Pharmaceutical Biology最新文献

{"title":"The extract of <i>buddleja officinalis</i> maxim. alleviates UVB-induced oxidative damage <i>via</i> the NRF2 pathway in HaCaT cells.","authors":"Xu Zhu, Zhongyi Chen, Bin Deng, Chunhao Yang, Fengkun Xiao","doi":"10.1080/13880209.2025.2540348","DOIUrl":"10.1080/13880209.2025.2540348","url":null,"abstract":"<p><strong>Context: </strong><i>Buddleja officinalis</i> Maxim., a prominent medicinal plant from the Scrophulariaceae family, is extensively distributed throught China, Korea, Vietnam, and Myanmar. This phytotherapeutic agent has demonstrated significant clinical efficacy in treating various ophthalmic disorders, such as xerophthalmia, infectious conjunctivitis, keratopathies, corneal ulcerations, and neuropathic ocular pain.</p><p><strong>Objective: </strong>To explore the potential photoprotective effects of <i>Buddleja officinalis</i> Maxim. extract (BOE) against UVB-induced oxidative damage in human immortalized keratinocytes.</p><p><strong>Materials and methods: </strong>In this study, we analyzed BOE components using HPLC and evaluated scavenging activities against 2, 2'-diphenyl-1-picrylhydrazyl (DPPH), 2,2-azinobis 3-ethylbenzothiazoline 6-sulfonate (ABTS), and Superoxide anion (O₂^·-) through biochemical assays. Cell viability was assessed with cell counting kit-8 assay (CCK-8) and lactate dehydrogenase (LDH) kits, intracellular reactive oxygen species (ROS) levels were quantified by flow cytometry, and cellular antioxidant enzyme activities were determined using commercial assay kits. To investigate specific antioxidant pathways, qPCR and Western blot analyses were performed.</p><p><strong>Results: </strong>The biochemical assays demonstrated that BOE possesses significant antioxidant activity. Additionally, BOE significantly alleviated the adverse effects of UVB exposure (30 mJ/cm²), which were characterized by decreased cell viability, elevated LDH activity, increased intracellular ROS levels, reduced activities of superoxide dismutase (SOD), decreased the levels of reduced glutathione (GSH), and increased Malondialdehyde (MDA) content. And the BOE modulates the antioxidant defense pathway by upregulating the mRNA and protein expression levels of nuclear factor erythroid 2-related factor 2(NRF2), heme oxygenase-1 (HO-1), and NAD(P)H: quinone oxidoreductase 1 (NQO1).</p><p><strong>Discussion and conclusions: </strong>Our findings indicate that the photoprotective efficacy of BOE makes it a promising candidate for incorporation as a natural component in pharmaceutical and cosmetic formulations.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"567-581"},"PeriodicalIF":4.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12333036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144795049","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 novel strategy for the protective effect of ginsenoside Rg1 against ovarian reserve decline by the PINK1 pathway.","authors":"Pengdi Yang, Meiling Fan, Ying Chen, Dan Yang, Lu Zhai, Baoyu Fu, Lili Zhang, Yanping Wang, Rui Ma, Liwei Sun","doi":"10.1080/13880209.2025.2453699","DOIUrl":"10.1080/13880209.2025.2453699","url":null,"abstract":"<p><strong>Context: </strong>The decline in ovarian reserve is a major concern in female reproductive health, often associated with oxidative stress and mitochondrial dysfunction. Although ginsenoside Rg1 is known to modulate mitophagy, its effectiveness in mitigating ovarian reserve decline remains unclear.</p><p><strong>Objective: </strong>To investigate the role of ginsenoside Rg1 in promoting mitophagy to preserve ovarian reserve.</p><p><strong>Materials and methods: </strong>Ovarian reserve function, reproductive capacity, oxidative stress levels, and mitochondrial function were compared between ginsenoside Rg1-treated and untreated naturally aged female <i>Drosophila</i> using behavioral, histological, and molecular biological techniques. The protective effects of ginsenoside Rg1 were analyzed in a <i>Drosophila</i> model of oxidative damage induced by tert-butyl hydroperoxide. Protein expression levels in the PINK1/Parkin pathway were assessed, and molecular docking and PINK1 mutant analyses were conducted to identify potential targets.