Pharmaceutical Biology最新文献

{"title":"Tumor organoids in cancer medicine: from model systems to natural compound screening.","authors":"Rong Cong, Can Lu, Xinying Li, Zhijie Xu, Yaqin Wang, Shusen Sun","doi":"10.1080/13880209.2025.2458149","DOIUrl":"10.1080/13880209.2025.2458149","url":null,"abstract":"<p><strong>Context: </strong>The advent of tissue engineering and biomedical techniques has significantly advanced the development of three-dimensional (3D) cell culture systems, particularly tumor organoids. These self-assembled 3D cell clusters closely replicate the histopathological, genetic, and phenotypic characteristics of primary tissues, making them invaluable tools in cancer research and drug screening.</p><p><strong>Objective: </strong>This review addresses the challenges in developing <i>in vitro</i> models that accurately reflect tumor heterogeneity and explores the application of tumor organoids in cancer research, with a specific focus on the screening of natural products for antitumor therapies.</p><p><strong>Methods: </strong>This review synthesizes information from major databases, including Chemical Abstracts, Medicinal and Aromatic Plants Abstracts, ScienceDirect, Google Scholar, Scopus, PubMed and Springer Link. Publications were selected without date restrictions, using terms such as 'organoid', 'natural product', 'pharmacological', 'extract', 'nanomaterial' and 'traditional uses'. Articles related to agriculture, ecology, synthetic work or published in languages other than English were excluded.</p><p><strong>Results and conclusions: </strong>The review identifies key challenges related to the efficiency and variability of organoid generation and discusses ongoing efforts to enhance their predictive capabilities in drug screening and personalized medicine. Recent studies utilizing patient-derived organoid models for natural compound screening are highlighted, demonstrating the potential of these models in developing new classes of anticancer agents. The integration of natural products with patient-derived organoid models presents a promising approach for discovering novel anticancer compounds and elucidating their mechanisms of action.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"89-109"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11789228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075290","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":"A triterpene-enriched natural extract from <i>Eucalyptus tereticornis</i> modulates the expression of genes involved in adipogenesis, lipolysis, and extracellular matrix remodeling in a primary human and mouse cell line adipocyte.","authors":"Sergio Acin, Alejandro Mejia-Garcia, Geysson Javier Fernandez, Norman Balcazar","doi":"10.1080/13880209.2025.2505443","DOIUrl":"10.1080/13880209.2025.2505443","url":null,"abstract":"<p><strong>Context: </strong>Obesity induces alterations in adipocyte size, tissue inflammation, vascularization, and extracellular matrix composition. Previous studies have shown that a leaf extract of <i>Eucalyptus tereticornis</i> Sm. (Myrtaceae), with ursolic acid, oleanolic acid, and ursolic acid lactone mixed with minor metabolites, provided a superior antiobesity effect than reconstituted triterpenoid mixtures in adipocyte cell lines and a pre-diabetic mouse model. Further identification of the molecular mechanisms of action of this mixture of triterpenes is required.</p><p><strong>Objective: </strong>This study analyzes the effect of the natural extract and its components on early RNA expression profiles in human primary cultured adipocytes and a mouse cell line.</p><p><strong>Materials and methods: </strong>RNA was sequenced using the DNBseq platform and the EnrichR software to perform gene enrichment analysis using the Gene Ontology database, Kyoto Encyclopedia of Genes and Genomes, and Reactome. To conduct clustering analysis, the normalized counts of each gene and applied k-means clustering were standardized.</p><p><strong>Results: </strong>The combination of molecules in the natural extract has an additive or synergic effect that increases the number of genes regulated associated with the biological functionality of differentiating adipocytes, with UAL playing a central role. The natural extract modulates PPAR, Wnt, and Extracellular Matrix organization pathways significantly in both cellular models. Remarkably, the extract downregulates the expression of genes involved in lipid metabolism, adipogenesis, and adipocyte fat load, such as PRKAR2B, LPIN1, FABP4, Scd1, MC5R, CD36, PEG10, and HMGCS1.</p><p><strong>Discussion and conclusions: </strong>Our study shows that <i>Eucalyptus tereticornis</i> extract is a promising option for treating adipocyte tissue dysfunction derived from obesity.