Naunyn-Schmiedeberg's archives of pharmacology最新文献

{"title":"Effects of 17β estradiol on blood pressure elevation in ovariectomized rats with collagen-induced arthritis via modulation of oxidative stress, inflammation, fibrosis, and apoptosis in the aorta involving TLR4/NOX4/NF-kβ and TGFβ1/fibronectin/α-SMA pathways.","authors":"Navishaa Govindasamy, Madhumanti Barman, Naguib Salleh, Nelli Giribabu, Huma Shahzad","doi":"10.1007/s00210-024-03700-9","DOIUrl":"10.1007/s00210-024-03700-9","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) can cause blood pressure (BP) elevation in estrogen-deficient, post-menopausal women; however, the underlying mechanisms are not well understood. In this study, the aortic involvement and its underlying mechanisms that contribute to the BP elevation in estrogen-deficient, RA condition were identified. Ovariectomy was performed to create a state of estrogen deficiency and RA was then induced in ovariectomized rats by using incomplete Freund's adjuvant and immune-mediated collagen type-II. Ovariectomized, RA-induced rats (Ovx + RA) were given either 17β-estradiol, baricitinib, or losartan. Direct blood pressure (BP) monitoring was made via cannulation of the carotid artery. Rats were then sacrificed and the aorta was harvested followed by H&E and Picrosirius staining to evaluate histological changes and collagen deposition. Oxidative stress, inflammation, apoptosis, growth, and fibrosis levels in the aorta were assessed by using molecular biological techniques. Mean arterial pressure (MAP) was significantly elevated in Ovx + RA rats when compared to sham and Ovx rats (p < 0.05). 17β-estradiol and losartan treatment significantly reduced the MAP and heart rate in Ovx + RA rats when compared to untreated Ovx + RA rats. Expression of iNOS, Nox2 and Nox4, TLR4, NF-ĸB, TNF-α, VEGF, FGF-2, αSMA, eNOS, and caspase-3 were elevated in the aorta of Ovx + RA rats and were reduced upon 17β-estradiol treatment. However, expression of TGFβ1, Bax-2, fibronectin, and Smad2 in the aorta of Ovx + RA rats was increased following 17β-estradiol treatment (p < 0.05 compared to without treatment). The presence of RA with estrogen deficiency enhanced the BP elevation due to changes in the aorta which could be ameliorated by estrogen.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"6941-6962"},"PeriodicalIF":3.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Examination of the effects of capecitabine treatment on the HT-29 colorectal cancer cell line and HCG 11, HCG 15, and HCG 18 lncRNAs in CRC patients before and after chemotherapy.","authors":"Abdulrasool M Hussein M S Alkharsan, Reza Safaralizadeh, Mohammad Khalaj-Kondori, Mohammadali HosseinpourFeizi","doi":"10.1007/s00210-024-03674-8","DOIUrl":"10.1007/s00210-024-03674-8","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is the third most common malignancy worldwide. Long noncoding RNAs (lncRNAs) are involved in several pathogenic pathways related to CRC. This study aimed to compare the expression profiles of HCG11, HCG15, and HCG18 genes in CRC patients before and after chemotherapy. Moreover, capecitabine's effects, which is a chemotherapeutic agent, were investigated on apoptosis, cell cycle, and the lncRNA expression in CRC using HT-29 cells. qRT-PCR was used to measure lncRNAs expression in patient and healthy tissues, and the HT-29 CRC cell line. Additionally, the diagnostic and prognostic utility of these lncRNAs were assessed using the ROC curve analysis. The MTT assay was used to evaluate the cytotoxicity of capecitabine, and by using flow cytometry, apoptosis induction and cell cycle progression were investigated. CRC patients expressed higher levels of HCG11 and HCG15 and lower levels of HCG18. Furthermore, those receiving capecitabine demonstrated a decrease in HCG11 and an increase in HCG18 expression. In the HT-29 cell line, capecitabine can also increase the expression of HCG18 and decrease the expression of HCG11 and HCG15. However, no statistically significant variations were determined in the expression of these lncRNAs in clinical variables. Additionally, the data show that HCG18 is a poor prognostic biomarker, and HCG11 and HCG18 are poor diagnostic biomarkers. Treatment with capecitabine caused an accumulation of sub-G1 cells, indicating a potent apoptotic effect on HT-29 cells. These findings confirmed capecitabine's anticancer effects and showed that it can increase HCG18 and reduce HCG11 and HCG15 expression.