European journal of pharmacology最新文献_第10页

Carnosol inhibits influenza A virus by disrupting the viral envelope and interfering with Jak2/STAT3 signaling pathway Carnosol通过破坏病毒包膜和干扰Jak2/STAT3信号通路抑制甲型流感病毒

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2025-04-09 DOI: 10.1016/j.ejphar.2025.177606

Lishan Sun , Yang Zhang , Can Xu , Zhongqiu Xu , Xiayu Chen , Wei Wang , Cui Hao

{"title":"Carnosol inhibits influenza A virus by disrupting the viral envelope and interfering with Jak2/STAT3 signaling pathway","authors":"Lishan Sun , Yang Zhang , Can Xu , Zhongqiu Xu , Xiayu Chen , Wei Wang , Cui Hao","doi":"10.1016/j.ejphar.2025.177606","DOIUrl":"10.1016/j.ejphar.2025.177606","url":null,"abstract":"<div><div>Carnosol is a natural diterpenoid compound derived from rosemary, a traditional Chinese herbal medicine used to treat many diseases. Recent studies have shown that carnosol has many pharmacological activities, including antioxidant, anti-inflammatory, and anticancer effects. In this study, the inhibitory activity and mechanism of action of carnosol against the influenza A virus (IAV) were investigated both <em>in vitro</em> and <em>in vivo</em>. Plaque and immunofluorescence assays were performed to evaluate the anti-IAV effects of carnosol <em>in vitro</em>. The antiviral mechanism was investigated using hemagglutination inhibition (HI) assay, virucidal assay, electron microscopy, and western blotting. anti-IAV activity <em>in vivo</em> was determined using a mouse pneumonia model combined with HE staining. The results showed that carnosol significantly inhibited H1N1 virus propagation <em>in vitro</em> and may block IAV infection by inactivating viral particles and interfering with some early stages of virus adsorption. The cellular Jak2/STAT3 signaling pathway may be involved in the anti-IAV effects of carnosol. Importantly, oral administration of carnosol significantly improved survival and reduced the symptoms of pneumonia in IAV-infected mice, comparable to the effect of oseltamivir. Thus, the natural compound carnosol has the potential to be developed as a novel anti-IAV agent.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"997 ","pages":"Article 177606"},"PeriodicalIF":4.2,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143823221","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}

引用次数: 0

Cilostazol attenuates cisplatin-induced acute liver injury by targeting the SIRT1/AMPK/PGC-1α signaling pathway, with an impact on miRNA-34a 西洛他唑通过靶向SIRT1/AMPK/PGC-1α信号通路，影响miRNA-34a，减轻顺铂诱导的急性肝损伤

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2025-04-09 DOI: 10.1016/j.ejphar.2025.177609

Ahmed Amr Raouf , Aya H. El-Kadem , Samia S. Sokar , Mamdouh A. Oraby , Nagla A. El-Shitany

