European journal of pharmacology最新文献

{"title":"Exploring 4th generation EGFR inhibitors: A review of clinical outcomes and structural binding insights","authors":"Amina Tariq ,&nbsp;Muhammad Shoaib ,&nbsp;Lingbo Qu ,&nbsp;Sana Shoukat ,&nbsp;Xiaofei Nan ,&nbsp;Jinshuai Song","doi":"10.1016/j.ejphar.2025.177608","DOIUrl":"10.1016/j.ejphar.2025.177608","url":null,"abstract":"<div><div>Epidermal growth factor receptor (EGFR) is a potential target for anticancer therapies and plays a crucial role in cell growth, survival, and metastasis. EGFR gene mutations trigger aberrant signaling, leading to non-small cell lung cancer (NSCLC). Tyrosine kinase inhibitors (TKIs) effectively target these mutations to treat NSCLC. While the first three generations of EGFR TKIs have been proven effective, the emergence of the EGFR-C797S resistance mutation poses a new challenge. To address this, various synthetic EGFR TKIs have been developed. In this review, we have summarized the EGFR TKIs reported in the past five years, focusing on their clinical outcomes and structure-activity relationship analysis. We have also explored binding modes and interactions between the binding pocket and ligands to provide insights into the mechanisms of these inhibitors, which contribute to advancements in targeted cancer therapy. Additionally, artificial Intelligence-driven methods, including recursive neural networks and reinforcement learning, have revolutionized EGFR inhibitor design by facilitating rapid screening, predicting EGFR mutations, and novel compound generation.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"997 ","pages":"Article 177608"},"PeriodicalIF":4.2,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143828953","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":"Harnessing marine resources for Alzheimer's therapy: A review integrating bioactivity and molecular docking","authors":"Hina Khalid ,&nbsp;Hassan Mohamed ,&nbsp;Adel Eltoukhy ,&nbsp;Muhammad Tariq Saeed ,&nbsp;Yuanda Song","doi":"10.1016/j.ejphar.2025.177611","DOIUrl":"10.1016/j.ejphar.2025.177611","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is a neurodegenerative condition resulting in cognitive impairment and the formation of neurofibrillary tangles and plaques in the brain. The drivers of AD's molecular progression and pathology include the accumulation of amyloid β protein (Aβ); thus, Aβ is an intervention target. However, the limitations in clinical trials of Aβ-targeted medicine and the failure to intervene in disease progression have raised concerns about the use of this drug and its veracious route. In particular, we comprehensively reviewed the potential effect of marine compounds and the mechanism of isolation and extraction from marine organisms resulting in the optimization of AD treatment. Furthermore, the hub compounds were docked with Beta-secretase receptors to strengthen the extrapolation of mechanistic interactions thus inhibiting the activity of an enzyme. An extensive review revealed that marine aquaculture and its byproducts are a promising source and isolated with green methods or less investment, ensuring their sustainability. MNPs harbor specific pharmacological features that enable them to exert neuroprotective effects by minimizing events such as Aβ peptide formation and reactive oxygen species (ROS) generation.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"997 ","pages":"Article 177611"},"PeriodicalIF":4.2,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143839118","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":"Effects of fluoxetine on the gene expression of hippocampus and gap inhibition in noise-induced hearing loss rats","authors":"Sujin Choi ,&nbsp;Hyun-Ju An ,&nbsp;Hyunjeong Yeo ,&nbsp;Soonchul Lee ,&nbsp;So Young Kim","doi":"10.1016/j.ejphar.2025.177565","DOIUrl":"10.1016/j.ejphar.2025.177565","url":null,"abstract":"<div><h3>Objective</h3><div>Fluoxetine was reported to restore critical period-like neural plasticity via alleviating perineuronal nets (PNNs). This study aimed to investigate the effect of fluoxetine on auditory processing and PNNs in auditory cortex and hippocampus.