{"title":"Syringin inhibits insulin resistance through the PI3K/AKT pathway.","authors":"Haitao Wang, Jianjian Han, Lu Yun, Xiaolei Wang","doi":"10.2478/acph-2026-0024","DOIUrl":"https://doi.org/10.2478/acph-2026-0024","url":null,"abstract":"<p><p>This study aims to investigate the effects of syringin on insulin resistance (IR) and its mechanisms using an IR model in HepG2 cells. IR was induced by 10<sup>4</sup> mol L<sup>-1</sup> insulin for 24 h, followed by syringin treatment at various concentrations for 48 h. Levels of glucose, triglycerides, TNF-α, IL-6, and GRP78 were measured, and protein expression of IRS-1, p-IRS-1, PI3K, p-PI3K, AKT, p-AKT, FoxO1, and p-FoxO1 was analysed by Western blot. Compared with controls, the IR model showed significant increases in glucose, triglycerides, TNF-α, IL-6, GRP78, and decreases in p-IRS1/IRS1, p-PI3K/PI3K, and p-AKT/AKT, with increased p-FoxO1/FoxO1 (all <i>p</i> < 0.01). Syringin (50-200 μg mL<sup>-1</sup>) significantly lowered glucose, triglycerides, TNF-α, IL-6, and GRP78, and reversed these signalling changes by upregulating p-IRS1/IRS1, p-PI3K/PI3K, p-AKT/AKT and downregulating p-FoxO1/FoxO1 (<i>p</i> < 0.05). Syringin effectively ameliorates insulin resistance in HepG2 cells, lowers glucose and triglycerides, and improves glucose-lipid metabolism, likely <i>via</i> the PI3K/AKT pathway.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"First-in-class HPLC-fluorescence method for quantification of roscovitine in plasma: Greenness assessment and application to pharmacokinetic studies in rats.","authors":"Ibrahim A Darwish, Nourah Z Alzoman","doi":"10.2478/acph-2026-0029","DOIUrl":"https://doi.org/10.2478/acph-2026-0029","url":null,"abstract":"<p><p>This research introduces a first-in-class high-performance liquid chromatography with fluorescence detection (HPLC-FD) method for the reliable quantification of ROS in plasma. The method relies on the native fluorescence of ROS, with excitation and emission set at 280 nm and 340 nm, resp. Sample preparation involved a simple one-step protein precipitation with methanol. Chromatographic resolution of ROS and pemigatinib (PEM), which served as the internal standard (IS), was achieved using Zorbax Eclipse Plus C18 HPLC column. The mobile phase consisted of methanol and formate buffer solution. The method was validated in compliance with ICH M10 guidelines. It showed linearity across concentration range of 50-1,500 ng mL<sup>-1</sup> (<i>R</i>² = 0.9991), with a lower limit of quantitation of 50 ng mL<sup>-1</sup>. Accuracy ranged from 96.8 to 103.4 %, and intra- and inter-day precision (RSD) were between 3.2 and 6.1 %. The method was successfully applied to quantify ROS in plasma samples from rats following administration of a single oral dose (25 mg kg<sup>-1</sup>), enabling the determination of key pharmacokinetic parameters, including <i>C</i> <sub>max</sub> (361.31 ng mL<sup>-1</sup>), <i>t</i> <sub>max</sub> (1.75 h, <i>t</i> <sub>½</sub> (2.867 h), <i>V</i> <sub>d</sub> (0.077 L kg<sup>-1</sup>), <i>CL</i> (0.018 L h<sup>-1</sup> kg<sup>-1</sup>), <i>AUC</i> (ng h mL<sup>-1</sup>) and and <i>MRT</i> (h). The greenness and practical applicability of the method were confirmed using four comprehensive independent metric tools. In comparison to previously reported bioanalytical approaches, the proposed method offers several practical advantages, such as reduced complexity and cost, a shorter run time, full validation, established greenness, and suitability for the clinical laboratory setting.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wenjie Ma, Nuan Jia, Hui Liao, Zhilei Li, Xiaodan Li
