Saudi Pharmaceutical Journal最新文献

{"title":"Towards standardized skin testing for drug-induced allergic reactions.","authors":"Moneerah AlGassim, Fatimah Alawami, Ghalia H Bakhsh, Samia Al-Shouli, Nada K Alhumaid, Abdullah A Alshehri, Fahad A Almughem, Yahya M K Tawfik, Rawan Fitaihi, Nasser D Aljohani, Abdullah O Alshehry, Essam A Tawfik","doi":"10.1007/s44446-025-00031-5","DOIUrl":"10.1007/s44446-025-00031-5","url":null,"abstract":"<p><p>Standardization of skin tests is essential for detecting allergen sensitization, confirming diagnoses, and guiding treatment of allergen-induced conditions. The rise in drug-induced reactions presents a challenge to healthcare practitioners, as incomplete or inaccurate drug allergy histories can compromise patient safety and result in medication errors. Drug hypersensitivity reactions (DHR) are akin to allergic responses, triggered by either the active ingredient or excipients in a drug. Distinguishing between a drug allergic reaction and a predictable adverse drug reaction (ADR) is vital in clinical practice. Cutaneous testing, a common diagnostic modality, uses non-irritant drug concentrations, tested and validated for key drug classes. This article collects up-to-date concentrations, serving as a reference for healthcare practitioners. These concentrations vary but are generally prepared by dissolving the commercial form of the drug's tablet or capsule content in normal saline, white petrolatum, or sterile water for irrigation. However, the lack of data and standardized protocols on optimal non-irritant drug concentrations for oral dosage forms has led to variability in these tests' sensitivity, specificity, and performance.</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"33 4","pages":"26"},"PeriodicalIF":3.4,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12240923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144592723","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":"Engineering stable Amlodipine suspensions for flexible compounding at King Khaled University Hospital.","authors":"Ehab Elzayat, Hadyah F Alotaibi, Mohamed H Al-Agamy, Lama A Alharabi, Mohammed R Alhuzani","doi":"10.1007/s44446-025-00028-0","DOIUrl":"10.1007/s44446-025-00028-0","url":null,"abstract":"<p><p>Extemporaneous liquid formulations are crucial for patients unable to swallow solid dosage forms. While the United States Pharmacopeia (USP) recommends a 3-month beyond-use date for extemporaneous Amlodipine suspensions, uncertainties persist regarding the impact of active pharmaceutical ingredient (API) source variability, the confirmation of extended in-use stability, and the practical challenges of adapting formulations to local market raw material availability. This study aimed to address these gaps by investigating the physicochemical and microbiological stability of extemporaneous Amlodipine suspensions prepared from different API sources and stored under simulated in-use and closed conditions for 3 months. Eight formulations were prepared using different dosage forms (tablets or capsules), manufacturers (brand or generic), strengths (5 mg or 10 mg), and storage conditions. Physical stability was assessed via organoleptic properties and pH measurements, chemical stability via a validated ultra-performance liquid chromatography-ultraviolet method, and microbiological stability through total aerobic microbial count and total yeast and mold count. All formulations demonstrated stability over 3 months at 5°C, with drug content maintained (mean 103.94% ± 1.79 SD, range 101.79-107%) of the initial concentration and no microbial growth detected, even under in-use conditions. No significant differences were observed between tablet- and capsule-based preparations. These findings confirm the United States Pharmacopeia's 3-month beyond-use date recommendation and highlight the potential for more flexible preparation methods, including alternatives required by local market shortages. Our findings also support a 3-month in-use stability, which could improve patient convenience, reduce medication waste, and provide a more sustainable compounding approach at King Khaled University Hospital.