Naunyn-Schmiedeberg's archives of pharmacology最新文献

{"title":"Retraction Note: Rottlerin and genistein inhibit neuroblastoma cell proliferation and invasion through EF2K suppression and related protein pathways.","authors":"Mumin Alper Erdogan, Ozlem Alkan Yılmaz","doi":"10.1007/s00210-025-03941-2","DOIUrl":"10.1007/s00210-025-03941-2","url":null,"abstract":"","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"4661"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476795","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":"Network pharmacological analysis and experimental verification of Zisheng Tongmai decoction in the treatment of premature ovarian failure.","authors":"Jiaru Wu, Mengjie Wen, Zecheng Wang, Kun Yu, Xinyue Jin, Chenxu Liu, Qiuhang Song, Guohong Zhang, Beibei Wu, Yunfeng Li","doi":"10.1007/s00210-024-03476-y","DOIUrl":"10.1007/s00210-024-03476-y","url":null,"abstract":"<p><p>Premature ovarian failure (POF) is a disease that seriously jeopardizes women's physical and mental health worldwide. Zisheng Tongmai decoction (ZSTMD), a famous Traditional Chinese Medicine (TCM) formula, has a marked effect on the clinical treatment of POF. This study investigated the potential mechanism of ZSTMD to improve POF through network pharmacology and experimental validation. The active components, key targets and potential mechanisms of ZSTMD against POF were predicted by network pharmacology and molecular docking. The POF model was induced in rats by cyclophosphamide (CTX) and subsequently gavaged with different doses of ZSTMD. KGN cells were treated with different concentrations of quercetin and CTX. Histopathological were observed via hematoxylin and eosin (H&E) staining and immunofluorescence staining. Serum estrogen levels were detected via ELISA. Protein expression was detected via Western blot. We identified quercetin as the main active ingredients targeting VEGFA. Molecular docking showed that VEGFA interacted well with the main active components of ZSTMD. In vivo experiments, ZSTMD significantly increased body weight and the ovarian index, significantly increased E2 and AMH, and decreased FSH and LH in POF rats. Histologic results showed that ZSTMD increased the number of follicles and vascular density in the ovary. It also increased VEGFA and CD31 protein expression. In vitro experiments, quercetin suppressed CTX-induced apoptosis in KGN cells and increased VEGFA protein expression. Our study demonstrated that ZSTMD improves POF by promoting angiogenesis through VEGFA target.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"3667-3680"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350394","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":"Network pharmacology-based strategy to reveal the mechanism of pinocembrin against ovarian cancer.","authors":"Guanghui Wang, Jianxiang Cheng, Meizhen Yao, Jing Li, Ting Chen, Jia Zhang, Wensheng Du, Youguo Chen","doi":"10.1007/s00210-024-03492-y","DOIUrl":"10.1007/s00210-024-03492-y","url":null,"abstract":"<p><p>Ovarian cancer stands as the foremost cause of mortality among gynaecological diseases globally, characterized by high morbidity and mortality. Pinocembrin, a flavonoid from natural plant sources, exhibits diverse pharmacological properties. Despite its known pharmacological activities, its specific role in ovarian cancer treatment remains scarcely reported, and its precise molecular mechanism remains elusive. This study integrates network pharmacology and molecular docking techniques to explore pinocembrin's potential mechanism in ovarian cancer treatment. The targets of pinocembrin were compiled from the several online databases. Ovarian cancer targets were identified using the GeneCards database, with common target genes determined by data aggregation. Protein-protein interactions were analysed using the STRING platform. Subsequent Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed. Molecular docking assessed the binding affinity between potential targets and active compounds. Finally, target validity was verified through in vitro experiments. We identified 163 potential pinocembrin targets for ovarian cancer treatment. GO and KEGG analyses revealed pinocembrin's involvement in protein kinase activity, protein phosphorylation, protein kinase complexes and cancer pathways in ovarian cancer treatment. Molecular docking demonstrated strong binding affinity between pinocembrin and most potential target active sites. In vitro experiments suggested pinocembrin's potential to induce apoptosis in ovarian cancer cells through the AKT1-mTOR signalling pathway. This study comprehensively elucidates pinocembrin's potential targets and mechanisms against ovarian cancer, aiming to provide promising candidates for developing novel and effective alternative and/or complementary nutritional supplements for the clinical treatment of ovarian cancer.