{"title":"Adverse event reporting of golimumab: A disproportionality analysis of the FDA Adverse Event Reporting System (FAERS) database.","authors":"Wenjie Ma, Nuan Jia, Hui Liao, Zhilei Li, Xiaodan Li","doi":"10.2478/acph-2026-0022","DOIUrl":"https://doi.org/10.2478/acph-2026-0022","url":null,"abstract":"<p><p>This study conducted a retrospective disproportionality analysis of 50,031 adverse drug event (ADE) reports from the FDA Adverse Event Reporting System (FAERS) database spanning Q2 2009 to Q3 2025, in which golimumab was identified as the primary suspect drug. Four disproportionality algorithms were simultaneously applied: the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS). A total of 397 positive signals were identified across 25 system organ classes (SOCs). The SOCs with concordant positive signals across all four algorithms were identified for infections and infestations and surgical and medical procedures. High-frequency signals included pneumonia, lower respiratory tract infection, influenza, nasopharyngitis, sinusitis and cellulitis. Comparison with the current prescribing information revealed several previously undocumented ADEs, including urinary tract infection, ear infection, flavivirus infection, Zika virus infection and Dengue fever. Twenty-nine positive malignancy signals absent from the prescribing information were identified, including basal cell carcinoma, colorectal cancer, cervical cancer and breast cancer. Time-to-onset analysis revealed that the risk of ADEs was the highest within the first few months of treatment initiation. Clinicians should rigorously monitor for infectious complications and malignancies when prescribing golimumab to ensure patient safety.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Analytical approach for conversion of conventional to green RP-HPLC methods for analysis of lipophilic neutral and basic active pharmaceutical ingredients.","authors":"Bojana Vulovska Trifunovska, Ana Atanasova, Packa Antovska, Katerina Brezovska, Aneta Dimitrovska, Natalija Nakov","doi":"10.2478/acph-2026-0021","DOIUrl":"https://doi.org/10.2478/acph-2026-0021","url":null,"abstract":"<p><p>Conventional RP-HPLC methods in pharmaceutical industry still dominantly rely on hazardous solvents like methanol (MeOH) and acetonitrile (ACN), presenting significant environmental and safety challenges. Although ethanol (EtOH) is recognized as greener alternative, isoeluotropic relationships between EtOH and these conventional solvents will broaden its implementation in routine HPLC analyses. To address this issue, the study presents an empirical approach using volu-metric fraction (<i>φ</i>) equivalence to establish initial chromatographic conditions, enabling predictable substitution of MeOH and ACN with EtOH in the LC mobile phase without altering other chromatographic parameters. The approach was established using adsorption (log-log) retention model across multiple C<sub>18</sub> stationary phases, applicable for lipophilic neutral and basic active pharmaceutical ingredients (APIs). For neutral APIs, <i>φ</i> MeOH ≈ 1.6 <i>φ</i> EtOH and <i>φ</i> ACN ≈ 1.1 <i>φ</i> EtOH, while for basic APIs <i>φ</i> MeOH ≈ 1.5 <i>φ</i> EtOH and <i>φ</i> ACN ≈ 1.0 <i>φ</i> EtOH. The general applicability was confirmed under isocratic conditions by successfully converting conventional RP-HPLC methods for an independent set of APIs into green, EtOH-based alternatives. Notably, this work extends previous research focused on lipophilic acidic to neutral and basic APIs, broadening its utility for the most widely used APIs in the pharmaceutical industry. The proposed framework supports sustainable analytical practices and improves laboratory safety without extensive method redevelopment.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149023636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A meta-analysis of the effects of <i>Zingiber officinale</i> on metabolic indices among patients with type 2 diabetes.","authors":"Qianjun Li, Min Li, Misbah Ullah Khan, Wei Cai","doi":"10.2478/acph-2026-0020","DOIUrl":"https://doi.org/10.2478/acph-2026-0020","url":null,"abstract":"<p><p>The metabolic effects of ginger (<i>Zingiber officinale</i>) on type 2 diabetes have been increasingly assessed in clinical trials, but the results remain inconsistent. In this updated meta-analysis, the Cochrane Library, Scopus, PubMed, Web of Science, and Google Scholar were searched from the inception to November 12, 2025, to find randomised controlled trials comparing the effect of ginger and placebo on the metabolic indexes of patients with type 2 diabetes. Pooling data from 13 articles with 837 participants indicated that treatment with ginger significantly decreased fasting blood sugar (FBS) (weighted