Naunyn-Schmiedeberg's archives of pharmacology最新文献

{"title":"Lycopene in male infertility.","authors":"Sina Vakili, Mohammad Samare-Najaf, Aliasghar Karimi, Bahia Namavar Jahromi, Mohsen Mohit, Mohammad Hashem Hashempur","doi":"10.1007/s00210-024-03520-x","DOIUrl":"https://doi.org/10.1007/s00210-024-03520-x","url":null,"abstract":"<p><p>Male infertility is a major concern around the world, and efforts to find effective therapies to improve reproductive results are continuing. Factors such as genetics, hormonal disorders, lifestyle, and environmental pollutants have been mentioned as the pathoetiology of male infertility. The treatment of male infertility is far from optimal despite the recent signs of progress provided by assisted reproductive technology. Therefore, many efforts are being made to improve the therapeutical approaches to male infertility, which generally target the factors involved in the pathophysiology of the disease. Lycopene is a naturally occurring pigment belonging to the carotenoid family, which imparts a vibrant red color to various fruits and vegetables. It is widely assumed that lycopene may be an optimal option for the improvement of male fertility, however, the verification its therapeutic potential in male infertility has not been comprehensively reviewed. The study discusses the ability of lycopene to improve semen parameters, including sperm morphology, and motility which are important determinants of male reproductive health. Moreover, lycopene's capacity to regulate sex hormones, such as testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which play crucial roles in sperm production and maturation is explained. Additionally, lycopene effects on specific signaling pathways involved in male fertility, including prokineticin-2 (PROK2) and PI3K/Akt pathways, that influence sperm function are clarified. Furthermore, the impacts of lycopene as a potent antioxidant in defending against oxidative stress, a leading cause of male infertility, are presented. Overall, the results indicate that lycopene may have beneficial effects on improving male fertility by increasing sperm parameters, modulating sex hormones and signaling pathways, and providing antioxidant protection. Due to limited reports, additional clinical data is required to confirm the positive effects of lycopene on male fertility in humans.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801774","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: Sensitization of MDA-MBA231 breast cancer cell to docetaxel by myricetin loaded into biocompatible lipid nanoparticles via sub-G1 cell cycle arrest mechanism.","authors":"Nazila Fathi Maroufi, Vahid Vahedian, Seyed Ali Miresmaeili Mazrakhondi, Wesam Kooti, Hosein Ajami Khiavy, Roya Bazzaz, Fatemeh Ramezani, Seyed Mohammadbagher Pirouzpanah, Marjan Ghorbani, Maryam Akbarzadeh, Hamed Hajipour, Saeed Ghanbarzadeh, Mehdi Sabzichi","doi":"10.1007/s00210-024-03709-0","DOIUrl":"https://doi.org/10.1007/s00210-024-03709-0","url":null,"abstract":"","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801776","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":"Bacopaside-I ameliorates motor dysfunction and neurodegeneration in rat model of Parkinson's disease.","authors":"Babita Singh, Shivani Pandey, Mohammad Rumman, Mrinal Gupta, Abbas Ali Mahdi","doi":"10.1007/s00210-024-03552-3","DOIUrl":"https://doi.org/10.1007/s00210-024-03552-3","url":null,"abstract":"<p><p>Chronic administration of Bacopa monnieri extract exerts neuroprotective potential in multiple animal models of neurodegenerative disorders such as Parkinson's disease (PD), Alzheimer's disease (AD), depression, and other cognitive impairments. However, the underlying mechanism of action remained unclear. Rotenone model of PD holds a great potential for investigating PD pathology and motor and nonmotor symptoms. Herein, we evaluated the neuroprotective effect of Bacopaside-I (BS-I), a major triterpenoid saponin of Bacopa monnieri extract, against rotenone-induced in vivo model of PD and explored the possible molecular mechanism. Rats were exposed to rotenone (2 mg/kg body weight) for a period of 4 consecutive weeks to induce PD-like behavior. BS-I (5, 15, and 45 mg/kg) was administered orally. Behavioral