Histone deacetylases (HDACs) are enzymes responsible for removing acetyl groups from histone proteins, resulting in chromatin condensation and the repression of genes. They regulate the expression of genes, the cell cycle, and multiple cellular processes. Hydroxamic acid is a well-recognized moiety characterized by its potent zinc-binding ability, making it an effective inhibitor of HDACs. A novel hydroxamic acid-based molecule, N1-(2,2'-bipyridin-6-yl)-N8-hydroxyoctanediamide (compound 3B), was previously synthesized, and the anticancer properties of the compound were examined in vitro in our laboratory. No prior toxicological study has been performed on this compound. Therefore, the current investigation focused on the acute oral toxicity of compound 3B in female BALB/c mice, adhering to OECD 423 guidelines. In this study, compound 3B was given orally at 300 mg/kg body weight (b.w.) or 2000 mg/kg b.w. The food consumption and body weight of the mice did not differ significantly between the control and treated groups. Variations were observed in the levels of a few of the biochemical markers. Histopathological examination revealed inflammatory infiltration and lesions in a few vital organs. The comprehensive investigation revealed that compound 3B exhibited moderate toxic effects at a relatively high dosage of 2000 mg/kg in few organs and caused alterations in biochemical markers; however, it did not result in any mortality, indicating that the LD50 value exceeded 2000 mg/kg. Compound 3B can be administered at concentrations less than 2000 mg/kg for subsequent studies.
{"title":"In vivo acute oral toxicity assessment of novel histone deacetylase 2 inhibitor.","authors":"Padmini Pai, Rachel Savio D'Mello, Shruthi Nayak, Pallavi Rao, Srinivas Oruganti, Kapaettu Satyamoorthy, Babitha Kampa Sundara","doi":"10.1186/s40360-025-01040-9","DOIUrl":"https://doi.org/10.1186/s40360-025-01040-9","url":null,"abstract":"<p><p>Histone deacetylases (HDACs) are enzymes responsible for removing acetyl groups from histone proteins, resulting in chromatin condensation and the repression of genes. They regulate the expression of genes, the cell cycle, and multiple cellular processes. Hydroxamic acid is a well-recognized moiety characterized by its potent zinc-binding ability, making it an effective inhibitor of HDACs. A novel hydroxamic acid-based molecule, N<sup>1</sup>-(2,2'-bipyridin-6-yl)-N<sup>8</sup>-hydroxyoctanediamide (compound 3B), was previously synthesized, and the anticancer properties of the compound were examined in vitro in our laboratory. No prior toxicological study has been performed on this compound. Therefore, the current investigation focused on the acute oral toxicity of compound 3B in female BALB/c mice, adhering to OECD 423 guidelines. In this study, compound 3B was given orally at 300 mg/kg body weight (b.w.) or 2000 mg/kg b.w. The food consumption and body weight of the mice did not differ significantly between the control and treated groups. Variations were observed in the levels of a few of the biochemical markers. Histopathological examination revealed inflammatory infiltration and lesions in a few vital organs. The comprehensive investigation revealed that compound 3B exhibited moderate toxic effects at a relatively high dosage of 2000 mg/kg in few organs and caused alterations in biochemical markers; however, it did not result in any mortality, indicating that the LD<sub>50</sub> value exceeded 2000 mg/kg. Compound 3B can be administered at concentrations less than 2000 mg/kg for subsequent studies.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145629089","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}
Pub Date : 2025-11-28DOI: 10.1186/s40360-025-01051-6
Yujing Fan, Junfu Zheng, Junnan Gu, Lei Li
{"title":"Epidemiology of drug-related liver injury among the elderly: a systematic review and meta-analysis of incidence, and risk factors.","authors":"Yujing Fan, Junfu Zheng, Junnan Gu, Lei Li","doi":"10.1186/s40360-025-01051-6","DOIUrl":"https://doi.org/10.1186/s40360-025-01051-6","url":null,"abstract":"","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145629114","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}
Pub Date : 2025-11-28DOI: 10.1186/s40360-025-01033-8
Zhiyu Liu, Juan Wang, Yuqi Li, Yang Zeng, Qilong Wu, Xinyao Zhu, Tao Zhou, Qingfu Deng
Background: Erectile dysfunction (ED) is a common male sexual disorder with a multifactorial etiology. The exposure to endocrine-disrupting chemicals (EDCs) has been increasingly linked to reproductive health disorders in both men and women. EDCs can interfere with hormonal signaling and physiological homeostasis, but their specific roles and mechanisms in contributing to ED remain inadequately elucidated.
