Pharmaceuticals最新文献

{"title":"Novel Approaches to Allergen Immunotherapy for Respiratory Allergies.","authors":"Mongkol Lao-Araya","doi":"10.3390/ph17111510","DOIUrl":"https://doi.org/10.3390/ph17111510","url":null,"abstract":"<p><p>Allergen immunotherapy (AIT) remains the cornerstone for managing respiratory allergies, offering long-term symptom relief, disease modification, and prevention of disease progression. While novel approaches like intralymphatic and epicutaneous immunotherapy and the combination of allergens with adjuvants show promise, traditional methods remain effective and safe. Hypoallergenic T-cell peptide vaccines and recombinant allergens require further research to confirm their clinical benefits. Passive immunotherapy, while demonstrating effectiveness in specific cases, needs exploration of its long-term efficacy and broader applicability. Combining AIT with biologics may enhance safety and treatment outcomes. Despite emerging innovations, allergen-specific immunotherapy with natural allergen extracts remains the primary disease-modifying treatment, offering long-term symptom relief and prevention of disease progression. Continued research is essential to refine and optimize allergen immunotherapy strategies, providing patients with more effective and personalized treatment options.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"17 11","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142731867","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":"Identification of Estrogen-Responsive Proteins in Mouse Seminal Vesicles Through Mass Spectrometry-Based Proteomics.","authors":"Ammar Kapic, Khadiza Zaman, Vien Nguyen, Katalin Prokai-Tatrai, Laszlo Prokai","doi":"10.3390/ph17111508","DOIUrl":"https://doi.org/10.3390/ph17111508","url":null,"abstract":"<p><p><b>Background:</b> Although estrogenic compounds promise therapeutic potential in treating various conditions, concerns regarding their endocrine-disrupting effects have been raised. Current methodologies for screening estrogenicity in rodent models are limited to the female-specific uterotrophic bioassay. Studies have reported enlargement of the seminal vesicles in orchiectomized males treated with estrogens. However, identifying estrogenicity strictly through changes in wet weights is uninformative regarding the molecular mechanisms of these agents. Therefore, protein-based biomarkers can complement and improve the sensitivity of weight-based assessments. To this end, we present a discovery-driven proteomic analysis of 17β-estradiol's effects on the seminal vesicles. <b>Methods:</b> We treated orchidectomized mice with the hormone for five days and used the vehicle-treated group as a control. Seminal vesicles were analyzed by shotgun approach using data-dependent nanoflow liquid chromatography-tandem mass spectrometry and label-free quantification. Proteins found to be differentially expressed between the two groups were processed through a bioinformatics pipeline focusing on pathway analyses and assembly of protein interaction networks. <b>Results:</b> Out of 668 identified proteins that passed rigorous validation criteria, 133 were regulated significantly by 17β-estradiol. Ingenuity Pathway Analysis^® linked them to several hormone-affected pathways, including those associated with immune function such as neutrophil degranulation. The altered protein interaction networks were also related to functions including endocrine disruption, abnormal metabolism, and therapeutic effects. <b>Conclusions:</b> We identified several potential biomarkers for estrogenicity in mouse seminal vesicles, many of them not previously linked with exogenous 17β-estradiol exposure.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"17 11","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142731961","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":"Berberine Mediates Exosomes Regulating the Lipid Metabolism Pathways to Promote Apoptosis of RA-FLS Cells.","authors":"Si-Fan Guo, Zhi-Bo Wang, Dan-Dan Xie, Ying Cai, Yan Wang, Xian Wang, Qiang Yang, Ai-Hua Zhang, Shi Qiu","doi":"10.3390/ph17111509","DOIUrl":"https://doi.org/10.3390/ph17111509","url":null,"abstract":"<p><p><b>Objectives</b>: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint damage and commonly linked to symptoms such as inflammation, swelling, and pain. Traditional Chinese Medicine offers complementary and integrative approaches in the management of rheumatoid arthritis, potentially providing additional options that may help address treatment challenges and enhance overall patient care. This paper explores the mechanism of action of berberine from the perspective of cellular exosomes by mediating exosomal contents and thus