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"6929-6940"},"PeriodicalIF":3.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Obacunone regulates ferroptosis in ovarian cancer through the Akt/p53 pathway.","authors":"Yue Zhao, Haiyue Liang, Xinmu Cui","doi":"10.1007/s00210-024-03738-9","DOIUrl":"10.1007/s00210-024-03738-9","url":null,"abstract":"<p><p>Ovarian cancer is characterized by a high rate of recurrence and a poor prognosis. Ferroptosis, a programmed cell death that is dependent on iron and lipid peroxidation, has emerged as a novel therapeutic target in recent years. This study investigated the effects of Obacunone, a naturally occurring compound present in citrus fruits, on the induction of ferroptosis in ovarian cancer via the Akt/p53 signaling pathway. SKOV3 and OVCAR3 ovarian cancer cell lines were utilized in vitro, while a BALB/c nude mouse model was employed for in vivo experiments. Cell proliferation was assessed utilizing the CCK-8 assay and EDU incorporation. The western blot technique was employed to assess the expression levels of proteins associated with the Akt/p53 signaling pathway. The ferroptosis inhibitor Fer-1 and the Akt activator SC79 were utilized to investigate the potential mechanism of action of Obacunone. Obacunone significantly inhibited the proliferation of ovarian cancer cells and induced ferroptosis, as evidenced by increased intracellular iron content, elevated lipid peroxidation levels, and abnormal mitochondrial morphology. Obacunone also decreased GSH levels, inhibited GPX4 expression and up-regulated ACSL4, as well as reduced Akt phosphorylation and enhanced p53 expression. In vivo experiments showed that Obacunone effectively inhibited tumor growth. Obacunone exhibits potential therapeutic significance through the modulation of the Akt/p53 signaling pathway, which may induce ferroptosis and inhibit the proliferation of ovarian cancer cells.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"7027-7039"},"PeriodicalIF":3.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel piperine derivative HJ-23 exhibits anti-colorectal cancer effects by activating the p53 pathway.","authors":"Meiqi Zhang, Ruotong Liu, Wentao Jiang, Hanxue Li, Siyi Zhang, Wenhao Cheng, Xiaoqing Ye, Jingliang He, Yuanyuan Liu, Aixin Jing, Yizhuo Song, Dan Wang, Xing Liu, Boyu Zhang, Xiujun Wang, Jing Ji","doi":"10.1007/s00210-024-03707-2","DOIUrl":"10.1007/s00210-024-03707-2","url":null,"abstract":"<p><p>There has been an increase in the incidence and poor prognosis of colorectal cancer in recent years. In several studies, piperine has been shown to inhibit colon cancer cell growth and induce apoptosis. This study aimed to investigate whether a novel piperine-derived compound, HJ-23 (2,2-difluorobenzo[d][1,3]dioxol-5-yl)(4-(2,4-difluorophenyl)piperazin-1-yl)methanone), can effectively inhibit the development of colorectal cancer through specific molecular mechanisms. The MTT method was used to evaluate the effect of HJ-23 on the viability of colorectal cancer cells. The effectiveness of the compound was further confirmed by antiproliferation experiments in cell and chicken embryo models. In addition, RNA sequencing (RNA-Seq) was used to analyze changes in gene expression, and gene set enrichment analysis (GSEA) was used to identify pathways regulated by HJ-23. MTT assay, clone formation assay, and chicken embryo assay all confirmed that HJ-23 could significantly inhibit the proliferation of colorectal cancer cells. RNA-Seq analysis showed that HJ-23 significantly downregulated the expression of the tumor proliferation marker Mki67. GSEA showed that HJ-23 mainly regulated cell proliferation and cell cycle processes by activating the p53 pathway and inhibiting the E2F transcription factor (E2F) pathway. HJ-23 exhibits significant anti-tumor effects by activating the p53 pathway and inhibiting tumor cell proliferation. These findings suggest that HJ-23 is a promising drug candidate for treating colorectal cancer.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"7121-7131"},"PeriodicalIF":3.