Methods: Network toxicology and enrichment analysis were used to identify potential targets and signaling pathways involved in ED induced by EDCs. Single-cell sequencing was conducted to analyze the expression profiles of these targets in corpus cavernosum tissue. Key regulatory molecules were identified through protein-protein interaction (PPI) network analysis. Core targets were selected using three machine learning algorithms to evaluate the association between EDCs and ED. Molecular docking simulations were further employed to verify the binding affinity between EDCs and target proteins, elucidating potential mechanisms of action.
Results: A total of 186 potential targets were identified. Single-cell sequencing revealed their expression characteristics. PPI analysis identified key regulatory molecules, and machine learning approaches pinpointed two core targets: CTNNB1 and HIF1A. Molecular docking confirmed that most EDCs exhibit stable binding to CTNNB1 and HIF1A, suggesting the involvement of associated signaling pathways in the development of ED.
Conclusions: This study systematically characterizes the molecular pathways through which EDCs contribute to ED, with CTNNB1 and HIF1A emerging as central players. The identification of these core targets provides a theoretical foundation for developing targeted interventions against environment-related ED and underscores the importance of mitigating EDC exposure in public health strategies.
{"title":"Exploring the impact of endocrine-disrupting chemicals on erectile dysfunction through network toxicology and machine learning.","authors":"Zhiyu Liu, Juan Wang, Yuqi Li, Yang Zeng, Qilong Wu, Xinyao Zhu, Tao Zhou, Qingfu Deng","doi":"10.1186/s40360-025-01033-8","DOIUrl":"10.1186/s40360-025-01033-8","url":null,"abstract":"<p><strong>Background: </strong>Erectile dysfunction (ED) is a common male sexual disorder with a multifactorial etiology. The exposure to endocrine-disrupting chemicals (EDCs) has been increasingly linked to reproductive health disorders in both men and women. EDCs can interfere with hormonal signaling and physiological homeostasis, but their specific roles and mechanisms in contributing to ED remain inadequately elucidated.</p><p><strong>Methods: </strong>Network toxicology and enrichment analysis were used to identify potential targets and signaling pathways involved in ED induced by EDCs. Single-cell sequencing was conducted to analyze the expression profiles of these targets in corpus cavernosum tissue. Key regulatory molecules were identified through protein-protein interaction (PPI) network analysis. Core targets were selected using three machine learning algorithms to evaluate the association between EDCs and ED. Molecular docking simulations were further employed to verify the binding affinity between EDCs and target proteins, elucidating potential mechanisms of action.</p><p><strong>Results: </strong>A total of 186 potential targets were identified. Single-cell sequencing revealed their expression characteristics. PPI analysis identified key regulatory molecules, and machine learning approaches pinpointed two core targets: CTNNB1 and HIF1A. Molecular docking confirmed that most EDCs exhibit stable binding to CTNNB1 and HIF1A, suggesting the involvement of associated signaling pathways in the development of ED.</p><p><strong>Conclusions: </strong>This study systematically characterizes the molecular pathways through which EDCs contribute to ED, with CTNNB1 and HIF1A emerging as central players. The identification of these core targets provides a theoretical foundation for developing targeted interventions against environment-related ED and underscores the importance of mitigating EDC exposure in public health strategies.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"203"},"PeriodicalIF":2.7,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12661834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145629150","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}
Pub Date : 2025-11-26DOI: 10.1186/s40360-025-01023-w
Xu Ma, Yingying Liu, Zhen Hua, Feng Jiang, Shuxia Shi, Kaile Wang, Jie Yu, Lei Zhang
<p><strong>Background: </strong>Recent research suggests a link between acetyl tributyl citrate (ATBC) exposure and an increased risk of coronary heart disease (CHD).</p><p><strong>Objective: </strong>This study investigated the molecular mechanisms underlying ATBC's potential role in CHD pathogenesis.