Pharmaceuticals最新文献

{"title":"Site-Specific Microparticle Inhalation Therapy: A New Approach to Nasopharyngeal Symptoms.","authors":"Eride Quarta, Fabio Sonvico, Ignazio La Mantia, Antonio Varricchio, Lucia Gloria, Massimiliano Minale, Niccola Funel, Francesca Buttini, Attilio Varricchio","doi":"10.3390/ph18091393","DOIUrl":"10.3390/ph18091393","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Inhalable Microparticles (IMPs) are part of a currently invading field of medicine. In fact, the anatomical district of Rhinopharynx represents a bed for many different pathologies and infections, where the dimension of drug aerosol Microparticles (MPs) represents a discriminating factor to success therapy. The aims of the present work are to demonstrate the efficacy of a new device and its aerosol reproducibility in the nebulization of suspensions to be deposited in the retropharynx. <b>Materials and Methods:</b> The Low-Angle Laser Light Scattering (LALLS) method was used to evaluate both the dimension and distribution of MPs. Six different APIs, used usually in Rhinopharynx pathology, were compared in order to investigate the dimension of MP emissions using four different devices. The results of a retrospective study including 74 subjects treated with standard therapy (ST) and the inhalation of nebulized Sobrerol (NS) were performed. Data regarding the persistence of clinical symptoms (i.e., cough and nasal constipation) were acquired. <b>Results:</b> No significant statistical differences among all the products tested (<i>p</i> > 0.05) were found. One device, Rinubes, demonstrated efficacy and robustness in the fine nebulization of all the pharmaceutical products analyzed. Rinubes delivered an aerosol cloud with significantly lower MMD (66.3 µm) than Mad Nasal and Spray-sol (142.1 and 116.0 µm, respectively), which would allow a higher fraction of drugs to be deposited in the retropharynx. The retrospective clinical study revealed that NS treatment showed higher odds of cough resolution (OR 9.18; <i>p</i> < 0.001) with respect to control ST and showed higher odds of nasal symptom resolution (OR 6.7; <i>p</i> = 0.043). <b>Conclusions:</b> Improved techniques for the administration of inhalable MPs (INPAD) represent significant progress in overcoming the biological and the anatomical barriers in controlling drug release at a specific site. The challenges of nasopharyngeal pathologies offer promising opportunities for the development of non-invasive drug delivery.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177703","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":"Mesoporous Silica Nanoparticles as Drug Delivery Systems.","authors":"Flórián Benkő, Katalin Kristó, Tamás Sovány","doi":"10.3390/ph18091392","DOIUrl":"10.3390/ph18091392","url":null,"abstract":"<p><p>Mesoporous silica nanocarriers (MSNs) have emerged as significant candidates in the pharmaceutical industry for drug delivery systems, suitable for a wide variety of drugs. Absorbing the active pharmaceutical ingredients (APIs) into the pores can be beneficial in several ways. The narrow pores may stabilize the APIs in an amorphous state, thereby improving its aqueous solubility and providing protection for the encapsulated drug against various factors in the human body, including enzymatic or chemical degradation, which enhances the bioavailability of the product. Beside the overview of their main characteristics, the present review focuses on the recent findings on MSNs form therapeutic and drug formulation perspective, including functionalization possibilities, as the size and surface of the particles influence the interactions with the cell membrane; therefore, the epithelial permeability of and release rate from the carrier, and may offer even targeted delivery in an organ-, tissue- or cell-specific manner, improving the therapy, also avoiding drug-related side effects.