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of sinapic acid's protective effects against ethanol-induced gastric ulcers in rats.","authors":"Fazile Nur Ekinci Akdemir, Mustafa Can Güler, Ersen Eraslan, Ayhan Tanyeli, Serkan Yildirim","doi":"10.1007/s00210-024-03733-0","DOIUrl":"10.1007/s00210-024-03733-0","url":null,"abstract":"<p><p>This study evaluates the protective effects of sinapic acid (SA), a polyphenolic compound with diverse biological activities, against ethanol-induced gastric ulcers in rats. A gastric ulcer model was established using ethanol (ETH), and the experimental groups received either omeprazole (OMEP, 20 mg/kg) or SA at doses of 20 mg/kg and 40 mg/kg via oral gavage for 14 days. Biochemical markers, including total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), malondialdehyde (MDA), and myeloperoxidase (MPO) activity, were assessed alongside proinflammatory cytokines (tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and IL-6) using ELISA. Histopathological and immunohistochemical analyses were conducted to evaluate tissue integrity and apoptosis. Statistical analysis was performed using one-way ANOVA, followed by Tukey's HSD test for post hoc comparisons. For non-parametric data, the Kruskal-Wallis test and Mann-Whitney U test were used. A p-value < 0.05 was considered statistically significant. Results revealed that SA significantly enhanced antioxidant defenses, as evidenced by elevated TAS levels and reductions in TOS, OSI, MPO activity, and MDA levels (p < 0.05). Additionally, SA treatment mitigated inflammation and apoptosis by decreasing TNF-α, IL-1β, IL-6, and Bax expression (p < 0.05). These effects were comparable to those observed with OMEP, a widely used clinical agent. Notably, the findings underscore SA's potential as a novel therapeutic agent for managing ethanol-induced gastric ulcers. By targeting oxidative stress and inflammatory pathways, SA could complement or serve as an alternative to current treatment strategies. Future research should focus on exploring SA's molecular mechanisms, dose optimization, and long-term efficacy in clinical settings, paving the way for its integration into therapeutic regimens for gastric mucosal injuries.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"7133-7145"},"PeriodicalIF":3.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gold nanoparticles mediate suppression of angiogenesis and breast cancer growth via MMP-9/NF-κB/mTOR and PD-L1/PD-1 signaling: integrative in vitro validation and network pharmacology insights.","authors":"Alaa Elmetwalli, Tarek El-Sewedy, Mervat G Hassan, Mohamed O Abdel-Monem, Jihan Hassan, Nadia F Ismail, Afrah Fatthi Salama, Junjiang Fu, Nasser Mousa, Deema Kamal Sabir, Ola El-Emam, Ghada Hamdy, Ali H El-Far","doi":"10.1007/s00210-024-03682-8","DOIUrl":"10.1007/s00210-024-03682-8","url":null,"abstract":"<p><p>Gold nanoparticles (AuNPs) have emerged as promising candidates for cancer therapy due to their unique physicochemical properties and biocompatibility. In this study, we investigate the synthesis, characterization, and therapeutic potential of AuNPs in breast cancer treatment. Further, it establishes a comprehensive understanding of the mechanisms by which AuNPs suppress angiogenesis and breast cancer growth, identifying novel targets and signaling nodes contributing to the anti-tumor effects of AuNPs. AuNPs were synthesized and characterized using UV-Vis, crystallography, transmission electron microscopy (TEM), and energy-dispersive X-ray spectroscopy (EDX). The cytotoxicity of AuNPs was evaluated in WI-38 normal cells and MCF-7 breast cancer cells using the MTT assay. Additionally, the antioxidant activity of AuNPs was assessed through free radical scavenging and lipid peroxidation inhibition assays. Gene expression and pathway enrichment analyses were performed to elucidate the molecular mechanisms underlying the therapeutic effects of AuNPs in breast cancer. UV-Vis spectroscopy confirmed the successful synthesis of AuNPs, with a strong peak observed at 488.9 nm. Crystallography and TEM analysis revealed the crystalline nature and uniform size distribution of AuNPs, respectively. AuNPs exhibited concentration-dependent cytotoxic effects on MCF-7 cells, significantly inhibiting cancer cell proliferation at lower concentrations. Moreover, AuNPs demonstrated potent antioxidant activity, surpassing the effectiveness of vitamin C in scavenging free radicals and inhibiting lipid peroxidation. Gene expression analysis revealed modulation of crucial cancer-related genes and signaling pathways, including MMP-9/NF-κB/mTOR, PD-L1 expression and PD-1 checkpoint pathway, TNF signaling pathway, and adipocytokine signaling pathway, suggesting their potential as novel therapeutics for breast cancer treatment. Our findings support the promising role of AuNPs as effective and targeted therapeutics for breast cancer treatment. Further research is warranted to elucidate the precise mechanisms of action and evaluate the clinical efficacy and safety of AuNP-based therapies in breast cancer patients.