Pharmacological research最新文献

{"title":"A theranostic photosensitizer-conjugated albumin co-loading with resiquimod for cancer-targeted imaging and robust photo-immunotherapy: Critical considerations from bench to bedside","authors":"Peng Sheng, Shi Zhou","doi":"10.1016/j.phrs.2025.107673","DOIUrl":"10.1016/j.phrs.2025.107673","url":null,"abstract":"","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"214 ","pages":"Article 107673"},"PeriodicalIF":9.1,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143510427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"USP19 deficiency enhances T-cell-mediated antitumor immunity by promoting PD-L1 degradation in colorectal cancer","authors":"Feng Shi ,&nbsp;Guang-Jing Li ,&nbsp;Yi Liu ,&nbsp;Hai-Meng Zhou ,&nbsp;Yue Zhang ,&nbsp;Si-Yi Wei ,&nbsp;Bo-Jun Zan ,&nbsp;Meng Gao ,&nbsp;Fei-Shan Chen ,&nbsp;Bo-Xin Li ,&nbsp;Bai-Qi Wang ,&nbsp;Ming-You Dong ,&nbsp;Run-Lei Du ,&nbsp;Xiao-Dong Zhang","doi":"10.1016/j.phrs.2025.107668","DOIUrl":"10.1016/j.phrs.2025.107668","url":null,"abstract":"<div><div>Colorectal cancer (CRC) is characterized by a highly immunosuppressive tumor microenvironment, which limits the effectiveness of current immunotherapies. Identifying strategies to overcome this resistance is critical for improving treatment outcomes. In this study, we discovered that USP19 plays a pivotal role in regulating T-cell-mediated antitumor immunity through a CRISPR/Cas9 sgRNA library screen and co-culture assays with activated T cells. We demonstrated that USP19 deficiency significantly enhances the susceptibility to T cell-mediated cytotoxicity in CRC cells, organoids, and mouse models. Transcriptomic sequencing (RNA-seq) revealed activation of the PD-1 pathway in tumor with USP19-deficiency cells. Mechanistic investigations revealed that USP19 directly stabilizes PD-L1 by binding to its intracellular domain and preventing its degradation via K48-linked ubiquitination and proteasomal pathways. Clinically, USP19 expression was found to be significantly elevated in CRC tissues and was positively associated with PD-L1 levels, advanced tumor grade, poor differentiation, and TP53 mutations, highlighting its potential as a biomarker for aggressive CRC. Importantly, in vivo experiments demonstrated that targeting USP19, in combination with αPD-L1 therapy, synergistically suppressed CRC progression. This combination not only reduced PD-L1 levels but also enhanced CD8⁺ T-cell activation and GzmB infiltration, resulting in robust antitumor effects. These findings establish USP19 as a key driver of immune evasion in CRC and suggest that targeting USP19 could enhance the efficacy of immunotherapy, providing a promising new avenue for CRC treatment.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"214 ","pages":"Article 107668"},"PeriodicalIF":9.1,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143512745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The dynamic role of ferroptosis in cancer immunoediting: Implications for immunotherapy","authors":"Jiarui Lan ,&nbsp;Dan Cai ,&nbsp;Shuang Gou ,&nbsp;Yulin Bai ,&nbsp;Huaqing Lei ,&nbsp;Yan Li ,&nbsp;Yu Chen ,&nbsp;Yueshui Zhao ,&nbsp;Jing Shen ,&nbsp;Xu Wu ,&nbsp;Mingxing Li ,&nbsp;Meijuan Chen ,&nbsp;Xiaobing Li ,&nbsp;Yuhong Sun ,&nbsp;Li Gu ,&nbsp;Wanping Li ,&nbsp;Fang Wang ,&nbsp;Chi Hin Cho ,&nbsp;Yan Zhang ,&nbsp;Xin Zheng ,&nbsp;Fukuan Du","doi":"10.1016/j.phrs.2025.107674","DOIUrl":"10.1016/j.phrs.2025.107674","url":null,"abstract":"<div><div>Currently, cancer immunotherapy strategies are primarily formulated based on the patient's present condition, representing a \"static\" treatment approach. However, cancer progression is inherently \"dynamic,\" as the immune environment is not fixed but undergoes continuous changes. This dynamism is characterized by the ongoing interactions between tumor cells and immune cells, which ultimately lead to alterations in the tumor immune microenvironment. This process can be effectively elucidated by the concept of cancer immunoediting, which divides tumor development into three phases: \"elimination,\" \"equilibrium,\" and \"escape.