</p><p><strong>Results: </strong>Ginsenoside Rg1 significantly mitigated ovarian reserve decline, enhancing offspring quantity and quality, increasing the levels of ecdysteroids, preventing ovarian atrophy, and elevating germline stem cell numbers in aged <i>Drosophila</i>. Ginsenoside Rg1 improved superoxide dismutase, catalase activity, and gene expression while reducing reactive oxygen species levels. Ginsenoside Rg1 activated the mitophagy pathway by upregulating PINK1, Parkin, and Atg8a and downregulating Ref(2)P. Knockdown of PINK1 in the ovary by RNAi attenuated the protective effects of ginsenoside Rg1. Molecular docking analysis revealed that the ginsenoside Rg1 could bind to the active site of the PINK1 kinase domain.</p><p><strong>Discussion and conclusions: </strong>Ginsenoside Rg1 targets PINK1 to regulate mitophagy, preserving ovarian reserve. These findings suggest the potential of ginsenoside Rg1 as a therapeutic strategy to prevent ovarian reserve decline.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"68-81"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059506","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":"Characterization of global research trends and prospects on celastrol, a principal bioactive ingredient of <i>Tripterygium wilfordii</i> Hook F: bibliometric analysis.","authors":"Huizi Ye, Yufang Wang, Xue Zhang, Lin Yang, Banglan Cai, Denghai Zhang, Bin Peng","doi":"10.1080/13880209.2024.2443424","DOIUrl":"10.1080/13880209.2024.2443424","url":null,"abstract":"<p><strong>Context: </strong>Celastrol, acknowledged as a prominent exemplar of the potential for transforming traditional medicinal compounds into contemporary pharmaceuticals, has garnered considerable attention owing to its extensive pharmacological activities. The increasing volume of publications concerning celastrol highlights its importance in current scientific inquiry. Despite the growing interest in this compound, a bibliometric analysis focused on this subject remains to be undertaken.</p><p><strong>Objective: </strong>Our study explored a bibliometric approach to identify and characterize global research trends and frontiers related to celastrol, including mapping research outputs, influential contributors, and thematic areas, as well as highlighting gaps and opportunities for future investigations.</p><p><strong>Materials and methods: </strong>In this study, we utilized the Web of Science Core Collection (WoSCC) to source and review articles related to celastrol published from 1997 to 2023. The bibliometric analysis was conducted using the R package 'Bibliometrix,' supplemented by visualization tools including CiteSpace, VOSviewer, and GraphPad Prism 10.</p><p><strong>Results: </strong>Celastrol related research papers have exhibited an upward trend annually and can be categorized into three distinct phases, each highlighting different areas of focus. China, the United States, and South Korea rank as the top three nations for publication volume, with varied research interests across these countries. Several prolific research teams have emerged, each with distinct areas of interest. Examining the primary research domains of celastrol (anti-inflammatory, anticancer, and toxicity) reveals a notable intersection between the first two domains.</p><p><strong>Discussion and conclusions: </strong>The scope and depth of celastrol research have been steadily expanding, with regional and team-specific variations. Key research areas include anti-inflammatory, anticancer, and toxicity studies. Future research is expected to focus on enhancing the effectiveness and reducing the toxicity of celastrol. Meanwhile, given the multi-target characteristics of celastrol's effects, integrating methods such as network biology and molecular simulation will provide a novel perspective for celastrol research.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"15-26"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915259","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":"Biologically active withanolides from <i>Physalis peruviana</i>.","authors":"Mayuramas Sang-Ngern, Ashley Fukuchi, Tamara P Kondratyuk, Eun-Jung Park, Charles J Simmons, Marisa M Wall, Sam E Lorch, John M Pezzuto, Leng Chee Chang","doi":"10.1080/13880209.2025.2488136","DOIUrl":"https://doi.org/10.1080/13880209.2025.2488136","url":null,"abstract":"<p><strong>Context: </strong><i>Physalis peruviana</i> L. (Solanaceae), also known as Poha, has been used in traditional medicine since pre-Columbian times, particularly in treating cancer.