Pharmaceutical Biology最新文献

{"title":"Unveiling the cytotoxicity of Red Sea <i>Moorena producens via</i> LC-QTOF-MS/MS chemical profiling, network pharmacology, and molecular docking.","authors":"Esraa M Abdelhady, Mohammed N A Khalil, Mohamed A Rabeh, Saad A Alshehri, Omar Sabry, Mona M Hashem","doi":"10.1080/13880209.2025.2534573","DOIUrl":"10.1080/13880209.2025.2534573","url":null,"abstract":"<p><strong>Context: </strong>Breast and liver cancers remain significant global health challenges, necessitating the discovery of novel anticancer agents. Marine cyanobacteria, such as <i>Moorena producens</i> belonging to the family: Oscillatoriaceae, are rich sources of bioactive compounds with potential anticancer properties.</p><p><strong>Objective: </strong>This study aims to identify and characterize bioactive compounds from <i>M. producens</i> and evaluate their anticancer activity against breast and liver cancer cell lines.</p><p><strong>Materials and methods: </strong><i>M. producens</i> was collected and authenticated using 16S rRNA sequencing. The ethanolic extract was analyzed using LC-QTOF-MS/MS to identify the potential bioactive metabolites. Network pharmacology analysis was employed to predict the potential targets of these compounds. The crude extract was fractionated, and the fractions were screened for the anticancer activity against MCF-7 and HepG2 cell lines.</p><p><strong>Results: </strong>LC-QTOF-MS/MS analysis identified 25 metabolites, including apocarotenoids, spirovetivane alkaloids, and toxins. Network pharmacology analysis suggested that malyngamide D, isomalyngamide I, mueggelone, 11,12-didehydrospironostoic acid, and 12-hydroxy-2-oxo-11-epi-hinesol were potential bioactive compounds targeting proto-oncogene tyrosine-protein kinase (Src), mitogen-activated protein kinase 3(MAPK3), and MAPK1 kinases. Molecular docking studies further supported these findings, with 11,12-didehydrospironostoic acid exhibiting strong binding affinities to Src and MAPK1 kinases. Among the nine fractions obtained, Fraction 1 showed the most potent anticancer activity against both MCF-7 and HepG2 cell lines, with IC₅₀ values, 59.63 ± 7.1 and 149.23 ± 0.9 µg/mL, respectively.</p><p><strong>Discussion and conclusion: </strong>The results of this study highlight the potential of <i>M. producens</i> as a source of novel anticancer compounds. Further investigation of the bioactive compounds in Fractions 1 and 2 may lead to the discovery of promising anticancer agents.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"549-566"},"PeriodicalIF":4.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12320260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760678","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}

{"title":"The natural statin α,β-dehydromonacolin K exerts anti-secretory effect in human intestinal epithelial cells via a nonsense-mediated mRNA decay-dependent mechanism.","authors":"Saravut Satitsri, Rungtiwa Khumjiang, Chittreeya Tansakul, Wararat Chiangjong, Nuttapon Apichaiyarat, Taya Kitiyakara, Yanisa Purintrapibal, Vatcharin Rukachaisirikul, Chatchai Muanprasat","doi":"10.1080/13880209.2025.2544930","DOIUrl":"10.1080/13880209.2025.2544930","url":null,"abstract":"<p><strong>Context: </strong>cAMP-induced intestinal chloride secretion plays a pivotal role in the pathogenesis of secretory diarrheas.</p><p><strong>Objective: </strong>In this study, we investigated the antisecretory effects of α,β-dehydromonacolin K, a derivative of lovastatin from <i>Aspergillus sclerotiorum</i>, on cAMP-induced chloride secretion in human T84 cells and fluid secretion in human colonoids.</p><p><strong>Materials and methods: </strong>Short-circuit current analyses and swelling assays were used to investigate the effects of α,β-dehydromonacolin K on chloride transport and fluid secretion, respectively. Proteomic analyses were performed to determine the potential anti-diarrheal mechanisms of α,β-dehydromonacolin K.