treating RA. <b>Methods</b>: With the help of flow cytometry and confocal laser scanning microscope, it was determined that berberine promotes apoptosis in RA-FLS cells, and then lipid metabolomics technology was applied to screen and characterize the exosomes of RA-FLS cells to identify lipid core biomarkers closely related to RA, which were then projected into various databases for comprehensive analysis. <b>Results</b>: The data analysis showed that berberine could call back 11 lipid core biomarkers closely associated with RA, and interactive visualization of the database revealed that these markers were mainly focused on lipid metabolism aspects such as fatty acid elongation, degradation, and biosynthesis, as well as the biosynthesis of unsaturated fatty acids or PPARA activation of gene expression, PPARα's role in lipid metabolism regulation, glycerophospholipid metabolism, mitochondrial fatty acid oxidation disorders, and organelle biogenesis and maintenance. <b>Conclusions</b>: Berberine exerts its therapeutic effect on RA by mediating exosomal contents and thus regulating multiple lipid-related biological pathways, affecting the PPARγ-NF-κB complex binding rate, CREB and EGR-1 expression, cellular phagocytosis, and other aspects needed to inhibit proliferation and inflammatory responses in RA-FLS. This study offers a research foundation for exploring the mechanism of action of berberine in the treatment of RA.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"17 11","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142731989","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":"Analgosedation in Pediatric Emergency Care: A Comprehensive Scoping Review.","authors":"Lorenzo Ciavola, Francesco Sogni, Benedetta Mucci, Eleonora Alfieri, Angela Tinella, Elena Mariotti Zani, Susanna Esposito","doi":"10.3390/ph17111506","DOIUrl":"https://doi.org/10.3390/ph17111506","url":null,"abstract":"<p><p>Effective management of pain and anxiety in pediatric emergency room is crucial for ensuring both the physical and emotional well-being of young patients. Analgosedation, a combination of analgesia and sedation, is commonly used to facilitate various procedures in children. However, selecting the optimal agent and administration route remains challenging due to the unique pharmacological profiles and side effects of available drugs. This scoping review aims to provide a comprehensive analysis of the pharmacological agents used for procedural analgosedation in pediatric emergency settings, focusing on their efficacy, safety, administration routes, and potential side effects. A systematic review of the literature was conducted, focusing on key agents such as ketamine, midazolam, dexmedetomidine, fentanyl, and nitrous oxide. Studies were included based on their relevance to pediatric procedural sedation, particularly in emergency settings. Literature analysis showed that ketamine and fentanyl are effective for managing moderate to severe pain, with a rapid onset of action. Fentanyl is preferred for acute pain management following fractures and burns, while ketamine and midazolam are commonly used for emergency analgosedation. Dexmedetomidine, which induces sedation similar to natural sleep, is particularly effective in preventing pain and agitation during procedures and is well tolerated in children, especially those with developmental disorders. Nitrous oxide, when used in a 50% oxygen mixture, offers a valuable option for conscious sedation during mildly to moderately painful procedures, maintaining respiratory and airway reflexes. No single drug is ideal for all pediatric patients and procedures and the choice of agent should be tailored to the specific clinical scenario, considering both the sensory and affective components of pain. Future research should prioritize large-scale comparative studies, the exploration of combination therapies, and the development of non-pharmacological adjuncts to enhance the safety and efficacy of pediatric analgosedation.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"17 11","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142731844","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":"Anti-Inflammatory and Antioxidant Activities of Eugenol: An Update.","authors":"Renan Oliveira Silva Damasceno, João Lucas Silva Pinheiro, Lucas Henrique Marques Rodrigues, Rebeca Carneiro Gomes, Allana Brunna Sucupira Duarte, Jeremias Justo Emídio, Lúcio Ricardo Leite Diniz, Damião Pergentino de Sousa","doi":"10.3390/ph17111505","DOIUrl":"https://doi.org/10.3390/ph17111505","url":null,"abstract":"<p><p>Medicinal plants are a rich source of bioactive compounds that possess pharmacological properties for preventing and treating inflammation-related diseases. Essential oils is a chemical class that contains many bioactive compounds, such as eugenol, which is capable of inhibiting or modulating the inflammatory response. This natural product emerges as a compound that promotes various biological activities, including antioxidant activity, which makes it useful in the food industry. Recently, its pharmacological applications have also been highlighted. So, this review aims to update and discuss the most recent findings on the anti-inflammatory and antioxidant activities of eugenol, along with its mechanisms of action and therapeutic potential for treating inflammation and oxidative imbalance conditions.