</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"33 4","pages":"23"},"PeriodicalIF":3.4,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12238434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144585475","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":"Facile indazole-endowed thiadiazole hybrid derivatives as antibacterial, anti-diabetic and thymidine phosphorylase inhibitors: An insight to experimental, in-vitro biological potential and computational approaches.","authors":"Sabeen Arshad, Aneela Maalik, Wajid Rehman, Yousaf Khan, Mohammed M Alanazi, Hina Sarfraz, Liaqat Rasheed","doi":"10.1007/s44446-025-00003-9","DOIUrl":"10.1007/s44446-025-00003-9","url":null,"abstract":"<p><p>In this study, a series of newly synthesized indazole-based thiadiazole hybrid derivatives (1-13) were successfully synthesized from indazole-based thiosemicarbazides starting from the 5-methyl-1H-indazole-3-carboxylic acid. The structure of the synthesized compounds were confirmed through different spectroscopic techniques i.e. FT-IR, ¹HNMR, ¹³CNMR and HRMS. Furthermore, the biological potency of the synthesized indazole based thiadiazole scaffolds were assessed through in-vitro screening against thymidine phosphorylase and α-glucosidase enzymes. The biological potential of the synthesized derivatives was found to be influenced by the size, nature and position of substituents on the hybrid scaffold. Some derivatives displayed significant inhibitory activity, with some exhibiting superior potency compared to standard reference drugs. Moreover, the inhibitory potential of the derivatives were compared with standard 7-Deazaxanthine (7DX) and acarbose. Notably, derivatives 1, 2, 3, 5, 7, and 8 demonstrated remarkable inhibitory activity against thymidine phosphorylase and α-glucosidase, respectively. In addition, based on docking studies, the synthesized indazole-based thiadiazole scaffolds showed good binding interactions with different amino acids. Comparing the analogs' binding affinities and molecular interactions with standard reference drugs revealed favorable mechanisms. Similarly, an ADMET analysis was performed on the synthesized derivatives in order to predict their pharmacokinetics and drug-like characteristics. Using ADMET profiler, it was determined that the derivatives possessed drug-like properties. As a result of this study, indazole based thiadiazole hybrid derivatives have been designed, synthesized, and biologically evaluated as potent dual inhibitors of thymidine phosphorylase and α-glucosidase. These scaffolds display significant inhibitory potential, which were further analysed by docking and ADMET studies, emphasizing their potential as potent compounds for the development of new therapeutic agents that target these enzymes.</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"33 4","pages":"20"},"PeriodicalIF":3.4,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12238446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144585400","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":"Excipients in pharmaceuticals: mechanisms of hypersensitivity and the role of global pharmacovigilance.","authors":"Ruba Malkawi, Lora Altahrawi","doi":"10.1007/s44446-025-00004-8","DOIUrl":"10.1007/s44446-025-00004-8","url":null,"abstract":"<p><p>Excipients are important inactive components in drug formulations that ensure stability, bioavailability, and patient compliance. However, emerging evidence suggests that certain excipients, once considered inert, can cause hypersensitivity reactions in certain individuals. Such reactions include mild erythema due to systemic anaphylaxis and create clinical challenges that are difficult to handle. This review presents a systematic review of the existing literature on excipient hypersensitivity, with specific attention paid to commonly implicated excipients such as polyethylene glycol (PEG), parabens, and tartrazine. Hypersensitivity mechanisms (immune-mediated [IgE, T-cell] and non-immune) are discussed, along with their clinical features and diagnostic challenges. In addition, geographic variations in reporting are discussed, which in turn focus on the role of pharmacovigilance in the reduction of risk. Geographic variations in excipient hypersensitivity reporting are also discussed, highlighting disparities in pharmacovigilance efforts across different regions. This review also discusses recent work, regulatory issues, and desensitization protocols for the control of hypersensitivity reactions. Persistent surveillance and individual strategies are needed to enhance patient safety in the context of excipient-induced hypersensitivity.</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"33 4","pages":"18"},"PeriodicalIF":3.4,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12237841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144585477","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":"Polyphenolic profile, hepatoprotective evaluation, and molecular docking study of three palm tree species (Family Arecaceae).","authors":"Fadila M Hamed, Heba E Elsayed, Mohamed S Mady, Merhan E Ali, Asmaa A Ahmed, Sabah H Elgayed, Doaa Abouelenein, Giovanni Caprioli, Yara E Mansour, Ahmed M Mustafa, Elsayed K El-Sayed, Fatma A Moharram","doi":"10.1007/s44446-025-00017-3","DOIUrl":"10.1007/s44446-025-00017-3","url":null,"abstract":"<p><p>Arecaceae species are renowned in traditional medicine for treating inflammation and liver disorders. Herein, we aimed to identify the phenolic constituents and the hepatoprotective potential of the aqueous