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":"https://doi.org/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":""},"PeriodicalIF":1.4,"publicationDate":"2026-04-09","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}
Acta PharmaceuticaPub Date : 2026-03-25Print Date: 2026-03-01DOI: 10.2478/acph-2026-0006
Yang Long, Yuan Xiao, Chun Chen, Chao Peng, Yuxi Zhang
{"title":"The effect of astragaloside IV on a model of isoproterenol-induced hypertrophic injury in H9c2 cells.","authors":"Yang Long, Yuan Xiao, Chun Chen, Chao Peng, Yuxi Zhang","doi":"10.2478/acph-2026-0006","DOIUrl":"https://doi.org/10.2478/acph-2026-0006","url":null,"abstract":"<p><p>The objective of this study was to explore the protective effect of astragaloside IV on a model of isoproterenol-induced (ISO) hyper-trophic injury in rat cardiomyocytes H9c2 (cell line derived from embryonic BD1X rat heart tissue). A cell hypertrophy injury model was established (H9c2 cells treated with 100 μmol L-1 ISO). The cells were divided into normal control, a model group, and an astragalo-side IV group at several concentrations. Astragaloside IV was pre-administered for 2 hours, followed by ISO treatment for 24 hours. Cell viability, cell surface area, apoptosis rate, lactate dehydrogenase (LDH) activity, reactive oxygen species (ROS), superoxide dismutase (SOD), the mRNA levels of Bcl-2, Bax, p62, and LC3, the protein expressions of Sirt1, p62, caspase-3, beclin, and p53 and the LC3II/LC3I ratio were detected. Astragaloside IV significantly alleviated ISO-induced hypertrophy injury in H9c2 cells, reduced cell surface area and LDH release, decreased apoptosis rate and intracellular ROS levels, increased SOD levels, upregulated the expressions of autophagy-related mRNA and proteins, and downregulated the expressions of apoptosis-related mRNA and proteins. Astragaloside IV can effectively inhibit ISO-induced hypertrophy and apoptosis in H9c2 cells, and its mechanism may be related to promoting auto-phagy and reducing oxidative stress.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"76 1","pages":"1-12"},"PeriodicalIF":1.4,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147508729","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":"H3 relaxin mediated neuroprotection in Alzheimer's disease pathology induced by streptozotocin in mouse models: Impact on memory improvement, autophagy and PI3K/Akt-mTOR signalling pathway.","authors":"Huiyu Zhao, Yuhong Sun, Shaik Althaf Hussain, Hua Gao","doi":"10.2478/acph-2026-0009","DOIUrl":"https://doi.org/10.2478/acph-2026-0009","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is characterised by β-amyloid (Aβ) plaque accumulation and tau hyperphosphorylation. H3 relaxin, a neuro-peptide, is known to exert neuroprotective effects. In this study, we investigated how H3 relaxin confers neuroprotection in a streptozotocin (STZ)-induced mouse model and modulates PI3K/Akt-mTOR signalling. Mice were divided into four groups (<i>n</i> = 6 per group): control (saline), STZ, STZ + H3 relaxin, and STZ + donepezil. Following STZ induction, H3 relaxin (1 µg per day) was administered intracerebro ventricularly (ICV) for 14 consecutive days, whereas donepezil (2.5 mg kg<sup>-1</sup> per day) was administered orally for the same duration. Cognitive performance was assessed using the Morris water maze (MWM) test. Aβ deposition in the cortex was evaluated through immunohistochemistry. Western blotting was conducted for tau phospho rylation, PI3K/Akt/mTOR signalling, and autophagy markers in the hippocampus. Oxidative stress and inflammation markers were measured using ELISA. H3 relaxin markedly improved memory by decreasing escape latency and duration while spending more time in the target quadrant in the MWM test. Additionally, H3 relaxin reduced Aβ plaque burden and tau phosphorylation (Ser396/404) while enhancing PI3K/Akt-mTOR signalling. Oxidative stress was attenuated, as evidenced by increased GSH and HO-1 levels and reduced MDA and H<sub>2</sub>O<sub>2</sub> concentrations. Moreover, markers of inflammation, NF-κB and TNF-α were suppressed. Overall, H3 relaxin ameliorated cognitive deficits in STZ-induced AD mice through modulation of impaired PI3K/Akt-mTOR signalling, reduction of Aβ and tau pathology, and promotion of autophagy.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"76 1","pages":"1-18"},"PeriodicalIF":1.4,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147508651","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 : 2026-03-25Print Date: 2026-03-01DOI: 10.2478/acph-2026-0003
Fawei Yuan, Dong Liu
