Pharmaceuticals最新文献

{"title":"Insights into Molecular Mechanisms of Polyphenolic Compounds from <i>Helichrysum italicum</i> by Inverse Molecular Docking Fingerprint Approach.","authors":"Veronika Furlan, Vid Ravnik, Urban Bren, Marko Jukić","doi":"10.3390/ph19040647","DOIUrl":"10.3390/ph19040647","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Natural compounds occupy a pharmacologically rich chemical space, characterized by abundant scaffolds, extensive functional group elaboration, and defined stereochemistry. In this context, <i>Helichrysum italicum</i>, a Mediterranean medicinal plant, represents a valuable source of polyphenols with multiple biological and pharmacological activities. <b>Methods</b>: Here, we introduce an inverse molecular docking fingerprint approach to systematically investigate eight major <i>Helichrysum italicum</i> polyphenols, including α-pyrones (arzanol, ethylpyrone), flavonols (gnaphaliin, kaempferol, quercetin), and flavanones (naringenin, pinocembrin, hesperetin). More than 40,000 human protein structures from the Protein Data Bank were screened to generate target-based inverse docking score fingerprints for each compound. <b>Results</b>: Hierarchical clustering of these fingerprints revealed shared binding patterns among structurally related polyphenols and enabled hypothesis generation regarding potential synergistic effects. Notably, favorable interactions were identified with PPARG and CARM1, supporting therapeutic relevance in inflammation and cancer, alongside additional targets associated with neurodegeneration and bone metabolism. <b>Conclusions</b>: This study establishes inverse docking fingerprints as a robust, mechanism-oriented method for natural product research and highlights <i>Helichrysum italicum</i> polyphenols as starting points for medicinal chemistry and drug discovery.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13118441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819712","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":"Short Peptide with Sequence of LAGAAHF, Identified from Edible Bird's Nest, Reduces Dermatitis Symptoms in Mice.","authors":"Queenie Wing Sze Lai, Yaxin Wang, Shengying Lin, Gary Ka Wing Yuen, Dusadee Ospondpant, Alex Xiong Gao, Tina Ting Xia Dong, Xuncai Liu, Qunyan Fan, Karl Wah Keung Tsim","doi":"10.3390/ph19040649","DOIUrl":"10.3390/ph19040649","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Native to the Indo-Pacific region, edible bird's nests (EBN; Yan Wo in Chinese) are the solidified saliva of swiftlets (<i>Aerodramus fuciphagus</i> and <i>A. maximus</i>) and have been consumed as a traditional functional food for centuries. However, the bioactive components and underlying mechanisms of EBN remain poorly understood. EBN consists of over 60% protein, much of which is heavily glycosylated, forming complex glycoconjugates that are resistant to enzymatic digestion. This study examines the properties of EBN-derived bioactive peptides and assesses their potential for skin moisturization and anti-inflammation when applied topically. <b>Methods</b>: EBN was double-boiled for an extended period, then digested with gastric enzymes to extract active peptides. Digestion was over 90% efficient, and peptide molecular weights were measured. The enzymatic digest was then fractionated using an activity-guided approach based on assays for skin moisturization and anti-inflammatory properties. <b>Results</b>: A novel bioactive heptapeptide, with the sequence LAGAAHF and designated EBN_P3, was identified and characterized. It attenuated TNF-α-induced inflammatory responses in HaCaT keratinocytes and alleviated dermatitis symptoms in a DNCB-induced C57BL/6 mouse model. <b>Conclusions</b>: EBN-derived peptides with skin moisturizing and anti-inflammatory activities hold significant promise for development into functional ingredients for skincare products.