</p><p><strong>Objective: </strong>To study the chemical composition and potential medicinal properties of Poha.</p><p><strong>Materials and methods: </strong>The fresh fruits and aerial parts of Poha were extracted. The isolation of extract yields a novel withanolide (physaperuvin K; <b>1</b>) from the edible fruit, and seven withanolides (<b>2</b>-<b>8</b>), including a rare chlorinated withanolide (physalolactone; <b>2</b>) from the aerial parts. Structure elucidation/determination was performed, some acetate derivatives were prepared (<b>2a</b>-<b>6a</b>), and the compounds were evaluated with <i>in vitro</i> assays indicative of anti-inflammatory activity.</p><p><strong>Results: </strong>The structure of <b>1</b> was elucidated through NMR spectroscopic analyses. The absolute configuration of compound <b>2</b> was determined using single-crystal X-ray diffraction. Compounds <b>1</b>, <b>2</b>, and <b>3</b> exhibited inhibition of tumor necrosis factor-α-induced nuclear factor-kappa B (NF-κB) activity with IC₅₀ values of 10, 60, and 40 nM, respectively, without causing cytotoxicity at a concentration of 50 μM. Furthermore, compounds <b>1</b>-<b>3</b> reduced nitric oxide (NO) production in lipopolysaccharide-activated RAW 264.7 mouse macrophage cells with IC₅₀ values ranging from 0.32 to 13.3 μM without overt cytotoxicity. Overall, acetylation did not significantly impact activity, except for compound <b>4</b>, wherein the IC₅₀ values in the NF-κB and NO assays were reduced from 11.0 to 0.33 μM, and 1.8 to 0.24 μM, respectively.</p><p><strong>Conclusions: </strong>These findings enhance our understanding of Poha's constituents and potential medicinal properties. One of the most bioactive compounds identified in this study, physaperuvin K, is found in edible fruit.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"334-343"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12035931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144039236","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>WDJ-S4</i>, a standardized herbal formula, promotes gastrointestinal motility via modulation of the acetylcholine pathway in a loperamide-induced functional dyspepsia mice.","authors":"Seung-Ju Hwang, Chang-Seob Seo, Dong-Cheol Baek, Tae-Wook Woo, Jing-Hua Wang, Jin-Seok Lee, Yu-Jin Choi, Ji-Yeon Gu, Dong-Seon Kim, Chang-Gue Son","doi":"10.1080/13880209.2025.2488134","DOIUrl":"https://doi.org/10.1080/13880209.2025.2488134","url":null,"abstract":"<p><strong>Context: </strong>WDJ-S4, a standardized herbal formula, has been prescribed for refractory functional dyspepsia (FD) in Korea, but the detailed mechanisms are lacking.</p><p><strong>Objective: </strong>The present study investigates the acceleration of gastrointestinal (GI) motility by WDJ-S4 and its potential mechanisms.</p><p><strong>Materials and methods: </strong>For five days, WDJ-S4 (50, 100 and 200 mg/kg) or mosapride (3 mg/kg) was orally given to BALB/c mice. After 20 h of fasting, loperamide (10 mg/kg, i.p.) was given to the mice except for normal group. To assess gastric emptying or intestinal propulsion, 500 μL of 0.05% phenol red or 200 μL of 5% charcoal diet was given once orally.</p><p><strong>Results: </strong>Loperamide delayed gastric emptying and intestinal propulsion, while WDJ-S4 ameliorated peristaltic dysfunction, evidenced by reductions of remaining phenol red in the stomach and a marked increase of charcoal propulsion in the intestine. WDJ-S4 also normalized levels of acetylcholine and acetylcholine-related enzymes, including choline acetyltransferase (ChAT) and acetylcholinesterase (AChE), in the gastric antrum and jejunum. C-kit level and smooth muscle contraction-related genes were elevated by WDJ-S4 in both the gastric antrum and jejunum.</p><p><strong>Conclusion: </strong>Overall, WDJ-S4 can effectively promote GI motility. The efficacy is associated with modulation of acetylcholine pathway and the interstitial cells of Cajal (ICCs) activation. All the results provide scientific evidence supporting the clinical usage of WDJ-S4 for FD.