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177581","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":"PROTACs and Glues: Striking Perspectives for Engineering Cancer Therapy À La Carte.","authors":"Jean-Marc Ferrero, Jocelyn Gal, Baharia Mograbi, Gérard Milano","doi":"10.3390/ph18091397","DOIUrl":"10.3390/ph18091397","url":null,"abstract":"<p><p>PROTACs are bifunctional small molecules that simultaneously bind a target protein and a component of the ubiquitin-proteasome system, thereby inducing selective degradation of the target. They represent a class of compounds capable of achieving the complete elimination of disease-relevant proteins. Molecular glues, by contrast, enhance existing surface complementarity between an E3 ligase and a target protein, promoting its ubiquitination and subsequent degradation. Both approaches are at the forefront of current efforts to overcome the long-standing challenge of undruggable tumor targets. In this context, AI-based strategies offer a powerful means to accelerate the discovery, optimization, and production of highly selective protein binders, streamlining access to potent degraders and maximizing therapeutic potential. These capabilities open new horizons for targeting a wide spectrum of previously inaccessible molecular pathways involved in cancer progression. Altogether, these advances position PROTACs and molecular glues as transformative agents for personalized oncology, particularly within the emerging paradigm of molecular tumor boards, where tailored therapeutic decisions and tumor-adapted drugs could be made rapidly accessible for a given patient.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177624","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":"Survival and Radiotherapy-Related Adverse Events in Patients Receiving Radiotherapy and Concurrent Metformin: A Systematic Review and Meta-Analysis of Randomised Controlled Trials and Cohort Studies.","authors":"Wan-Chuen Liao, Hala Shokr, Corinne Faivre-Finn, Clare Dempsey, Kaye Janine Williams, Li-Chia Chen","doi":"10.3390/ph18091390","DOIUrl":"10.3390/ph18091390","url":null,"abstract":"<p><p><b>Background</b>: It remains unclear whether metformin, a widely used antidiabetic medication, has any influence on the survival outcomes or treatment-related toxicities of radiotherapy in cancer patients. Given metformin's potential anti-cancer properties, including its ability to inhibit tumour growth through the modulation of cellular metabolism and enhancement of radiosensitivity, its impact on radiotherapy outcomes warrants thorough investigation. This study aimed to evaluate the impact of metformin on survival and adverse events among cancer patients receiving radiotherapy. <b>Methods</b>: Database searches were conducted in MEDLINE, EMBASE, Web of Science, Scopus, and PubMed (2000-2025) to retrieve studies of adults with cancer treated with radiotherapy and concurrent metformin. Metformin users were compared with non-users. The pooled overall survival rate was presented in terms of odds ratio (OR) and 95% confidence interval (95%CI). Diabetic subgroup analyses and meta-regression by cancer type were conducted. ORs and 95%CIs of radiotherapy-related adverse events were presented by cancer type. <b>Results</b>: This study identified 25 articles. The pooled overall survival rate showed no significant difference between metformin users and non-users across subgroups (ORs: 1.00-1.77). Conflicting survival trends were observed for prostate, oesophageal, and non-small cell lung cancer across diabetic conditions. Metformin users with breast cancer exhibited a significantly lower risk of heart failure (OR: 0.72; 95%CI: 0.56-0.94) and heart events (OR: 0.72; 95%CI: 0.59-0.88). <b>Conclusions</b>: Metformin did not significantly impact overall survival but may reduce heart-related adverse events in breast cancer patients based on limited data. Further research is needed on cancer types and diabetic conditions.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177672","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":"Herbal Medicine and Lifestyle Modifications for People with Obesity: A Single-Center, Retrospective, Observational Study.","authors":"Minwoo Bang, Suyong Shin, Jungsang Kim, Minwhee Kang, Donghun Lee, Junho Kim, Chunghee Kim, Jiyoung Son, Seungyeon Choi, Seonghyeon Jeon, Dasol Park, Byungsoo Kang, Jungtae Leem","doi":"10.3390/ph18091396","DOIUrl":"10.3390/ph18091396","url":null,"abstract":"<p><p><b>Objectives</b>: Conventional Western treatments for obesity are associated with various adverse events (AEs). This study aimed to determine the treatment response and safety assessment of an integrative Korean medicine