\" Consequently, adjusting immunotherapy regimens based on these distinct phases may enhance patient survival and improve prognosis. Targeting ferroptosis is an emerging area in cancer immunotherapy, and our findings reveal that the antioxidant systems associated with ferroptosis possess dual roles, functioning differently across the three phases of cancer immunoediting. Therefore, this review delve into the dual role of the ferroptosis antioxidant system in tumor development and progression. It also propose immunotherapy strategies targeting ferroptosis at different stages, ultimately aiming to illuminate the significant implications of targeting ferroptosis at various phases for cancer immunotherapy.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"214 ","pages":"Article 107674"},"PeriodicalIF":9.1,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143527523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiac fibroblast-derived mitochondria-enriched sEVs regulate tissue inflammation and ventricular remodeling post-myocardial infarction through NLRP3 pathway","authors":"Yuanyuan Zhao ,&nbsp;Ya Hu ,&nbsp;Yifei Wang ,&nbsp;Hao Qian ,&nbsp;Chenxu Zhu ,&nbsp;Hongjian Dong ,&nbsp;Chunshu Hao ,&nbsp;Yao Zhang ,&nbsp;Zhenjun Ji ,&nbsp;Xinxin Li ,&nbsp;Yue Chen ,&nbsp;Rongfeng Xu ,&nbsp;Jie Jiang ,&nbsp;Hailong Cao ,&nbsp;Genshan Ma ,&nbsp;Lijuan Chen","doi":"10.1016/j.phrs.2025.107676","DOIUrl":"10.1016/j.phrs.2025.107676","url":null,"abstract":"<div><div>Resident cardiac fibroblasts (CFs) play crucial roles in sensing injury signals and regulating inflammatory responses post-myocardial infarction (MI). Damaged mitochondria can be transferred extracellularly via various mechanisms, including extracellular vesicles (EVs). In this study, we aimed to investigate whether CFs could transfer damaged mitochondrial components via small EVs (sEVs) and elucidate their role in regulating inflammatory responses post-MI. Left anterior descending coronary artery ligation was performed in mice. Mitochondrial components in sEVs were detected using nanoflow cytometry. Differential protein expression in sEVs from normoxia and normoglycemia CFs (CFs-Nor-sEVs) and CFs post oxygen-glucose deprivation (CFs-OGD-sEVs) was identified using label-free proteomics. CFs-sEVs were co-cultured with mouse bone marrow-derived macrophages (BMDMs) to assess macrophage inflammatory responses. Effects of intramyocardial injection of CFs-sEVs were assessed in MI mice in the absence or presence of NLRP3 inhibitor CY-09. Results demonstrated that mitochondrial components were detected in CFs-derived sEVs post-MI. Damaged mitochondrial components were enriched in CFs-OGD-sEVs (CFs-mt-sEVs), which promoted pro-inflammatory phenotype activation of BMDMs in vitro. Myocardial injection of CFs-mt-sEVs enhanced tissue inflammation, aggravated cardiac dysfunction, and exacerbated maladaptive ventricular remodeling post-MI in vivo. Mechanistically, above effects were achieved via activation of NLRP3 and above effects could be reversed by NLRP3 inhibitor CY-09. This study indicates that CFs could transfer damaged mitochondrial components via the sEVs post-MI, promote macrophage inflammatory activation and exacerbate maladaptive ventricular remodeling post MI by activating NLRP3. Our findings highlight the potential therapeutic effects of inhibiting CFs-mt-sEVs and NLRP3 to improve cardiac function and attenuate ventricular remodeling post-MI.