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"218-228"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11986872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144028097","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":"Yiqi Wenyang decoction protects against the development of atherosclerosis by inhibiting vascular inflammation.","authors":"Shuang Hua, Lingling Sun, Han Zhang, Chiwen Shiu, Shujie Zhang, Yao Zhu, Xingqun Yan, Ping Gu, Zhe Huang, Weimin Jiang","doi":"10.1080/13880209.2025.2492650","DOIUrl":"https://doi.org/10.1080/13880209.2025.2492650","url":null,"abstract":"<p><strong>Context: </strong>Vascular inflammation is a key process in the pathogenesis of atherosclerosis, which is regulated by NF-κB pathway. Yiqi Wenyang decoction (YQWY), a Traditional Chinese medicine (TCM) formula, has anti-inflammatory properties and may inhibit this pathway, potentially offering anti-atherosclerotic effects.</p><p><strong>Objective: </strong>The purpose of this study is to investigate the effects of YQWY on atherosclerosis and the underlying mechanism. Materials and methods: ApoE^-/- mice were fed a Western diet and administered with YQWY (low or high dose), atorvastatin, or vehicle for 13 weeks. The size of atherosclerotic plaques was assessed using ORO staining. Vascular inflammation was evaluated with IF or IHC staining. The mechanisms and signaling pathways underlying the effect of YQWY on vasculature were studied using transcriptomic analysis and were validated <i>in vitro</i> in endothelial cells and macrophages.</p><p><strong>Results: </strong>YQWY attenuated atherosclerotic plaque development which was associated with reduced vascular inflammation as demonstrated by transcriptomic analysis of aorta. This was verified by reduced expression of proinflammatory chemokines, adhesion molecules, and inflammatory cytokines in aortas from YQWY-treated mice at both mRNA and protein levels. Mechanistically, YQWY suppressed NF-κB activation in endothelial cells and, to a lesser extent, macrophages possibly.</p><p><strong>Discussion and conclusions: </strong>YQWY protects against vascular inflammation and atherosclerosis by suppressing NF-κB pathway, suggesting the potential of YQWY and its active ingredients as novel anti-atherosclerotic therapeutics.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"264-274"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12010649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144010614","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":"Integrated pharmacoanalysis, bioinformatics analysis, and experimental validation to identify the ingredients and mechanisms of Xiao-Luo-Wan in uterine fibroids treatment.","authors":"Yonghui Yu, Haojun Zhang, Fang Yang, Hong Liu","doi":"10.1080/13880209.2025.2485905","DOIUrl":"https://doi.org/10.1080/13880209.2025.2485905","url":null,"abstract":"<p><strong>Context: </strong>Xiao-Luo-Wan (XLW), a classical prescription in traditional Chinese medicine, has therapeutic effects on uterine fibroids (UFs). Herein, its anti-UF effects were examined using a systematic pharmacological method.</p><p><strong>Objective: </strong>To explore the active ingredients of XLW <i>via</i> mass spectrometry and its potential effects on UFs by network pharmacology, molecular docking, and experimental validation.</p><p><strong>Materials and methods: </strong>A mass spectrometer was used to scrutinize the composition of the XLW drug-containing serum. The critical targets and potential mechanisms of XLW against UFs were predicted by network pharmacology and molecular docking. Next, human uterine leiomyoma cells (UMCs) were treated with 20%, 30%, or 40% XLW serum for 24 h, 48 h or 72 h. Cell viability was analyzed <i>via</i> a CCK-8 assay, and cell apoptosis and the cell cycle were examined <i>via</i> flow cytometry. The predicted targets were further identified by RT-PCR and western blotting.