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"7087-7105"},"PeriodicalIF":3.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The \"specific\" P-glycoprotein inhibitor zosuquidar (LY335979) also weakly inhibits human organic cation transporters.","authors":"Gzona Bajraktari-Sylejmani, Rajamanikkam Kamaraj, Dirk Theile, Petr Pávek, Johanna Weiss","doi":"10.1007/s00210-024-03743-y","DOIUrl":"10.1007/s00210-024-03743-y","url":null,"abstract":"<p><p>Zosuquidar (LY335979) is a widely used experimental P-glycoprotein (P-gp) inhibitor, which is commended as very potent but also as very specific for P-gp. In this in vitro and in silico study, we demonstrated for the first time that zosuquidar also inhibits organic cation transporters (OCT) 1-3, albeit less potently than P-gp. This still has to be kept in mind when zosuquidar is used to inhibit cellular efflux of P-gp substrates that are concurrently transported into the cells by OCTs. To avoid interference in these assays, zosuquidar concentrations should be kept below 1 µM.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"7147-7153"},"PeriodicalIF":3.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vincristine exerts antiglioma effects by inhibiting the PI3K/AKT signaling pathway: A mechanistic study based on network pharmacology, bioinformatics analysis, and experimental validation.","authors":"Zhihua Chen, Jiahong Wang, Ting He, Donggen Rao, Ziyang Wang, Jianming Zhu","doi":"10.1007/s00210-024-03693-5","DOIUrl":"10.1007/s00210-024-03693-5","url":null,"abstract":"<p><p>In clinical settings, glioma patients often develop secondary resistance to first-line chemotherapy drugs. Vincristine has been reported for its application in cancer chemotherapy, but its molecular mechanism of action remains unclear. This study aimed to identify potential targets of vincristine in glioma using network pharmacology and to experimentally validate the possible molecular mechanisms against glioma. First, the potential targets of vincristine were predicted using CTD, SwissTargetPrediction, and TargetNet databases. Differential expression analysis and WGCNA algorithm were employed on glioma data from the GEO database to obtain important glioma-related target genes, which were then used to identify the anti-glioma targets of vincristine. The intersecting targets were input into the String database to construct a PPI network, and core targets were identified using the cytohubba plugin in Cytoscape. GO and KEGG analyses were conducted to investigate the functional and pathway enrichment of the intersecting targets. The expression and prognostic significance of the core targets were validated using data from the TCGA and HPA databases. Finally, the anti-glioma proliferation effect of vincristine was validated through CCK-8 assay, flow cytometry for cell cycle analysis, RT-qPCR, and Western blotting. A total of 175 vincristine targets and 1673 glioma targets were identified, with 11 shared targets between vincristine and glioma tissues. Network pharmacology studies suggested that CDC25B, CDK4, CDK6, TOP2A, and the PI3K/AKT signaling pathway might be important core targets and pathways through which vincristine exerts its anti-glioma effects. In vitro experiments confirmed that vincristine successfully inhibited U87 cell proliferation and induced G1 phase arrest via the PI3K/AKT signaling pathway, thereby reducing cell growth. The study results indicate that the PI3K/AKT signaling pathway may be involved in the mechanism by which vincristine inhibits the proliferation of glioma cells.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"7107-7120"},"PeriodicalIF":3.