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819811","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":"Comparative Pharmacological Profiling of Psychotherapeutic Drugs Reveals a Functional Taxonomy Based on Direct Inhibition of Smooth Muscle Excitability.","authors":"María Jesús Castrillejo, Alfonso Velasco, Juan F Mielgo-Ayuso, Jesús Pérez, Manuel Garrosa, Carlos Alberto Rodríguez-Arias, Diego Fernández-Lázaro","doi":"10.3390/ph19040645","DOIUrl":"10.3390/ph19040645","url":null,"abstract":"<p><p><b>Background:</b> Autonomic side effects are a major determinant of tolerability for many psychotherapeutic drugs. While often attributed to receptor-mediated mechanisms, the potential contribution of direct modulation of smooth muscle excitability remains poorly characterized at a comparative pharmacological level. <b>Methods:</b> A systematic comparative pharmacological profiling of a broad panel of psychotherapeutic drugs (antidepressants, antipsychotics, and anxiolytics) was conducted using a standardized ex vivo model. Potassium chloride (KCl, 105 mM) was used to induce depolarization-dependent contraction in three isolated smooth muscle preparations (rat uterus, rat vas deferens, and guinea-pig ileum). Inhibitory potency (IC₅₀), dose-dependency, and tissue consistency were integrated to define functional inhibitory profiles. <b>Results:</b> Psychotherapeutic drugs exhibited marked heterogeneity in their ability to inhibit K⁺-induced smooth muscle contraction. Integrative analysis stratified compounds into four distinct functional profiles: (i) High Inhibitory Liability (e.g., nortriptyline, paroxetine), characterized by low micromolar IC₅₀ values and dose-dependent inhibition across multiple tissues; (ii) Non-Selective Inhibition (e.g., flunarizine, cinnarizine), showing consistent but dose-independent inhibition; (iii) Tissue-Dependent Inhibition (e.g., risperidone, reboxetine); and (iv) Minimal Inhibition (e.g., moclobemide). Agents classified within the High Inhibitory Liability profile correspond to drugs known to carry a higher clinical burden of autonomic adverse effects. <b>Conclusions:</b> This study reveals a previously underrecognized pharmacodynamic dimension of psychotherapeutic drugs and establishes a comparative functional taxonomy based on their direct, non-receptor-mediated inhibition of smooth muscle excitability. The identified profiles provide a mechanism-informed framework for contextualizing autonomic side-effect liability and may support improved safety evaluation in psychotherapeutic drug development.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13118299/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819721","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":"Targeting the Ras-Ral Signaling Axis in Type 2 Diabetes Mellitus: A Dual-Modulation Approach to Correcting Insulin Resistance and β-Cell Dysfunction.","authors":"Narayanan Thulasi, Kannan Harithpriya, Kumar Ganesan, Kunka Mohanram Ramkumar","doi":"10.3390/ph19040648","DOIUrl":"10.3390/ph19040648","url":null,"abstract":"<p><p>Type 2 diabetes mellitus (T2DM) is driven by insulin resistance and β-cell dysfunction. While Ras GTPases are known for oncogenic signaling, emerging evidence implicates the Ras-Ral axis as a critical regulator of glucose homeostasis. This review synthesizes the distinct roles of Ras and Ral in metabolism. Ras hyperactivation promotes insulin resistance and inflammation via MAPK/PI3K pathways, whereas RalA supports GLUT4 translocation and insulin granule exocytosis. We propose a dual-pathway hypothesis: T2DM pathophysiology involves an imbalance characterized by excessive Ras signaling and insufficient Ral-mediated metabolic actions. Consequently, we explore the therapeutic potential of rebalancing this axis through combinatorial strategies, that selectively inhibit pathogenic Ras while enhancing protective Ral activity. We critically evaluate current Ras-targeted agents (e.g., farnesyltransferase inhibitors, allele-specific inhibitors) and discuss the emerging frontier of Ral-specific enhancers. Finally, we outline key translational challenges and future directions for validating this axis as a target for precision medicine in T2DM.