data (rotarod, foot printing, and grip strength test) suggest that BS-I plays a significant role in attenuating the motor function deficit. Exposure to rotenone reduces the dopamine level and increases oxidative stress, while BS-I treatment reversed these changes. Furthermore, chronic administration of BS-I increased the expression levels of dopamine transporter (DAT) and vesicular monoamine transporter (VMAT) genes and the numbers of tyrosine hydroxylase (TH)-positive neurons as compared to rotenone-exposed animals. Our study established the neuroprotective role of BS-I in PD model and laid the foundation for further evaluation of BS-I-based drug in future studies.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801612","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":"Correction: Thrombin receptor PAR4 cross-activates the tyrosine kinase c-met in atrial cardiomyocytes.","authors":"Claudia Mittendorff, Issam Abu-Taha, Lena Kassler, Tobias Hustedt, Stephanie Wolf, Johannes G Bode, Markus Kamler, Dobromir Dobrev, Anke C Fender","doi":"10.1007/s00210-024-03703-6","DOIUrl":"https://doi.org/10.1007/s00210-024-03703-6","url":null,"abstract":"","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801696","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":"Pyroptosis was suppressed by 20-hydroxyecdysone through Lin28b-mediated let-7d in vascular endothelial cells.","authors":"Danli Chen, Jianjun Yang, Lingxuan Ren, Zihan Zheng, Zhen Jin, Jiazheng Wen, Jianyu He, Rongcheng Ding, Jianjiang Wang, Rong Lin, Qiang Song","doi":"10.1007/s00210-024-03591-w","DOIUrl":"https://doi.org/10.1007/s00210-024-03591-w","url":null,"abstract":"<p><p>20-hydroxyecdysone (20E), a natural polyhydroxylated steroid, has exhibited anti-inflammatory effects across various diseases. This study investigates the potential connection between 20E's anti-inflammatory properties and the RNA-binding protein Lin28b, which is notably upregulated in TNF-α-stimulated endothelial cells. Herein, we discovered that 20E can selectively downregulate Lin28b expression without affecting its paralog Lin28a. Notably, 20E treatment could significantly attenuate pyroptosis, an inflammatory form of programmed cell death, as evidenced by reduced IL-1β and LDH release, and fewer propidium iodide (PI)-positive cells. Subsequent protein analysis revealed that 20E inhibited the enhanced expressions of key pyroptosis-associated proteins, GSDMD, GSDMD-N, and GSDME-N. Besides, this suppression of Lin28b and pyroptosis may be partially mediated through TNFR1. Additionally, 20E upregulated let-7 miRNA, particularly let-7d, a critical downstream target of Lin28b. To elucidate the role of Lin28b in 20E-mediated pyroptosis attenuation, we performed Lin28b overexpression and silencing experiments. Overexpressing Lin28b negated 20E's inhibition of LDH release and PI-related fluorescence, exacerbating GSDMD and GSDME cleavage. Conversely, Lin28b knockdown augmented the suppressive effect of 20E on pyroptosis, which was reversed by a let-7d inhibitor. Co-transfection with let-7d mimic and Lin28b plasmid demonstrated let-7d's role in mitigating pyroptosis aggravated by Lin28b overexpression. Overall, this study demonstrates that 20E may mitigate GSDMD and GSDME-mediated pyroptosis in HUVECs through the Lin28b/let-7d-dependent signaling pathway. These results highlight the potential of 20E as a promising inhibitor of pyroptosis, offering new insights into its anti-inflammatory mechanisms.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801775","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":"Treatment of cancer-associated fibroblast-like cells with celecoxib enhances the anti-cancer T helper 1/Treg responses in breast cancer.","authors":"Arash Samoudi, Firoozeh Abolhasani-Zadeh, Ali Afgar, Elnaz Jalilian, Hamid Zeinalynezhad, Ladan Langroudi","doi":"10.1007/s00210-024-03641-3","DOIUrl":"https://doi.org/10.1007/s00210-024-03641-3","url":null,"abstract":"<p><p>Tumor inflammation, as one of the hallmarks of cancer, has been the target for anti-cancer treatments. Celecoxib is a selective inhibitor of the enzyme cycloxygenase-2 (COX-2) and inhibits the production of PGE2, which is an important mediator of tumor inflammation produced by cancer