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"374-386"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12086905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094534","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":"Research progress of Chinese medicinal monomers in the process of melanoma occurrence.","authors":"Yan Shang, Hailong Zhao","doi":"10.1080/13880209.2024.2445695","DOIUrl":"10.1080/13880209.2024.2445695","url":null,"abstract":"<p><strong>Context: </strong>Melanoma's aggressiveness and resistance to radiotherapy highlight an urgent need for innovative treatments. Traditional Chinese medicine (TCM) offers a unique approach through its 'four natures' theory-cold, cool, warm, and hot.</p><p><strong>Objective: </strong>This review aims to explore the potential of TCM's 'four natures' herbal monomers in melanoma treatment, providing an alternative to conventional therapies.</p><p><strong>Materials & methods: </strong>A systematic literature review was conducted by accessing various databases, including Baidu Scholar, PubMed, Science Citation Index Expanded (SCIE), and China National Knowledge Infrastructure (CNKI), to synthesize the most recent findings on traditional Chinese medicine monomers. Furthermore, this review elucidated the mechanisms underlying their role in melanoma retention.</p><p><strong>Results: </strong>TCM's multi-component, multi-target approach has shown promise in addressing melanoma's complexity, with specific monomers demonstrating the ability to modulate tumor behavior.</p><p><strong>Discussion and conclusions: </strong>The 'four natures' theory in TCM presents a novel perspective for melanoma treatment, warranting further investigation into its clinical applications and potential integration with modern oncology.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"53-67"},"PeriodicalIF":4.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11727062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142953117","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":"Overview of current research on traditional Chinese medicine in skin disease treatment: a bibliometric analysis from 2014 to 2024.","authors":"Lin Li, Lanfang Zhang, Yuan Li, Yuan Cai, Xue Wen, Chenjie Zheng, Chuyan Wu, Yunlei Bao, Feng Jiang, Nana Sun, Ni Zeng","doi":"10.1080/13880209.2024.2443415","DOIUrl":"10.1080/13880209.2024.2443415","url":null,"abstract":"<p><strong>Context: </strong>Recent research has revealed significant advancements in the field of traditional Chinese medicine (TCM) for skin diseases. However, there is a lack of visualization analysis within this research domain.</p><p><strong>Objective: </strong>To analyze the research directions and advancements in TCM research in skin diseases.</p><p><strong>Materials and methods: </strong>Publications related to TCM in skin diseases from 2014 to 2024 were searched on the Web of Science Core Collection (WoSCC), VOSviewer, CiteSpace, and the R package \"bibliometrix\" were employed to visualize and analyze the retrieved data.</p><p><strong>Results: </strong>The study included 527 articles published in 25 countries. The number of publications consistently increased from 2014 to 2024. The Guangzhou University of Chinese Medicine was the most noteworthy institution in this field. Among the journals in this domain, the <i>Journal of Ethnopharmacology</i> was the most popular, and most frequently co-cited journal. Chuanjian Lu published the most papers and Yin-Ku Lin was the most frequently co-cited author. Among keywords, \"psoriasis\" appeared the most frequently. Additionally, several emerging research hotspots were identified, indicating the transition from traditional Chinese therapies to investigations of the molecular interactions and network pharmacology of Chinese herbs in treatment of skin diseases over the past decade.</p><p><strong>Discussion and conclusion: </strong>This visualization analysis summarizes the research directions and advancements in TCM research on skin diseases. It presents a comprehensive examination of the latest research frontiers and trends and serves as a valuable reference for scholars engaged in the study of TCM research.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"27-41"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Apium graveolens</i> L. alleviates acute lung injury in human A-549 cells by reducing NF-κB and NLRP3 inflammasome signaling.","authors":"Lan-Chi Hsieh, Shu-Ling Hsieh, Tsu-Ni Ping, Yi-Chun Huang, Ssu-Jung Lin, Hsing-Yu Chi, Chih-Chung Wu","doi":"10.1080/13880209.2024.2433994","DOIUrl":"10.1080/13880209.2024.2433994","url":null,"abstract":"<p><strong>Background: </strong><i>Apium graveolens</i> L. (celery) is a dietary vegetable with anti-inflammatory properties. It has the potential to treat acute lung injury (ALI) caused by COVID-19 or other diseases.