{"title":"Sedation management in mechanically ventilated intensive care unit patients: Meta-analysis review.","authors":"Fawei Yuan, Dong Liu","doi":"10.2478/acph-2026-0003","DOIUrl":"10.2478/acph-2026-0003","url":null,"abstract":"<p><p>Sedation is crucial for managing mechanically ventilated intensive care unit (ICU) patients, but agents differ in their effects. Propofol, benzodiazepines and <i>α</i> <sub>2</sub>-agonists are commonly used, yet their comparative impact remains unclear. This review searched OVID MEDLINE and Embase from January 2006 to June 2025 for randomised controlled trials in adult ICU patients. The primary outcome was duration of mechanical ventilation; secondary outcomes were ICU length of stay, delirium and mortality. Twenty-six trials (<i>N</i> = 4,993) were included. Dexmedetomidine significantly shortened mechanical ventilation (mean difference [MD] -0.60 days; 95 % CI -0.89 to -0.31), with larger effects <i>versus</i> midazolam (MD -1.25 days) and mixed comparators (MD -1.23 days), but not <i>versus</i> propofol (MD -0.34 days). ICU stay was also reduced (MD -0.94 days; 95 % CI -1.49 to -0.39). Delirium risk decreased (odds ratio [OR] 0.58; 95 % CI 0.38-0.87). No mortality difference was found. Dexmedetomidine is therefore associated with a modest but clinically meaningful reduction in ventilation time, ICU stay and delirium, particularly when compared with benzodiaze-pines, though benefits over propofol are less certain.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":" ","pages":"1-13"},"PeriodicalIF":1.4,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145909989","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 : 2026-03-25Print Date: 2026-03-01DOI: 10.2478/acph-2026-0008
Amal Aloud, Hayat Alzahrani, Shaista Arzoo, Raeesa Mohammed, Islam A Alredah, Alaa R Khatab
{"title":"Beneficial effect of omega-3 fatty acids supplementation on leaky gut, inflammation and oxidative stress in propionic acid-induced autism in aged rats.","authors":"Amal Aloud, Hayat Alzahrani, Shaista Arzoo, Raeesa Mohammed, Islam A Alredah, Alaa R Khatab","doi":"10.2478/acph-2026-0008","DOIUrl":"https://doi.org/10.2478/acph-2026-0008","url":null,"abstract":"<p><p>This study examined the effects of omega-3 fatty acids supplementation on gut barrier integrity, systemic inflammation, neurotrans-mission and oxidative stress, in an aged rat model of propionic acid (PPA)-induced neurotoxicity. Twenty-four aged male rats were divided into four groups: control, omega-3, PPA and PPA + omega-3. Serum cytokines, tight-junction proteins (TJP1), dopamine, serotonin, short-chain fatty acids (SCFAs), oxidative stress markers, and histopathology of the brain and small intestine were evaluated. PPA exposure significantly increased tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and reduced TJP1 expression, confirming gut barrier disruption and systemic inflammation. Omega-3 fatty acids supplementation selectively reduced IL-6 but did not reverse PPA-induced TNF-α elevation or oxidative stress. CLDN2 expression increased in PPA + omega-3 rats, suggesting a compensatory but incomplete barrier response. Dopamine, serotonin, and SCFA levels showed upward trends with supplementation but were not statistically significant. Histological analysis demonstrated partial preservation of neuronal and intestinal structure in the PPA + omega-3 group. Overall, omega-3 fatty acids exerted modest anti-inflammatory effects but failed to fully restore oxidative balance or barrier integrity in aged rats, suggesting that omega-3 fatty acids may be more effective as a preventive rather than restorative intervention in ageing-related gut-brain axis disruption.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"76 1","pages":"1-17"},"PeriodicalIF":1.4,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147508588","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 : 2026-03-25Print Date: 2026-03-01DOI: 10.2478/acph-2026-0007
Kang Hu, Anran Zhang, Yuan Shi, Huizhen Yuan, Xiangxi Kong, Jun Ma
