Frontiers in Pharmacology最新文献

{"title":"Neurological adverse events associated with baclofen: a pharmacovigilance study based on FDA adverse event reporting system.","authors":"Yunhan Zhao, Haoxiang Hu, Jiesheng Mao, Jianghai He, Yihan Zhang, Xiaokai Yang","doi":"10.3389/fphar.2025.1569602","DOIUrl":"10.3389/fphar.2025.1569602","url":null,"abstract":"<p><strong>Background: </strong>Baclofen, a centrally acting muscle relaxant, is widely utilized for the management of muscle spasms and alcohol use disorders associated with conditions. However, its neurological safety and tolerability in a large population remain limited. This study aimed to assess the neurological safety and potential risks of baclofen in the real world.</p><p><strong>Methods: </strong>Data covering the period from the first quarter of 2004 to the third quarter of 2024 were collected from the Food and Drug Administration Adverse Event Reporting System (FAERS). Four disproportionality analysis methods were employed: the Reporting Odds Ratio, the Proportional Reporting Ratio, Bayesian Confidence Propagation Neural Network, and the Multi-item Gamma Poisson Shrinkage (MGPS). These methods were used to detect and evaluate adverse events Adverse drug events associated with baclofen. Additionally, the time to onset analysis was conducted.</p><p><strong>Results: </strong>A total of 432 neurological-related preferred terms (PTs) were identified. The number of PT that were positive for all four algorithms was 40, and the top 5 PT were Hypotonia, Encephalopathy, Coma, Unresponsive to stimuli, and Cerebrospinal fluid leakage. The top 5 PTs for ROR values are Intracranial hypotension [ROR 66.24 (55.45-79.13)], Cerebrospinal fluid leakage [ROR 51.34 (45.84-57.51)], Autonomic dysreflexia [ROR 47.4 (32.27-69.63)], Basal ganglion degeneration [ROR 33.03 (18.54-58.84)], Sciatic nerve palsy [ROR 21.6 (11.14-41.87)]. The median onset time for baclofen -related ADEs was 27 days. Most cases (n = 241, 55.5%) occurred within the first month of baclofen administration. In an analysis of severe vs. non-severe ADEs, the study found that the incidence of severe cases was higher than that of non-severe cases, with no gender-related differences observed.</p><p><strong>Conclusion: </strong>This study identified clinically significant PTs using four different algorithms and performed gender subgroup analysis. The TTO analysis indicated that the onset of most ADEs occurred within 27 days. Furthermore, the frequency of severe ADEs was higher than that of non-severe ones. Clinicians should closely monitor for neurological adverse effects caused by baclofen, particularly severe ADEs, and consider individualized dosing strategies. Further research based on real-world data is needed to validate these findings.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1569602"},"PeriodicalIF":4.4,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12116621/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sphingosine 1-phosphate receptor 1 modulators exert neuroprotective effects in central nervous system disorders.","authors":"Shouming Chen, Lan Wu, Bingchen Lang, Guoyan Zhao, Wensheng Zhang","doi":"10.3389/fphar.2025.1516991","DOIUrl":"10.3389/fphar.2025.1516991","url":null,"abstract":"<p><p>The sphingosine 1-phosphate (S1P) signaling pathway has important and diverse functions. S1P receptors (S1PRs) are involved in the regulation of lymphocyte trafficking, cardio-cerebral function, vascular permeability, and bronchiolar tone, and have been recognized as therapeutic targets for a variety of diseases. A number of drugs related to the S1P signaling pathway have been approved for clinical use in the treatment of multiple sclerosis, and many similar drugs are also currently being tested in clinical trials at various stages. It appears that S1PR modulators may not only be useful for the treatment of multiple sclerosis, but may also have therapeutic effects on other types of central nervous system (CNS) disorders. The present review focuses on the therapeutic potential of S1PR1 modulators for treating disorders of the CNS.