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"214 ","pages":"Article 107676"},"PeriodicalIF":9.1,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143524106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plant-derived nanovesicles as novel nanotherapeutics for alleviating endothelial cell senescence-associated vascular remodeling induced by hypertension","authors":"Fengxia Lin ,&nbsp;Luhua Xu ,&nbsp;Qiuting He ,&nbsp;Zetao Chen ,&nbsp;Weiwei Zhang ,&nbsp;Jin Tu ,&nbsp;Yinzhi Song ,&nbsp;Fanjia Zhong ,&nbsp;Sheng Lin ,&nbsp;Rongfeng Yang ,&nbsp;Zhicong Zeng","doi":"10.1016/j.phrs.2025.107675","DOIUrl":"10.1016/j.phrs.2025.107675","url":null,"abstract":"<div><div>Endothelial cell senescence contributes to vascular remodeling in hypertension, a condition that lacks specific clinical treatments. While plant-derived nanovesicles have shown anti-inflammatory properties that reduce endothelial inflammation, their role in endothelial cell senescence is less understood. Here, we isolated and purified nanovesicles from <em>Semen Sinapis albae</em> (SDNVs), a traditional Chinese medicine with antihypertensive properties, and evaluated their therapeutic effects on vascular remodeling in spontaneously hypertensive rats (SHRs) compared to nifedipine, a standard antihypertensive drug. SDNVs were as effective as nifedipine in reducing blood pressure and exceeded nifedipine in mitigating vascular wall thickening, collagen fiber disarray, and in decreasing senescence markers in aortic tissues. In <em>vitro</em>, SDNVs inhibited angiotensin II-induced senescence in human umbilical vein endothelial cells (HUVECs). miRNA and mRNA sequencing revealed that SDNVs downregulate CD38 expression through miR393a delivery, mediating their anti-senescence effects. Our results suggest that SDNVs significantly alleviate hypertension-associated vascular remodeling by targeting CD38 via miR393a, thus reducing endothelial cell senescence. Compared to conventional drugs like nifedipine, SDNVs offer a potentially more effective approach to vascular remodeling. These insights may guide the development of novel therapeutics for hypertension-induced vascular remodeling.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"214 ","pages":"Article 107675"},"PeriodicalIF":9.1,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143510426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut microbiota-derived metabolites: Potential targets for cardiorenal syndrome","authors":"Yuchen Lai ,&nbsp;Yujie Zhu ,&nbsp;Xihui Zhang ,&nbsp;Shifang Ding ,&nbsp;Fang Wang ,&nbsp;Jincen Hao ,&nbsp;Zhaomeng Wang ,&nbsp;Congqi Shi ,&nbsp;Yongjin Xu ,&nbsp;Lemin Zheng ,&nbsp;Wei Huang","doi":"10.1016/j.phrs.2025.107672","DOIUrl":"10.1016/j.phrs.2025.107672","url":null,"abstract":"<div><div>The characteristic of cardiorenal syndrome (CRS) is simultaneous damage to both the heart and kidneys. CRS has caused a heavy burden of mortality and incidence rates worldwide. The regulation of host microbiota metabolism that triggers heart and kidney damage is an emerging research field that promotes a new perspective on cardiovascular risk. We summarize current studies from bench to bedside of gut microbiota-derived metabolites to better understand CRS in the context of gut microbiota-derived metabolites. We focused on the involvement of gut microbiota-derived metabolites in the pathophysiology of CRS, including lipid and cholesterol metabolism disorders, coagulation abnormalities and platelet aggregation, oxidative stress, endothelial dysfunction, inflammation, mitochondrial damage and energy metabolism disorders, vascular calcification and renal fibrosis, as well as emerging therapeutic approaches targeting CRS metabolism in gut microbiota-derived metabolites which provides an innovative treatment approach for CRS to improve patient prognosis and overall quality of life.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"214 ","pages":"Article 107672"},"PeriodicalIF":9.1,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Knowledge of the genetics of human pain gained over the last decade from next-generation sequencing","authors":"Dario Kringel ,&nbsp;Jörn Lötsch","doi":"10.1016/j.phrs.2025.107667","DOIUrl":"10.1016/j.phrs.2025.107667","url":null,"abstract":"<div><div>Next-generation sequencing (NGS) technologies have revolutionized pain research by providing comprehensive insights into genetic variation across the genome. Recent studies have expanded the known spectrum of mutations in genes such as <em>SCN9A</em> and <em>NTRK1</em>, which are commonly mutated in hereditary sensory neuropathies. NGS has uncovered critical alternative splicing events and