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mercuric chloride induced reproductive toxicity associated with oxidative damage in male Wistar albino rat, Rattus norvegicus.","authors":"M P Sampada, Muniswamy David","doi":"10.1007/s00210-024-03585-8","DOIUrl":"10.1007/s00210-024-03585-8","url":null,"abstract":"<p><p>In the field of toxicology, male reproductive hazards attributed to metal exposure is a fast-developing issue. Mercury has been identified as an environmental pollutant that causes potential adverse impacts on organisms. This study aimed to assess the reprotoxic consequences of mercuric chloride (HgCl₂). Five groups of sexually mature albino rats were given oral mercuric chloride (HgCl₂) treatment. (G1) control group received saline treatment; (G2) (5.25 mg/kg of HgCl₂ for 30 days); (G3) (5.25 mg/kg of HgCl₂ for 60 days); (G4) (10.5 mg/kg of HgCl₂ for 30 days); (G5) (10.5 mg/kg of HgCl₂ for 60 days). The hormonal levels, sperm count, sperm motility, sperm viability, and reproductive organ weight, including body weight, were substantially reduced, whereas the sperm abnormality rate was enhanced in rat groups treated with HgCl₂. The analysis revealed that the effect size (Cohen's d) for sperm parameters, including sperm count, motility and viability, were extremely high across all groups, except for sperm abnormality in group 2 (d = 0.59) and group 3 (d = 0.18), where moderate and small effect sizes were observed respectively, and this suggests a significant impact of the intervention on sperm parameters. The administration of HgCl₂ resulted in the induction of oxidative stress in testis that is manifested by substantially enhanced lipid peroxidation (MDA) with a substantial decrease in activity of antioxidant enzymes like catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH), and glutathione peroxidase (GPx) in testes of mercury-treated groups. Concomitantly, there was downregulation in the mRNA levels of the genes involved in spermatogenesis, namely Hsp-70, insulin-like growth factor (IGF), glutathione-S-transferase, and p53 in the testis. The expression of antiapoptotic protein B cell lymphoma (Bcl-2) was decreased, and conversely, the expression of cell proliferative protein Ki-67 was increased in a dose- and duration-dependent manner. Histopathological studies showed degenerative changes in the testis, epididymis, prostate gland, and seminal vesicle, compared to the control group. All the evidence suggests that after mercury exposure, there may be an imbalance between the body's defenses against free radicals and antioxidants, making the testis more susceptible to oxidative damage. This imbalance could potentially have a detrimental effect on the function of the male reproductive system.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"7273-7299"},"PeriodicalIF":3.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142910001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotective effect of niacin in a rat model of obesity induced by high-fat-rich diet.","authors":"Natasha Manzoor, Noreen Samad, Sheraz Ahmed Bhatti, Ali Irfan, Sadaf Ahmad, Gamal A Shazly, Yousef A Bin Jardan","doi":"10.1007/s00210-024-03687-3","DOIUrl":"10.1007/s00210-024-03687-3","url":null,"abstract":"<p><p>This study investigates the impact of a high-fat-rich diet (HFRD) on behavioral, biochemical, neurochemical, and histopathological studies using the hypothalamus of rats following niacin (NCN) administration. The rats were divided into HFRD and normal diet (ND)-fed groups and administered selected doses of NCN, i.e., 25 mg/mL/kg (low dose) and 50 mg/mL/kg (high dose), for 8 weeks. The grouping of male rats (n = 8) was as follows: (i) Vehicle (Veh) + ND; (ii) ND + NCN (low dose); (iii) ND + NCN (high dose); (iv) Veh + HFRD; (v) HFRD + NCN (low dose); and (vi) HFRD + NCN (high dose). Behavioral tests assessed depression-like symptoms and spatial memory; after that, the hypothalamus was isolated for various analyses of sacrificed animals. NCN at both doses decreased food intake and growth rate in both diet groups and demonstrated antidepressant and memory-enhancing effects. HFRD-induced oxido-neuroinflammation decreased with both doses of NCN. HFRD-induced decreases in serotonergic neurotransmission, 5-HT1A receptor expression, and morphological alterations in the rat's hypothalamus were normalized by both doses of NCN. In conclusion, NCN, as a potential antioxidant and neuromodulator, can normalize feeding behavior and produce antidepressant and memory-improving effects in a rat model of obesity following HFRD intake.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"6801-6820"},"PeriodicalIF":3.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}