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1516991"},"PeriodicalIF":4.4,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12116545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioactive fraction isolated from <i>Curcuma angustifolia</i> rhizome exerts anti-diabetic effects <i>in vitro, in silico</i> and <i>in vivo</i> by regulating AMPK/PKA signaling pathway.","authors":"P Kavya, M Gayathri","doi":"10.3389/fphar.2025.1570533","DOIUrl":"10.3389/fphar.2025.1570533","url":null,"abstract":"<p><p><i>Curcuma angustifolia</i> Roxb. is a therapeutic herb and a member of the Zingiberaceae family. A potential bioactive fraction was isolated from the methanolic extract of <i>Curcuma angustifolia</i> rhizome using column chromatography, and it was characterised using ¹H-NMR, GCMS and FTIR analyses. The bioactive fraction showed no toxic effects on the HepG2 cell line and it demonstrated inhibition of α-amylase and α-glucosidase enzymes <i>in vitro with</i> IC₅₀ values of 2.75 ± 0.09 and 4.9 ± 0.07 µM, respectively. Molecular docking analysis also showed that nerolidol, the major constituent of the bioacive fraction inhibits α-amylase and α-glucosidase enzymes competitively, supporting <i>in vitro</i> antihyperglycemic activity. ADMET analysis showed that nerolidol has the necessary physicochemical parameters for drug-likeness. It also complies with Lipinski's rule, indicating that its chemical structure is appropriate for designing safe and bioavailable oral drug. The antidiabetic efficacy of the isolated bioactive fraction was validated in type 2 diabetic albino wistar rats induced with a high-fat diet and a low dose (35 mg/kg bw) of streptozotocin. After 28 days of intervention, the lower and higher doses of the bioactive fraction (100 and 200 mg/kg BW) substantially decreased fasting blood glucose levels and ameliorated hyperglycemia, glucose intolerance, insulin resistance, and hyperlipidemia. The higher dose of bioactive fraction significantly ameliorated liver, kidney, and lipid profiles compared to the standard drug metformin and exhibited lower toxicity in the liver, kidney, pancreas, and epididymal adipose tissue than the lower dose of the bioactive fraction. Gene expression studies revealed that the bioactive fraction upregulated AMPK through downregulating PKA, a mechanism similar to the action of metformin. The results indicate that the isolated bioactive fraction could be a natural alternative to synthetic antidiabetic medications.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1570533"},"PeriodicalIF":4.4,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12116452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations between ionomic profile and metabolic abnormalities in a murine model of sodium sulfide induced alopecia areata.","authors":"Luning Li, Zhen Sun, Wenxue Sun, Yujuan Zhai, Na Ding, Wei Wang","doi":"10.3389/fphar.2025.1507348","DOIUrl":"10.3389/fphar.2025.1507348","url":null,"abstract":"<p><strong>Background: </strong>Alopecia areata (AA) is a common autoimmune disorder marked by non-scarring hair loss, which imposes significant psychosocial stress on patients. To investigate key metabolites and ions involved in AA's pathogenesis, we utilized gas chromatography-mass spectrometry (GC-MS) for non-targeted metabolomics and inductively coupled plasma mass spectrometry (ICP-MS) for ionomics.</p><p><strong>Methods: </strong>A total of 36 six-week-old Kunming mice were divided into control (n = 12), an AA model (n = 12), and tofacitinib-treated groups (n = 12). A mouse model of AA was established by sodium sulfide (Na₂S) induction in both the model and treatment groups, while the treatment group (n = 12) received tofacitinib treatment at a dose of 1 mg/kg. GC-MS was used to determine the metabolic profiling in serum samples, and ICP-MS was applied to assess ionomic changes in the serum samples. Potential metabolites and ions were identified using orthogonal partial least squares-discriminant analysis (OPLS-DA). Subsequently, MetaboAnalyst 5.0 and the Kyoto Encyclopedia of Genes and Genomes database (KEGG) were used to map the metabolic pathways. Spearman correlation analysis was conducted to identify relationships and potential regulatory interactions between differential metabolites and individual ions.</p><p><strong>Results: </strong>Metabolomics analysis revealed that D-lactic acid, glycolic acid, linoleic acid, petroselinic acid, and stearic acid are key differential metabolites between the control, AA model, and tofacitinib groups. Pathway analysis highlighted that the biosynthesis of unsaturated fatty acids and linoleic acid metabolism are pivotal pathways implicated in the onset and progression of AA. Furthermore, ionomics analysis identified magnesium, aluminum, titanium, and nickel as differential ions among the three groups. The integrated metabolomics and ionomics analysis indicated that linoleic acid, a key differential metabolite according to the KEGG database, shows a positive correlation with phosphorus, vanadium, magnesium, and zinc. Among these, Mg²⁺ (Mg²⁺) play a crucial role in modulating CD8⁺ T cell infiltration, thereby influencing the disease progression in AA.