Frontiers in Pharmacology最新文献

{"title":"Brief summary of the regulatory frameworks of regenerative medicine therapies.","authors":"Jinah Yoon, Sukhyang Lee, Min Jung Kim, Jung-Hyun Kim","doi":"10.3389/fphar.2024.1486812","DOIUrl":"10.3389/fphar.2024.1486812","url":null,"abstract":"<p><p>The rapid advancements in regenerative medicine (RM), including cell therapies, gene therapies, tissue-engineered products, and combined RM advanced therapies, require the development of regulatory frameworks. The global landscape of regulatory frameworks presents diverse approaches to the oversight of these therapies, posing challenges in the global application of RM. This paper reviews the regulatory frameworks for RM across the United States, European Union, Japan, Canada, Australia, Taiwan, and South Korea and compares the unique features of the respective legislations.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"15 ","pages":"1486812"},"PeriodicalIF":4.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255425","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":"Baicalin: a potential therapeutic agent for acute kidney injury and renal fibrosis.","authors":"Xiaoming Li, Rui Xu, Dan Zhang, Ji Cai, He Zhou, Tao Song, Xianyao Wang, Qinghong Kong, Liujin Li, Zhaohui Liu, Zhixu He, Zhengzhen Tang, Jun Tan, Jidong Zhang","doi":"10.3389/fphar.2025.1511083","DOIUrl":"10.3389/fphar.2025.1511083","url":null,"abstract":"<p><p>Acute kidney injury (AKI) is a common critical clinical disease that is linked to significant morbidity, recurrence, and mortality. It is characterized by a fast and prolonged loss in renal function arising from numerous etiologies and pathogenic pathways. Renal fibrosis, defined as the excessive accumulation of collagen and proliferation of fibroblasts within renal tissues, contributes to the structural damage and functional decline of the kidneys, playing a pivotal role in the advancement of Chronic Kidney Disease (CKD). Until now, while continuous renal replacement therapy (CRRT) has been utilized in the management of severe AKI, there remains a dearth of effective targeted therapies for AKI stemming from diverse etiologies. Similarly, the identification of specific biomarkers and pharmacological targets for the treatment of renal fibrosis remains a challenge. Baicalin, a naturally occurring compound classified within the flavonoid group and commonly found in the Chinese herb Scutellaria baicalensis, has shown a range of pharmacological characteristics, such as antioxidant, anti-inflammatory, antifibrotic, antitumor and antiviral effects, as evidenced by research studies. Research shows that Baicalin has potential in treating kidney diseases like AKI and renal fibrosis. This review aims to summarize Baicalin's progress in these areas, including its molecular mechanism, application in treatment, and absorption, distribution, metabolism, and excretion. Baicalin's therapeutic effects are achieved through various pathways, including antioxidant, anti-inflammatory, antifibrosis, and regulation of apoptosis and cell proliferation. Besides, we also hope this review may give some enlightenment for treating AKI and renal fibrosis in clinical practice.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1511083"},"PeriodicalIF":4.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11795133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254064","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":"<i>Ex vivo</i> biotransformation of lady's mantle extracts via the human gut microbiota: the formation of phenolic metabolites and their impact on human normal and colon cancer cell lines.","authors":"Katarzyna Jakimiuk, Aleksandra Kruk, Marta Kinga Lemieszek, Jakub W Strawa, Sebastian Granica, Adrian Wiater, Michał Tomczyk","doi":"10.3389/fphar.2025.1504787","DOIUrl":"10.3389/fphar.2025.1504787","url":null,"abstract":"<p><strong>Introduction: </strong>For centuries, various species from the genus <i>Alchemilla</i> have been utilized in traditional medicine worldwide. Among them, <i>Alchemilla vulgaris</i> L. (Rosaceae) stands out as a promising herbal drug candidate due to its phytochemicals displaying anti-inflammatory and antioxidant properties.</p><p><strong>Methods: </strong>In our study, we investigated the interaction between the human gut microbiota and lady's mantle herb extract (AV) following the biotransformation of the extract's constituents and their impact on colorectal cancer cells (HT-29) and normal CCD 841 CoN epithelial cells. The <i>A. vulgaris</i> herb metabolites were obtained by incubating the extract (AV) with human fecal slurries from three healthy donors (D1, D2, and D3).