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"17 11","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142731892","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":"Ultra-High-Performance Liquid Chromatography-Tandem Mass Spectrometry Analysis of Δ9-Tetrahydrocannabinol and Cannabidiol in Commercial Suk-Saiyasna Herbal Remedy: Applying Hansen Solubility Parameters for Sample Extraction to Ensure Regulatory Compliance.","authors":"Suwimon Sumontri, Wanna Eiamart, Sarin Tadtong, Weerasak Samee","doi":"10.3390/ph17111502","DOIUrl":"https://doi.org/10.3390/ph17111502","url":null,"abstract":"<p><strong>Background: </strong>Suk-Saiyasna is a traditional Thai herbal remedy that comprises 12 distinct herbs. Among these, cannabis leaves constitute 12 of the total 78 components in this formulation. This study specifically examines the portion of the cannabis plant, which accounts for approximately 15.8% of the overall herbal composition used in the entire remedy. According to the Thailand Narcotics Act of 2022, the Δ9-tetrahydrocannabinol (Δ9-THC) concentration in herbal extracts must not exceed 0.2% by weight. This study aims to quantify the levels of Δ9-THC and cannabidiol (CBD) in commercial Suk-Saiyasna products.</p><p><strong>Methodology: </strong>This research utilizes Hansen Solubility Parameters (HSPs) to identify the optimal solvent for ultrasonic extraction, thereby maximizing cannabinoid yield. An advanced method was developed employing ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), compliant with AOAC standards to meet regulatory guidelines. The method validation emphasized specificity, linearity, sensitivity, accuracy, and precision.</p><p><strong>Results: </strong>Dichloromethane was chosen due to its favorable HSP values, enabling highly efficient extraction of Δ9-THC and CBD, achieving recovery rates of over 99.9% after the second extraction. This investigation benefits from the accuracy of the UHPLC-MS/MS technique in quantifying cannabinoids in commercial products, with Δ9-THC concentrations observed between 0.00231% and 0.14218%, and CBD concentrations ranging from 0.00002% to 0.01541%, all remaining below the legal limit.</p><p><strong>Conclusions: </strong>The variability in cannabinoid concentrations among various commercial products highlights the need for standardization in the herbal industry. This finding underscores the critical role of rigorous quality control measures in ensuring the safety and efficacy of cannabis-derived products.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"17 11","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142732060","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":"Kinin B1- and B2-Receptor Subtypes Contract Isolated Bovine Ciliary Muscle: Their Role in Ocular Lens Function and Intraocular Pressure Reduction.","authors":"Najam A Sharif, Madura Kulkarni-Chitnis, Anthonia Okolie, Ya Fatou Njie-Mbye, Sunny E Ohia","doi":"10.3390/ph17111501","DOIUrl":"https://doi.org/10.3390/ph17111501","url":null,"abstract":"<p><p><b>Background:</b> Bradykinin is an endogenously produced nonapeptide with many physiological and pathological functions that are mediated by two pharmacologically defined receptor subtypes, B1- and B2-receptors. Current studies sought to characterize the functional bradykinin (BK) receptors present in freshly isolated bovine ciliary muscle (BCM) using an organ-bath tissue contraction system. <b>Methods:</b> Cumulative longitudinal isometric tension responses of BCM strips (4-5 mm) were recorded before and after the addition of test compounds to BCM strips hooked up to an isometric strain gauge transducer system. <b>Results:</b> BK and its analogs (7-11 concentrations) contracted BCM in a biphasic concentration-dependent manner. The first high affinity/potency phase accounted for 40-60% of the maximal contraction by each of BK (potency, EC₅₀ = 0.9 ± 0.3 nM), Lys-BK (EC₅₀ = 0.7 ± 0.1 nM), Met-Lys-BK (EC₅₀ = 1 ± 0.1 nM), Hyp3-BK (EC₅₀ = 1 ± 0.2 nM), RMP-7 (EC₅₀ = 3.5 ± 0.5 nM), and Des-Arg⁹-BK (EC₅₀ = 