{"title":"Cilostazol attenuates cisplatin-induced acute liver injury by targeting the SIRT1/AMPK/PGC-1α signaling pathway, with an impact on miRNA-34a","authors":"Ahmed Amr Raouf , Aya H. El-Kadem , Samia S. Sokar , Mamdouh A. Oraby , Nagla A. El-Shitany","doi":"10.1016/j.ejphar.2025.177609","DOIUrl":"10.1016/j.ejphar.2025.177609","url":null,"abstract":"<div><div>The dominant chemotherapeutic agent, cisplatin (CP), is widely used to manage various cancer types. Despite its effectiveness, CP use is associated with severe hepatotoxicity. Cilostazol (CSZ), a selective phosphodiesterase III inhibitor, has recently demonstrated remarkable anti-inflammatory and anti-apoptotic properties in different diseases. Additionally, it exhibits hepatoprotective effects against various forms of liver injury. Hence, this study aimed to assess the potential hepatoprotective and ameliorative effects of CSZ on CP-induced acute liver injury (ALI) and to elucidate the underlying molecular mechanisms. To achieve this, ALI was induced by a single injection of CP (20 mg/kg; i.p.) in male Wistar rats pretreated with CSZ (5 or 10 mg/kg) administered orally for one week. The findings revealed that CSZ effectively reversed CP-induced hepatic dysfunction, as evidenced by notable liver function tests and improvements in histological examination. Additionally, CSZ protected against CP-mediated liver oxidative stress by decreasing MDA levels while increasing GSH and GPx levels and enhancing SOD activity. Furthermore, CSZ exhibited a potent anti-inflammatory effect, reducing the expression of pro-inflammatory cytokines, including NF-κB, IL-1β, and TNF-α. Regarding hepatocyte apoptosis, CSZ suppressed Bax immunoexpression and caspase-3 and caspase-9 levels while enhancing Bcl-2 expression, thereby mitigating hepatic cell death. The hepatoprotective effects of CSZ could be attributed to the regulation of the miRNA-34a/AMPK/SIRT1/PGC-1α signaling pathway, leading to the activation of the Nrf2/HO-1-mediated antioxidative defense mechanism. In conclusion, CSZ could be a promising therapeutic agent for preventing CP-induced ALI, potentially improving the quality of life for cancer patients.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"997 ","pages":"Article 177609"},"PeriodicalIF":4.2,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143823223","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}

引用次数: 0

Exploring 4th generation EGFR inhibitors: A review of clinical outcomes and structural binding insights 探索第四代表皮生长因子受体抑制剂：临床结果和结构结合见解综述

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2025-04-09 DOI: 10.1016/j.ejphar.2025.177608

Amina Tariq , Muhammad Shoaib , Lingbo Qu , Sana Shoukat , Xiaofei Nan , Jinshuai Song

{"title":"Exploring 4th generation EGFR inhibitors: A review of clinical outcomes and structural binding insights","authors":"Amina Tariq , Muhammad Shoaib , Lingbo Qu , Sana Shoukat , Xiaofei Nan , Jinshuai Song","doi":"10.1016/j.ejphar.2025.177608","DOIUrl":"10.1016/j.ejphar.2025.177608","url":null,"abstract":"<div><div>Epidermal growth factor receptor (EGFR) is a potential target for anticancer therapies and plays a crucial role in cell growth, survival, and metastasis. EGFR gene mutations trigger aberrant signaling, leading to non-small cell lung cancer (NSCLC). Tyrosine kinase inhibitors (TKIs) effectively target these mutations to treat NSCLC. While the first three generations of EGFR TKIs have been proven effective, the emergence of the EGFR-C797S resistance mutation poses a new challenge. To address this, various synthetic EGFR TKIs have been developed. In this review, we have summarized the EGFR TKIs reported in the past five years, focusing on their clinical outcomes and structure-activity relationship analysis. We have also explored binding modes and interactions between the binding pocket and ligands to provide insights into the mechanisms of these inhibitors, which contribute to advancements in targeted cancer therapy. Additionally, artificial Intelligence-driven methods, including recursive neural networks and reinforcement learning, have revolutionized EGFR inhibitor design by facilitating rapid screening, predicting EGFR mutations, and novel compound generation.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"997 ","pages":"Article 177608"},"PeriodicalIF":4.2,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143828953","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}

引用次数: 0

Harnessing marine resources for Alzheimer's therapy: A review integrating bioactivity and molecular docking 利用海洋资源治疗阿尔茨海默病：生物活性与分子对接的研究进展

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2025-04-09 DOI: 10.1016/j.ejphar.2025.177611

Hina Khalid , Hassan Mohamed , Adel Eltoukhy , Muhammad Tariq Saeed , Yuanda Song