</p><p><strong>Objective: </strong>To investigate the effects of <i>Apium graveolens</i> water extract (AGWE) on ALI in human lung A-549 cells induced by lipopolysaccharide (LPS).</p><p><strong>Materials and methods: </strong>A-549 cells were treated with AGWE for 24 h and then stimulated with 10 μg/mL LPS for another 24 h. The effects of AGWE on cell viability, the inflammatory response, oxidative stress, and apoptosis and their regulatory factors, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and NLR family pyrin domain containing 3 (NLRP3) inflammasome signaling activation were analyzed.</p><p><strong>Results: </strong>Treatment with 5-50 μg/mL AGWE reversed the decrease in cell viability caused by LPS (<i>p</i> < 0.05). AGWE can reduce interleukin (IL)-1β, IL-6, IL-18, and TNF-α levels; their EC₅₀ values are 61.4, 65.7, 37.8, and 79.7 μg/mL, respectively. AGWE can reduce reactive oxygen species and thiobarbituric acid reactive substances in A-549 cells induced by LPS. AGWE also reduced the levels of apoptosis (EC50 of 74.8 μg/mL) and its regulators (Bid; Caspase-9, -8, and -3; Bax) and increased the levels of the mitochondrial membrane potential in A-549 cells induced by LPS. AGWE can also decrease the protein levels of NLRP3 and Caspase-1 and the activation of NF-κB signaling in A-549 cells induced by LPS.</p><p><strong>Conclusions: </strong>These results show that 10 and 50 μg/mL AGWE can reduce the acute inflammation induced by LPS by reducing NF-κB and NLRP3 inflammasome signaling and mitochondria-dependent apoptosis pathways.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"1-13"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11648134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818844","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":"Total flavonoids of litchi seed inhibit breast cancer metastasis by regulating the PI3K/AKT/mTOR and MAPKs signaling pathways.","authors":"Xin Yang, Shoushi Liu, Ying Liu, Yuanshuo Wang, Dianxin Cui, Taijin Lan, Dan Zhu, Zhiheng Su, Erwei Hao, Lilan Qin, Hongwei Guo","doi":"10.1080/13880209.2025.2488135","DOIUrl":"https://doi.org/10.1080/13880209.2025.2488135","url":null,"abstract":"<p><strong>Context: </strong>Total flavonoids from <i>Litchi chinensis</i> Sonn. (Sapindaceae) seeds (TFLS) effectively attenuate stem cell-like properties in breast cancer cells. However, their pharmacological effects and mechanisms in suppressing breast cancer metastasis remain unclear.</p><p><strong>Objective: </strong>This study aimed to elucidate the inhibitory effects and underlying mechanisms of TFLS on breast cancer metastasis.</p><p><strong>Materials and methods: </strong>The antiproliferative, migratory, and invasive activities of breast cancer cells following TFLS treatment were evaluated using CCK-8, wound-healing, and transwell assays. The epithelial-mesenchymal transition (EMT) biomarkers were evaluated <i>via</i> Western blot analysis. The anti-metastatic effects of TFLS were further validated <i>in vivo</i> using zebrafish and mouse models. Network pharmacology methodology was utilized to predict potential targets and signaling pathways, which were subsequently corroborated by Western blot. Potential active compounds were identified through molecular docking, and the chemical constituents of TFLS were analyzed and characterized using UPLC-QTOF/MS.</p><p><strong>Results: </strong>TFLS suppressed the proliferation of MDA-MB-231 and MDA-MB-468 cells, with IC₅₀ values of 44.47 μg/mL and 37.35 μg/mL at 72 h, respectively. It effectively suppressed breast cancer metastasis <i>in vitro</i>, demonstrated by a marked reduction in cellular motility and invasiveness, alongside the reversal of EMT. Consistent with pathway enrichment analysis, network pharmacology revealed that TFLS reduced the phosphorylation levels of PI3K, AKT, mTOR, JNK, ERK, and p38 in breast cancer cells. Molecular docking identified seven potential active ingredients, and UPLC-MS/MS confirmed the presence of key compounds, including procyanidin A2.</p><p><strong>Discussion and conclusion: </strong>TFLS effectively inhibits breast cancer cell proliferation, migration, and invasion <i>in vitro</i> by reversing the EMT phenotype, while suppressing metastasis <i>in vivo</i>. These effects are likely mediated <i>via</i> the attenuation of the PI3K/AKT/mTOR and MAPK signaling pathways.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"229-249"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12001861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144015311","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":"Delivery of small interfering RNA through lyophilized natural lipid nanoparticles: effects of natural lipid selection.","authors":"Hangjie Wang, Wei Li, Junyan Chen, Rong Chen, Yuwei Qi, Linshuang Shen, Kaidi Chen, Lewei Dai, Yuxin Sheng, An Wang, Hong Wang, Chujian Chen, Xiao Cheng, Mancang Gu","doi":"10.1080/13880209.2025.2498169","DOIUrl":"https://doi.org/10.1080/13880209.2025.2498169","url":null,"abstract":"<p><strong>Context: </strong>Lipid nanoparticles (LNPs) are the primary non-viral vectors for siRNA delivery. However, synthetic lipids face issues, such as low lysosomal escape efficiency and high cost.