</div></div><div><h3>Methods</h3><div>Sprague-Dawley rats were exposed 2–20 kHz, 115 dB sound pressure level noise for 3 h per day from postnatal day 1–3 to postnatal day 21. After completion of noise exposure, 10 mg/kg/day of fluoxetine was administered for 19 days. There were four groups of rats according to the presence of noise exposure and fluoxetine treatment, vehicle, noise + vehicle, fluoxetine, and noise + fluoxetine rats. The gene expression changes of hippocampus were analyzed using RNA sequencing.</div></div><div><h3>Results</h3><div>In the auditory cortex, the expression of aggrecan (ACAN) was lower in noise-exposed rats than vehicle rats, while the noise + fluoxetine rats presented higher expression levels of ACAN which was comparable with that of the vehicle rats (<em>p</em> = 0.01 in Mann-Whitney <em>U</em> test; 146 ± 15 vs. 100 ± 11). In the hippocampus, the expression of brain-derived neurotrophic factor (BDNF) was lower in noise + vehicle rats while noise + fluoxetine rats presented higher expression of BDNF than noise + vehicle rats (<em>p</em> &lt; 0.001 in Mann-Whitney <em>U</em> test; 389 ± 21 vs. 249 ± 16). The RNA sequencing of the hippocampus predicted the down regulation of genes involving extracellular matrix organization when compared noise + vehicle vs. noise + fluoxetine rats.</div></div><div><h3>Conclusion</h3><div>The fluoxetine administration in noise exposed rats improved the gap inhibition ability. The noise exposure decreased expression of BDNF and modulated the expression of genes related with extracellular matrix organization which was partially reversed after fluoxetine treatment.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"996 ","pages":"Article 177565"},"PeriodicalIF":4.2,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143815925","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":"Neuroprotective effect of Perillyl alcohol in sporadic Alzheimer's disease in rats","authors":"Dolly Chauhan ,&nbsp;Kajal Bagri ,&nbsp;Rahul Deshmukh","doi":"10.1016/j.ejphar.2025.177558","DOIUrl":"10.1016/j.ejphar.2025.177558","url":null,"abstract":"<div><div>As people age, Alzheimer's disease, a neurological disorder that develops gradually, affects their memory and cognitive abilities. The two hallmarks of Alzheimer's disease are intracellular buildup of neurofibrillary tangles and extracellular β-amyloid plaques. In this work, the effects of Perillyl alcohol on experimental sporadic Alzheimer-type dementia produced by intracerebroventricular streptozotocin were investigated. Rats that received streptozotocin infusion experienced cholinergic hypofunction, increased oxidative-nitritive stress, and impaired memory and learning. Between 15 and 27 days following the initial streptozotocin infusion, 13 days of treatment with Perillyl alcohol (25, 50, and 100 mg/kg p.o.) significantly improved learning and memory in Morris water maze and object recognition test paradigms.</div><div>Perillyl also significantly reduced oxidative-nitritive stress, as seen by a decrease in malondialdehyde and nitrite, and restored reduced glutathione and catalase levels. Acetylcholinesterase activity significantly increased in the current model, indicating cholinergic hypofunction and enhanced neuronal cell damage. Treatment with Perillyl alcohol also significantly decreased the increase in acetylcholinesterase activity, indicating that Perillyl alcohol may be able to prevent neuronal damage and restore cholinergic functions. Perillyl alcohol has been shown to improve spatial memory processing, which may be due to its antioxidant properties and capacity to restore cholinergic functioning. However, more study is required to understand the molecular mechanisms of POH that enhance cognition or prevent neurotoxic damage, which could support its application in neuroprotective effect.