</p><p><strong>Results: </strong>In T84 cells, α,β-dehydromonacolin K inhibited cAMP-induced chloride secretion with an IC₅₀ of ∼ 6.32 μM. Apical chloride current analyses demonstrated that α,β-dehydromonacolin K inhibited CFTR chloride channels stimulated by cAMP agonists with an IC₅₀ of ∼ 1 μM. Basolateral potassium current analyses indicated that α,β-dehydromonacolin K had no effect on basolateral potassium channel activities. In a three-dimensional (3D) model of human colonoids, α,β-dehydromonacolin K (20 µM) suppressed both cAMP-induced and calcium-induced fluid secretion by ∼ 70%. Proteomic analyses of human colonoids revealed that α,β-dehydromonacolin K interacted with 33 proteins, including those associated with non-sense-mediated mRNA decay (NMD). Notably, the inhibitory effects of α,β-dehydromonacolin K on cAMP-induced chloride and fluid secretion were significantly diminished in the presence of SMG1i, an inhibitor of serine/threonine-protein kinase SMG1 involved in NMD, suggesting that α,β-dehydromonacolin K inhibits cAMP-induced chloride-driven fluid secretion in human intestinal epithelial cells by mechanisms involving SMG1-dependent NMD pathways.</p><p><strong>Discussion and conclusions: </strong>α, β-Dehydromonacolin K represents a promising class of natural compounds that exert antisecretory effects in human intestinal epithelia <i>via</i> a novel mechanism of action involving SMG1 in NMD pathways.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"645-662"},"PeriodicalIF":4.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12377102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144964806","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}

{"title":"Adjuvant potential of <i>Satureja hortensis</i> metabolites with antibiotics against Gram-positive and Gram-negative bacterial strains.","authors":"Marah Alburqan, Annamária Kincses, Melinda Paizs, Anita Barta, Katalin Veres, Antal Csámpai, Morteza Yazdani, Judit Hohmann","doi":"10.1080/13880209.2025.2572669","DOIUrl":"10.1080/13880209.2025.2572669","url":null,"abstract":"<p><strong>Context: </strong>The global rise in bacterial resistance to existing antibiotics has led to increased mortality rates and escalating healthcare costs, underscoring the urgent need for new classes of antibacterial agents that can act synergistically with current antimicrobials.</p><p><strong>Objective: </strong>This study aimed to isolate bioactive compounds from <i>Satureja hortensis</i> L. (Lamiaceae) and evaluate their effects in combination with ciprofloxacin (CIP), ampicillin (AMP), gentamicin (GEN), and tetracycline (TET).</p><p><strong>Materials and methods: </strong>The adjuvant potential of naringenin (N), 5,6-dihydroxy-7,3',4'-trimethoxyflavone (TMF), cilicione-a (Cil), rosmarinic acid (Rs), rosmarinic acid methyl ester (MRs), and fulgidic acid was evaluated by determining the minimum inhibitory concentrations (MICs) of selected antibiotics in presence of sub-inhibitory concentrations of these compounds. The assays were performed against ten bacterial strains using the twofold broth microdilution method. Test samples were prepared in 96-well microtiter plates, incubated at 37 °C for 18 h, and dimethyl sulfoxide was used as the solvent control.</p><p><strong>Results: </strong>N, Rs, and MRs reduced the MIC value of GEN from 0.78 µM to 0.097 µM against the drug-resistant <i>Escherichia coli</i> AG100 strain. Additionally, the combinations of N and MRs with CIP reduced its MIC from 3.125 µM to 0.39 µM against <i>Klebsiella pneumoniae</i>. A MIC reduction (from 50 µM to 12.5 µM) was observed against the methicillin- and oxacillin-resistant <i>Staphylococcus aureus</i> strain when N, Cil, Rs, and MRs were combined with AMP. The MIC changed from 0.125 µM to 0.03125 µM against <i>Bacillus subtilis</i> when N and TMF were combined with GEN.</p><p><strong>Discussion and conclusions: </strong>These findings highlight the potential of such combinations to enhance antibiotic efficacy, lower the required dosages, and contribute to mitigating the emergence of antimicrobial resistance.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"716-729"},"PeriodicalIF":6.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12532358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145302592","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}