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"3803-3815"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365852","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":"Development of a new micellar formulation of carvedilol and curcumin to enhance blood pressure reduction in a spontaneously hypertensive rat model.","authors":"Yanina Alejandra Santander Plantamura, Miguel Allo, Jennifer Riedel, Pedro Fuentes, Ana Sol Riesco, Ezequiel Bernabeu, Mariana Garcés, Pablo Evelson, Susana Gorzalczany, Andrea Carranza, Christian Höcht, Diego Chiappetta","doi":"10.1007/s00210-024-03537-2","DOIUrl":"10.1007/s00210-024-03537-2","url":null,"abstract":"<p><p>Cardiovascular diseases remain a leading cause of morbidity and mortality worldwide, requiring innovative therapeutic strategies. This project explores a nano-pharmaceutical approach to enhance the efficacy of cardiovascular drugs, focusing on carvedilol and curcumin. These agents, known for their potential cardiovascular benefits, are encapsulated within Soluplus® micelles to form a novel drug delivery system. The novelty of this formulation lies in its ability to significantly improve the solubility of both carvedilol and curcumin, which have traditionally been limited by their hydrophobic nature. By utilizing Soluplus® micelles, we have developed a unique delivery system that optimizes the therapeutic potential of both drugs. The nanomicelles were meticulously characterized for drug loading, size distribution, and morphological features. The carvedilol and curcumin release patterns were investigated, revealing sustained and controlled release profiles. Additionally, the antioxidant capacity of the micellar formulation was evaluated, demonstrating the preservation of curcumin's antioxidative properties. In vivo studies using spontaneously hypertensive male rats explored the pharmacokinetics and hemodynamic effects of the nanomicellar system. These results indicated successful encapsulation of both drugs without altering their plasma profiles. Furthermore, the administration of carvedilol and curcumin micelles exhibited a more significant reduction in mean arterial pressure compared to individual drug administration, suggesting a potential synergistic effect. In conclusion, this nano-pharmaceutical approach offers a promising avenue for cardiovascular therapy, providing a platform for combined drug delivery and potential synergistic effects. The optimized formulation could lead to improved patient outcomes and enhanced cardiovascular health.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"4165-4177"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470320","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":"Harnessing the power of miRNAs for precision diagnosis and treatment of male infertility.","authors":"Ahmed S Doghish, Elsayed G E Elsakka, Hebatallah Ahmed Mohamed Moustafa, Alaa Ashraf, Sherif S Abdel Mageed, Osama A Mohammed, Mustafa Ahmed Abdel-Reheim, Mohamed Bakr Zaki, Hanan Elimam, Nehal I Rizk, Sarah A Omran, Shimaa A Farag, Donia G Youssef, Ahmed I Abulsoud","doi":"10.1007/s00210-024-03594-7","DOIUrl":"10.1007/s00210-024-03594-7","url":null,"abstract":"<p><p>Infertility is a multifactorial reproductive system disorder, and most infertility cases occur in men. Semen testing is now thought to be the most important diagnostic test for infertile men; nonetheless, because of its limitations, the cause of infertility remains unknown for 40% of infertile men. Semen assessment's shortcomings indicate the need for improved and innovative diagnostic techniques and biomarkers worldwide. Non-coding RNAs with a length of roughly 18-22 nucleotides are called microRNAs (miRNAs). Most of our protein-coding genes are post-transcriptionally regulated by them. These molecules are unusual in bodily fluids, and aberrant variations in their expression can point to specific conditions like infertility. As a result, fresh potential biomarkers for the diagnosis and prognosis of various forms of male infertility may be represented by miRNAs. This review examined the most recent research revealing the association between different miRNAs' functions in male infertility and their expression patterns. Also, it aims to figure out the most recent strategies that could be applied for using such miRNAs as possible therapeutic targets for infertility treatment.