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"996 ","pages":"Article 177558"},"PeriodicalIF":4.2,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802883","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":"Unveiling EIF5A2: A multifaceted player in cellular regulation, tumorigenesis and drug resistance","authors":"Xifeng Xiong ,&nbsp;Yanli Du ,&nbsp;Peng Liu ,&nbsp;Xinye Li ,&nbsp;Xudong Lai ,&nbsp;Haixiong Miao ,&nbsp;Bo Ning","doi":"10.1016/j.ejphar.2025.177596","DOIUrl":"10.1016/j.ejphar.2025.177596","url":null,"abstract":"<div><div>The eukaryotic initiation factor 5A2 gene (EIF5A2) is a highly conserved and multifunctional gene that significantly influences various cellular processes, including translation elongation, RNA binding, ribosome binding, protein binding and post-translational modifications. Overexpression of EIF5A2 is frequently observed in multiple cancers, where it functions as an oncoprotein. Additionally, EIF5A2 is implicated in drug resistance through the regulation of various molecular pathways. In the review, we describe the structure and functions of EIF5A2 in normal cells and its role in tumorigenesis. We also elucidate the molecular mechanisms associated with EIF5A2 in the context of tumorigenesis and drug resistance. We propose that the biological roles of EIF5A2 in regulating diverse cellular processes and tumorigenesis are clinically significant and warrant further investigation.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"997 ","pages":"Article 177596"},"PeriodicalIF":4.2,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802887","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":"Biostability, in vivo antiviral activity against respiratory syncytial virus, and pharmacokinetic profiles of (−)-borneol esters","authors":"Anastasiya S. Sokolova ,&nbsp;Alina A. Okhina ,&nbsp;Anna A. Shtro ,&nbsp;Artem M. Klabukov ,&nbsp;Anastasia V. Galochkina ,&nbsp;Yulia V. Nikolaeva ,&nbsp;Galina D. Petukhova ,&nbsp;Olga I. Yarovaya ,&nbsp;Artem D. Rogachev ,&nbsp;Dmitriy S. Baev ,&nbsp;Alina V. Fatyanova ,&nbsp;Tatyana G. Tolstikova ,&nbsp;Nariman F. Salakhutdinov","doi":"10.1016/j.ejphar.2025.177567","DOIUrl":"10.1016/j.ejphar.2025.177567","url":null,"abstract":"<div><div>Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract infections, particularly in vulnerable populations such as infants and the elderly. In this study, we evaluated the metabolic stability, <em>in vivo</em> antiviral activity, and pharmacokinetic profiles of (−)-borneol esters, which were identified as potent RSV inhibitors through screening of a compound library. Two hit compounds, ST-2 and AS-645, caused a reduction in viral titers in RSV-infected mice. Intranasal administration of ST-2 proved more effective than oral one and showed enhanced antiviral activity and improved pharmacokinetic properties. Additionally, ST-2 manifested superior metabolic stability in human blood compared to murine and rat blood, suggesting that carboxylesterase activity is a key factor in the hydrolysis resistance. Given that carboxylesterase activity is higher in mouse blood than in human blood, this difference likely contributes to the observed stability of ST-2 in human blood. Molecular modeling confirmed the role of carboxylesterase in the hydrolysis of (−)-borneol esters. These findings suggest that ST-2 has potential for further development of drugs for RSV and other viral infections.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"996 ","pages":"Article 177567"},"PeriodicalIF":4.2,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795044","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":"Eco-friendly nanotherapeutics: Metallic nanoparticles for targeting breast cancer","authors":"Darakhshan Javaid,&nbsp;Shahid Yousuf Ganie,&nbsp;Syed Sanober Qadri,&nbsp;Adfar Reyaz,&nbsp;Mohd Salim Reshi","doi":"10.1016/j.ejphar.2025.177603","DOIUrl":"10.1016/j.ejphar.2025.177603","url":null,"abstract":"<div><div>Breast cancer continues to be a major cause of death among women globally, with triple-negative breast cancer (TNBC) presenting a particularly difficult challenge due to its aggressive behaviour and the lack of effective treatment options. Nanotechnology, particularly the use of silver nanoparticles (AgNPs), has emerged as a promising avenue in oncological research. This