10 ± 0.4nM) (mean ± SEM, n = 3-8). The second lower activity phase of contraction potency values for these peptides ranged between 100 nM and 3 µM. In the presence of a selective B1-receptor antagonist (R715; 0.1-10 µM), the concentration-response curves to Des-Arg9-BK (B1-receptor agonist) were still observed, indicating activation of B2-receptors by this kinin. Likewise, when B2-receptors were completely blocked by using a B2-selective antagonist (WIN-64338; 1-10 µM), BK still induced BCM contraction, now by stimulating B1-receptors. <b>Conclusions:</b> This agonist/antagonist profile of BCM receptors indicated the presence of both B1- and B2-receptor subtypes, both being responsible for contracting this smooth muscle. The BCM kinin receptors may be involved in changing the shape of the ocular lens to influence accommodation, and since the ciliary muscle is attached to the trabecular meshwork through which aqueous humor drains, endogenously released kinins may regulate intraocular pressure.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"17 11","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142731925","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":"Benign Evolution of Complex Regional Pain Syndrome (CRPS) Type 1 in Patients Treated with Intravenous Neridronate: A Single-Center Real-Life Experience.","authors":"Jacopo Ciaffi, Gianluca Festuccia, Claudio Ripamonti, Luana Mancarella, Veronica Brusi, Federica Pignatti, Lucia Lisi, Lisa Berti, Piero Ruscitti, Cesare Faldini, Francesco Ursini","doi":"10.3390/ph17111500","DOIUrl":"https://doi.org/10.3390/ph17111500","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the long-term effects of intravenous neridronate treatment in patients with complex regional pain syndrome type 1 (CRPS) in a real-life setting.</p><p><strong>Methods: </strong>We conducted a retrospective study on consecutive CRPS patients treated at our hospital from February 2018 to July 2023. All were treated within three months of the onset of CRPS symptoms. The Patient-Reported Outcomes Measurement Information System 29-Item Health Profile (PROMIS-29) version 2.1 was administered. The main outcome of interest was the evolution of the PROMIS-29 scores from baseline to the last follow-up visit. Patients were categorized as \"complete responders\" or \"non-complete responders\". The association of clinical and demographic variables with a complete response was analyzed using chi-square tests and univariate logistic regression.</p><p><strong>Results: </strong>Thirty-six patients were included, with a median follow-up time of 4.8 years. A significant improvement was noted in the mean numerical pain rating scale (from 6.4 ± 1.9 to 3.1 ± 2.4, <i>p</i> < 0.001), as well as across all PROMIS-29 domains. Physical function improved from 34.2 ± 4.9 to 49.2 ± 9.9, <i>p</i> < 0.001; anxiety from 58.0 ± 6.7 to 49.6 ± 6.9, <i>p</i> < 0.001; depression from 55.3 ± 6.3 to 47.7 ± 6.6, <i>p</i> < 0.001; fatigue from 55.7 ± 7.7 to 50.9 ± 8.7, <i>p</i> < 0.001; sleep disturbance from 53.8 ± 6.8 to 51.3 ± 6.6, <i>p</i> = 0.034; social roles and activities from 41.8 ± 5.2 to 51.8 ± 8.9, <i>p</i> < 0.001; and pain interference from 64.1 ± 5.9 to 52.4 ± 9.9, <i>p</i> < 0.001. The likelihood of achieving a complete response was associated with the male sex, foot or ankle injuries (compared to hand and wrist injuries), and a younger age. No association was found with the type of inciting event or with the body mass index.</p><p><strong>Conclusions: </strong>Our real-life data indicate that early treatment with neridronate leads to substantial benefits in patients affected by CRPS type 1. The strongest responses are seen in young patients, males, and those with lower limb involvement.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"17 11","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142731986","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":"M2e-Derived Peptidyl and Peptide Amphiphile Micelles as Novel Influenza Vaccines.","authors":"Megan C Schulte, Agustin T Barcellona, Xiaofei Wang, Adam G Schrum, Bret D Ulery","doi":"10.3390/ph17111503","DOIUrl":"https://doi.org/10.3390/ph17111503","url":null,"abstract":"<p><p><b>Background:</b> A significant problem with current influenza vaccines is their reliance on predictions of the most prevalent strains for the upcoming season, with inaccurate forecasts greatly reducing the overall efficacy of the immunization campaign. A universal influenza vaccine, which leverages epitopes conserved across many, if not all, strains of influenza, could reduce the need for extremely accurate forecasting. The highly conserved ectodomain of the influenza M2 protein contains a B cell epitope in the M2_2-16 