mean difference (WMD) -16.22 mg per 100 mL, 95 % confidence interval (CI) (-25.49, -6.95), I<sup>2</sup> = 85.67 %), hemoglobin A1c (HbA1c) (WMD -0.49 %, 95 % CI (-0.86, -0.12), I<sup>2</sup> = 98.14 %), triglyceride level (WMD -17.04 mg per 100 mL, 95 % CI (-28.61, -5.47), I<sup>2</sup> = 71.30 %), and low-density lipoprotein cholesterol (LDL-C) (WMD -5.5 mg per 100 mL, 95 % CI (-10.98, -0.01), I<sup>2</sup> = 83.99 %). However, the beneficial effects of ginger on body mass index (BMI), homeostasis model assessment for insulin resistance (HOMA-IR), total cholesterol, high-density lipo-protein-cholesterol (HDL-C), and systolic and diastolic blood pressure did not meet the threshold of statistical significance. Ginger was more effective at a daily dose of less than 2000 mg (powdered rhizome of <i>Zingiber officinale</i> administered orally) and in males, individuals younger than 54 years, and individuals with a baseline HbA1c of more than 8 %.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sara Y Aldeghaither, Mohammad A Alfhili, Jawaher Alsughayyir
{"title":"Anacardic acid, a histone acetyltransferase inhibitor, stimulates hemolysis and eryptosis through energy depletion and calcium accumulation.","authors":"Sara Y Aldeghaither, Mohammad A Alfhili, Jawaher Alsughayyir","doi":"10.2478/acph-2026-0026","DOIUrl":"https://doi.org/10.2478/acph-2026-0026","url":null,"abstract":"<p><p>Histone acetyltransferase (HAT) inhibitors are promising epigenetic anticancer therapeutics. However, challenges remain regarding tissue specificity and off-target toxicity. This study presents a preclinical safety assessment of the HAT inhibitor anacardic acid (AA) in erythrocytes, given that anaemia is a clinically significant complication of chemotherapy. Freshly isolated erythrocytes were cultured <i>in vitro</i> with and without 1-10 µmol L<sup>-1</sup> of AA, then markers and mechanisms of cell death were examined by fluorescence-activated cell sorting, spectrophotometry, and potentiometry. AA treatment induced marked hemolysis independently of oxidative stress, which was paralleled by Ca<sup>2+</sup> accumulation and phosphatidylserine (PS) trans location. Morphological abnormalities were also observed upon AA treatment, including eryptotic loss of volume and elliptocyte phenotype. Co-treatment of AA with ATP, acetylsalicylic acid, NSC23766, or polyethylene glycol conferred significant cytoprotective effects. AA is cytotoxic to erythrocytes, causing both hemolysis and eryptosis, through non-genomic mechanisms involving Ca<sup>2+</sup> signalling, metabolic exhaustion, K<sup>+</sup> depletion, shrinkage and elliptocytic morphological aberrations. This toxic effect is sensitive to cyclooxygenase and Rac1 GTPase inhibition.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acta PharmaceuticaPub Date : 2026-06-30Print Date: 2026-06-01DOI: 10.2478/acph-2026-0013
Paulina Apostolova, Marija Atanasova Lazareva, Katarina Davalieva, Marija Arev, Dino Karpicarov, Petre Makreski, Irena Slaveska Spirevska, Ivana Mitrevska, Aleksandar Dimovski, Sanja Vranješ-Đurić, Emilija Janevik-Ivanovska
{"title":"Freeze-dried kit formulation and physicochemical assessment of a daratumumab-based radiopharmaceutical.","authors":"Paulina Apostolova, Marija Atanasova Lazareva, Katarina Davalieva, Marija Arev, Dino Karpicarov, Petre Makreski, Irena Slaveska Spirevska, Ivana Mitrevska, Aleksandar Dimovski, Sanja Vranješ-Đurić, Emilija Janevik-Ivanovska","doi":"10.2478/acph-2026-0013","DOIUrl":"10.2478/acph-2026-0013","url":null,"abstract":"<p><p>Daratumumab is a fully human anti-CD38 monoclonal antibody with strong potential as a targeting vector for therapeutic radionuclides. This study aimed to develop a freeze-dried daratumumab immunoconjugate kit by selecting a suitable chelator (DOTA-NHS, <i>p</i>-SCN-Bn-DOTA, or <i>p</i>-SCN-Bn-1B4M-DTPA) for the <sup>177</sup>Lu-labelling, optimising the freeze-drying formulation, and evaluating the physicochemical properties and purity profiles. Conjugation performed in carbonate buffer at elevated temperature enhanced chelator incorporation and supported the selection of daratumumab-<i>p</i>-SCN-Bn-DOTA as the most suitable candidate, achieving