review explores into the escalating field of green synthesis of nanoparticles, emphasizing sustainable approaches utilizing plant-based resources. Critical factors influencing nanoparticle synthesis, including reaction conditions, precursor types, and plant phytochemicals, are explored alongside advanced characterization techniques essential for evaluating nanoparticle properties. Special focus is given to the phytofabrication of silver nanoparticles and their multifaceted roles in breast cancer treatment, with detailed insights into their mechanisms, such as inducing apoptosis, generating reactive oxygen species (ROS), and disrupting mitochondrial function, particularly in TNBC cells. The review further highlights the advantages of plant-derived AgNPs, such as biocompatibility and reduced toxicity, while addressing challenges like scalability, reproducibility, and regulatory hurdles. Concluding with future prospects, this paper reflects the potential of green-synthesized AgNPs as a keystone in next-generation cancer therapeutics, paving the way for innovative and eco-friendly approaches in oncology.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"996 ","pages":"Article 177603"},"PeriodicalIF":4.2,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794699","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":"Dipeptidyl peptidase 3 induces myocardial ischemia-reperfusion injury by mediating mitophagy and the intrinsic apoptotic pathway","authors":"Xiao Wang,&nbsp;Yaofeng Xie,&nbsp;Hongjiao Du,&nbsp;Cheng Chang,&nbsp;Chunyang Tian,&nbsp;Yuyao Yin,&nbsp;Xiaodong Li,&nbsp;Yilong Pan","doi":"10.1016/j.ejphar.2025.177592","DOIUrl":"10.1016/j.ejphar.2025.177592","url":null,"abstract":"<div><h3>Background</h3><div>Dipeptidyl peptidase 3 (DPP3) is a zinc-dependent hydrolase that is regarded as a “myocardial inhibitor”. However, the role of DPP3 in myocardial ischemia-reperfusion injury (MIRI) remain to be investigated. The present study aimed to investigate the potential role of DPP3 in MIRI and elucidate the underlying mechanisms.</div></div><div><h3>Methods</h3><div>The AC16 cardiomyocyte cell line was used to investigate the interactions between DPP3 and its protein interactors, and assess its effects on the apoptosis of cardiomyocytes following oxygen glucose deprivation/reperfusion (OGD/R) treatment <em>in vitro</em>. An animal model of ischemia/reperfusion (I/R) injury was established using C57BL/6J mice for <em>in vivo</em> analyses. The role of DPP3 and the underlying mechanisms were investigated both <em>in vitro</em> and <em>in vivo</em> following DPP3 knockdown and overexpression.</div></div><div><h3>Results</h3><div>DPP3 interacted with Parkinson’s disease protein 7 (Park7), and DPP3 overexpression altered the expression levels of proteins related to the intrinsic apoptotic pathway and autophagy. This significantly downregulated the mitochondrial expression of cytochrome C, thereby exacerbating mitochondrial injury and increasing the rate of apoptosis following reperfusion. DPP3 knockdown reversed these effects; however, the simultaneous knockdown of DPP3 and Park7 did not confer the beneficial effects observed with DPP3 knockdown alone. DPP3 knockdown alleviated the extent of myocardial injury and improved cardiac function in the mouse model of I/R injury.</div></div><div><h3>Conclusions</h3><div>The study demonstrated that DPP3 mediates mitophagy and apoptosis in MIRI through its interaction with Park7. These findings have important implications, suggesting that targeting DPP3 and its associated signaling pathways may serve as a potential therapeutic strategy, and that the downregulation of DPP3 can potentially alleviate MIRI.