{"title":"Essential oils expose diverse targets on non-enveloped ScV-L-A totivirus.","authors":"Algirdas Valys, Živilė Strazdaitė-Žielienė, Algirdas Mikalkėnas, Jurga Būdienė, Enrika Celitan, Saulius Serva, Elena Servienė","doi":"10.1080/13880209.2025.2555815","DOIUrl":"10.1080/13880209.2025.2555815","url":null,"abstract":"<p><strong>Context: </strong>The spread of novel viruses substantiates the need for alternative antiviral agents. Plant-based extracts, such as essential oils (EOs), are highly relevant due to their generally human-friendly nature and broad spectrum of bioactive properties. Most EO antiviral activity is targeting enveloped viruses. <i>Orthototiviridae</i> family yeast virus ScV-L-A offers a novel, safe, non-enveloped virus model system for antiviral substance evaluation.</p><p><strong>Objective: </strong>This study aimed to investigate the antiviral efficacy of EOs and their constituents against non-enveloped ScV-L-A totivirus.</p><p><strong>Materials and methods: </strong>The composition of EOs was determined using GC-MS. Native ScV-L-A viral particles were prepared from yeast cells <i>via</i> cesium chloride gradient ultracentrifugation. The antiviral effect of EOs and their principal components was evaluated by following the synthesis of radio-labeled viral transcripts. TEM was employed to investigate the impact of target substances on ScV-L-A capsid integrity.</p><p><strong>Results: </strong>Tested EOs inhibited viral RNA polymerase activity in both liquid and vapor phases. Citral-rich EOs exhibited the strongest antiviral action, with lemon myrtle EO possessing the lowest half-maximal inhibitory concentration and highest timewise efficacy. Coriander and mandarin EOs showed the lowest polymerase-inhibiting capacity. EOs were more efficient compared to the action of single compounds. All EOs except for that of mandarin, dominated by limonene, were more effective in the liquid rather than the vapor phase. Tea tree and mandarin EOs were found to damage ScV-L-A capsid structure.</p><p><strong>Discussion and conclusion: </strong>This study highlighted the efficacy of EOs in targeting non-enveloped viruses and revealed their potential for sustainable control of viral infection.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"663-682"},"PeriodicalIF":6.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12427481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033979","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}

{"title":"<i>Rubus caesius</i> leaves and stems in antiaging skin care products: antityrosinase, anticollagenase, antimicrobial activity, and transdermal distribution of main phenolic acids.","authors":"Anna Hering, Anna Nowak, Anna Muzykiewicz-Szymańska, Rafał Tomasz Hałasa, Łukasz Kucharski, Paula Ossowicz-Rupniewska, Alina Kastsevich, Yahor Ivashchanka, Justyna Stefanowicz-Hajduk","doi":"10.1080/13880209.2025.2576002","DOIUrl":"10.1080/13880209.2025.2576002","url":null,"abstract":"<p><strong>Context: </strong>The skin is the largest organ of the body, and its proper care significantly influences the well-being of the entire organism. Therefore, the ingredients of cosmetics and dermocosmetics should inhibit processes leading to inflammation and degradation of skin macromolecules.</p><p><strong>Objective: </strong>To select the most promising <i>Rubus caesius</i> L. extract for use in cosmetic and dermocosmetic applications.</p><p><strong>Materials and methods: </strong>Water and ethanol extracts from leaves and stems of <i>Rubus caesius</i> L. (European dewberry, Rosaceae) were tested for their antioxidant properties, protective effects against pathogenic bacterial strains and the influence on tyrosinase and collagenase activity. The most biologically active extracts were selected and analyzed using the HPLC method to estimate the content of major phenolic acids and their ability to penetrate into and through porcine skin from hydrogels.</p><p><strong>Results: </strong>Ethanol extracts from <i>Rubus caesius</i> L. demonstrated significant biological activity, particularly in scavenging the ABTS radical and inhibiting tyrosinase and collagenase activity. Furthermore, ethanol extracts were effective against pathogenic bacteria, but not against commensal skin microbiota. Ethanol extracts from leaves and stems were rich in phenolic acids. The permeation experiment through porcine skin from hydrogels revealed that gallic acid and neochlorogenic acid from ethanol leaves extract exhibited the highest permeation capability.</p><p><strong>Discussion and conclusion: </strong>The ethanol extract demonstrated substantial activity in protecting the skin against pathogens, oxidative stress, and macromolecular degradation. The presence and transdermal permeability of phenolic acids were also confirmed. These findings highlight the high potential of <i>Rubus caesius</i> leaf ethanol extract for inclusion in cosmetic and dermocosmetic formulations.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"731-753"},"PeriodicalIF":6.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12584836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145431892","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}