methanol extract (AME) of Aiphanes eggersii, Carpoxylon macrospermum, and Jubaeopsis caffra leaves, in a drug-induced liver injury in vivo model. The AMEs are considered safe until the maximum tested dose (5 g/kg). The two selected screening doses, 500 and 1000 mg/kg, displayed antioxidant activity with significant (P < 0.05) decline in the liver/body weight ratios (19.1-29.7%), liver enzymes (25.9-63.4%), and malondialdehyde (39.3-63.8%), while increasing reduced glutathione (2.1-3.2 folds) and superoxide dismutase (2.2-3.1 folds). Moreover, they demonstrated a significant anti-inflammatory effect (P < 0.05) with decline in NF-_KB p65 (32.7-64.5%), tumor necrosis factor-alpha (24.9-64.4%), and interleukin-1β (18.7-64.2%). Ultimately, significant (P < 0.05) antiapoptotic effects from the declined BAX (31.8-65.6%) and caspase-3 (23-69%), while increasing Bcl2 (2.7-5.7 folds). Ultimately, the histopathological investigation showed obvious hepatoprotective efficacy. The HPLC-MS/MS profiling revealed high phenolic content. As key phenolic attributes, chlorogenic acid is major in C. macrospermum and J. caffra, while vanillic in A. eggersii. Rutin is the principal flavonol in the three extracts (365.852-57970.205 μg/Kg), followed by hyperoside (62.764-7379.297 μg/Kg) and hesperidin (1225.976-1575.550 μg/Kg). The docking results show that rutin and hesperidin achieved the best fitting to SOD-1, with binding scores of -8.24 and -8.36 kcal/mol, while -8.0671 and -7.1735 kcal/mol with caspase-3, respectively with stable conformations revealed by 100 ns MD. In all, the investigated species exert significant hepatoprotective activity, at least partly, to their constitutive flavonoids and phenolic acids. However, further clinical investigation is still needed.</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"33 4","pages":"21"},"PeriodicalIF":3.0,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12238460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144585401","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":"Evaluation of the impact of Roclaglamide on MDA-MB-231 human breast adenocarcinoma cells by cell culture and molecular approaches.","authors":"Ruaa Sandakli, Ismail Saadoun, Ban Al-Joubori, Muhammad Nasir Khan Khattak","doi":"10.1007/s44446-025-00023-5","DOIUrl":"10.1007/s44446-025-00023-5","url":null,"abstract":"<p><p>1H - 2,3,3a,8b-tetrahydrocyclopenta[b]benzofuran, known as Rocaglamide (RocA) has gained recognition for its potential as a plant-derived therapeutic agent in cancer treatment. This study evaluates the impact of RocA on MDA-MB-231 human breast adenocarcinoma cells. Rocaglamide's effect was comprehensively evaluated through cell culture and molecular approaches with a series of experimental procedures. Cell viability was assessed using the MTT assay which determined the compound's cytotoxic effects. Following this, apoptosis induction in cancer cells was examined through Annexin V-FITC staining and flow cytometric analysis, providing insight into Rocaglamide's apoptotic mechanism of action. Additionally, the proliferation of cancer cells was evaluated by Propidium Iodide (PI) staining, elucidating Rocaglamide's antiproliferative effects on breast cancer cells. Furthermore, protein expression levels were analyzed using the Human XL Oncology Array Kit, shedding light on Rocaglamide's molecular targets and effect on various signaling pathways as demonstrated by how rocaglamide particularly attenuate the activity of proteins crucial for angiogenesis and tumor progression. MTT assay revealed a time-dependent decrease in cell viability. When treating MDA-MB-231 breast cancer cells with increasing concentrations of RocA, significant morphological changes were observed. Wound healing assay to evaluate the impact of RocA on cell migration indicated the induction of slight apoptosis in breast cancer cells. Flow cytometry-based apoptosis assay revealed that the total cell death in treated cells reached around 15%, compared to 7.9% in the untreated group. The expression of key oncogenic proteins after treatment of MDA-MB-231 cells with RocA indicated a noticeable reduction of VEGFA, AXL, and PAI-1 when compared to the untreated control. However, SNAIL1 and Endoglin increased significantly relative to untreated controls. Collectively, the findings demonstrate Rocaglamide's potential as a therapeutic agent for breast cancer and offer valuable insights into its mechanisms of action.