{"title":"Harnessing marine resources for Alzheimer's therapy: A review integrating bioactivity and molecular docking","authors":"Hina Khalid , Hassan Mohamed , Adel Eltoukhy , Muhammad Tariq Saeed , Yuanda Song","doi":"10.1016/j.ejphar.2025.177611","DOIUrl":"10.1016/j.ejphar.2025.177611","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is a neurodegenerative condition resulting in cognitive impairment and the formation of neurofibrillary tangles and plaques in the brain. The drivers of AD's molecular progression and pathology include the accumulation of amyloid β protein (Aβ); thus, Aβ is an intervention target. However, the limitations in clinical trials of Aβ-targeted medicine and the failure to intervene in disease progression have raised concerns about the use of this drug and its veracious route. In particular, we comprehensively reviewed the potential effect of marine compounds and the mechanism of isolation and extraction from marine organisms resulting in the optimization of AD treatment. Furthermore, the hub compounds were docked with Beta-secretase receptors to strengthen the extrapolation of mechanistic interactions thus inhibiting the activity of an enzyme. An extensive review revealed that marine aquaculture and its byproducts are a promising source and isolated with green methods or less investment, ensuring their sustainability. MNPs harbor specific pharmacological features that enable them to exert neuroprotective effects by minimizing events such as Aβ peptide formation and reactive oxygen species (ROS) generation.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"997 ","pages":"Article 177611"},"PeriodicalIF":4.2,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143839118","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}

引用次数: 0

Antifibrotic therapeutic strategies in systemic sclerosis: Critical role of the Wnt/β-catenin and TGF-β signal transduction pathways as potential targets 系统性硬化症的抗纤维化治疗策略：Wnt/β-catenin和TGF-β信号转导通路作为潜在靶点的关键作用

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2025-04-08 DOI: 10.1016/j.ejphar.2025.177607

Leyla Bagheri , Mohammad Javanbakht , Sheida Malekian , Bahareh Heshmat Ghahderijani , Sadra Taghipour , Fatemeh Davari Tanha , Mohammadhosein Ranjkesh , Luca Cegolon , Shi Zhao

{"title":"Antifibrotic therapeutic strategies in systemic sclerosis: Critical role of the Wnt/β-catenin and TGF-β signal transduction pathways as potential targets","authors":"Leyla Bagheri , Mohammad Javanbakht , Sheida Malekian , Bahareh Heshmat Ghahderijani , Sadra Taghipour , Fatemeh Davari Tanha , Mohammadhosein Ranjkesh , Luca Cegolon , Shi Zhao","doi":"10.1016/j.ejphar.2025.177607","DOIUrl":"10.1016/j.ejphar.2025.177607","url":null,"abstract":"<div><div>Systemic sclerosis (SSc) is a prototypic fibrosing disorder characterized by widespread fibrosis and immune dysregulation. Current evidence highlights the intricate cross-talk between the canonical Wnt/β-catenin signaling pathway and transforming growth factor-beta (TGF-β) signaling, both of which play fundamental roles in the pathogenesis of fibrosis. This review aims to elucidate the central role of the Wnt/β-catenin-TGF-β pathway and TGF-β signal transduction pathway in fibrotic diseases, focusing on SSc. We summarized evidence from cellular biology studies, animal model investigations and clinical observations to provide a comprehensive view of the mechanisms causing pathological fibrosis. In addition, we explore the possibilities of antifibrotic therapeutic strategies against Wnt/β-catenin-TGF-β signaling to counteract fibrosis, delineating approaches for treatment of SSc patients by targeting these interconnected signaling pathways.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"999 ","pages":"Article 177607"},"PeriodicalIF":4.2,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143936856","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}

引用次数: 0

Oxyberberine revokes letrozole-induced polycystic ovarian syndrome and depression-like behavior in female Sprague-Dawley rats Oxyberberine撤销雌性Sprague-Dawley大鼠来曲唑诱导的多囊卵巢综合征和抑郁样行为

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2025-04-08 DOI: 10.1016/j.ejphar.2025.177613

Manoj P. Dandekar , Manasi Tadas , Srilakshmi Satthi , Aditi Jangli , Arbaz Sujat Shaikh , Siva Nageswara Rao Gajula , Venkata Rao Kaki , Rajesh Sonti