treatment (IKMT), consisting of herbal medicine (HM) and lifestyle modification (LM), for weight loss (WL) in people with obesity. <b>Methods</b>: The electronic medical records of outpatients from July 2021 to May 2023 at a Daeat Korean medicine clinic in Seoul were retrospectively reviewed. A total of 3161 patients were evaluated using bioelectrical impedance analysis (BIA) and blood pressure (BP) index. Moreover, the treatment response to IKMT in the 24 best cases (WL within BMI < 23 kg/m²) was evaluated using BIA and BP index, and the safety profile was determined by analyzing AEs. <b>Results</b>: The mean age was 38.2 ± 11.39 years, and the mean duration of treatment was 142.62 ± 104.92 days (approximately 20 weeks). The mean WL was 8.02 ± 6.67 kg (change from the baseline, 8.71%). Of the 3161 participants, 2146 had a WL of ≥5%. The best-case subgroup (<i>n</i> = 24; age 36.54 ± 11.64 years) achieved 23.02 ± 4.07 kg WL and reached BMIs < 23 kg/m² in 7.83 ± 2.54 months; among those with BP indices available (<i>n</i> = 21), reductions were statistically significant. In this subgroup, the mean treatment duration was 8.71 ± 2.46 months (range, 5-15), exceeding the 6-month safety guideline for Ephedrae Herba-containing HM, and no serious AEs were observed. At the 7-month follow-up, 11 patients maintained a statistically significant WL. <b>Conclusions</b>: This is the first Korean study to apply the professional collaboration of IKMT and dietician-led LM to people with obesity. IKMT combined with LM appears to be a safe and effective approach for obesity management. Prospective studies are needed to confirm these findings and establish standardized treatment protocols.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177690","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":"Baicalin-Myricetin-Coated Selenium Nanoparticles Mitigate Pathology in an Aβ1-42 Mice Model of Alzheimer's Disease.","authors":"Rosa Martha Pérez Gutiérrez, Julio Téllez Gómez, José María Mota Flores, Mónica Corea Téllez, Alethia Muñiz Ramírez","doi":"10.3390/ph18091391","DOIUrl":"10.3390/ph18091391","url":null,"abstract":"<p><p><b>Background</b>: Current Alzheimer's disease (AD) treatments primarily focus on symptom management and offer limited potential to arrest disease progression. To address this limitation, we developed baicalin-myricetin (BM) functionalized selenium nanoparticles (SeNPs), termed BMSe@BSA, aimed at multi-targeted neuroprotection. <b>Materials and Methods</b>: BMSe@BSA nanoparticles were synthesized via a gel-sol technique using bovine serum albumin (BSA), ascorbic acid, selenous acid, and BM. Interactions among BSA, BM, and SeNPs were characterized by microscopy and spectrometry. Cytotoxicity was assessed on RAW 264.7 and PC12 cells to determine biocompatibility. Neuroinflammation and cognitive function were evaluated in C57BL6/J mice challenged with Aβ1-42. Recognition memory was tested through open-field exploration, novel object recognition (NOR), and T-maze assays. Inflammatory markers (IL-1β and TNF-α) and microglial changes in the cerebral cortex were quantified, while amyloid fibril morphology was assessed using atomic force microscopy (AFM). <b>Results</b>: Spectroscopic analysis verified successful BM functionalization. Transmission electron microscopy revealed a spherical morphology with an average particle size of 90.57 nm, zeta potential of 27.2 mV, and a polydispersity index (PDI) of 0.270. BM entrapment efficiency reached approximately 90%. Cytotoxicity assays confirmed the nanoparticles' safety, with no toxicity observed at concentrations up to 400 µg/mL after 4 h of incubation. BMSe@BSA effectively inhibited amyloid fibril formation, downregulated pro-inflammatory cytokine expression, preserved neuronal integrity, and significantly enhanced cognitive performance in AD mouse models. Conclusion: BMSe@BSA appear as a potential nanotherapeutic approach for targeted brain delivery and multi-pathway intervention in Alzheimer's disease.