</p><p><strong>Conclusion: </strong>Tofacitinib inhibits CD8⁺ T cell infiltration in hair follicles affected by sodium sulfide-induced AA by modulating the linoleic acid metabolism-Mg²⁺ pathway. Our findings offer new insights and potential avenues for the clinical diagnosis and treatment of AA, suggesting that targeting metabolic and ionic pathways could enhance therapeutic outcomes.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1507348"},"PeriodicalIF":4.4,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12117264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ginsenoside in the treatment of type 2 diabetes and its complications: a promising traditional chinese medicine.","authors":"Yingying Liu, Yang Ju, Yanjun Wang, Xiaoyan Cui, Yunwei Sun, Ping Hu, Yan Chen","doi":"10.3389/fphar.2025.1593780","DOIUrl":"10.3389/fphar.2025.1593780","url":null,"abstract":"<p><p>Type 2 diabetes mellitus (T2DM), a chronic condition commonly observed in adults, particularly among the elderly, is characterized by a dysfunctional insulin response that impairs blood glucose regulation, resulting in persistent hyperglycemia. Ginseng, a medicinal plant with significant economic value and a longstanding history of therapeutic use in Asia, has shown efficacy against various diseases. Extensive clinical and experimental studies highlight ginsenosides, its primary bioactive compounds, for their multiple therapeutic effects across a range of conditions, including endocrine, cardiovascular, and central nervous system disorders. Various ginsenoside types have demonstrated potential in lowering blood glucose levels, reducing insulin resistance, and alleviating complications through the modulation of key protein targets and signaling pathways. This review consolidates the pharmacological actions and mechanisms of distinct ginsenosides in managing diabetes and its complications, offering a theoretical foundation for further pharmacological research and novel drug development for T2DM treatment, while also providing robust theoretical support for future clinical applications.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1593780"},"PeriodicalIF":4.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Flunarizine as a potential repurposed drug for the serotonin transporter inhibition: an integrated approach for therapeutic development against major depressive disorder.","authors":"Abdelbaset Mohamed Elasbali, Ahmed S Ali, Taj Mohammad, Mohd Adnan, Anas Shamsi, Md Imtaiyaz Hassan","doi":"10.3389/fphar.2025.1599297","DOIUrl":"10.3389/fphar.2025.1599297","url":null,"abstract":"<p><p>Major depressive disorder (MDD) is a serious neuropsychiatric condition that affects millions of people worldwide, causing significant psychological distress and lifestyle deterioration. The serotonin transporter, which plays a critical role in regulating the uptake of serotonin (5-HT) back into presynaptic cells, is a primary target for antidepressants. Though selective serotonin reuptake inhibitors (SSRIs) are still the pharmacologic treatment of choice, alternative methods remain in demand to enhance the efficacy of treatment and offer more therapeutic options. Drug repurposing provides an efficient solution to speed up antidepressant research because it identifies existing FDA-approved medications that might inhibit the serotonin transporter. A virtual screening method was integrated into the study that examined 3620 FDA-approved drugs to discover new repurposed serotonin transporter-inhibiting molecules. The binding affinity, structural stability, and inhibitory potential were assessed using molecular docking and molecular dynamics (MD) simulations. Among the screened compounds, Flunarizine, a well-known calcium channel blocker, emerged as a promising serotonin transporter inhibitor due to its strong and stable binding configuration within the transporter's active site. Detailed molecular docking studies revealed that Flunarizine formed key interactions with critical residues of the serotonin transporter, suggesting its potential as an effective modulator. Subsequent 500-nanosecond MD simulations further confirmed the stability of the serotonin transporter-Flunarizine complex, demonstrating minimal structural deviations and maintaining crucial dynamic properties throughout the simulation trajectory. These findings highlight Flunarizine's potential for repurposing as a novel therapeutic agent targeting serotonin transport modulation. The study provides a solid foundation for further preclinical and clinical investigations into the antidepressant repurposing of Flunarizine.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1599297"},"PeriodicalIF":4.