</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"33 4","pages":"22"},"PeriodicalIF":3.4,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12238422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144585476","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":"Exploring chemical constituents and anti-inflammatory mechanisms of Semiaquilegiae Radix via an integrated strategy combining UHPLC-Q-TOF-MS analysis, network pharmacology and molecular docking.","authors":"Gengyi Shang, Xun Gao, Rong Guo, Ying Zhang, Chenfeng Zhang, Yun Shi, Kunming Qin","doi":"10.1007/s44446-025-00012-8","DOIUrl":"10.1007/s44446-025-00012-8","url":null,"abstract":"<p><p>Semiaquilegiae Radix demonstrates significant anti-inflammatory potential. However, comprehensive investigations into its anti-inflammatory effects remain sparse. This study seeks to systematically explore the chemical composition of Semiaquilegiae Radix and its underlying anti-inflammatory mechanisms utilizing Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS), network pharmacology, and molecular docking techniques. Initially, the chemical constituents of Semiaquilegiae Radix were identified and characterized via UHPLC-Q-TOF-MS/MS. Subsequently, the relevant targets were predicted and screened through databases such as PharmMapper and SwissTargetPrediction, in conjunction with protein-protein interaction (PPI) network analysis. Next, Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genome (KEGG) enrichment analyses were performed using the Metascape platform. Eventually, molecular docking was carried out via AutoDock Vina and visualized results with PyMOL. From Semiaquilegiae Radix, 19 active compounds were identified, 18 showing activity against inflammation-related targets. 510 drug targets were identified, 188 of which intersected with inflammation-related targets and PPI network analysis pinpointed six core potential targets. These overlapping targets are involved in several critical signaling pathways, including the AGE-RAGE signaling pathway in diabetic complications and pathways related to lipid metabolism and atherosclerosis. Molecular docking showed the primary seven active compounds can effectively bind to key targets. This study elucidates the chemical constituents of Semiaquilegiae Radix and highlights its multi-compound, multi-target, and multi-pathway mechanisms of action against inflammation. This research method provides a robust theoretical foundation for further experimental validation and the development of novel anti-inflammatory therapies.</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"33 4","pages":"19"},"PeriodicalIF":3.4,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12237846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144585399","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":"Emerging for non-invasive heparin delivery systems: recent advances, barriers, solutions, and applicability.","authors":"Musa Albatsh","doi":"10.1007/s44446-025-00022-6","DOIUrl":"10.1007/s44446-025-00022-6","url":null,"abstract":"<p><p>Nowadays, the use of unfractionated low molecular weight heparins through intravenous and subcutaneous routes has been limited by several delivery challenges. These include pharmacological activity fluctuations, bleeding issues, and numerous manufacturing restrictions. To address these issues, several efforts have been taken to find alternative routes for this medication. Unfortunately, the past and recent reviews were mainly explored the oral dosage forms of heparin and the other possible indications in practice. This review focuses on emerging efficient and non-invasive heparin options such as buccal, sublingual, oral, rectal and vaginal, transdermal, pulmonary and nasal. To do that, the past and recent studies were categorized into three main groups: (1) Conventional invasive heparin delivery methods; (2) Novel non-invasive heparin delivery systems; and (3) Heparin-based nanoparticles. The main challenges to use non-invasive heparin delivery systems were found to be negative charge and high molecular weight of heparin. Besides, the biological, biophysical, and pharmacological constraints could also limit the benefits of these alternatives. To overcome these issues, the following mechanisms have been used to enhance the delivery of heparin through several routes: (1) Improvement of cell-membrane penetration, (2) Changing of the tight-junctions, (3) Promoting the lipophilicity and (4) Preserving against acidic pH of the stomach. The applicability of alternative delivery options for heparin was mainly affected by overcoming the main penetration barriers. Nanoparticles were found to be effective in increasing the permeability, absorption, bioavailability and bioactivity of heparin.