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"997 ","pages":"Article 177592"},"PeriodicalIF":4.2,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794554","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":"The sodium-glucose cotransporter 2 inhibitor tofogliflozin induces vasodilation of rabbit femoral artery by activating Kv channels, the SERCA pump, and the sGC/cGMP pathway","authors":"Wenwen Zhuang ,&nbsp;Minju Park ,&nbsp;Junsu Jeong ,&nbsp;Hye Ryung Kim ,&nbsp;YeEun Jang ,&nbsp;Mi Seon Seo ,&nbsp;Jin Ryeol An ,&nbsp;Hongzoo Park ,&nbsp;Won-Kyo Jung ,&nbsp;Il-Whan Choi ,&nbsp;Won Sun Park","doi":"10.1016/j.ejphar.2025.177595","DOIUrl":"10.1016/j.ejphar.2025.177595","url":null,"abstract":"<div><div>Tofogliflozin is a sodium-glucose cotransporter 2 inhibitor widely used to treat type 2 diabetes mellitus, but it also exhibits cardio-protective effects. This study investigated the vasodilatory action of tofogliflozin using rabbit femoral artery rings pre-contracted with phenylephrine (1 μM). The results showed the concentration-dependent induction of vasodilation by tofogliflozin, a response that remained unchanged following endothelial removal, pretreatment with the nitric oxide synthase inhibitor L-NAME (100 μM), or the inhibition of low- and intermediate-conductance Ca²⁺-activated K⁺ channels using apamin (1 μM) in combination with TRAM-34 (1 μM). Furthermore, pretreatment with the voltage-dependent K⁺ (Kv) channel inhibitor 4-AP (3 mM) reduced the vasodilatory effects of tofogliflozin whereas pretreatment with the ATP-sensitive K⁺ channel inhibitor glibenclamide (10 μM) or the large-conductance Ca²⁺-activated K⁺ channel inhibitor paxilline (1 μM) did not. Notably, our findings indicated that Kv7.X, rather than Kv1.5 or Kv2.1, is the primary Kv subtype involved in tofogliflozin-induced vasodilation. The vasodilatory effects of tofogliflozin were also significantly inhibited in femoral arterial rings pretreated with the sarco/endoplasmic reticulum Ca²⁺-ATPase (SERCA) pump inhibitors thapsigargin (1 μM) and cyclopiazonic acid (10 μM). Tofogliflozin-induced vasodilation was unaltered in arterial rings exposed to the adenylyl cyclase inhibitor SQ 22536 (50 μM), the protein kinase A (PKA) inhibitor KT 5720 (1 μM), and the protein kinase G inhibitor KT 5823 (1 μM) whereas it was effectively reduced by the soluble guanylyl cyclase (sGC) inhibitor ODQ (10 μM). These findings suggest that tofogliflozin-induced vasodilation is mediated by the activation of the SERCA pump, the sGC/cGMP pathway, and Kv channels.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"996 ","pages":"Article 177595"},"PeriodicalIF":4.2,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143792309","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":"Fisetin and resveratrol exhibit senotherapeutic effects and suppress cellular senescence in osteoarthritic cartilage-derived chondrogenic progenitor cells","authors":"Justin Jacob ,&nbsp;Aditya Aggarwal ,&nbsp;Shalmoli Bhattacharyya ,&nbsp;Daisy Sahni ,&nbsp;Vinit Sharma ,&nbsp;Anjali Aggarwal","doi":"10.1016/j.ejphar.2025.177573","DOIUrl":"10.1016/j.ejphar.2025.177573","url":null,"abstract":"<div><div>Chondrogenic progenitor cells (CPCs) in the articular cartilage of knee osteoarthritis (OA) patients exhibit cellular senescence and its associated secretory phenotype (SASP). We hypothesized that the senescence of CPCs can be suppressed using natural compounds. This study aimed to evaluate the senotherapeutic effects of fisetin and resveratrol to suppress the cellular senescence in CPCs. <em>In vitro</em>, pre-treatment of CPCs with increasing doses of fisetin and resveratrol (5μM–100μM) were non-cytotoxic, decreased the senescence index and dampened the expression of cellular senescence markers, p53 and p38MAPK. Additionally, SASP-related genes and proteins (MMP-9, MMP13) and inflammatory mediators (IL-1β, TGF-β, and IL-6) were downregulated. Further, <em>in silico</em> analysis confirmed the high binding affinity of these natural drugs to OA-related proteins. Overall, fisetin and resveratrol dampened the senescence of CPCs by downregulating the p53 effector protein and effectively reducing the SASP. From this study, natural compound candidates proved to be potential drug candidates that suppress senescence via p53.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"997 ","pages":"Article 177573"},"PeriodicalIF":4.2,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794773","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}