facilitated single-cell transcriptomics, revealing cellular heterogeneity within tissues. An NGS-based classifier predicted extremely high opioid requirements with 80 % accuracy, highlighting the importance of tailoring opioid therapy based on genetic profiles. Key genes such as <em>GDF5</em>, <em>COL11A1</em>, and <em>TRPV1</em> have been linked to osteoarthritis risk and pain sensitivity, while <em>HLA-DRB1</em>, <em>TNF</em>, and <em>P2X7</em> play critical roles in inflammation and pain modulation in rheumatoid arthritis. Innovative tools, such as an atlas of the somatosensory system in neuropathic pain, have been developed based on NGS data, focusing on the dorsal root and trigeminal ganglia. This approach allows the analysis of cellular changes during the development of chronic pain. In the study of rare variants, NGS outperforms single nucleotide variant candidate studies and classical genome-wide association approaches. The complex data generated by NGS enables integrated multi-omics approaches, allowing deeper exploration of the molecular and cellular basis of pain perception. In addition, the characterization of non-coding RNAs has opened new therapeutic avenues. NGS-based pain research faces challenges related to complex data analysis and interpretation of rare genetic variants with unknown biological functions. Nevertheless, NGS offers significant potential for improving personalized pain management and highlights the need for interdisciplinary collaboration to translate findings into clinical practice.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"214 ","pages":"Article 107667"},"PeriodicalIF":9.1,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective effects and mechanisms of quercetin in animal models of hyperuricemia: A systematic review and meta-analysis","authors":"Xueren Bian ,&nbsp;Zhihao Ge ,&nbsp;Xuannan Chen ,&nbsp;Shutian Zhong ,&nbsp;Lu Li ,&nbsp;Wanfeng Xu ,&nbsp;Bo Li ,&nbsp;Suhong Chen ,&nbsp;Guiyuan Lv","doi":"10.1016/j.phrs.2025.107665","DOIUrl":"10.1016/j.phrs.2025.107665","url":null,"abstract":"<div><div>Quercetin, a prevalent natural flavonoid found in various medicinal plants, including <em>Dendrobium officinale</em> Kimura &amp; Migo, has garnered attention for its potential health benefits. However, foundational animal studies investigating the effects of quercetin on lowering uric acid levels remain insufficiently established, and the number of related clinical studies is limited. This scarcity hinders the practical application of quercetin in managing hyperuricemia. We systematically searched for preclinical studies published by December 2024 in nine databases, such as PubMed, Web of Science, and Embase. The results of our meta-analysis showed that, compared with the model group, quercetin not only effectively alleviated the pathological injury of the kidney and liver and improved the renal function indexes in the animal model of hyperuricemia but also played a role in lowering uric acid by modulating multiple signaling pathways such as oxidative stress, lipid metabolism, and transporter proteins. Quercetin showed a more substantial effect in decreasing serum creatinine levels (SMD = −4.29, 95 % CI [−6.48, −2.10], <em>P</em> = 0.0001), blood urea nitrogen levels (SMD = −3.08, 95 % CI [−4.80, −1.35], <em>P</em> = 0.0005), and Up-regulate organic anion transporter 1 mRNA expression levels (SMD = 2.72, 95 %CI [0.45, 4.99], <em>P</em> = 0.02) compared to the positive control group. Sensitivity analyses confirmed the stability of the results, while the subgroup analysis indicates that the treatment course may be the main source of heterogeneity. The results of the Dose-efficacy analysis suggested that quercetin had a more substantial protective effect against hyperuricemia at a gavage dose of 100–200 mg/kg. However, to more accurately assess the effects of quercetin on hyperuricemia, it is essential to conduct additional high-quality, large-scale animal trials to validate our findings.