{"title":"Dose-response assessment of neuroactive botanical extracts and their bioactive constituents using microelectrode array (MEA) recordings in rat primary cortical cultures.","authors":"Regina G D M van Kleef, J Pepijn Wopken, Julie Krzykwa, Constance A Mitchell, Remco H S Westerink","doi":"10.1080/13880209.2025.2583834","DOIUrl":"10.1080/13880209.2025.2583834","url":null,"abstract":"<p><strong>Context: </strong>Use of botanicals is increasing. While often considered as safe, neuromodulatory effects have been demonstrated previously.</p><p><strong>Objective: </strong>Establish the neuroactive potential of 13 botanical extracts. For 8 of these, we made a direct comparison with their major constituent.</p><p><strong>Materials and methods: </strong>We used microelectrode array (MEA) recordings of primary rat cortical cultures to evaluate dose-response relationships on neuronal network function <i>in vitro</i>.</p><p><strong>Results: </strong>Exposure to extracts from milk thistle, usnea, green tea, aristolochia, and ephedra mildly inhibited neuronal activity with distinct neuronal activity phenotypes. Extracts of tripterygium, yohimbe, kratom, and kava strongly inhibited neuronal activity. Despite differences in the degree of inhibition, all inhibitory extracts show No Observed Effect Levels (NOELs) of 1-5 µg/mL. Exposure to aconite, blue cohosh, goldenseal and oleander induced specific activity phenotypes characterized by hyperexcitation and/or intensification of (network) burst activity. While the extracts exhibit a narrow effective dose range, the extracts from aconite, goldenseal and oleander are most potent with NOELs of 0.25-0.5 µg/mL.</p><p><p>Silybin B (milk thistle), epigallocatechin gallate (green tea), yohimbine (yohimbe), dihydrokavain (kava), mitragynine (kratom), aconitine (aconite), berberine (goldenseal) and oleandrin (oleander) were tested to investigate if the distinct neuronal activity phenotypes, indicative for the presence of multiple modes of action, are due to the known bioactive constituents of the extracts. For most constituents the activity phenotype is comparable to the extract, although the extract generally has a higher potency.</p><p><strong>Discussion and conclusion: </strong>Botanical extracts and constituents evoke diverse activity phenotypes, highlighting the complexity of hazard characterization of botanicals.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"754-777"},"PeriodicalIF":6.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12599351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145471582","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}

{"title":"Mechanism of action of genistein on breast cancer and differential effects of different age stages.","authors":"Zhebin Xiang, Bo Ma, Xiujun Pei, Wenjie Wang, Weilun Gong","doi":"10.1080/13880209.2025.2469607","DOIUrl":"10.1080/13880209.2025.2469607","url":null,"abstract":"<p><strong>Context: </strong>Genistein, a soy-derived isoflavone, exhibits structural similarities with 17β-estradiol and demonstrates antioxidant, anti-inflammatory, and estrogenic properties. Despite its low bioavailability limiting its clinical application, it shows potential for breast cancer prevention and treatment.</p><p><strong>Objective: </strong>This review aims to summarize the pharmacological effects and molecular mechanisms of genistein in breast cancer, focusing on its therapeutic potential, strategies to overcome bioavailability limitations, and its role in personalized medicine. Differential impacts among population subgroups are also discussed.</p><p><strong>Methods: </strong>A systematic review was conducted using PubMed, ScienceDirect, and Google Scholar databases. Studies were selected based on their focus on genistein's mechanisms of action, strategies to enhance its bioavailability, and interactions with other therapies.