</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"33 3","pages":"17"},"PeriodicalIF":3.4,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12162448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276387","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":"Arabic version of the patient education materials assessment tool (PEMAT): translation and validation.","authors":"Marwan A Alrasheed, Aliyah Almobarak, Hisham M Alfayyadh, Abdulelah Alkahtani, Bander Balkhi","doi":"10.1007/s44446-025-00013-7","DOIUrl":"10.1007/s44446-025-00013-7","url":null,"abstract":"<p><strong>Background: </strong>Patient education materials (PEMs) are essential for enhancing health literacy and supporting informed decision-making. The Patient Education Materials Assessment Tool (PEMAT) is a widely recognized instrument for evaluating the understandability and actionability of PEMs. However, the absence of an Arabic version of PEMAT has restricted its applicability among Arabic-speaking populations. This study aims to translate and validate the Arabic versions of PEMAT-P (for print materials) and PEMAT-AV (for audiovisual materials).</p><p><strong>Methods: </strong>A systematic translation and cultural adaptation process was conducted following established guidelines. This included forward translation, back-translation, expert review, and cognitive debriefing. A total of 42 participants were recruited to evaluate the reliability of the Arabic PEMAT versions. Test-retest reliability was assessed using the Intraclass Correlation Coefficient (ICC), and internal consistency was evaluated with Cronbach's Alpha. Pearson correlation and the Standard Error of Measurement (SEM) were also calculated.</p><p><strong>Results: </strong>The Arabic PEMAT-P demonstrated moderate reliability in the understandability domain (ICC = 0.69, Cronbach's Alpha = 0.82) and strong reliability in the actionability domain (ICC = 0.74, Cronbach's Alpha = 0.85). The Arabic PEMAT-AV showed substantial reliability in the understandability domain (ICC = 0.77, Cronbach's Alpha = 0.87), but moderate reliability in the actionability domain (ICC = 0.64, Cronbach's Alpha = 0.78). Minimal discrepancies were observed between the original and back-translated versions, supporting the tool's linguistic and conceptual equivalence.</p><p><strong>Conclusion: </strong>The Arabic-translated PEMAT-P and PEMAT-AV are reliable tools for evaluating patient education materials. Their implementation can enhance health literacy and patient engagement in Arabic-speaking populations. Future research should focus on improving the actionability of audiovisual materials.</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"33 3","pages":"15"},"PeriodicalIF":3.4,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12141174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144227367","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":"Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.","authors":"Dian Jamel Salih, Saraa Hanna Barsoom, Ghazwan Fawzi Ahmed, Shler Qasim Hussien, Qais Al Ismaeel, Asaad A B Alasady, Tahseen A Alsalim, Ahmed Mohammed Salih","doi":"10.1007/s44446-025-00018-2","DOIUrl":"10.1007/s44446-025-00018-2","url":null,"abstract":"<p><strong>Background: </strong>Immune evasion in non-small cell lung cancer (NSCLC) is largely mediated by programmed death-ligand 1 (PD-L1), which is upregulated by interferon-gamma (IFN-γ)-induced STAT1 activation. Targeting this pathway may improve immunotherapy outcomes. Curcumin, a natural polyphenol, has been reported to modulate various oncogenic signaling pathways, but its role in inhibiting IFN-γ-driven PD-L1 expression in NSCLC remains unclear.</p><p><strong>Methodology: </strong>The NSCLC cell line A549 were treated with curcumin (50 µM) for 2 h before stimulation with IFN-γ (500 U/ml). Western blot, qRT-PCR, and immunofluorescence microscopy were used to evaluate STAT1 phosphorylation, PD-L1 expression, and the localization of phosphorylated STAT1 (p-STAT1). The expression of interferon-stimulated genes (ISGs), including SOCS1 and ISG15, was also examined. Additionally, the Resazurin assay was performed to assess cell viability.</p><p><strong>Results: </strong>IFN-γ significantly induced STAT1 phosphorylation, leading to a time-dependent upregulation of PD-L1 expression. Immunofluorescence confirmed that p-STAT1 is translocated to nucleus. Curcumin treatment inhibited STAT1 phosphorylation by 68% (p < 0.001), leading to a marked reduction in PD-L1 expression. Moreover, curcumin suppressed IFN-γ-induced SOCS1 (63%) and ISG15 (54%) expressions, indicating a broader effect on STAT1-mediated immune evasion. Finally, curcumin enhanced IFN-γ-mediated growth inhibition, reducing cell viability by 47% at 48 h (p < 0.01).</p><p><strong>Conclusion: </strong>Curcumin effectively inhibits IFN-γ-induced STAT1 phosphorylation and PD-L1 expression, downregulates ISGs, and enhances IFN-γ-mediated tumor suppression. These findings suggest that curcumin may serve as a therapeutic adjuvant in NSCLC, potentially improving immune checkpoint inhibitor (ICI) efficacy.</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"33 3","pages":"16"},"PeriodicalIF":3.4,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12141184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144227368","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}