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819739","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":"RETRACTED: Huang et al. Adenine Inhibits the Invasive Potential of DLD-1 Human Colorectal Cancer Cell via the AMPK/FAK Axis. <i>Pharmaceuticals</i> 2021, <i>14</i>, 860.","authors":"Chien-Wei Huang, You-Cian Lin, Chia-Hung Hung, Han-Min Chen, Jiun-Tsai Lin, Chau-Jong Wang, Shao-Hsuan Kao","doi":"10.3390/ph19040646","DOIUrl":"https://doi.org/10.3390/ph19040646","url":null,"abstract":"<p><p>The journal retracts the article, \"Adenine Inhibits the Invasive Potential of DLD-1 Human Colorectal Cancer Cell via the AMPK/FAK Axis\" [...].</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13107893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147779124","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":"Identification and Functional Analysis of Targets of Dehydrodiisoeugenol in Bladder Cancer Based on Chemoproteomics-Based Profiling.","authors":"Zhao Zhai, Fan Wu, Guoli Sheng, Bin Jia, Bolin Jia, Peng Du, Yong Zhang","doi":"10.3390/ph19040651","DOIUrl":"10.3390/ph19040651","url":null,"abstract":"<p><p><b>Background/Objectives:</b> The clinical management of bladder cancer is severely impeded by high recurrence rates and the rapid emergence of chemoresistance, necessitating the discovery of novel therapeutic agents with distinct mechanisms of action. Dehydrodiisoeugenol (DHE), a bioactive neolignan, exhibits potent anti-tumor efficacy, yet its direct molecular targets and mode of action remain elusive. <b>Methods</b>: To deconvolute the mechanism of DHE, we integrated a phenotypic screening approach using 2D cell lines and 3D patient-derived organoids with a chemoproteomics-based activity-based protein profiling (ABPP) strategy. We synthesized a functionalized photoaffinity probe to capture the specific interactome of DHE under physiological conditions and validated targets via cellular thermal shift assays (CETSA), quantitative mass spectrometry, and 100 ns molecular dynamics (MD) simulations. <b>Results</b>: DHE exhibited potent dose-dependent cytotoxicity in bladder cancer cells, with IC50 values of 39.23 μM in T24 and 34.58 μM in 5637 cells. In 3D patient-derived organoids, DHE significantly reduced viability (<i>p</i> < 0.0001). Using a dual-filtering ABPP strategy, we identified 65 high-confidence candidate targets, prioritizing PTPN1 (PTP1B) as the primary functional interactor. Comparative molecular docking and 100 ns MD analyses showed that multiple stereoisomers of DHE could adopt plausible PTPN1-binding modes. Mechanistically, organoid proteomics indicated that DHE engagement with PTPN1 disrupts ER membrane homeostasis, thereby modulating the PI3K-Akt signaling axes. <b>Conclusions</b>: These findings establish PTPN1 as a critical druggable vulnerability in bladder cancer and define the molecular basis for the therapeutic potential of DHE. This study highlights the power of combining chemoproteomics with physiological 3D models to accelerate the translation of natural products into precision cancer therapies.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13118370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819594","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":"An Overview of the Presence of Cephalosporin Antibiotics in Aquatic Environments.","authors":"Ramona-Alexandra Ciausu, Mircea Nicusor Nicoara, Ionut-Alexandru Chelaru, Gabriel Andrei Andronic, Alin Stelian Ciobica, Dorel Ureche","doi":"10.3390/ph19040650","DOIUrl":"10.3390/ph19040650","url":null,"abstract":"<p><p><b>Background:</b> Cephalosporins, widely used β-lactam antibiotics, are becoming significant environmental pollutants, primarily due to their high use and persistence. They are released into the environment mainly through wastewater treatment plants, agricultural runoff, and hospital discharge, with particularly high concentrations recorded in effluents. Conventional wastewater treatment methods have inadequate removal efficiency, while advanced treatments, such as ozonation, activated carbon adsorption, and advanced oxidation processes, although more efficient, may produce