</p><p><strong>Methods: </strong>Using "Acetyl tributyl citrate" as a search term, relevant targets were retrieved from the ChEMBL database. The standard simplified molecular input line entry system (SMILES) notation of ATBC was submitted to the SwissTargetPrediction database. All the targets obtained were compiled to create a target database for ATBC. Functional enrichment analysis and gene set enrichment analysis (GSEA) were performed to explore the potential pathogenic mechanisms of ATBC. The GSE66360 dataset was used as the training dataset, while GSE48060 and GSE60993 served as validation datasets. A total of 107 combinations of eleven machine learning algorithms, including Random Forest (RF), Elastic Net (Enet), support vector machine (SVM), least absolute shrinkage and selection operator (LASSO) regression, Ridge regression, gradient boosting with component-wise linear model (glmBoost), partial least squares regression for generalized linear model (plsRglm), linear discriminant analysis (LDA), extreme gradient boosting (XGBoost), Naive Bayes, and stepwise generalized linear model (Stepglm), were applied to identify the model with the highest area under the curve (AUC) as the best diagnostic model. Additionally, receiver operating characteristic (ROC) curves were used to identify key hub genes. Single-cell transcriptomic data were employed to locate these hub genes, while molecular docking further validated the binding capacity between ATBC and its hub targets. This included converting the ligand to 3D format, performing molecular docking, and calculating the binding affinity and hydrogen bond formation between the molecules. The binding site with the lowest predicted binding affinity was selected for visualization.</p><p><strong>Result: </strong>By integrating ATBC targets with CHD core modules, we identified genes associated with ATBC-induced CHD. Using the RF algorithm, we constructed the optimal diagnostic model and identified key hub genes, including MMP9, NLRP3, and PLAU. These genes were closely associated with glucose and lipid metabolism disorders, induction of estrogen resistance, and vascular inflammation. Furthermore, NLRP3 was predominantly expressed in monocytes, while PLAU showed higher expression in fibroblasts and endothelial cells. The molecular docking results indicated that the calculated predicted binding affinities were all less than or equal to -5.0 kcal/mol. This confirmed the binding affinities of ATBC with MMP9 and PLAU, and supported their involvement in the pathogenesis of coronary heart disease.</p><p><strong>Conclusion: </strong>Our study predicted ATBC's potential mechanisms in CHD progression and identified key
{"title":"The effect of acetyl tributyl citrate on coronary heart disease: a comprehensive computational analysis.","authors":"Xu Ma, Yingying Liu, Zhen Hua, Feng Jiang, Shuxia Shi, Kaile Wang, Jie Yu, Lei Zhang","doi":"10.1186/s40360-025-01023-w","DOIUrl":"https://doi.org/10.1186/s40360-025-01023-w","url":null,"abstract":"<p><strong>Background: </strong>Recent research suggests a link between acetyl tributyl citrate (ATBC) exposure and an increased risk of coronary heart disease (CHD).</p><p><strong>Objective: </strong>This study investigated the molecular mechanisms underlying ATBC's potential role in CHD pathogenesis.</p><p><strong>Methods: </strong>Using \"Acetyl tributyl citrate\" as a search term, relevant targets were retrieved from the ChEMBL database. The standard simplified molecular input line entry system (SMILES) notation of ATBC was submitted to the SwissTargetPrediction database. All the targets obtained were compiled to create a target database for ATBC. Functional enrichment analysis and gene set enrichment analysis (GSEA) were performed to explore the potential pathogenic mechanisms of ATBC. The GSE66360 dataset was used as the training dataset, while GSE48060 and GSE60993 served as validation datasets. A total of 107 combinations of eleven machine learning algorithms, including Random Forest (RF), Elastic Net (Enet), support vector machine (SVM), least absolute shrinkage and selection operator (LASSO) regression, Ridge regression, gradient boosting with component-wise linear model (glmBoost), partial least squares regression for generalized linear model (plsRglm), linear discriminant analysis (LDA), extreme gradient boosting (XGBoost), Naive Bayes, and stepwise generalized linear model (Stepglm), were applied to identify the model with the highest area under the curve (AUC) as the best diagnostic model. Additionally, receiver operating characteristic (ROC) curves were used to identify key hub genes. Single-cell transcriptomic data were employed to locate these hub genes, while molecular docking further validated the binding capacity between ATBC and its hub targets. This included converting the ligand to 3D format, performing molecular docking, and calculating the binding affinity and hydrogen bond formation between the molecules. The binding site with the lowest predicted binding affinity was selected for visualization.