</p><p><strong>Results: </strong>Genistein exerted anticancer effects by modulating estrogen receptor β (ERβ), inhibiting angiogenesis, arresting the cell cycle, and inducing apoptosis. Its antioxidant properties help mitigate tumor-associated oxidative stress. Bioavailability enhancement strategies, such as nanoparticle and lipid-based formulations, show promise. Age-dependent effects were evident, with distinct responses observed in prepubertal, menopausal, and postmenopausal populations, underscoring its potential for personalized therapies. Furthermore, genistein influences epigenetic modifications, including DNA methylation and miRNA expression, bolstering its anticancer efficacy.</p><p><strong>Conclusion: </strong>Genistein is a promising candidate for breast cancer therapy, particularly for personalized treatment. Strategies to enhance bioavailability and further clinical research are essential to optimize its therapeutic potential and evaluate its efficacy in combination therapies.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"141-155"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11864014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493093","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}

{"title":"Naringenin inhibits ferroptosis to reduce radiation-induced lung injury: insights from network Pharmacology and molecular docking.","authors":"Junlin Jiang, Xianhui Deng, Chengkai Xu, Yaxian Wu, Jianfeng Huang","doi":"10.1080/13880209.2025.2465312","DOIUrl":"10.1080/13880209.2025.2465312","url":null,"abstract":"<p><strong>Context: </strong>Naringenin is a natural flavanone with potent pharmacological properties. It has demonstrated therapeutic potential in treating various diseases and organ injuries, including radiation-induced lung injury (RILI). Ferroptosis is a newly type of cell death, and naringenin has been shown to attenuates ferroptosis.</p><p><strong>Objective: </strong>To evaluate the inhibitory effect and molecular mechanism of naringenin on ferroptosis during RILI process.</p><p><strong>Materials & methods: </strong>Firstly, BEAS-2B and HUVECs cells were pre-incubated with naringenin for 1 h prior to 8 Gy of X-ray irradiation to evaluate oxidative stress, inflammation, and the mRNA levels of ferroptosis-related genes. Next, target genes of naringenin, RILI, and ferroptosis were identified using the TCMSP, SwissTargetPrediction, and GeneCards databases. The target network was constructed with Cytoscape and STRING. Finally, the core target genes were identified through <i>in vitro</i> experiments by qRT-PCR, western blot and immunofluorescence staining.</p><p><strong>Results: </strong>Naringenin effectively reduced radiation-induced increasement of oxidative stress, inflammation, and ferroptosis markers in both cell lines. Network pharmacology identified 14 target genes, with prostaglandin endoperoxide synthase (PTGS2) and Valosin-containing protein (VCP) mRNA levels being prominent, which were crucial for ferroptosis regulation. Molecular docking revealed strong binding interactions between naringenin and the two target proteins. Subsequently, experimental validation confirmed that naringenin reduced the elevated levels of PTGS2 and VCP induced by radiation.</p><p><strong>Discussion & conclusion: </strong>Naringenin alleviates radiation-induced lung damage by inhibiting ferroptosis, with PTGS2 and VCP emerging as potential therapeutic targets.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"1-10"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11841155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449905","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}