toxic by-products. Recent studies emphasize the importance of improved detection and monitoring techniques and advocate for stricter effluent regulations. Despite growing research attention, important knowledge gaps remain, including limited long-term field monitoring, insufficient data on environmentally realistic exposure scenarios, and incomplete assessment of transformation-product toxicity. <b>Methods:</b> The search strategy used the <i>SCOPUS</i> and <i>PUBMED</i> databases with the keywords \"cephalosporin\" AND \"aquatic environment\", resulting in 341 records. After applying predefined inclusion and exclusion criteria, 110 peer-reviewed English-language studies meeting predefined thematic inclusion criteria and relevant to the occurrence, environmental fate, ecotoxicological effects, antimicrobial resistance, and removal of cephalosporins in aquatic environments were included in the narrative synthesis. <b>Results:</b> The literature on cephalosporins in aquatic environments has expanded significantly from 1978 to 2025, prompted by concerns about pharmaceutical contamination and antibiotic resistance. Studies from 2016 to 2025 used advanced and multidisciplinary monitoring techniques, revealed key pollution sources such as wastewater treatment plants and hospitals, and correlated antibiotic residues with resistance genes, highlighting the need for continued monitoring and mitigation efforts. Ecotoxicological and fate studies further indicate that transformation processes may generate products with altered or increased toxicity, complicating environmental risk assessment. <b>Conclusions:</b> The literature shows increasing attention to cephalosporins in aquatic environments, reporting associations with antimicrobial resistance and adverse effects on aquatic organisms, including potential toxicity from transformation products. This review highlights the need for integrated monitoring, standardized toxicity assessment, and improved treatment strategies within a One Health framework.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819671","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":"Osteocytes in the Metastatic Bone Niche: Mechanistic Pathways and Therapeutic Targets.","authors":"Alhomam Dabaliz, Mohamad Bakir, Lana Fatash, Mais Aldoush, Khalid Said Mohammad","doi":"10.3390/ph19040644","DOIUrl":"10.3390/ph19040644","url":null,"abstract":"<p><p>Osteocytes, once viewed mainly as passive bone-embedded cells, are now recognized as active regulators of the metastatic bone niche. Emerging evidence indicates that these cells integrate mechanical, inflammatory, and tumor-derived cues to influence metastatic seeding, dormancy, reactivation, and lesion progression in bone. This review synthesizes current understanding of osteocyte contributions to skeletal metastasis. We discuss core signaling axes, including osteocyte-derived RANKL/OPG balance, Wnt antagonists (sclerostin/DKK1), mechanotransduction pathways (Piezo1 signaling and connexin-43 hemichannels), and osteocyte paracrine mediators (extracellular vesicles and senescence-associated factors), and examine how each axis modulates tumor cell dormancy, osteolysis, or osteoblastic progression. We then review translational strategies targeting osteocytes, recent preclinical and clinical insights. Emerging biomarkers (e.g., serum sclerostin, DKK1, bone turnover markers) and immune-skeletal imaging approaches are also considered. Controversies, including the paradoxical effects of sclerostin blockade and the identity of in vivo RANKL sources, are discussed. Finally, we outline key knowledge gaps and propose endpoints for future trials. In summary, an osteocyte-centric perspective reveals novel targets and strategies for managing bone metastases, guiding future translational research.