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12120357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The flavonoid of <i>Dracocephalum heterophyllum</i> Benth. ameliorates cerebral small vessel disease by inhibiting the autophagy via Angs-Tie2 signaling pathway.","authors":"Lin Liu, Wen He, Sijing Liu, Yang Li, Peng Wang, Fang Yan, Wenjing Yang, Yongxue Yang, Jinlin Guo","doi":"10.3389/fphar.2025.1500307","DOIUrl":"10.3389/fphar.2025.1500307","url":null,"abstract":"<p><strong>Background: </strong>Cerebral small vessel disease (CSVD) is a common cause of stroke and vascular cognitive impairment. It is urgent to find drugs targeting CSVD. This study explores the therapeutic potential of the flavonoid (DHBF) derived from <i>Dracocephalum heterophyllum</i> Benth., a traditional Tibetan medicine used for cardiovascular diseases, in treating CSVD and its underlying mechanisms.</p><p><strong>Methods: </strong>Spontaneously hypertensive rats (24-weeks-old) were treated with DHBF for 8 weeks. The Morris water maze test, laser speckle contrast imaging, photoacoustic tomography, HE and Nissl staining were used to evaluate the effect of DHBF in CSVD rats. Network pharmacology and UPLC-MS were used to identify DHBF components and potential mechanisms. Human umbilical vein endothelial cells (HUVECs) were exposed to 10% O₂ to mimic CSVD conditions, and the effects of DHBF on proliferation, migration, and autophagy were evaluated. The expression levels of Angs, Tie2, LC3-Ⅱ/Ⅰ and p62 were detected by qRT-PCR and WB analyses. Molecular docking and lentivirus-mediated Ang2 knockdown/overexpression were performed to validate DHBF's targeting of Ang2.</p><p><strong>Results: </strong>DHBF alleviated vessel injury, improved learning and memory abilities, and increased cerebral blood perfusion and oxygen supply capacity in 24-week-old CSVD rats (<i>p</i> < 0.05). A total of 31 components of DHBF were identified by UPLC-Q-Orbitrap HRMS. Results indicated that DHBF alleviated CSVD by promoting cell proliferation, migration and invasion while inhibiting autophagy in endothelial cell. This regulation was associated with alterations in the Angs-Tie2 pathway and its downstream proteins, including decreased levels of Ang2, Tie2, LC3-Ⅱ/LC3-Ⅰ and increased the levels of Ang1 and p62 (<i>p</i> < 0.05). Knocking down Ang2 showed regulatory effects similar to those observed with DHBF intervention, while overexpression of Ang2 showed opposite effects. In addition, Ang2 overexpression attenuated the regulatory effects of DHBF on Angs-Tie2 pathways and autophagy in HUVECs. These results demonstrated that DHBF alleviated CSVD via inhibiting Ang2, which might be related to danshensu, lonicerin, 8-hydroxyquinoline, esculetin, isophorone, and ethyl caffeate.</p><p><strong>Conclusion: </strong>In summary, DHBF exerts a therapeutic effect on CSVD by inhibiting Ang2, regulating the Angs-Tie2 pathway, and inhibiting endothelial autophagy. This study proposed a potential effective target for CSVD, provided data to support subsequent drug development for this condition.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1500307"},"PeriodicalIF":4.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12107102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First-line treatment of hepatocellular carcinoma: a propensity-matched analysis of tyrosine kinase inhibitors combined with TACE, with or without PD-1 inhibitors.","authors":"Yanjun Shen, Yawen Xu, Ying Teng, Xiaoyan Ding, Jinglong Chen","doi":"10.3389/fphar.2025.1533471","DOIUrl":"10.3389/fphar.2025.1533471","url":null,"abstract":"<p><strong>Objective: </strong>This study attempted to comprehensively assess the clinical outcomes of cases with progressive HCC (pHCC) undergoing treatment with TKI and ICI in conjunction with TACE, as compared to the combination of TKI with TACE alone.</p><p><strong>Methods: </strong>From March 2019 to January 2022, this cohort comprised 82 cases who received TACE in conjunction with TKI and 52 cases who were treated with TACE plus TKI alone. The propensity scores was used to mitigate selection bias.</p><p><strong>Results: </strong>The multivariate analysis further reinforced that liver cirrhosis (HR = 1.233, 95% CI: 1.024-1.484, P = 0.027), tumor diameter (HR = 1.283, 95% CI: 1.086-1.515, P = 0.003), and the treatment strategy (HR = 0.495, 95% CI: 0.264-0.793, P = 0.000) were independently linked to OS, underscoring their prognostic relevance.</p><p><strong>Conclusion: </strong>Incorporating TACE, TKI, and ICI remarkably enhanced both PFS and OS relative to TACE with TKI alone, positioning it as a more efficacious first-line therapeutic strategy for unresectable HCC, while maintaining an acceptable safety profile in clinical settings.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1533471"},"PeriodicalIF":4.