</p><p><strong>Result: </strong>By integrating ATBC targets with CHD core modules, we identified genes associated with ATBC-induced CHD. Using the RF algorithm, we constructed the optimal diagnostic model and identified key hub genes, including MMP9, NLRP3, and PLAU. These genes were closely associated with glucose and lipid metabolism disorders, induction of estrogen resistance, and vascular inflammation. Furthermore, NLRP3 was predominantly expressed in monocytes, while PLAU showed higher expression in fibroblasts and endothelial cells. The molecular docking results indicated that the calculated predicted binding affinities were all less than or equal to -5.0 kcal/mol. This confirmed the binding affinities of ATBC with MMP9 and PLAU, and supported their involvement in the pathogenesis of coronary heart disease.</p><p><strong>Conclusion: </strong>Our study predicted ATBC's potential mechanisms in CHD progression and identified key ","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"201"},"PeriodicalIF":2.7,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12659310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145629161","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}
Pub Date : 2025-11-26DOI: 10.1186/s40360-025-01032-9
Tokuhiro Yamada, Aya Kimura, Takashi Juri, Koichi Suehiro, Takashi Mori
{"title":"Preconditioning with hydrogen gas produces cardioprotective effects through autophagy activation in rat cardiomyocytes.","authors":"Tokuhiro Yamada, Aya Kimura, Takashi Juri, Koichi Suehiro, Takashi Mori","doi":"10.1186/s40360-025-01032-9","DOIUrl":"https://doi.org/10.1186/s40360-025-01032-9","url":null,"abstract":"","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"202"},"PeriodicalIF":2.7,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12659236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145629121","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}
This study aimed to develop and validate a novel ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous determination of iloperidone (ILP) and its metabolites P88, P95 in rat plasma and to investigate drug-drug interaction (DDI) between shikonin and ILP in Sprague-Dawley rats. The separation of the analytes was performed on a UPLC BEH C18 column in the mobile phase (acetonitrile and water with 0.1% formic acid) with the flow rate of 0.4 mL/min. The quantitative analysis was performed in positive ion mode. A total of 10 Sprague-Dawley rats were divided into two groups: control group (1.0 mg/kg ILP alone) and experimental group (20 mg/kg shikonin plus 1.0 mg/kg ILP) to investigate the influence of shikonin on ILP metabolism in rats. We successfully established a quick UPLC-MS/MS analytical method for simultaneously detecting ILP and its two metabolites in rat plasma. Linearity, matrix effect, recovery, accuracy, precision and stability of this quantitative method was satisfied with Food and Drug Administration (FDA) guidelines. In addition, in vitro studies demonstrated that shikonin significantly inhibited CYP3A4- and CYP2D6-mediated metabolism in both rat liver microsomes (RLM) and human liver microsomes (HLM). Furthermore, we found the main pharmacokinetic parameters of ILP, such as AUC(0-t) and the peak plasma concentration (Cmax), were obviously changed, which were about twice higher in experimental group than the values in control group. The data demonstrated that shikonin obviously changed the main pharmacokinetics of ILP and its metabolites in rats. In the future clinical use, we should pay more attention to the concomitant application of shikonin and ILP in humans.
{"title":"Simultaneous determination of iloperidone and its metabolites in rat plasma using a novel UPLC-MS/MS method: an application for drug-drug interaction.","authors":"Xiaohai Chen, Dongxin Chen, Hualu Wu, Hailun Xia, Tian Lan, Ren-Ai Xu","doi":"10.1186/s40360-025-01037-4","DOIUrl":"10.1186/s40360-025-01037-4","url":null,"abstract":"<p><p>This study aimed to develop and validate a novel ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous determination of iloperidone (ILP) and its metabolites P88, P95 in rat plasma and to investigate drug-drug interaction (DDI) between shikonin and ILP in Sprague-Dawley rats. The separation of the analytes was performed on a UPLC BEH C18 column in the mobile phase (acetonitrile and water with 0.1% formic acid) with the flow rate of 0.4 mL/min. The quantitative analysis was performed in positive ion mode. A total of 10 Sprague-Dawley rats were divided into two groups: control group (1.0 mg/kg ILP alone) and experimental group (20 mg/kg shikonin plus 1.0 mg/kg ILP) to investigate the influence of shikonin on ILP metabolism in rats. We successfully established a quick UPLC-MS/MS analytical method for simultaneously detecting ILP and its two metabolites in rat plasma. Linearity, matrix effect, recovery, accuracy, precision and stability of this quantitative method was satisfied with Food and Drug Administration (FDA) guidelines. In addition, in vitro studies demonstrated that shikonin significantly inhibited CYP3A4- and CYP2D6-mediated metabolism in both rat liver microsomes (RLM) and human liver microsomes (HLM). Furthermore, we found the main pharmacokinetic parameters of ILP, such as AUC<sub>(0-t)</sub> and the peak plasma concentration (C<sub>max</sub>), were obviously changed, which were about twice higher in experimental group than the values in control group. The data demonstrated that shikonin obviously changed the main pharmacokinetics of ILP and its metabolites in rats. In the future clinical use, we should pay more attention to the concomitant application of shikonin and ILP in humans.