cells and cells of the tumor microenvironment. In this study, we aimed at inhibiting COX-2 using celecoxib, expressed in cancer-associated fibroblast (CAF)-like cells isolated from breast cancer and evaluated the alterations in their cytokine profile and gene expression. CAF-like cells were isolated by explant culture from 13 breast cancer tissues. Simultaneously, peripheral blood mononuclear cells (PBMCs) were isolated from patients' blood. CAF-like cells were treated with 10 µM of celecoxib and expression of genes COX-2, smooth muscle actin-alpha (α-SMA), and production of prostaglandin E2 (PGE2), Interleukin 10 (IL10), and transforming growth factor beta1 (TGF-β1) was evaluated. Next, PBMCs were co-cultured with celecoxib-treated CAF-like cells and the expression of genes T-bet, Foxp3, GATA-3; production of cytokines IFN-ɣ, IL-10, IL-4, TGF-β1, and the mediator PGE2 were assessed by real-time-PCR and ELISA, respectively. Isolated CAF-like cells showed expression of fibroblast activation protein (FAP). Treatment with celecoxib was able to efficiently reduce the production of PGE2 and the expression of α-SMA in isolated CAF-like cells. Furthermore, PBMCs in co-culture with these cells showed enhanced Th1 phenotype including T-bet and IFNγ expression and decreased the phenotypical markers of regulatory T cells such as FoxP3 and IL-10 and TGF-β1 production. Our study shows the important role of COX-2 in CAFs by promoting immune suppression. Our results suggested that high expression of COX-2 in CAFs may serve as a new therapeutic, targeting CAFs in enhancing immune responses in breast cancer treatment.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801777","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 effect of acetylcholinesterase inhibitor rivastigmine in pentylenetetrazole-induced kindling model of epilepsy in rats.","authors":"Elif Türkdönmez Ak, Büşra Okuyucu, Burcu Hatipoğlu, Gökhan Arslan","doi":"10.1007/s00210-024-03679-3","DOIUrl":"https://doi.org/10.1007/s00210-024-03679-3","url":null,"abstract":"<p><p>This study aimed to investigate the role of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitor rivastigmine (RIVA) in the pentylenetetrazole (PTZ)- induced kindling model of epilepsy. The current study consists of three steps; 1) Saline or RIVA (0.5, 1, and 2 mg/kg) was administered intraperitoneally (i.p.) 15 min before PTZ (35 mg/kg) during the kindling process and seizure behaviors were observed; 2) Single doses of RIVA (0.25, 0.5, and 1 mg/kg; i.p.) was administered to the electrode implanted kindled rats 15 min before PTZ and electrocorticogram (ECoG) recordings were obtained; 3) Low-dose of RIVA (0.5 mg/kg) was administered to the kindled rats for 14 consecutive days and after 24 h PTZ was administered and ECoG recordings were obtained. In addition, 24 h after the PTZ injection, the hippocampus was extracted and mRNA expression levels of N-methyl D-aspartate receptor subunit 2B (NR2B) and brain-derived neurotrophic factor (BDNF) were measured by qPCR analysis. Only low-dose of RIVA increased resistance against kindling. Single and long-term administration of low-dose RIVA increased the latency to the first myoclonic jerk, decreased the duration of generalized tonic-clonic seizures, and reduced the seizure stage in kindled rats. Long-term low-dose RIVA treatment decreased the mRNA expressions of NR2B and BDNF, which were increased after PTZ kindling. Low-dose of RIVA showed anticonvulsant properties, while high doses did not. RIVA exerts its anticonvulsant effect probably through NMDAR-BDNF pathways. Our results suggest that the use of RIVA may not be harmful and even reduce seizure severity in epileptic patients with convulsions.