{"title":"Oxyberberine revokes letrozole-induced polycystic ovarian syndrome and depression-like behavior in female Sprague-Dawley rats","authors":"Manoj P. Dandekar , Manasi Tadas , Srilakshmi Satthi , Aditi Jangli , Arbaz Sujat Shaikh , Siva Nageswara Rao Gajula , Venkata Rao Kaki , Rajesh Sonti","doi":"10.1016/j.ejphar.2025.177613","DOIUrl":"10.1016/j.ejphar.2025.177613","url":null,"abstract":"<div><div>Polycystic ovarian syndrome (PCOS) is a prevalent endocrine disorder in reproductive-age women, which also negatively perturbs person's psychiatric health. Herein, we investigated the effect of oxyberberine on PCOS- and depression-like phenotypes in female Sprague-Dawley rats. To generate PCOS- and depression-like phenotypes, rats were injected with letrozole (1 mg/kg/day for 21 days) and exposed to 14 days of chronic-unpredictable mild stress (CUMS). We synthesized oxyberberine from its natural parent phytoconstituent i.e., berberine. Rats underwent letrozole + CUMS exposure displayed an increased number of neutrophils in a vaginal smear test indicating a PCOS-like phenotype (i.e., disrupted estrus cycle). Moreover, these rats also showed anhedonia-, depression-, and anxiety-like behaviors in the sucrose-preference test, forced-swimming test, and elevated plus-maze test. Peroral administration of oxyberberine for 21 days, at 50 and 100 mg/kg doses, reversed letrozole + CUMS generated perturbations in rats. The total exploratory behavior in the open field test remained unaffected across the treatment groups. Oxyberberine treatment also restored the organ-weight index of the ovary and uterus and follicular development of the ovary. Systemic and uterine levels of oxyberberine were found to be 0.17–0.80 ng/mL and 1.03–3.62 ng/mL, respectively measured using a liquid chromatography-mass spectrometry assay. Oxyberberine also positively modulated the levels of catalase and malondialdehyde in intestine and spleen, and testosterone and luteinizing hormones in the systematic circulation and CYP17A1, CYP19A1, and SHBG expression in the ovary. These results suggest that oxyberberine improves PCOS- and depression-like phenotypes in rats by modulating testosterone hormone, CYP17A1, CYP19A1, and SHBG enzyme expression in the ovary.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"997 ","pages":"Article 177613"},"PeriodicalIF":4.2,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143844060","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}

引用次数: 0

The antidepressant potential of (2R,6R)-hydroxynorketamine: A detailed review of pre-clinical findings （2R,6R）-羟诺氯胺酮的抗抑郁潜能：临床前研究的详细回顾

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2025-04-08 DOI: 10.1016/j.ejphar.2025.177604

Isis Koutrouli , Kristýna Mazochová , Rachel R. Horsley

{"title":"The antidepressant potential of (2R,6R)-hydroxynorketamine: A detailed review of pre-clinical findings","authors":"Isis Koutrouli , Kristýna Mazochová , Rachel R. Horsley","doi":"10.1016/j.ejphar.2025.177604","DOIUrl":"10.1016/j.ejphar.2025.177604","url":null,"abstract":"<div><div>Depression affects hundreds of millions globally, and in 2019, esketamine, an S-enantiomer of ketamine, was approved for treatment-resistant depression (TRD). While effective, esketamine carries risks, including abuse potential and adverse effects even at low doses. As a result, ketamine's metabolite, (2<em>R,</em>6<em>R</em>)-hydroxynorketamine ((2<em>R,</em>6<em>R</em>)-HNK), has garnered attention for its potential antidepressant effects without these drawbacks.</div><div>This selective review evaluates preclinical behavioral evidence for (2<em>R,</em>6<em>R</em>)-HNK's antidepressant properties, focusing on rodent studies that used established depression models. Results showed that (2<em>R,</em>6<em>R</em>)-HNK reduced behavioral despair, anhedonia, anxiety, and social avoidance in both stressed and non-stressed rodents. Antidepressant effects were observed at doses between 5 and 125 mg/kg, with rapid onset (30 min) and long-lasting effects (up to 21 days). However, some studies failed to demonstrate significant antidepressant effects at doses below 40 mg/kg, often in models with pre-induced depression. No significant adverse effects were reported, but data on side effects were limited.</div><div>In conclusion, (2<em>R,</em>6<em>R</em>)-HNK shows promise as a next-generation antidepressant. However, further research is needed to fully understand its long-term safety and mechanisms, and to determine its advantages over existing treatments like esketamine, particularly for TRD patients.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"999 ","pages":"Article 177604"},"PeriodicalIF":4.2,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143936854","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}