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"200"},"PeriodicalIF":2.7,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12649037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145602247","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}
Pub Date : 2025-11-25DOI: 10.1186/s40360-025-01054-3
Susan Sabbagh, Zahra Ganjirad, Leila Jafaripour, Reza Norouzirad
{"title":"Anti-fibrotic and anti-inflammatory effects of D-limonene in improving liver cirrhosis induced by bile duct ligation in male rat.","authors":"Susan Sabbagh, Zahra Ganjirad, Leila Jafaripour, Reza Norouzirad","doi":"10.1186/s40360-025-01054-3","DOIUrl":"https://doi.org/10.1186/s40360-025-01054-3","url":null,"abstract":"","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145602197","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}
Pub Date : 2025-11-25DOI: 10.1186/s40360-025-01028-5
Yuhua Huang, Jie Huang, Xing Zhang
Background: Cepharanthine (CEP), a kind of isoquinoline alkaloid extracted from stephania, is applied in the treatment of cancer. This study aimed to explore the antitumor effects and specific mechanism of CEP on oral squamous cell carcinoma (OSCC) in vitro and in vivo.
Methods: The anticancer effects of CEP were studied by evaluating cell apoptosis, viability, migration, and invasion of OSCC cells. The epithelial-mesenchymal transition (EMT) related proteins levels were detected using qRT-PCR and western blot methods. Moreover, the N6-methyladenosine (m6A) modification of high mobility histone A2 (HMGA2) was determined by methylated RNA immune-precipitation (MeRIP) assay.
Results: We found that CEP suppressed the proliferation and EMT of OSCC cells. Moreover, CEP treatment increased the expression of METTL14 and suppressed m6A modification of FOXL2. Additionally, Overexpression of METTL14 reversed the effects of CEP and induced the aggressiveness of OSCC cells.
Conclusion: CEP impeded the proliferation and EMT of OSCC cells via m6A-induced inactivation of HMGA2/FOXL2 axis, relieving the carcinogenic behaviors of OSCC.
{"title":"Cepharanthine inhibits the proliferation and epithelial-mesenchymal transition of oral squamous cell carcinoma via HMGA2/FOXL2 axis.","authors":"Yuhua Huang, Jie Huang, Xing Zhang","doi":"10.1186/s40360-025-01028-5","DOIUrl":"10.1186/s40360-025-01028-5","url":null,"abstract":"<p><strong>Background: </strong>Cepharanthine (CEP), a kind of isoquinoline alkaloid extracted from stephania, is applied in the treatment of cancer. This study aimed to explore the antitumor effects and specific mechanism of CEP on oral squamous cell carcinoma (OSCC) in vitro and in vivo.</p><p><strong>Methods: </strong>The anticancer effects of CEP were studied by evaluating cell apoptosis, viability, migration, and invasion of OSCC cells. The epithelial-mesenchymal transition (EMT) related proteins levels were detected using qRT-PCR and western blot methods. Moreover, the N6-methyladenosine (m6A) modification of high mobility histone A2 (HMGA2) was determined by methylated RNA immune-precipitation (MeRIP) assay.</p><p><strong>Results: </strong>We found that CEP suppressed the proliferation and EMT of OSCC cells. Moreover, CEP treatment increased the expression of METTL14 and suppressed m6A modification of FOXL2. Additionally, Overexpression of METTL14 reversed the effects of CEP and induced the aggressiveness of OSCC cells.</p><p><strong>Conclusion: </strong>CEP impeded the proliferation and EMT of OSCC cells via m6A-induced inactivation of HMGA2/FOXL2 axis, relieving the carcinogenic behaviors of OSCC.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"197"},"PeriodicalIF":2.7,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12648982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145602215","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}
Pub Date : 2025-11-25DOI: 10.1186/s40360-025-01021-y
Eatemad A Awadalla, Ola Mohamed, Ahmed Abdelsadik, Hoda S Sherkawy, Abd El-Kader M Abd El-Kader
Background: Lipopolysaccharide (LPS)-induced neuroinflammation is widely used as an animal model for studying the mechanisms of neuroinflammation. Crocin, an active component of saffron (Crocus sativus L), possesses several beneficial properties. The present study aimed to investigate the role of crocin in alleviating hippocampal toxicity induced by LPS in rats.