</p><p><strong>Results: </strong>After incubating the AV extract with the human gut microbiota (AVD1-AVD3 samples), thirty-three metabolites were detected and characterized by LC-MS. Among them, one was identified as urolithin C. The AV and AVD1-AVD3 extracts and their metabolites exhibit various levels of antiproliferative and cytotoxic activities against cancer cells. Their biological effect might be linked to the changes and direct activity of bioavailable metabolites. Samples from AVD1, AVD2, and AVD3 increase the lactate dehydrogenase (LDH) released from damaged colon cancer cells in a dose-dependent manner. At 250 μg/mL, AVD1, AVD2, and AVD3 elevated the LDH level by 12.6%, 25.3%, and 30.0%, respectively. The biotransformed samples also showed significantly higher antiproliferative activity than the AV extract. The most active sample from donor 3 (AVD3) reached IC₅₀ = 471 μg/mL.</p><p><strong>Discussion: </strong>The differences in anticancer effect might be linked to the changes and direct activity of bioavailable metabolites. The non-transformed AV extract affected neither normal nor cancer colon cells, indicating the beneficial effect of the biotransformation procedure on the anticancer properties of the evaluated extracts. The above results clearly indicate that microbial metabolism is a crucial factor that is potent in altering the biological activity of lady's mantle extract.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1504787"},"PeriodicalIF":4.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794788/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255431","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":"PBMCs gene expression predicts liver fibrosis regression after successful HCV therapy in HIV/HCV-coinfected patients.","authors":"Ana Virseda-Berdices, Óscar Brochado-Kith, Juan Berenguer, Juan González-García, Leire Pérez-Latorre, Carmen Busca, Cristina Díez, Rafael Micán, Amanda Fernández-Rodríguez, María Ángeles Jiménez-Sousa, Salvador Resino","doi":"10.3389/fphar.2024.1436198","DOIUrl":"10.3389/fphar.2024.1436198","url":null,"abstract":"<p><strong>Background: </strong>HCV eradication with antiviral treatment reduces hepatic disease, but some patients remain at risk of progression to cirrhosis despite HCV clearance. We aimed to examine the association between peripheral blood mononuclear cells (PBMCs) gene expression before HCV therapy and a pronounced decrease in the liver stiffness measurement (LSM) value in HIV/HCV-coinfected patients after HCV treatment and achievement of sustained virological response (SVR).</p><p><strong>Methods: </strong>We performed a retrospective study in 48 HIV/HCV-coinfected patients who started anti-HCV treatment with at least advanced fibrosis (LSM ≥9.5). Total RNA was extracted from PBMCs at baseline, and poly(A) RNA sequencing was performed. The outcome was an LSM reduction greater than 50% (LSMred>50%) about 48 weeks after HCV treatment.</p><p><strong>Results: </strong>Seven patients (14.5%) reduced LSM by over 50%. We found 47 significant differentially expressed (SDE) genes associated with reaching an LSMred>50% after achieving HCV eradication, 42 upregulated and 5 downregulated in the LSMred>50% group. Ten and five of these upregulated genes were classified into two significantly enriched KEGG pathways: cell cycle and progesterone-mediated oocyte maturation (q-value <0.05), respectively. Two SDE genes achieved excellent discrimination ability: NCAPG had an AUROC of 0.908, NHLRC1 of 0.879, and a logistic regression model with these two genes of 0.955.</p><p><strong>Conclusion: </strong>A pre-treatment gene expression signature in PBMCs was associated with liver fibrosis regression (LSMred>50%) after achieving HCV clearing with HCV therapy in HIV/HCV-coinfected patients, where two SDE genes (<i>NCAPG</i> and <i>NHLRC1</i>) showed the greatest predictive capacity, which could be used as a noninvasive marker of liver fibrosis regression.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"15 ","pages":"1436198"},"PeriodicalIF":4.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255428","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":"Characterizing the plasma protein binding profiles of chemistry diversified antisense oligonucleotides in human and mouse plasma using an ultrafiltration method.","authors":"Cassandra Yun, Kazuki Fukami, Raku Shinkyo, Rongrong Rosa Jiang","doi":"10.3389/fphar.2024.1481937","DOIUrl":"10.3389/fphar.2024.1481937","url":null,"abstract":"<p><strong>Introduction: </strong>Plasma protein binding plays a significant role in influencing the pharmacokinetic and pharmacodynamic properties of drugs. This study focuses on examining two pairs of sequence-matched ASOs: phosphorodiamidate morpholino oligomers (PMOs) and 2'-O-methoxyethyl/phosphorothioate (MOE/PS)-modified ASOs, to assess their plasma protein binding profiles.</p><p><strong>Methods: </strong>The binding of both PMO and MOE/PS-modified ASOs was investigated using an ultrafiltration method combined with hybridization electrochemiluminescence, allowing for the measurement of the unbound fraction (<i>f</i>u) in both mouse and human plasma. To further characterize the interaction between ASOs and plasma proteins, individual binding measurements were taken for five major proteins in human plasma: human serum albumin, α1-acid glycoprotein, human γ-globulin, low-density lipoprotein, and high-density lipoprotein.