{"title":"Sophoridine inhibits proliferation and migration by targeting PIM1 in breast cancer.","authors":"Lu Chen, Yuting Xia, Liangliang Min, Yuqin Zhang, Da Huang, Yulu Zhang, Aihua You, Zhihua Li","doi":"10.1080/13880209.2025.2537123","DOIUrl":"10.1080/13880209.2025.2537123","url":null,"abstract":"<p><strong>Context: </strong>Sophoridine, an alkaloid quinolizidine derived from <i>Sophora flavescens</i> Aiton (Fabaceae), has strong anti-tumor activity in a variety of malignancies. Nevertheless, the effects and underlying mechanism of sophoridine on breast cancer are not fully understood.</p><p><strong>Objective: </strong>To identify the key targets and potential pharmacological mechanisms of sophoridine against breast cancer.</p><p><strong>Materials and methods: </strong>MCF-10A, MCF-7 and MDA-MB-231 cells were treated with sophoridine for 24 or 48 h. MTT, colony formation assay, flow cytometry, wound healing, and Transwell assay were employed to illustrate the anti-tumor effects of sophoridine on breast cancer. Network pharmacology and molecular docking were used to determine the targets for sophoridine in breast cancer, and confirmed by molecular dynamics simulation and CETSA-western blot assay. Additionally, the functional rescue and signaling pathway regulated by sophoridine was analyzed.</p><p><strong>Results: </strong>Sophoridine suppressed the proliferation, migration, and invasion of breast cancer cells. The IC₅₀ value of sophoridine for 48 h in MCF-10A, MCF-7 and MDA-MB-231 was 363 μM, 87.96 μM and 81.07 μM, respectively. PIM1 was the key target for sophoridine in breast cancer. Furthermore, PIM1 overexpression significantly reversed the suppressive impacts of sophoridine on growth and migration in breast cancer cells. Mechanistically, sophoridine inhibited the phosphorylation of ASK1 and activated JNK/p38 MAPK signaling pathway by downregulating PIM1 expression, and thus exhibited anti-tumor effects.</p><p><strong>Discussion and conclusion: </strong>Taken together, sophoridine relies on targeting PIM1 to inhibit cell proliferation and migration in breast cancer, which might be related to the activation of ASK1/MAPK axis, suggesting the therapeutic potential of sophoridine for breast cancer.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"503-523"},"PeriodicalIF":4.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12302398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708387","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}

{"title":"Harmine derivative H-2-168 induces the death of <i>Echinococcus granulosus</i> by regulating mitochondrial fusion and fission.","authors":"Yuehong Gong, Meiling Zhao, Meichi Pan, Yicong Zhao, Junpeng Liu, Hao Wen, Jianhua Wang","doi":"10.1080/13880209.2025.2485898","DOIUrl":"10.1080/13880209.2025.2485898","url":null,"abstract":"<p><strong>Context: </strong>H-2-168 has pharmacological effects similar to those of harmine, with less toxicity. The health of cells and organisms depends on a delicate balance between mitochondrial fusion and fission.</p><p><strong>Objective: </strong>This study investigated the roles of H-2-168 and mitochondrial fusion and fission in <i>Echinococcus granulosus</i>.</p><p><strong>Materials and methods: </strong>Notably, <i>E. granulosus</i> were isolated from fresh sheep livers, and then treated with H-2-168 (25 μg/mL), mitochondrial division inhibitor 1 (Mdivi-1, 25 μg/mL) or the combination of H-2-168:Mdivi-1 (25 μg/mL:12.5 μg/mL). After 24 h of culture, the indices related to <i>E. granulosus</i> were measured. Additionally, Drp1 was knocked down to explore its effects on <i>E. granulosus</i> growth.</p><p><strong>Results: </strong>The EC₅₀ values of H-2-168, Mdivi-1 and H-2-168:Mdivi-1 against <i>E. granulosus</i> were 44.171, 117.882 and 32.924 μg/mL, respectively. Compared with H-2-168 or Mdivi-1, the combination of H-2-168 and Mdivi-1 showed better inhibitory effects on <i>E. granulosus</i> viability, as well as increased levels of ROS and LDH, decreased ATP levels, inhibited mitochondrial activity and reduced mitochondrial membrane potential (<i>p</i> < 0.05), with the upregulation of Caspase-3, Cyt-c, Drp1, Fis1 and downregulation of Bcl-2, Mfn2 and OPA1. Additionally, <i>Drp1</i> knockdown was successfully performed in <i>E. granulosus</i>, which significantly inhibited <i>E. granulosus</i> viability (<i>p</i> < 0.05) and further downregulated Mfn2 expression induced by H-2-168.</p><p><strong>Discussion and conclusion: </strong><i>Drp1</i> is closely associated with mitochondrial fusion and fission, and H-2-168 may promote <i>E. granulosus</i> death through disrupting the balance between mitochondrial fusion and fission.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"188-200"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11980216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795892","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}