</p><p><strong>Results: </strong>There were 16 chemical components identified in XLW drug-containing serum, with 53 target genes predicated in the treatment of UFs. The molecular binding of core targets, including TRIM9, NF-κB and p38MAPK, was relatively stable to components, especially buergerinin B, cedrol and ent-15B-16-epoxy- kauan-17-ol. The <i>in vitro</i> experiments revealed that the IC₅₀ of XLW in UMCs was 63.21%, and the anti-UF effects of XLW may be closely associated with targets that inhibit cell proliferation and promote cell apoptosis by regulating TRIM9, NF-κB and p38MAPK expression.</p><p><strong>Discussion and conclusions: </strong>The integration of mass spectrometry, network pharmacology, molecular docking and biological experiments revealed the key constituents of XLW and its pharmacological mechanism in UFs, which may help in the discovery of therapeutic agents for treating UFs.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"201-217"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11999358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993849","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":"Antidepressant activity of flavones from traditional Chinese medicine: a meta-analysis.","authors":"Qing Wang, Youyuan Lu, Xue Mi, Caiyan Yang, Wei Ma, Changbo Xia, Hanqing Wang","doi":"10.1080/13880209.2025.2467374","DOIUrl":"10.1080/13880209.2025.2467374","url":null,"abstract":"<p><strong>Context: </strong>Flavones, the key active components in Traditional Chinese Medicine (TCM), have demonstrated antidepressant activity. Given the numerous animal studies conducted, a systematic analysis is essential to provide a valuable reference for future research.</p><p><strong>Object: </strong>This study investigated the antidepressant activity of flavones based on animal models and summarized the underlying mechanisms.</p><p><strong>Methods: </strong>We systematically searched 7 bibliographic Databases as of August 12, 2023, such as Web of Science, PubMed, China National Knowledge Infrastructure, etc. The meta-analysis was performed using either the random or fixed-effect model, supplemented by trial sequential analysis (TSA). The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach was used to assess the quality of evidence.</p><p><strong>Results: </strong>A total of 25 studies involving 458 mice were included, identifying five flavones (baicalin, baicalein, apigenin, luteolin, vitexin) with antidepressant activity. Compared to the control group, flavones significantly reduced immobility time in forced swimming and tail suspension tests. Flavones also decreased serum and hippocampal levels of interleukin (IL)-1β and tumor necrosis factor-alpha (TNF-α), reduced nuclear factor kappa B (NF-κB) levels, and increased brain-derived neurotrophic factor (BDNF) levels. Relative to the positive group, flavones raised IL-6, sucrose preference rate, and corticosterone (CORT) levels, with no significant differences in other factors. The TSA showed the efficacy of flavones for treating depression with adequate 'information size' for the primary outcome.</p><p><strong>Conclusions: </strong>The results demonstrate that flavones exert protective effects against depression in mice, primarily by stimulating neurotrophic factors and modulating inflammatory pathways. These findings emphasize their potential as promising candidates for the development of novel antidepressant therapies.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"156-169"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11864034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493085","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":"Hyaluronic acid-engineered milk extracellular vesicles to target triple negative breast cancer through CD44.","authors":"Filipa A Soares, Beatriz Salinas, Salette Reis, Cláudia Nunes","doi":"10.1080/13880209.2025.2511807","DOIUrl":"10.1080/13880209.2025.2511807","url":null,"abstract":"<p><strong>Context: </strong>Cancer therapy remains a challenge in healthcare, particularly in the context of triple-negative breast cancer (TNBC), where targeted therapies are still scarce.</p><p><strong>Objective: </strong>Addressing this issue, our study explores a novel targeting approach using small extracellular vesicles (sEVs) isolated from cow milk, functionalized with hyaluronic acid (HA) to target the overexpressed cluster of differentiation 44 (CD44) cell surface receptor in TNBC cells.