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"3271-3296"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624345","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":"Unleashing the potential of Genistein and its derivatives as effective therapeutic agents for breast cancer treatment.","authors":"Eskandar Qaed, Wu Liu, Marwan Almoiliqy, Rawan Mohamed, Zeyao Tang","doi":"10.1007/s00210-024-03579-6","DOIUrl":"10.1007/s00210-024-03579-6","url":null,"abstract":"<p><p>Breast cancer remains one of the leading causes of cancer-related deaths among women worldwide. Genistein (Gen), a phytoestrogen soy isoflavone, has emerged as a promising agent in the prevention and treatment of breast cancer due to its ability to function as a natural selective estrogen receptor modulator (SERM). This review explores the multifaceted mechanisms through which Gen and its derivatives exert their anticancer effects, including modulation of the PI3K/Akt signaling pathway, regulation of apoptosis, inhibition of angiogenesis, and impacts on DNA methylation and enzyme functions. We discuss the dual roles of Gen in both enhancing and inhibiting estrogen receptor (ER)-dependent pathways., highlighting its complex interactions with ERα and ERβ. Furthermore, the review examines the synergistic effect of combining Gen with conventional chemotherapeutic agents such as doxorubicin, cisplatin, and selenium, as well as other natural compounds like lycopene. Clinical studies suggest that while isoflavones may not significantly influence breast cancer progression in general, the high consumption of soy isoflavones is associated with reduced recurrence rates in breast cancer survivors. Importantly, Gen's ability to modulate key signaling pathways and enhance the efficacy of existing treatments improves its potential as a valuable adjunct in breast cancer therapy. In conclusion, Gen and its derivatives offer a novel and promising approach for treatment of breast cancer. Continued research into their mechanisms of action and clinical applications will be essential in optimizing their therapeutic potential and translating these findings into effective clinical interventions.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"3321-3343"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644569","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":"Retraction Note: Enhancement of cardiac angiogenesis in a myocardial infarction rat model using selenium alone and in combination with PTXF: the role of Akt/HIF-1α signaling pathway.","authors":"Mohamed M Elseweidy, Sousou I Ali, Mohamed A Shaheen, Asmaa M Abdelghafour, Sally K Hammad","doi":"10.1007/s00210-025-03935-0","DOIUrl":"10.1007/s00210-025-03935-0","url":null,"abstract":"","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"4665"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542749","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":"Effects of Crocus sativus and its active constituents on cytochrome P450: a review.","authors":"Pooneh Bathaei, Mohsen Imenshahidi, Nasser Vahdati-Mashhadian, Hossein Hosseinzadeh","doi":"10.1007/s00210-024-03525-6","DOIUrl":"https://doi.org/10.1007/s00210-024-03525-6","url":null,"abstract":"<p><p>Cytochrome P450 (CYP) enzymes play an important role in the biotransformation of drugs and endogenous substances. Clinical medications and herbal remedies can either enhance or inhibit the activity of CYP enzymes, leading to potential drug interactions between herbal supplements and prescribed medications. Such interactions can lead to serious consequences, especially for drugs with a narrow therapeutic index, such as digoxin, warfarin, and cyclosporine A. In this review article, we provide an updated review of the impact of saffron, and its active constituents, safranal and crocin, on the 12 major human CYP enzymes and possible drug interactions between saffron and prescription drugs. The available evidence indicates that saffron and its active constituents affect the expression or activity of some CYP isoforms, including the CYP1A1/2, CYP3A4, and CYP2E1 subfamily. Considering the important role of these CYPs in the biotransformation of frequently prescribed medications and the activation of procarcinogen into carcinogenic metabolites, it can be expected that the consumption of saffron and its active constituents may influence the pharmacokinetics and toxicity of several substances. In particular, given the critical role of CYP3A4 in drug metabolism, and saffron's inhibitory impact on this CYP enzyme, it appears that saffron's most significant interaction is linked to its inhibition of CYP3A4. In addition, the inhibitory effect of saffron on CYP1A1/2, and CYP2E1 expression can play a role in the chemopreventive effect of this herbal medicine. Additional research is crucial for evaluating the clinical significance of these interactions in patients who consume saffron along with prescription drugs and determining the dose that can lead to drug interactions.