Method: Forty male albino rats were randomly divided into five groups. Group I served as a control. Group II intraperitoneally (i.p.) injected with LPS (1 mg/kg/day) for a week. Groups III, IV, and V were treated by oral gavage with captopril (50 mg/kg/day), crocin (50 mg/kg/day), and a combination of both captopril (50 mg/kg/day) and crocin (50 mg/kg/day), respectively for 30 consecutive days, starting on the 8th day after LPS i.p. injection. During the therapy schedule, rats were tested for memory and learning abilities. Hippocampal samples were collected for biochemical, histological, immunohistochemical, and morphometric studies. Biochemical evaluation included nuclear factor kappa B, inflammatory cytokines (tumor necrosis factor-α and interleukin-1β), amyloid beta, angiotensin-converting enzyme, markers of the cholinergic system (acetylcholinesterase and choline acetyltransferase), antioxidant enzymes (catalase and superoxide dismutase) and an oxidative stress indicator (malondialdehyde). Histological examinations, as well as immunohistochemical and histomorphometric analysis, were also performed on hippocampal tissue.
Results: The results revealed biochemical, histological, and immunohistochemical alterations in the hippocampus of the LPS group. Most of these alterations showed satisfactory improvements in hippocampal tissue when LPS-administered rats were treated with captopril and crocin, either separately or in combination.
Conclusion: The present study suggests that crocin acts as a promising therapeutic agent for alleviating memory impairments and neuroinflammation induced by LPS.
{"title":"Biochemical, histopathological, and immunohistochemical study on the ameliorative effect of crocin against lipopolysaccharide‑induced hippocampal toxicity in male albino rats.","authors":"Eatemad A Awadalla, Ola Mohamed, Ahmed Abdelsadik, Hoda S Sherkawy, Abd El-Kader M Abd El-Kader","doi":"10.1186/s40360-025-01021-y","DOIUrl":"10.1186/s40360-025-01021-y","url":null,"abstract":"<p><strong>Background: </strong>Lipopolysaccharide (LPS)-induced neuroinflammation is widely used as an animal model for studying the mechanisms of neuroinflammation. Crocin, an active component of saffron (Crocus sativus L), possesses several beneficial properties. The present study aimed to investigate the role of crocin in alleviating hippocampal toxicity induced by LPS in rats.</p><p><strong>Method: </strong>Forty male albino rats were randomly divided into five groups. Group I served as a control. Group II intraperitoneally (i.p.) injected with LPS (1 mg/kg/day) for a week. Groups III, IV, and V were treated by oral gavage with captopril (50 mg/kg/day), crocin (50 mg/kg/day), and a combination of both captopril (50 mg/kg/day) and crocin (50 mg/kg/day), respectively for 30 consecutive days, starting on the 8th day after LPS i.p. injection. During the therapy schedule, rats were tested for memory and learning abilities. Hippocampal samples were collected for biochemical, histological, immunohistochemical, and morphometric studies. Biochemical evaluation included nuclear factor kappa B, inflammatory cytokines (tumor necrosis factor-α and interleukin-1β), amyloid beta, angiotensin-converting enzyme, markers of the cholinergic system (acetylcholinesterase and choline acetyltransferase), antioxidant enzymes (catalase and superoxide dismutase) and an oxidative stress indicator (malondialdehyde). Histological examinations, as well as immunohistochemical and histomorphometric analysis, were also performed on hippocampal tissue.</p><p><strong>Results: </strong>The results revealed biochemical, histological, and immunohistochemical alterations in the hippocampus of the LPS group. Most of these alterations showed satisfactory improvements in hippocampal tissue when LPS-administered rats were treated with captopril and crocin, either separately or in combination.</p><p><strong>Conclusion: </strong>The present study suggests that crocin acts as a promising therapeutic agent for alleviating memory impairments and neuroinflammation induced by LPS.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"198"},"PeriodicalIF":2.7,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12648831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145602088","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}
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