引用次数: 0

Effects of fluoxetine on the gene expression of hippocampus and gap inhibition in noise-induced hearing loss rats 氟西汀对噪声性听力损失大鼠海马基因表达及间隙抑制的影响

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2025-04-07 DOI: 10.1016/j.ejphar.2025.177565

Sujin Choi , Hyun-Ju An , Hyunjeong Yeo , Soonchul Lee , So Young Kim

{"title":"Effects of fluoxetine on the gene expression of hippocampus and gap inhibition in noise-induced hearing loss rats","authors":"Sujin Choi , Hyun-Ju An , Hyunjeong Yeo , Soonchul Lee , So Young Kim","doi":"10.1016/j.ejphar.2025.177565","DOIUrl":"10.1016/j.ejphar.2025.177565","url":null,"abstract":"<div><h3>Objective</h3><div>Fluoxetine was reported to restore critical period-like neural plasticity via alleviating perineuronal nets (PNNs). This study aimed to investigate the effect of fluoxetine on auditory processing and PNNs in auditory cortex and hippocampus.</div></div><div><h3>Methods</h3><div>Sprague-Dawley rats were exposed 2–20 kHz, 115 dB sound pressure level noise for 3 h per day from postnatal day 1–3 to postnatal day 21. After completion of noise exposure, 10 mg/kg/day of fluoxetine was administered for 19 days. There were four groups of rats according to the presence of noise exposure and fluoxetine treatment, vehicle, noise + vehicle, fluoxetine, and noise + fluoxetine rats. The gene expression changes of hippocampus were analyzed using RNA sequencing.</div></div><div><h3>Results</h3><div>In the auditory cortex, the expression of aggrecan (ACAN) was lower in noise-exposed rats than vehicle rats, while the noise + fluoxetine rats presented higher expression levels of ACAN which was comparable with that of the vehicle rats (<em>p</em> = 0.01 in Mann-Whitney <em>U</em> test; 146 ± 15 vs. 100 ± 11). In the hippocampus, the expression of brain-derived neurotrophic factor (BDNF) was lower in noise + vehicle rats while noise + fluoxetine rats presented higher expression of BDNF than noise + vehicle rats (<em>p</em> < 0.001 in Mann-Whitney <em>U</em> test; 389 ± 21 vs. 249 ± 16). The RNA sequencing of the hippocampus predicted the down regulation of genes involving extracellular matrix organization when compared noise + vehicle vs. noise + fluoxetine rats.</div></div><div><h3>Conclusion</h3><div>The fluoxetine administration in noise exposed rats improved the gap inhibition ability. The noise exposure decreased expression of BDNF and modulated the expression of genes related with extracellular matrix organization which was partially reversed after fluoxetine treatment.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"996 ","pages":"Article 177565"},"PeriodicalIF":4.2,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143815925","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}

引用次数: 0

Pro-histaminergic drug restores balance, promotes microgliogenesis and modulates neuroinflammation after vestibular injury 前组胺能药物恢复平衡，促进小胶质细胞生成，调节前庭损伤后的神经炎症

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2025-04-07 DOI: 10.1016/j.ejphar.2025.177600

Jessica Trico , Emna Marouane , Isabelle Watabe , Agnes Lapotre , Alain Tonetto , Andreas Zwergal , Christian Chabbert , Brahim Tighilet