</p><p><strong>Results: </strong>The results showed a notable difference in plasma protein binding between the two types of ASOs, with MOE/PS-modified ASOs exhibiting significantly higher binding compared to PMOs. The <i>f</i>u, plasma values revealed no significant species difference between mouse and human plasma. Additionally, a saturation point for <i>f</i>u, plasma was observed in MOE/PS-modified ASOs at concentrations above 1 μM, whereas PMOs did not show saturation even at concentrations up to 10 μM. Notably, human γ-globulins were found to have a predominant binding affinity for both MOE/PS and PMO ASOs at physiological concentrations, surpassing human serum albumin, the most abundant plasma protein.</p><p><strong>Discussion: </strong>The results suggest that the chemistries of the ASOs, particularly their modifications, are key determinants of their binding profiles. The study also highlights the important, though previously overlooked, role of human γ-globulins in the plasma protein binding of ASOs. This could have implications for understanding ASO distribution and tissue disposition, which may inform the development and optimization of ASO-based therapies.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"15 ","pages":"1481937"},"PeriodicalIF":4.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11795045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255426","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":"Exploring the hemoglobin-to-red blood cell distribution width ratio (HRR) to peripheral arterial disease nexus: a comprehensive analysis of NHANES data from 1999 to 2004.","authors":"Zhihai Yu, Bin Lu, Rui Han, Can Tu","doi":"10.3389/fphar.2025.1529155","DOIUrl":"10.3389/fphar.2025.1529155","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the correlation between the Hemoglobin-to-Red Blood Cell Distribution Width Ratio (HRR) and Peripheral Artery Disease (PAD) prevalence, utilizing data from the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2004.</p><p><strong>Methods: </strong>The study employed a cross-sectional design, analyzing data from 5,196 participants aged 40 and above. PAD was diagnosed using the Ankle-Brachial Index (ABI), with ABI less than 0.9 indicating PAD. HRR, calculated as the ratio of hemoglobin (HB) to red blood cell distribution width (RDW), was stratified into quartiles. Covariates included demographic and clinical variables such as BMI, lipid profiles, and diabetes status. Logistic regression analysis was conducted to assess the relationship between HRR and PAD, adjusting for potential confounders.</p><p><strong>Results: </strong>The study found that higher HRR quartiles were associated with a decreased risk of PAD. After adjusting for confounders, the odds ratios for PAD in relation to the second, third, and fourth quartiles of HRR compared to the first quartile were 0.71, 0.62, and 0.44, respectively (P < 0.001). A one-unit increase in HRR corresponded to a 56% reduction in the probability of PAD. ROC analysis indicated HRR as a stronger protective factor for PAD compared to other variables. Stratified analyses revealed that younger age and lower BMI amplified the protective effect of HRR on PAD.</p><p><strong>Conclusion: </strong>The study demonstrated a significant inverse relationship between HRR and PAD, suggesting that HRR may serve as a protective factor against PAD. This finding highlights the potential role of HRR in the pathogenesis of PAD and its clinical implications.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1529155"},"PeriodicalIF":4.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254746","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":"Corrigendum: Notoginsenoside R1 protects against diabetic cardiomyopathy through activating estrogen receptor α and its downstream signaling.","authors":"Bin Zhang, Jingyi Zhang, Chenyang Zhang, Xuelian Zhang, Jingxue Ye, Shihuan Kuang, Guibo Sun, Xiaobo Sun","doi":"10.3389/fphar.2024.1488083","DOIUrl":"https://doi.org/10.3389/fphar.2024.1488083","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fphar.2018.01227.].</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"15 ","pages":"1488083"},"PeriodicalIF":4.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255427","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":"Drivers of innovation value: simulation for new drug pricing evaluation based on system dynamics modelling.","authors":"Qian Xing, Wendi Cheng, Wei Wang, Chunlin Jin, Haiyin Wang","doi":"10.3389/fphar.2025.1474856","DOIUrl":"10.3389/fphar.2025.1474856","url":null,"abstract":"<p><strong>Objectives: </strong>Paying for the innovative value of drugs is an important means of mitigating healthcare system duplication and enhancing patient health. Assessing and exploiting the factors influencing innovation premium to forecast trends and shortcomings within the pharmaceutical innovation ecosystem.