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of autophagy by the PI3K-AKT pathway in <i>Astragalus membranaceus</i> -<i>Cornus officinalis</i> to ameliorate diabetic nephropathy.","authors":"Rui Zhang, Xushan Lan, Wenhui Zhu, Lifan Wang, Peng Liu, Ping Li","doi":"10.3389/fphar.2025.1505637","DOIUrl":"10.3389/fphar.2025.1505637","url":null,"abstract":"<p><strong>Aims and background: </strong>Autophagy plays an increasingly significant role in diabetic nephropathy (DN), but the mechanism by which autophagy participates in DN injury is not well understood. Our previous studies have shown that <i>Astragalus membranaceus - Cornus officinalis</i> (AM-CO) improves DN lipid metabolism disorders, however, the exact mechanism of which is also not well defined. The aim of this study was to investigate the therapeutic effects of AM-CO officinalis on DN and the mechanism of action on DN using lipidomic techniques and network pharmacological approaches.</p><p><strong>Experimental methods: </strong>The <i>in vivo</i> experiments were carried out using the KKAy mice model with the intervention of AM-CO. Analysis of kidney and serum samples from KKAy mice treated with AM-CO using lipidomic technology to obtain biomarkers for the treatment of DN and to identify the main targets associated with DN; Analyse potential signalling pathways for the treatment of DN using network pharmacology methods. <i>In vitro</i> experiments were performed with PA-induced HK-2 cells and results verified by protein blotting and immunofluorescence.</p><p><strong>Results: </strong>Lipidomic analysis revealed 363 differential metabolites in serum and 195 differential metabolites in kidney tissue, which were compared and analysed to find their common differential metabolites belonging to the phosphatidylethanolamine (PE) classes, respectively. In addition, PE plays a vital functiona in the process of autophagy. And the network analysis results speculated that Calycosin (Cal), a major component of AM-CO, could ameliorate DN injury by regulating autophagy through modulating the PI3K-AKT signaling pathway. <i>In vivo</i> experiments showed that AM-CO could induce autophagy, an increase in LC3II expression and a decrease in P62 expression. Meanwhile, <i>in vitro</i> experiments showed that Cal could also increase the expression of LC3II and inhibit the protein expression levels of p62, PI3K, P-AKT and AKT. The addition of a PI3K activator resulted in a reversal of protein expression.</p><p><strong>Conclusion: </strong>In conclusion, Cal can ameliorate the injury in DN by regulating autophagy, and PI3K-AKT is the main pathway for its regulation of autophagy and a key pathway for the action of AM-CO.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1505637"},"PeriodicalIF":4.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Probiotic biofilm modified bioceramics for bone defect healing via osteogenesis, angiogenesis, and immune modulation.","authors":"Junwei Su, Huiyun Gu, Xiang Huang, Ying Yuan, Yunchang Zhao, Fan Yang, Yong Zhao","doi":"10.3389/fphar.2025.1588023","DOIUrl":"10.3389/fphar.2025.1588023","url":null,"abstract":"<p><p>The failure to repair bone defects in a timely manner has a detrimental effect on patients' quality of life and functional status. Consequently, there are increasing demands for medical interventions to promote healing of bone defects. However, the local inflammation induced by implants and the side effects associated with the systemic use of drugs have prompted research into the development of bioactive materials. Recent reports have indicated that oral administration of <i>Lactobacillus acidophilus</i> (LA) can act as an immunomodulator. In this study, we have strategically designed bioceramic scaffolds modified with inactivated LA biofilms (LA@BC) through UV irradiation for localized application of LA. The biosafety of the scaffold was validated at the cellular and animal levels to ensure that it can be safely used without bacteraemia. LA@BC achieved M1 to M2 polarization of macrophages <i>in vitro</i> by reducing the secretion of inflammatory factors. In addition, LA@BC enhanced the osteogenic effect of bone marrow mesenchymal stem cells by modulating the Wnt/β-catenin signaling pathway. Furthermore, osteogenesis and angiogenesis complement each other. LA@BC exerted a positive effect on the angiogenic effect of endothelial cells. In a rat cranial defect model, LA@BC upregulated the expression of RUNX2, OCN, CD31, and IL-10 in tissues, again demonstrating potent immunomodulatory and osteogenic effects. In conclusion, this bioactive scaffold provides a new strategy for clinical bone repair.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1588023"},"PeriodicalIF":4.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}