antihypertensive, anti-asthma, anti-epilepsy, and other therapeutic effects. It is extracted from pearl millet, hawthorn, pigeon bean, mung bean, and other medicinal plants. Vitexin has received widespread attention because of its significant anti-tumor effect. It induces apoptosis and anti-tumor angiogenesis, inhibits tumor cell migration and invasion, regulates tumor cell autophagy and immunity, and increases patient sensitivity to radiotherapy and chemotherapy. It has a significant anti-tumor effect on breast, prostate, liver, cervical, and colon cancers, gliomas, and other malignant tumors. This review demonstrates the latest research progress on the anti-tumor effects and potential mechanisms of vitexin. It summarizes its anti-tumor mechanism to provide new theoretical support and reference for cancer treatment.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"124-134"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A hydrogen sulphide-releasing non-steroidal anti-inflammatory, ATB-346, significantly attenuates human myometrial contractions.","authors":"Ana Mijušković, Susan Wray, Sarah Arrowsmith","doi":"10.1007/s43440-024-00643-z","DOIUrl":"10.1007/s43440-024-00643-z","url":null,"abstract":"<p><strong>Background: </strong>Spontaneous preterm birth is the leading cause of perinatal morbidity and mortality. Tocolytics are drugs used to inhibit uterine contractions in cases of imminent preterm birth, however, few are effective in stopping labour once initiated and all have side effects. Combination approaches involving drugs that target multiple signalling pathways that regulate contractions may increase efficacy, reduce dosage and improve tolerability. Both non-steroidal anti-inflammatory drugs (NSAIDs) and hydrogen sulphide (H₂S)-releasing compounds can reduce myometrial contractions. In a novel approach we evaluated the tocolytic properties of ATB-346-a H₂S-releasing derivative of the NSAID naproxen, shown clinically to reduce pain and inflammation in arthritis.</p><p><strong>Methods: </strong>Using organ baths, paired strips of human myometrium were exposed to increasing concentrations of ATB-346, or equimolar concentrations (10µM and 30µM) of the parent drug, naproxen, or the H₂S-releasing moiety, 4-hydroxy-thiobenzamide (TBZ), alone. The ability of ATB-346 versus the individual components of ATB-346 to decrease ex vivo spontaneous contractions was investigated, and the potency was compared to a known H₂S donor, Na₂S.</p><p><strong>Results: </strong>Acute application of Na₂S produced a concentration-dependent decrease in force amplitude and force integral (area under the curve) of contraction. ATB-346 produced a more profound decrease in contraction compared to equimolar concentrations of naproxen or TZB alone and was more potent than the equivalent concentration of Na₂S.</p><p><strong>Conclusions: </strong>ATB-346 exhibits potent tocolytic properties in human myometrium. These exciting results call for further exploration of ATB-346, with a view to repurposing this or similar drugs as novel therapies for delaying preterm labour.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"287-294"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11743401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142133443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomics analysis in rats reveals convergent mechanisms between major depressive disorder and dietary zinc deficiency.","authors":"Łukasz Gąsior, Bartłomiej Pochwat, Monika Zaręba-Kozioł, Jakub Włodarczyk, Andreas Martin Grabrucker, Bernadeta Szewczyk","doi":"10.1007/s43440-024-00681-7","DOIUrl":"10.1007/s43440-024-00681-7","url":null,"abstract":"<p><strong>Background: </strong>Preclinical and clinical studies have shown that dietary zinc deficiency can lead to symptoms similar to those observed in major depressive disorder (MDD). However, the underlying molecular mechanisms remain unclear. To investigate these mechanisms, we examined proteomic changes in the prefrontal cortex (PFC) and hippocampus (HP) of rats, two critical brain regions implicated in the pathophysiology of depression.</p><p><strong>Methods: </strong>Rats were fed diets either adequate in zinc (ZnA, 50 mg Zn/kg) or deficient in zinc (ZnD, <3 mg/kg) for four weeks. High-throughput proteomic analysis was used to detect changes in protein expression, supplemented by enzyme activity assay for mitochondrial complexes I and IV, examining their functional impacts.</p><p><strong>Results: </strong>ZnD led to significant alterations in protein expression related to zinc transport and mitochondrial function. Proteomic analysis revealed changes in zinc transporter family members such as Slc30a1 (6.64 log2FC), Slc30a3 (-2.32 log2FC), Slc30a4 (2.87 log2FC), Slc30a5 (5.90 log2FC), Slc30a6 (1.50 log2FC), and Slc30a7 (2.17 log2FC) in the PFC, and Slc30a3 (-1.02 log2FC), Slc30a5 (-1.04 log2FC), and Slc30a7 (1.08 log2FC) in the HP of rats subjected to ZnD. Furthermore, ZnD significantly affected essential mitochondrial activity proteins, including Atp5pb (3.25 log2FC), Cox2 (2.28 log2FC), Atp5me (2.04 log2FC), Cyc1 (2.30 log2FC), Cox4i1 (1.23 log2FC), Cox7c (1.63 log2FC), and Cisd1 (1.55 log2FC), with a pronounced decrease in complex I activity in the PFC.</p><p><strong>Conclusions: </strong>Our study demonstrates that ZnD leads to significant proteomic changes in the PFC and HP of rats. Specifically, ZnD alters the expression of zinc transporter proteins and proteins critical for mitochondrial function. The significant decrease in complex I activity in the PFC further underscores the impact of ZnD on mitochondrial function. These results highlight the molecular mechanisms by which ZnD can influence brain function and contribute to symptoms similar to those observed in depression.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"145-157"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11743416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142771312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}