{"title":"Sexually dimorphic and time-dependent influence of active avoidance learning by vilazodone in C57BL/6J mice.","authors":"Kang Hu, Anran Zhang, Yuan Shi, Huizhen Yuan, Xiangxi Kong, Jun Ma","doi":"10.2478/acph-2026-0007","DOIUrl":"https://doi.org/10.2478/acph-2026-0007","url":null,"abstract":"<p><p>The effects of vilazodone (VZD) on the acquisition of active avoidance behavior were examined in C57BL/6J mice. Both female and male mice were assigned to three groups (<i>n</i> = 8 per group per sex): the vehicle control group (VEH), the 0.5 mg kg<sup>-1</sup> vilazodone lower dose group (VZD0.5) and the 1 mg kg<sup>-1</sup> vilazodone higher dose group (VZD1.0). Spontaneous locomotion and anxiety-like behaviour were assessed after drug administration intraperitoneally in an open field test (OFT). Another cohort of mice was trained in a three-day shuttle box active avoidance test (AAT) after drug administrations with the aim of evaluating the effects of VZD on the acquisition of active avoidance behaviour. In the OFT, VZD decreased freezing time in the corner area in both female and male mice, indicating reduced anxiety-like behaviours. In the AAT, the active avoidance rate was significantly improved on day 1 in female mice and day 2 in male mice, suggesting that VZD facilitated active avoidance learning with sexual dimorphism. Furthermore, the increased active avoidance rates were negatively correlated with freezing time during training. Interestingly, these group differences and correlations diminished on day 3, implying that the facilitation was restricted to early training phases. Collectively, VZD facilitates the acquisition of active avoidance behaviour in mice with distinct sexual dimorphism and temporal dynamics.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"76 1","pages":"1-15"},"PeriodicalIF":1.4,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147508692","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 : 2026-03-25Print Date: 2026-03-01DOI: 10.2478/acph-2026-0001
Zhu Wang, Guoping Gan, Haiping Yao
{"title":"Gastrointestinal risk profile of tigecycline, omadacycline and eravacycline: Evidence from the FDA adverse event reporting system.","authors":"Zhu Wang, Guoping Gan, Haiping Yao","doi":"10.2478/acph-2026-0001","DOIUrl":"10.2478/acph-2026-0001","url":null,"abstract":"<p><p>This study assessed the gastrointestinal (GI) safety profiles of tigecycline, omadacycline, and eravacycline through a retrospective disproportionality analysis of reports submitted to the FDA Adverse Event Reporting System (FAERS) between the second quarter of 2005 and the first quarter of 2024. Among 3,261 adverse event reports associated with these agents, 809 (24.8 %) involved gastrointestinal disorders, with tigecycline accounting for the largest proportion (588 reports), followed by omadacycline (197) and eravacycline (24). Disproportionality analysis revealed that gastrointestinal disorders ranked among the top three system organ classes for all three drugs, with positive signals observed for tigecycline (ROR = 1.63), omadacycline (ROR = 3.04), and eravacycline (ROR = 1.79), the strongest association being with omadacycline. While most GI events were consistent with known safety information, several unexpected signals were identified, including gastrointestinal haemorrhage, melena, small-intestinal obstruction, tongue discolouration, and intestinal perforation for tigecycline, as well as lip swelling and tongue discolouration for omadacycline. The median onset times of GI events were 4, 0, and 2.5 days for tigecycline, omadacycline, and eravacycline, respectively, with nearly half of the events occurring within three days of treatment initiation. These findings reveal distinct GI safety patterns among newer tetracycline-derived antibiotics and underscore the importance of early and route-specific monitoring in clinical practice.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":" ","pages":"1-20"},"PeriodicalIF":1.4,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145779695","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 : 2026-03-25Print Date: 2026-03-01DOI: 10.2478/acph-2026-0005
Ivana Mitrevska, Marina Chachorovska, Gjorgji Petrushevski
{"title":"Predictive analytical workflow for rapid structure elucidation and <i>in silico</i> toxicological qualification of an unidentified impurity in cefixime granules for oral suspension.","authors":"Ivana Mitrevska, Marina Chachorovska, Gjorgji Petrushevski","doi":"10.2478/acph-2026-0005","DOIUrl":"https://doi.org/10.2478/acph-2026-0005","url":null,"abstract":"<p><p>During in-use stability testing of cefixime granules for oral suspension, an impurity with a relative retention time of 0.19 was consistently detected and increased during storage. To ensure regulatory compliance and patient safety, the impurity was structurally identified and toxicologically qualified. A laboratory-scale formulation and commercial products were studied under refrigerated and ambient conditions. The impurity was isolated by automated fraction collection and characterised by liquid chromatography-mass spectrometry and tandem mass spectrometry. Kinetic evaluation showed pseudo-first-order formation, with faster accumulation at ambient temperature. The impurity was identified as a <i>γ</i>-lactone degradation product of cefixime, present as multiple stereoisomers stabilised under acidic conditions. <i>In silico</i> toxicological assessment using complementary platforms indicated no additional structural alerts, no mutagenic potential, and negligible acute toxicity. The impurity forms only after prolonged storage of reconstituted suspensions and is classified as an ICH M7 Class 5 impurity, requiring no further genotoxicity testing. The applied analytical-computational workflow provides an efficient approach for impurity qualification in <i>β</i>-lactam antibiotics.