radiolabelling yield up to 99.8 % without additional purification. Among the evaluated freeze-dried formulations, a saline-based, buffer-free sucrose-mannitol formulation containing polysorbate 20 (S.F5) provided the most favourable characteristics, including minimal residual moisture and the highest monomer purity with non-detectable HMWS species under the applied SE-HPLC conditions. ATR-FTIR and Raman spectroscopy confirmed preservation of the antibody structural integrity after conjugation and freeze-drying. In an <i>in vitro</i> study using human serum, [<sup>177</sup>Lu]Lu-daratumumab-<i>p</i>-SCNBn-DOTA maintained higher radiochemical purity for 168 h than [<sup>177</sup>Lu]Lu-daratumumab-<i>p</i>-SCN-Bn-1B4MDTPA, indicating greater stability. These results support the feasibility of a ready-to-use freeze-dried daratumumab-<i>p</i>-SCN-Bn-DOTA kit for the <sup>177</sup>Lu-labelling.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":" ","pages":"1-16"},"PeriodicalIF":1.8,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148040240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acta PharmaceuticaPub Date : 2026-06-30Print Date: 2026-06-01DOI: 10.2478/acph-2026-0014
Erim Bešić, Valerije Vrček, Davor Šakić
{"title":"Electron paramagnetic resonance studies of free radicals: The research legacy of Janko N. Herak.","authors":"Erim Bešić, Valerije Vrček, Davor Šakić","doi":"10.2478/acph-2026-0014","DOIUrl":"10.2478/acph-2026-0014","url":null,"abstract":"<p><p>This review presents a chronological analysis of the scientific contributions of Professor Janko N. Herak (1937-2025), a Croatian biophysicist whose research played a major role in the development of electron para-magnetic resonance (EPR) spectroscopy in Croatia and significantly advanced the study of free radicals in biological systems. Beginning with his early work at Duke University under the mentorship of Prof. Walter Gordy, Herak investigated radiation-induced radicals in nucleic acid bases, nucleosides, and related biomolecules using EPR spectroscopy. During subsequent decades at the Ruđer Bošković Institute and later at the University of Zagreb Faculty of Pharmacy and Biochemistry, he conducted extensive studies of free radicals in irradiated single crystals of nucleic acid constituents, elucidating mechanisms of radical formation, hydrogen transfer, and structural rearrangements. His research later expanded to the investigation of oxidative processes in biological macromolecules, particularly the slow oxidation of plasma lipoproteins, where EPR spectroscopy and kinetic modelling provided insight into radical-mediated lipid peroxidation and the physicochemical basis of lipoprotein modification. In parallel, Herak explored long-range charge migration in nucleobase crystals and investigated metal-nucleobase interactions, integrating experimental EPR and ENDOR spectroscopy with theoretical modelling. These studies contributed to a deeper understanding of radical stabilisation, electronic structure, and energy transfer in ordered molecular systems. By situating Herak's work within the broader development of radiation chemistry and magnetic resonance spectroscopy, this review highlights the methodological rigour, conceptual contributions, and lasting scientific impact of his research on free radicals and biologically relevant molecular systems.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"76 2","pages":"1-22"},"PeriodicalIF":1.8,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acta PharmaceuticaPub Date : 2026-06-30Print Date: 2026-06-01DOI: 10.2478/acph-2026-0016
Ana Penava, Lais Pessanha De Carvalho, Jana Held, Goran Poje, Zrinka Rajić, Ivana Perković