region, making it a promising candidate as a universal influenza vaccine. Unfortunately, free peptide antigens alone are limited as vaccines due to their poor stability and weak immunogenicity in vivo. To improve the potential of peptide vaccines, immunostimulatory micellar nanoparticles can be generated from them by lipid conjugation (i.e., peptide amphiphiles-PAs). <b>Methods:</b> M2_2-16 peptides and Palm₂K-M2_2-16-(KE)₄ PAs were synthesized and characterized. BALB/c mice were subcutaneously vaccinated with these formulations, and ELISAs were conducted on serum collected from the vaccinated mice to evaluate induced antibody responses. <b>Results:</b> Unlike other peptide antigens previously studied, the unmodified M2_2-16 peptide micellized without any peptidyl or lipid modifications. M2_2-16 peptidyl micelles (PMs) were spherical with largely undefined secondary structure somewhat different from the cylindrical, β-sheet-containing Palm₂K-M2_2-16-(KE)₄ peptide amphiphile micelles (PAMs). Differences in physical properties were found to correlate with slightly different immune responses with PAMs eliciting higher antibody titers after the initial immunization, whereas both micelle types elicited strong IgG titers after a prime-boost regimen. <b>Conclusions:</b> These results suggest the viability of PAMs as single-dose vaccines, while both PMs and PAMs show potential using a multi-dose immunization approach.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"17 11","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142731385","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":"Levamisole Ameliorates Rheumatoid Arthritis by Downregulating the PI3K/Akt Pathway in SD Rats.","authors":"Mu Guo, Xiangbin Yu, Zesheng Yang, Hanlu Zheng, Jiahui Zhang, Junxiang Wang, Yiqi Liao, Weirui Huang, Zhaolong Lin, Yingxue Yan, Nengfu Qiu, Jianmin Chen, Yue Yu","doi":"10.3390/ph17111504","DOIUrl":"https://doi.org/10.3390/ph17111504","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Rheumatoid arthritis (RA) is a systemic chronic autoimmune disease characterized by a protracted course, high rates of morbidity, and disability yet lacks effective therapeutic modalities. Levamisole (LVM), an immunomodulatory drug, has been clinically reported for its potential in RA treatment, while its therapeutic mechanism toward RA remains to be elucidated. Hence, this study provides theoretical support for the application of LVM in the treatment of RA. <b>Methods:</b> This study employed male Sprague-Dawley (SD) rats to construct the adjuvant-induced arthritis (AIA) model, administering LVM orally (5 mg/kg, 15 mg/kg, and 45 mg/kg) for 25 days. An evaluation of LVM's therapeutic effects on RA was conducted through arthritis index scores, paw pad thickness, paw volume, hematoxylin and eosin (H&E) staining, 3D microcomputed tomography (micro-CT) scans, serum levels of pro-/anti-inflammatory cytokines, and serum biochemical indicators. Western blotting and immunohistochemistry staining were utilized to measure the expression levels of phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) proteins in synovial and ankle joint tissues. <b>Results:</b> Treatment with the median dose of LVM (15 mg/kg, M-LVM) significantly reduced the arthritis index (<i>p</i> < 0.01), paw pad thickness (<i>p</i> < 0.001), and paw volume (<i>p</i> < 0.01) without affecting body weight. Additionally, M-LVM alleviated inflammatory lesions in the synovium and ankle joints and also normalized serum levels of interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and transforming growth factor-beta (TGF-β). The Model group exhibited significant increases in serum levels of alkaline phosphatase (ALP) (<i>p</i> < 0.01), creatine kinase (CK) (<i>p</i> < 0.05), and glucose (GLU) (<i>p</i> < 0.001) compared with the Control group; however, M-LVM effectively regulated these parameters to normal levels. Western blotting and immunohistochemistry staining revealed that PI3K-/Akt-related proteins were highly expressed in the synovial and ankle joint tissues of rats in the Model group, while treatment with M-LVM significantly reduced the expression of these proteins. Furthermore, histological examination of major organs (heart, liver, lungs, kidneys, and thymus) showed no significant pathological changes, with the exception of the spleen, where M-LVM ameliorated splenic lesions. <b>Conclusions:</b> We demonstrate that LVM at an optimal dose substantially relieves synovitis and bone erosion in AIA rats by inhibiting the PI3K/Akt signaling pathway.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"17 11","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142731978","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}