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753665","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":"5-aminosalicylic acid alleviates colitis and protects intestinal barrier function by modulating gut microbiota in mice.","authors":"Jingjing Wang, Xiaoxin Wang, Mingjie Jiang, Tao Lang, Leilei Wan, Juanjuan Dai","doi":"10.1007/s00210-024-03485-x","DOIUrl":"10.1007/s00210-024-03485-x","url":null,"abstract":"<p><p>5-aminosalicylic acid (5-ASA) is widely used in the treatment of ulcerative colitis (UC), but its anti-inflammatory mechanism is complex and has not been fully understood. DSS model was used to test the effect of 5-ASA. Tight junction and Ki-67 were detected by western blot, immunofluorescence, and immunohistochemistry or qPCR. 16S rRNA gene sequencing of gut microbiota and subsequent bioinformatics and statistical analysis were performed to identify the specific bacteria which were associated with the treatment effect of 5-ASA. GC-MS was performed to test short-chain fatty acids (SCFAs). Antibiotic-treated mice were used to demonstrate the key role of endogenous gut microbiota. Here, we found that 5-ASA alleviated dextran sulfate sodium (DSS)-induced colitis in mice. Moreover, 5-ASA significantly repaired the intestinal barrier. At the molecular level, 5-ASA markedly raised the expression of tight junction proteins including JAM-A and occludin and cell proliferation marker Ki-67 in mice. In addition, bacterial 16S rRNA gene sequencing and bioinformatics analysis showed that 5-ASA significantly modulated the DSS-induced gut bacterial dysbiosis. In detail, it stimulated the growth of protective bacteria belonging to Faecalibaculum and Dubosiella, which were negatively correlated with colitis parameters, and blocked the expansion of pro-inflammatory bacteria such as Escherichia-Shigella and Oscillibacter, which were positively correlated with colitis in mice. Meanwhile, 5-ASA increased the cecal acetate level. Most notably, 5-ASA was no longer able to treat colitis and reverse gut barrier dysfunction in antibiotic-treated mice that lacked endogenous gut microbiota. Our data suggested that the anti-inflammatory activity of 5-ASA required the inherent intestinal flora, and the gut microbiota was a potential and effective target for the treatment of ulcerative colitis.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"3681-3695"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350382","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":"Safety assessment of novel oxadiazole derivatives in acute and sub-acute toxicity studies.","authors":"Syeda Rida Zainab, Jehan Zeb Khan, Humaira Nadeem, Muhammad Khalid Tipu, Nadeem Irshad","doi":"10.1007/s00210-024-03474-0","DOIUrl":"10.1007/s00210-024-03474-0","url":null,"abstract":"<p><p>1,3,4-Oxadiazole is a fascinating heterocyclic compound with a unique five-membered ring structure containing nitrogen and oxygen atoms. It has garnered significant attention for its interactions and activities within biological systems. This versatility has led to the production of several ligands using this compound as a pharmacophore. This study evaluates the acute toxicity of three oxadiazole derivatives (1,3,4-Bromo, Chloro, and Iodo) followed by a 28 days sub-acute study involving four different doses of each derivative. The study followed the guideline, the Organization for Economic Cooperation and Development (OECD) outlined, specifically OECD Guidelines 425 for the acute toxicity study and OECD Guidelines 407 for the sub-acute study. In the acute toxicity study, a high dose of 2000 mg/kg was administered to male and female rats to establish lethal dose 50 (LD50) values, and the rats were closely monitored for 14 days. The subsequent sub-acute study involved the administration of four different doses (1.25, 2.5, 5, and 10 mg/kg) of each derivative to male and female rats for 28 days. Throughout both studies, careful monitoring for signs of toxicity and comprehensive hematological, biochemical, and histological analysis were carried out thoroughly. The results of the acute toxicity study indicated that all three derivatives had LD50 values exceeding 2000 mg/kg, and the rats did not display significant signs of toxicity. Similarly, no organ or systemic toxicity was observed in the repeated dose sub-acute study for any of the three derivatives. In conclusion, based on the findings of these studies, it was determined that the derivatives are safe for further investigation of their pharmacological activity.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"3631-3653"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350398","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}