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177422","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":"Design, Synthesis, and Biological Evaluation of Novel Multitarget 7-Alcoxyamino-3-(1,2,3-triazole)-coumarins as Potent Acetylcholinesterase Inhibitors.","authors":"Nathalia F Nadur, Larissa de A P Ferreira, Daiana P Franco, Luciana L de Azevedo, Lucas Caruso, Thiago da S Honório, Priscila de S Furtado, Alice Simon, Lucio M Cabral, Tobias Werner, Holger Stark, Arthur E Kümmerle","doi":"10.3390/ph18091398","DOIUrl":"10.3390/ph18091398","url":null,"abstract":"<p><p><b>Background</b>: Multitarget-directed ligands (MTDLs), particularly those combining cholinesterase inhibition with additional mechanisms, are promising candidates for Alzheimer's disease (AD) therapy. Based on our previous identification of a dual-active coumarin derivative, we designed a new series of 7-alkoxyamino-3-(1,2,3-triazole)-coumarins. <b>Methods</b>: These compounds were synthesized by a new Sonogashira protocol and evaluated for AChE and BChE inhibition, enzymatic kinetics, molecular docking, neurotoxicity in SH-SY5Y cells, neuroprotection against H₂O₂-induced oxidative stress, and additional interactions with H₃R and MAOs. <b>Results</b>: All derivatives inhibited AChE with IC₅₀ values of 4-104 nM, displaying high selectivity over BChE (up to 686-fold). Kinetic and docking studies indicated mixed-type inhibition involving both CAS and PAS. The most potent compounds (<b>1h</b>, <b>1j</b>, <b>1k</b>, <b>1q</b>) were non-neurotoxic up to 50 µM, while <b>1h</b> and <b>1k</b> also showed neuroprotective effects at 12.5 µM. Selected derivatives (<b>1b</b>, <b>1h</b>, <b>1q</b>) demonstrated multitarget potential, including H₃R affinity (K_i as low as 32 nM for <b>1b</b>) and MAO inhibition (IC₅₀ of 1688 nM for <b>1q</b>). <b>Conclusions</b>: This series of coumarin-triazole derivatives combines potent and selective AChE inhibition with neuroprotective and multitarget activities, highlighting their promise as candidates for AD therapy.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177733","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":"Puerarin Inhibits Proliferation, Migration and Invasion of Colon Cancer Cells and Induces Apoptosis via Suppression of the PI3K/AKT Signaling Pathway.","authors":"Lin Chen, Xuhong Li, Shijie Zhao, Mengyu Hao, Heng Wang, Zhi Zhou, Xinyu Xiong, Die Yuan, Piao Luo, Luwen Wang, Di Pan, Xiangchun Shen, Yue Zhang, Yan Chen","doi":"10.3390/ph18091378","DOIUrl":"10.3390/ph18091378","url":null,"abstract":"<p><p><b>Background</b>: Colon cancer is one of the most prevalent gastrointestinal malignancies worldwide, with high mortality and limited therapeutic options. Puerarin, a flavonoid compound derived from <i>Pueraria lobata</i>, has shown anticancer potential, but its molecular mechanisms against colon cancer remain unclear. <b>Methods and Results</b>: In this study, human colon cancer Caco-2 cells were treated with various concentrations of puerarin. Cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and apoptosis were evaluated using CCK-8, wound healing, Transwell, immunofluorescence, flow cytometry, and Western blot assays. Puerarin significantly inhibited Caco-2 cell proliferation in a dose- and time-dependent manner. It suppressed migration and invasion by increasing E-cadherin and reducing Vimentin expression. Apoptosis was induced via upregulation of BAX and downregulation of Bcl-2. Network pharmacology and KEGG analysis suggested PI3K/AKT signaling as a core regulatory pathway. Western blotting confirmed that puerarin reduced phosphorylation of PI3K and AKT. PI3K activator 740 Y-P promoted EMT and inhibited apoptosis, whereas puerarin and the PI3K inhibitor LY294002 reversed these effects. <b>Conclusions</b>: Puerarin exerts significant antitumor effects on Caco-2 colon cancer cells by inhibiting proliferation, migration, and EMT, while promoting apoptosis. These effects are mediated primarily through suppression of the PI3K/AKT signaling pathway. This study provides a theoretical basis for the use of puerarin as a natural therapeutic agent in colon cancer treatment.