{"title":"<i>β</i>-Carboline and chloroquine hybrids as potent antiplasmodial agents: Design, synthesis and biological evaluation.","authors":"Ana Penava, Lais Pessanha De Carvalho, Jana Held, Goran Poje, Zrinka Rajić, Ivana Perković","doi":"10.2478/acph-2026-0016","DOIUrl":"https://doi.org/10.2478/acph-2026-0016","url":null,"abstract":"<p><p>A series of thirteen novel <i>β</i>-carboline and chloroquine (CQ) hybrids was designed and synthesized. The compounds were evaluated for <i>in vitro</i> antiplasmodial activity against <i>Plasmodium falciparum</i> strains 3D7 (CQ-sensitive) and Dd2 (multidrug-resistant). All compounds exhibited potent activity, with <i>IC</i> <sub>50</sub> values in the nanomolar to low micromolar range, while retaining potency against the resistant strain (1.0 to 365.5 nmol L<sup>-1</sup> for 3D7 and from 2.2 to 2415.3 nmol L<sup>-1</sup> for Dd2 strain). Several compounds were more active against Dd2, then against 3D7 strain with resistance index (RI) lower than 1. Moreover, nearly all compounds showed lower RI values compared to CQ which additionally underscores their outstanding activity. At the highest tested concentration (250 μmol L<sup>-1</sup>), no cytotoxicity was observed in HepG2 cells, resulting in favourable selectivity indices expressed as lower limits. Overall, the obtained results confirm strong antiplasmodial activity of the <i>β</i>-carboline and chloroquine hybrids as promising antiplasmodial candidates, particularly due to their activity against resistant strains and improved selectivity.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"76 2","pages":"1-26"},"PeriodicalIF":1.8,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acta PharmaceuticaPub Date : 2026-06-30Print Date: 2026-06-01DOI: 10.2478/acph-2026-0010
Haichun Yu, Ashraf Albrakati, Ejaz Akbar Wani, Ying Li
{"title":"Pelargonidin protects retinal ganglion cells in a streptozotocin-induced diabetic rat model by reducing intraocular pressure, suppressing TGF-β and activating JAK2/STAT3 signalling pathway.","authors":"Haichun Yu, Ashraf Albrakati, Ejaz Akbar Wani, Ying Li","doi":"10.2478/acph-2026-0010","DOIUrl":"10.2478/acph-2026-0010","url":null,"abstract":"<p><p>Diabetic retinopathy (DR) is one of the primary causes of vision impairment, affecting individuals with diabetes, and is marked by the neurodegeneration of the retina along with increased intraocular pressure (IOP). This study sought to determine the effects of pelargonidin on extracellular matrix (ECM) modulation and the inhibition of transforming growth factor-β (TGF-β) and Janus Kinase 2/Signal Transducer and Activator of Transcription 3 (JAK2/STAT3) pathway in retinal ganglion cells of streptozotocin-induced diabetic rats. Male Sprague-Dawley rats (180-200 g) were rendered diabetic by intraperitoneal administration of streptozotocin (STZ). The rats were divided into 5 groups: control, diabetic model (STZ), STZ + low dose pelargonidin (12.5 mg kg<sup>-1</sup> per day), STZ + medium dose pelargonidin (25 mg kg-1 per day) and STZ + high dose pelargonidin (50 mg kg<sup>-1</sup> per day). IOP was monitored using a tonometer. Whole-mount retinal immunofluorescence staining using RNA-binding protein with multiple splicing (RBPMS) was performed to assess retinal ganglion cell (RGC) density. Protein expression levels of apoptotic markers, ECM components, and TGF-β and JAK2/STAT3 signalling pathways were evaluated by Western blotting. Pelargonidin treatment dose-dependently reduced the elevated IOP. Importantly, immunofluorescence analysis revealed a marked dose-dependent preservation of retinal ganglion cell (RGC) density: STZ-induced RGC loss was significantly reversed by pelargonidin, with the highest dose restoring RGC density to near-control or higher levels in both the central and peripheral retina. This was achieved <i>via</i> modulation of apoptosis-related proteins through the upregulation of Bcl-xL, Bcl-2, and downregulation of Bad, Bax and cleaved caspase-3. Furthermore, pelargonidin modulated ECM remodelling protein expression in the RGC layer. In particular, TGF-β2/Smad2/3 signalling was downregulated, and the JAK2/STAT3 pathway was upregulated. By reducing IOP, preserving RGC density, modulating ECM deposition, inhibiting TGF-β and upregulating the JAK2/STAT3 pathway, pelargonidin exerts protective effects against diabetic retinal injury. The results of this study further confirm the pharmacological potential of pelargonidin as a therapeutic agent for diabetic retinopathy.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":" ","pages":"1-15"},"PeriodicalIF":1.8,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147653602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}