</p><p><strong>Objective: </strong>This study aimed to use three natural lipids to construct LNPs, optimize their preparation and freeze-drying processes, and evaluate their siRNA delivery efficiency <i>in vitro</i>.</p><p><strong>Materials and methods: </strong><i>Coix</i> seed lipid [<i>Coix lacryma-jobi</i> L. var. <i>mayuen</i> (Roman.) Stapf (Poaceae), CSL], <i>Brucea javanica</i> seed lipid [<i>Brucea javanica</i> (L.) Merr. (Simaroubaceae), BJL], and Soybean oil [<i>Glycine max</i> (L.) Merr. (Fabaceae), SO] were used to construct LNPs. The Z-average size, zeta potential, Polymer Dispersity Index, and N/P ratio of the LNPs were characterized. Transmission electron microscope was used for morphology observation and the MTS assay for cytotoxicity. Confocal laser scanning microscope assessed cell uptake, lysosomal escape, and co-localization of lipid droplets. The efficiency of siRNA knockdown was evaluated in three cells using qPCR and Western blot. The freeze-drying processes were optimized.</p><p><strong>Results: </strong>The optimal LNPs exhibited a size of 160-180 nm, zeta of 44-50 mV, and PDI of <0.2. At 200 μg/mL, the LNPs did not affect cell viability. CSL-LNPs, BJL-LNPs, and SO-LNPs reduced KRAS^G12D mRNA levels in AsPC-1 cells by 67.87 ± 3.89, 47.18 ± 7.65, and 42.52 ± 8.90%, respectively. Freeze-dried LNPs retained their basic physical properties and the three LNPs reducing KRAS^G12D mRNA levels by 58.47 ± 4.00, 51.83 ± 4.57, and 38.00 ± 4.89%, respectively.</p><p><strong>Discussion and conclusion: </strong>Natural lipids are promising components for LNPs construction, offering new avenues for siRNA delivery in gene therapy.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"343-356"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12051533/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144007342","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":"Involvement of ionomic metabolism of both the cerebrospinal fluid and the spinal cord in the analgesic efficacy of matrine in rats.","authors":"Jin-Lu Huang, Chen-Yue Tang, Yao Fu, Li-Li Wan, Jie Li, Xi-Peng Sun, Jia-Lu Hu, Yue-Yi Zhang, Li-Ying Qu, Miao-Jia Fu, Yuan-Yuan Zhang, Le Ma, Cheng Guo, Jiu-Geng Chen","doi":"10.1080/13880209.2025.2492872","DOIUrl":"https://doi.org/10.1080/13880209.2025.2492872","url":null,"abstract":"<p><strong>Context: </strong>Matrine has antinociceptive properties, and spinal cord ionomic changes are involved in bone cancer pain.</p><p><strong>Objective: </strong>To investigate the relationship between ionomic metabolism in cerebrospinal fluid (CSF) and spinal cord and matrine's analgesic efficacy.</p><p><strong>Materials and methods: </strong>The antinociceptive effects of matrine were identified in rats <i>via</i> intraperitoneal (i.p.) injection using the tail-immersion and formalin tests. Pharmacodynamic parameters for matrine against formalin-induced pain were calculated with nonlinear regression analysis. Inductively coupled plasma mass spectrometry (ICP-MS) technology was utilized to detect contents of the ionome in CSF and spinal cord. Variations in ionomic metabolism in different treated groups were examined using Pearson's correlation coefficients and principal component analysis (PCA).</p><p><strong>Results: </strong>In the tail-immersion test, matrine significantly prolonged tail-flick latency in rats. Matrine also dose-dependently yielded analgesia against formalin-induced biphasic pain, with an onset at around 10 min post-injection and a duration of 100 min. The ED₅₀ and E_max values were 19.01 mg/kg and 71.86% for phase I and 40.30 mg/kg and 81.51% for phase II, respectively. Pearson's correlation coefficient study and PCA revealed significant reprogramming of ionomic metabolism in the CSF and the spinal cord in the NM (normal saline + matrine), NF (normal saline + formalin), and FM (formalin + matrine) groups, compared to the NN (normal saline + normal saline) group.</p><p><strong>Discussion and conclusions: </strong>These findings broaden the known analgesic spectrum of matrine and provide novel insights into the involvement of ionomic metabolism in its analgesic efficacy.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"275-287"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12020144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144037418","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":"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}