</p><p><strong>Materials & methods: </strong>A method for isolating sEVs from cow milk was optimized, and the obtained sEVs were fully characterized in terms of size, morphology, and protein markers. Subsequently, milk-derived sEVs were covalently bound with HA of varying molecular weights (MW, 20-60 kDa, 250 kDa, 1000-1600 kDa) and binding and internalization dynamics were investigated. Breast cancer cell lines, MDA-MB-231 (TNBC and CD44+) and MCF-7 (CD44-), were used as <i>in vitro</i> models to evaluate CD44 selectivity.</p><p><strong>Results: </strong>The binding and internalization studies unveiled enhanced selectivity of functionalized sEVs for CD44-overexpressing cells compared to non-functionalized sEVs. Notably, higher MW HA exhibited enhanced binding capacity, with partial internalization occurring through CD44 endocytic mechanisms.</p><p><strong>Discussion and conclusion: </strong>In summary, this work introduces a sEVs isolation method and sheds light on the role of HA MW in enhancing cellular uptake of CD44 overexpressing cancer cells.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"411-427"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12143002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144226186","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":"Wen-Shen-Tong-Luo-Zhi-Tong Decoction alleviates bone loss in aged mice by suppressing LONP1-mediated macrophage senescence.","authors":"Qinfeng Zhou, Kaixuan Wang, Cong Wang, Xiaoxian Sun, Lining Wang, Jie Sun, Yalan Pan, Muzhe Li, Zitong Zhao, Shijie Zhou, Qing Wang, Yafeng Zhang, Yong Ma, Yang Guo","doi":"10.1080/13880209.2025.2537125","DOIUrl":"10.1080/13880209.2025.2537125","url":null,"abstract":"<p><strong>Context: </strong>Aging leads to senile osteoporosis (SOP), marked by bone loss and increased fracture risk. Macrophages, as active immune cells in bone tissue, play an important role in osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) during aging. Wen-Shen-Tong-Luo-Zhi-Tong Decoction (WSTLZTD), a traditional Chinese herbal formula, has been clinically validated for its efficacy in treating SOP. However, the specific mechanisms by which WSTLZTD exerts its anti-SOP effects-particularly through modulating macrophage senescence-remain unclear.</p><p><strong>Objective: </strong>The study aims to elucidate the role of WSTLZTD in macrophage senescence and SOP.</p><p><strong>Materials and methods: </strong>Aged mice received low, medium, high-dose WSTLZTD. Bone loss was evaluated via micro-computed tomography, hematoxylin and eosin staining and osteocalcin, tartrate-resistant acid phosphatase marker analysis. Macrophage senescence detection (β-galactosidase staining, p16, p21) and molecular mechanisms by Western blot, immunohistochemistry, immunofluorescence method were investigated. Macrophage-conditioned medium's effects on BMSC osteogenesis and mitochondrial function were assessed through alkaline phosphatase, Alizarin Red S staining, reactive oxygen species and JC-1 mitochondrial membrane potential (ΔΨm) assays.</p><p><strong>Results: </strong><i>In vivo</i> experiments demonstrated that WSTLZTD effectively ameliorated macrophage senescence and osteoporosis in naturally aged mice. Mechanistically, high-dose WSTLZTD attenuated senescence in bone marrow-derived macrophages by mediating LONP1, concurrently suppressing the cyclic GMP-AMP synthase (cGAS)/STING signaling pathway in BMSCs, thereby enhancing osteogenic differentiation of BMSCs. <i>In vitro</i> studies further confirmed that WSTLZTD-containing serum attenuated the senescent phenotype of macrophages. Notably, the LONP1 inhibitor, LONP1-IN-2, was found to diminish the anti-senescence effects of WSTLZTD on macrophages and BMSC osteogenesis.</p><p><strong>Discussion and conclusion: </strong>WSTLZTD potentially modulate macrophage senescence via LONP1, which subsequently suppresses the activation of the cGAS/STING pathway in BMSCs, ultimately promoting their osteogenic differentiation and ameliorating osteoporosis.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"524-548"},"PeriodicalIF":4.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12305870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732706","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}