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819583","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 Molecular Structures of Liquid and Glassy Nifedipine and Felodipine and Their Incorporation into PVP.","authors":"Chris J Benmore, Stephen K Wilke, Samrat Amin, Richard Weber, Pamela A Smith, Stephen R Byrn, Olivia Gibbons, Ethan Earl, Stephen Davidowski, Jeffery L Yarger","doi":"10.3390/ph19040638","DOIUrl":"10.3390/ph19040638","url":null,"abstract":"<p><p><b>Background</b>: Amorphous drug formulations are commonly used to improve the solubility and bioavailability of poorly soluble molecular pharmaceuticals, yet less is known about their molecular conformations and local bonding interactions than their crystalline phases. <b>Methods</b>: High-energy X-ray diffraction structure factor measurements have been made on liquid and glassy nifedipine (NIF), felodipine (FEL), NIF 1:3 polyvinylpyrrolidone (PVP), and FEL 1:3 PVP wt.% mixtures. The corresponding X-ray pair distribution functions have been interpreted using empirical potential structure refinement using different models and density functional theory conformer calculations. <b>Results</b>: In both NIF and FEL, the NH···O inter-molecular hydrogen bonds between the pyridyl nitrogen and ester carbonyls are found to be considerably weaker than those observed in the crystalline polymorphs. For nifedipine, it is proposed that either inter-molecular NH…ON nitro bonds are present and/or a fraction (<20%) of conformational changes, with the aryl ring flipped, occur in the liquid state. For felodipine, the models indicate significant disorder associated with the methyl and ethyl side chains in the liquid state, with the main peak intensity at 3.0 Å arising from intra-molecular Cl-Cl atom pairs. When nifedipine molecules are incorporated into PVP, our models show they possess stronger NH···O bonds to the PVP polymer than felodipine molecules, which have stronger affinity for bonding to the polymer than to other felodipine molecules. <b>Conclusions</b>: The amorphous forms of both NIF and FEL show much weaker hydrogen bonding than found in their crystalline phases. Liquid NIF also exhibits configurations which are not observed in the crystal phases.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819833","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":"PPAR-α Agonist Suppresses Expression of Immune Mediators in B Cells in a Murine Model of Systemic Lupus Erythematosus.","authors":"Haneen A Al-Mazroua, Hussain N Alhamami, Mushtaq A Ansari, Ahmed Nadeem, Sabry M Attia, Saleh A Bakheet, Abdulaziz M S Alsaad, Hatun A Alomar, Alaa A Alanteet, Sheikh F Ahmad","doi":"10.3390/ph19040642","DOIUrl":"10.3390/ph19040642","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by immune dysregulation that leads to widespread inflammation and damage across multiple organs. B lymphocytes play a vital role in SLE, with abnormal development and activation leading to autoreactive antibody production and immune complex formation, which damages tissues. <b>Methods:</b> The PPARα agonist WY14643 has anti-inflammatory effects in various inflammatory conditions, including CNS diseases. We investigated whether WY14643 decreases inflammatory mediator production in CD45R⁺ cells in the MRL/lpr mouse model of SLE. Flow cytometry was used to evaluate WY14643's impact on the expression of IFN-γ, IL-6, iNOS, MCP-1, IL-1α, IL-2, Notch-1, Notch-3, GITR, and NF-κB p65 in splenic CD45R⁺ B cells. Additionally, we assessed the effect of WY14643 on the mRNA levels of these markers in the kidney using RT-PCR. <b>Results:</b> WY14643 decreased inflammatory markers such as CD45R⁺IFN-γ⁺, CD45R⁺IL-6⁺, CD45R⁺iNOS⁺, CD45R⁺MCP-1⁺, CD45R⁺IL-1α⁺, CD45R⁺IL-2⁺, CD45R⁺Notch1⁺, CD45R⁺Notch3⁺, CD45R⁺GITR⁺, and CD45R⁺NF-κB p65⁺ in splenic cells from MRL/lpr mice. Furthermore, WY14643 also lowered mRNA expression of IFN-γ, IL-6, iNOS, MCP-1, IL-2, IL-1α, Notch-1, Notch-3, GITR, and NF-κB p65 in the kidney. <b>Conclusions:</b> This study shows that WY14643 inhibits the production of inflammatory mediators and significantly reduces autoimmune features, including kidney inflammation, in MRL/lpr mice. Our results indicate that WY14643, a PPAR-α agonist, could be a potential therapy for lupus nephritis.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819707","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}