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"76 1","pages":"1-25"},"PeriodicalIF":1.4,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147508690","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":"Pan-Cdk inhibitor ZK304709 suppresses Cdc20 expression and potentiates the anticancer activity of apcin in HeLa cervical cancer cells.","authors":"Xiangyang Le, Qingsong Chen, Shuyang Cao, Gaoyun Hu, Qianbin Li, Zhuo Chen","doi":"10.2478/acph-2026-0002","DOIUrl":"10.2478/acph-2026-0002","url":null,"abstract":"<p><p>Cell division cycle 20 homologue (Cdc20), a key regulator of the anaphase-promoting complex/cyclosome (APC/C), is frequently overexpressed in human cancers and represents a promising therapeutic target. However, monotherapy targeting Cdc20 has shown limited efficacy, partly due to compensatory activation of cyclin-dependent kinase 1 (Cdk1). In this study, we investigated the combinatorial potential of the pan-Cdk inhibitor ZK304709 with the Cdc20 inhibitor apcin in HeLa cervical cancer cells. Transcriptomic analysis revealed that both <i>CDC20</i> and <i>CDK1</i> are upregulated in cervical cancer tissues. Mechanistically, apcin treatment induced cyclin B1 accumulation and enhanced Cdk1 phosphorylation at Thr161, suggesting feedback activation. In contrast, ZK304709 reduced <i>p</i>-Cdk1(T161) levels and suppressed Cdc20 expression at both protein and mRNA levels. Functionally, the combination of apcin and ZK304709 synergistically inhibited cell proliferation and induced G2/M phase arrest in HeLa cells. These findings demonstrate that dual inhibition of Cdk1 and Cdc20 disrupts compensatory signalling pathways and enhances antitumour efficacy in HeLa cells, providing a rational strategy for combination therapy in cervical cancer.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":" ","pages":"1-13"},"PeriodicalIF":1.4,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145779710","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":"Comparative biodistribution analysis of umbilical cord mesenchymal stromal cells <i>via</i> different administration routes in rabbit models.","authors":"Liang Xiao, Chunlin Liu, Yuqian Wang, Fucheng Xiao, Jiahua Cai, Shoukang Qu, Xiaojuan Xu, Xiaoliang Wang, Yue Liu, Yutao Peng, Jia Liu","doi":"10.2478/acph-2026-0004","DOIUrl":"10.2478/acph-2026-0004","url":null,"abstract":"<p><p>Umbilical cord mesenchymal stem cells (UC-MSCs) have shown therapeutic potential in renal diseases due to their homing ability. This study compared the effects of three administration routes (intravenous, local renal injection, and interventional injection) on UC-MSC distribution in kidney tissue. Eighteen New Zealand rabbits were assigned to the three groups (<i>n</i> = 6 each), and DiI-labelled UC-MSCs were tracked using confocal microscopy to evaluate their distribution in the kidney, lung, and brain. Local renal injection led to high MSC concentrations at the injection site, but distribution to the contralateral kidney was minimal and comparable to that of intravenous injection. Intravenous delivery <i>via</i> the marginal ear vein was simple and convenient but resulted in limited renal homing (< 1 %) and no significant difference between kidneys. Interventional injection achieved the highest delivery efficiency (12.4 %) and a more uniform renal distribution. Notably, inflammatory cytokine levels (IL-6, TNF-α, IL-10) were significantly elevated in the local injection group (<i>p</i> < 0.05). These results indicated that the choice of administration route critically affects MSC targeting and therapeutic potential, and interventional injection may offer the most effective strategy for precise UC-MSC delivery in renal therapy.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":" ","pages":"1-17"},"PeriodicalIF":1.4,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145909976","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}