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177573","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":"Lipoprotein(a)/CD36 Interaction Drives IL-6/RhoA-GTP Signaling and miRNA Epigenetic Regulation in Coronary Artery Spasm.","authors":"Yen-Kuang Lin, Tsung-Han Hsieh, Chi-Tai Yeh, Vijesh Kumar Yadav, Iat-Hang Fong, Kuang-Tai Kuo, Nicholas G Kounis, Patrick Hu, Ming-Yow Hung","doi":"10.3390/ph18091384","DOIUrl":"10.3390/ph18091384","url":null,"abstract":"<p><p><b>Background:</b> Lipoprotein(a) [Lp(a)]-induced inflammation contributes to coronary artery spasm (CAS) by the contraction of vascular smooth muscle cells. However, the interaction between Lp(a) and soluble CD36 (sCD36)/interleukin (IL)-6/RAS Homolog Family Member A (RhoA)-GTP signaling pathway has not been evaluated. <b>Methods:</b> We investigated the relevance of Lp(a)/CD36 signaling in CAS patient monocyte-derived macrophages (PMDMs) and a human coronary artery smooth muscle cell (HCASMC) line using expression profile correlation analyses, molecular docking, RNA sequencing, flow cytometry, immunoblotting, and quantitative reverse transcription polymerase chain reaction. <b>Results:</b> Plasma Lp(a) and sCD36 levels in 41 CAS patients were significantly higher (<i>p</i> = 0.001) and positively correlated (r² = 0.3145, <i>p</i> < 0.001), a trend not observed in 36 non-CAS controls. RNA sequencing indicated a significant co-overexpression of CD36 and RhoA in Lp(a)-treated CAS PMDMs and HCASMCs, of which the mRNA and protein expression of CD36 and RhoA were significantly enhanced (<i>p</i> < 0.001) dose-dependently. Lp(a) rather than LDL preferentially induced CD80+ PMDM (M1) polarization. In HCASMCs, the CD36 knockdown using either short hairpin RNA or natural biflavonoid amentoflavone suppressed Lp(a)-upregulated protein expression of CD36, RhoA-GTP, IL-6, tumor necrosis factor (TNF)-α, nuclear factor (NF)-κB, and CD80; however, overexpressed CD36 increased their levels. Lp(a) decreased and amentoflavone increased the epigenetic expression of CD36 inhibitors, miR-335-5p, and miR-448, respectively. Reciprocally, an miRNA inhibitor or mimic could magnify or diminish Lp(a)-induced CD36, TNF-α, NF-κB and IL-6 expressions in HCASMCs, respectively. <b>Conclusions:</b> Elevated Lp(a) levels upregulate the CD36-dependent TNF-α/NF-κB/IL-6/RhoA-GTP signaling pathway in CAS PMDMs and HCASMCs, indicating that Lp(a)/CD36 inflammatory signaling, HCASMC activation, and macrophage M1 polarization mediate CAS development.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177662","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 Senotherapeutic Effects of APPA (Apocynin [AP] and Paeonol [PA]) on Senescent Human Chondrocytes.","authors":"Mercedes Fernández-Moreno, Tamara Hermida-Gómez, Carlos Vaamonde-Garcia, Sara Paniagua-Barro, Nicholas Larkins, Alan Reynolds, Francisco J Blanco","doi":"10.3390/ph18091386","DOIUrl":"10.3390/ph18091386","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Osteoarthritis (OA) is a complex joint disease involving chronic inflammation, aging, and obesity, affecting nearly 6 million people worldwide. Senescent cells in OA are linked to increased inflammation, oxidative stress, and DNA damage, making them potential therapeutic targets. APPA, a combination of apocynin (AP) and paeonol (PA), has shown anti-inflammatory and antioxidant properties. This study evaluated the effects of APPA on cellular senescence in human articular chondrocytes. <b>Methods</b>: Using a chondrocyte cell line (T/C-28a2) and primary human chondrocytes, senescence was induced with etoposide and Oncostatin M (Eto + OSM), followed by treatment with APPA, AP, or PA. Senescence markers (SA-β-gal, <i>P21</i>_<i>CDKN1A</i>_), apoptosis, proliferation (Ki67), and rps6 protein levels were analyzed. <b>Results</b>: APPA significantly reduced SA-β-gal activity and <i>p21</i> expression in cell model-effects not replicated by AP or PA alone. APPA increased early apoptosis and dual-labeled senescent-apoptotic cells, along with total cell numbers and rps6 levels. It also altered Ki67 expression in different cell subpopulations, suggesting effects on proliferation. <b>Conclusions</b>: This study suggests that APPA exerts senotherapeutic effects on human senescent chondrocytes. A reduction in SA-β-gal together with an increase in cell numbers and the proliferation marker Ki67 suggests possible senomorphic effects, whereas a reduction in SA-β-Gal accompanied by an increase in apoptosis indicates senolytic activity. These findings support recent evidence that the distinction between senolytic and senomorphic agents is 'fuzzy'.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177337","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}