{"title":"Pro-histaminergic drug restores balance, promotes microgliogenesis and modulates neuroinflammation after vestibular injury","authors":"Jessica Trico , Emna Marouane , Isabelle Watabe , Agnes Lapotre , Alain Tonetto , Andreas Zwergal , Christian Chabbert , Brahim Tighilet","doi":"10.1016/j.ejphar.2025.177600","DOIUrl":"10.1016/j.ejphar.2025.177600","url":null,"abstract":"<div><div>Vestibular compensation is a neurobiological process that allows the recovery of impaired vestibular functions after unilateral vestibular damage. Among the post-injury plasticity mechanisms expressed in the vestibular nuclei (VN) that promote the restoration of balance function, neurogliogenesis and excitability changes appear to be in the forefront. At the central level, the vestibular syndrome expression results from an electrophysiological imbalance between both VN, known to activate the central histaminergic system. In this study, we aimed to investigate the impact of pharmacological modulation of the central histaminergic system on balance function recovery and its underlying post-injury mechanisms in the deafferented VN. For this purpose, we used a histamine analog, betahistine dihydrochloride (BD), which increases histamine synthesis and release in the VN through its histamine H3 autoreceptor antagonistic properties. The effect of BD treatment was tested in 3 animal groups: a UVN BD group subjected to unilateral vestibular neurectomy (UVN) treated orally during 10 days (50 mg/kg/day), a UVN placebo group (control), and a SHAM group. We show for the first time, in a UVN rodent model, the effects of BD on the reduction of the vestibular syndrome and highlight new targets and impact of this drug at the cellular level. Indeed, the results show that treatment with BD significantly attenuates the number of astrocytes and microglia which are key components of neuroinflammation. BD also prioritizes the differentiation of neoformed cells towards a microglia phenotype. These results, which need to be confirmed and further investigated by identifying the histaminergic receptors responsible for this effect, may lead to new therapeutic targets in vestibular pathology.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"998 ","pages":"Article 177600"},"PeriodicalIF":4.2,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886583","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}

引用次数: 0

Neuroprotective effect of Perillyl alcohol in sporadic Alzheimer's disease in rats 紫苏醇对散发性阿尔茨海默病大鼠的神经保护作用

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2025-04-05 DOI: 10.1016/j.ejphar.2025.177558

Dolly Chauhan , Kajal Bagri , Rahul Deshmukh

{"title":"Neuroprotective effect of Perillyl alcohol in sporadic Alzheimer's disease in rats","authors":"Dolly Chauhan , Kajal Bagri , Rahul Deshmukh","doi":"10.1016/j.ejphar.2025.177558","DOIUrl":"10.1016/j.ejphar.2025.177558","url":null,"abstract":"<div><div>As people age, Alzheimer's disease, a neurological disorder that develops gradually, affects their memory and cognitive abilities. The two hallmarks of Alzheimer's disease are intracellular buildup of neurofibrillary tangles and extracellular β-amyloid plaques. In this work, the effects of Perillyl alcohol on experimental sporadic Alzheimer-type dementia produced by intracerebroventricular streptozotocin were investigated. Rats that received streptozotocin infusion experienced cholinergic hypofunction, increased oxidative-nitritive stress, and impaired memory and learning. Between 15 and 27 days following the initial streptozotocin infusion, 13 days of treatment with Perillyl alcohol (25, 50, and 100 mg/kg p.o.) significantly improved learning and memory in Morris water maze and object recognition test paradigms.</div><div>Perillyl also significantly reduced oxidative-nitritive stress, as seen by a decrease in malondialdehyde and nitrite, and restored reduced glutathione and catalase levels. Acetylcholinesterase activity significantly increased in the current model, indicating cholinergic hypofunction and enhanced neuronal cell damage. Treatment with Perillyl alcohol also significantly decreased the increase in acetylcholinesterase activity, indicating that Perillyl alcohol may be able to prevent neuronal damage and restore cholinergic functions. Perillyl alcohol has been shown to improve spatial memory processing, which may be due to its antioxidant properties and capacity to restore cholinergic functioning. However, more study is required to understand the molecular mechanisms of POH that enhance cognition or prevent neurotoxic damage, which could support its application in neuroprotective effect.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"996 ","pages":"Article 177558"},"PeriodicalIF":4.2,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802883","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}

引用次数: 0