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"213 ","pages":"Article 107665"},"PeriodicalIF":9.1,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143474773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding TGR5: A comprehensive review of its impact on cerebral diseases","authors":"Zehan Zhang ,&nbsp;Yifei Zhang ,&nbsp;Hongye Peng,&nbsp;Qingqian Yu,&nbsp;Xiangdong Kang,&nbsp;Ying Liu,&nbsp;Yuxiao Zheng,&nbsp;Fafeng Cheng,&nbsp;Xueqian Wang,&nbsp;Feng Li","doi":"10.1016/j.phrs.2025.107671","DOIUrl":"10.1016/j.phrs.2025.107671","url":null,"abstract":"<div><div>Currently, unraveling the enigmatic realm of drug targets for cerebral disorders poses a formidable challenge. Takeda G protein-coupled receptor 5 (TGR5), also known as G protein-coupled bile acid receptor 1, is a specific bile acid receptor. Widely distributed across various tissues, TGR5 orchestrates a myriad of biological functions encompassing inflammation, energy metabolism, fatty acid metabolism, immune responses, cellular proliferation, apoptosis, and beyond. Alongside its well-documented implications in liver diseases, obesity, type 2 diabetes, tumors, and cardiovascular diseases, a growing body of evidence accentuates the pivotal role of TGR5 in cerebral diseases. Thus, this comprehensive review aimed to scrutinize the current insights into the pathological mechanisms involving TGR5 in cerebral diseases, while contemplating its potential as a promising therapeutic target for cerebral diseases.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"213 ","pages":"Article 107671"},"PeriodicalIF":9.1,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143474824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SIRT1: A likely key for future therapeutic strategies for pain management","authors":"Sara Ilari ,&nbsp;Saverio Nucera ,&nbsp;Lucia Carmela Passacatini ,&nbsp;Rosamaria Caminiti ,&nbsp;Valeria Mazza ,&nbsp;Roberta Macrì ,&nbsp;Maria Serra ,&nbsp;Federica Scarano ,&nbsp;Valentina Malafoglia ,&nbsp;Ernesto Palma ,&nbsp;Francesca Oppedisano ,&nbsp;Jessica Maiuolo ,&nbsp;Carlo Tomino ,&nbsp;Vincenzo Mollace ,&nbsp;Carolina Muscoli","doi":"10.1016/j.phrs.2025.107670","DOIUrl":"10.1016/j.phrs.2025.107670","url":null,"abstract":"<div><div>Sirtuin 1 (SIRT1), a NAD+ -dependent histone deacetylase, plays a crucial role in mitigating oxidative stress, regulating inflammation, and maintaining mitochondrial function. Reduced SIRT1 activity has been linked to elevated pro-inflammatory cytokines, mitochondrial dysfunction, and chronic pain, all of which are observed in long COVID pathology. Emerging evidence identifies mitochondrial dysfunction and oxidative stress as central contributors to these symptoms. Increases reactive oxygen species (ROS) such as superoxide, nitric oxide, and peroxynitrite, leading to oxidative damage, chronic inflammation, and central/peripheral sensitization. Nutraceuticals, particularly the polyphenolic fraction of bergamot (BPF), have demonstrated potent antioxidant, anti-inflammatory, and antiviral properties. This study highlights BPF’s ability to modulate SIRT1 activity in a rat model of inflammation and hyperalgesia. It provides novel evidence of SIRT1 nitration within the nucleus as a key event in inflammatory pain pathogenesis. BPF administration preserved SIRT1 activity, reduced oxidative stress markers such as malondialdehyde (MDA) and 8-hydroxydeoxyguanosine (8-OHdG), and minimized post-translational modifications of nuclear proteins, including nitration, acetylation, and carbonylation. Additionally, it alleviated hyperalgesia and allodynia. These findings underscore the therapeutic potential of polyphenols like BPF in reducing oxidative stress and inflammation-driven pain. By activating SIRT1, BPF may provide relief for pain conditions. Further research on SIRT1-targeted therapies is essential to combat inflammation and oxidative stress, preventing chronic conditions and enhancing treatment options.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"213 ","pages":"Article 107670"},"PeriodicalIF":9.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143453159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}