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792093","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 path of GPR87: from a P2Y-like receptor to its role in cancer progression.","authors":"Katrin Sak","doi":"10.1007/s00210-024-03684-6","DOIUrl":"https://doi.org/10.1007/s00210-024-03684-6","url":null,"abstract":"<p><p>GPR87 is a G protein-coupled seven-transmembrane receptor first described as an orphan receptor in 2001. Despite its high structural homology to several extracellular nucleotide-activated P2Y receptors and sharing conserved sequence motifs in transmembrane regions, identification of endogenous ligands from the class of nucleotides and their analogues has failed for GPR87. Although lysophosphatidic acid was proposed to be a natural ligand for this cell surface receptor, these data are preliminary and inconsistent, and IUPHAR is currently considering GPR87 as an orphan receptor. Thus, the endogenous ligands and physiological functions of GPR87 are still required to be determined and/or confirmed. The remarkably higher expression of GPR87 in human malignant tissues compared to the normal healthy ones clearly suggests that this receptor may be involved in the development and progression of cancerous neoplasms. Therefore, in this review article, the main focus is placed on the oncogenic role of GPR87 in various human malignancies, presenting it as a potential novel target site for therapeutic interventions using both humanized monoclonal antibodies and gene therapy but also selective antagonists which are still waiting for their identification. Furthermore, the importance of the expression of GPR87 as a predictive biomarker for evaluating the prognosis and overall survival of cancer patients is also highlighted.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785515","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":"Correction: Development and characterization of formulations based on combinatorial potential of antivirals against genital herpes.","authors":"Mahesh Gaikwad, Amal George, Aparna Sivadas, Kavitha Karunakaran, Sudheesh N, Siddappa N Byrareddy, Chiranjay Mukhopadhyay, Piya Paul Mudgal, Madhur Kulkarni","doi":"10.1007/s00210-024-03668-6","DOIUrl":"https://doi.org/10.1007/s00210-024-03668-6","url":null,"abstract":"","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786322","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":"Mechanisms of ferroptotic and non-ferroptotic organ toxicity of chemotherapy: protective and therapeutic effects of ginger, 6-gingerol and zingerone in preclinical studies.","authors":"Ademola C Famurewa, Roland E Akhigbe, Mina Y George, Yemi A Adekunle, Precious A Oyedokun, Tunmise M Akhigbe, Amos A Fatokun","doi":"10.1007/s00210-024-03623-5","DOIUrl":"https://doi.org/10.1007/s00210-024-03623-5","url":null,"abstract":"<p><p>Chemotherapy (CT) is one of the flagship options for the treatment of cancers worldwide. It involves the use of cytotoxic anticancer agents to kill or inhibit the proliferation of cancer cells. However, despite its clinical efficacy, CT triggers side effect toxicities in several organs, which may impact cancer patient's quality of life and treatment outcomes. While the side effect toxicity is consistent with non-ferroptotic mechanisms involving oxidative stress, inflammation, mitochondrial impairment and other aberrant signalling leading to apoptosis and necroptosis, recent studies show that ferroptosis, a non-apoptotic, iron-dependent cell death pathway, is also involved in the pathophysiology of CT organ toxicity. CT provokes organ ferroptosis via system Xc^-/GPX-4/GSH/SLC7A11 axis depletion, ferritinophagy, iron overload, lipid peroxidation and upregulation of ferritin-related proteins. Cisplatin (CP) and doxorubicin (DOX) are common CT drugs indicated to induce ferroptosis in vitro and in vivo. Studies have explored natural preventive and therapeutic strategies using ginger rhizome and its major bioactive compounds, 6-gingerol (6G) and zingerone (ZG), to combat mechanisms of CT side effect toxicity. Ginger extract, 6G and ZG mitigate non-ferroptotic oxidative inflammation, apoptosis and mitochondrial dysfunction mechanisms of CT side effect toxicity, but their effects on CT-induced ferroptosis remain unclear. Systematic investigations are, therefore, needed to unfold the roles of ginger, 6G and ZG on ferroptosis involved in CT side effect toxicity, as they are potential natural agents for the prevention of CT toxicity. This review reveals the ferroptotic and non-ferroptotic toxicity mechanisms of CT and the protective mechanisms of ginger, 6G and ZG against CT-induced, ferroptotic and non-ferroptotic organ toxicities.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786323","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}