</p><p><strong>Methods: </strong>Utilizing system dynamics, this research constructs a decision evaluation system for new drug pricing in Japan. It integrates various decision-making factors across dimensions such as value premium, marketability premium, pediatric premium, and SAKIGAKE premium, employing Vensim PLE software for simulation purposes.</p><p><strong>Results: </strong>Under the current policy framework, pharmaceutical innovation is on the rise, with significant policy effects observable after 5 years. The most substantial growth in value occurs in medications for rare diseases and niche markets, with effects varying in the short to medium term and stabilizing over the long term. Sensitivity analysis highlights that factors like combination therapies, faster mechanisms of action, and novel therapeutic parts notably influence the value dimension. Other significant factors include obtaining national certifications, addressing indications lacking standard treatments, and demonstrating superior efficacy. The study also identifies underexploited opportunities related to the use of evidence in pricing decisions.</p><p><strong>Conclusion: </strong>Clinical outcomes are pivotal in shaping drug pricing, influencing both patient and healthcare provider preferences, and thereby affecting market uptake and competitive dynamics. Regulatory frameworks that prioritize unmet medical needs or superior drug efficacy are essential. Future enhancements to the model should incorporate more real-world evidence and expand regulatory considerations to better reflect the dynamic nature of the healthcare sector and support equitable, outcome-based drug pricing.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1474856"},"PeriodicalIF":4.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254327","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":"Effect of β-blocker on clinical outcomes in patients with traumatic brain injury: a retrospective propensity-matched study.","authors":"Yaxin Zhang, Tingting Liu, Wenwen Ji, Guangdong Wang","doi":"10.3389/fphar.2025.1465657","DOIUrl":"10.3389/fphar.2025.1465657","url":null,"abstract":"<p><strong>Background: </strong>Traumatic brain injury (TBI) represents a significant public health challenge due to its complex management. β-blockers may offer neuroprotective benefits, but their impact on TBI outcomes remains unclear. This study aims to evaluate the effect of β-blocker use on clinical outcomes in TBI patients.</p><p><strong>Methods: </strong>This retrospective cohort study included adult TBI patients, categorized into β-blocker and non-β-blocker groups. Propensity score matching (PSM) was utilized to balance baseline characteristics. Mortality was assessed through the application of multivariable Cox regression models and Kaplan-Meier survival curves. Subgroup analyses examined the consistency of the results.</p><p><strong>Results: </strong>A total of 1,516 patients were included in the study, with 750 receiving β-blocker therapy and 766 not receiving it. After PSM, 473 pairs of patients were matched. The analysis indicated that β-blockers significantly reduce 28-day mortality (HR 0.43, 95% CI: 0.31-0.60, P < 0.001). However, patients receiving β-blocker had considerably longer hospital stays (7.89 days vs. 5.45 days, P < 0.001) and ICU stays (2.94 days vs. 2.33 days, P < 0.001).</p><p><strong>Conclusion: </strong>β-blocker therapy is associated with improved short-term outcomes in patients with TBI, particularly in those with mild (GCS 13-15) and severe (GCS 3-8) TBI. However, no significant benefit was observed in patients with moderate TBI (GCS 9-12). This therapy may also prolong hospital and ICU stays.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1465657"},"PeriodicalIF":4.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254428","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":"<i>Periplanta americana</i> extract regulates the Th17/Treg cell balance via Notch1 in ulcerative colitis.","authors":"Yanqiu Zheng, Huibiao Li, Shiyu Qi, Fan Xiao, Jinbin Song, Shiyin Liu, Xinlin Chen, Yanwu Li, Muyuan Chen","doi":"10.3389/fphar.2024.1534772","DOIUrl":"10.3389/fphar.2024.1534772","url":null,"abstract":"<p><strong>Background: </strong><i>Periplanta americana</i> extract (PAE), a traditional Chinese medicine (TCM) from <i>Shen Nong Ben Cao Jing</i>, has been used to treat ulcerative colitis (UC), various types of wounds and ulcers, infantile malnutrition, palpitation, asthma, and so on. However, the exact mechanisms of PAE in UC have still not been fully revealed. The study aims to explore the therapeutic effects and mechanisms of PAE in UC.</p><p><strong>Methods: </strong>The efficacy of PAE was evaluated using a DSS-induced UC mice model and the colon inflammation and mucosal barrier were comprehensively assessed. Furthermore, Network pharmacological analysis was utilized to identify potential targets and signaling pathways of PAE in the UC treatment. The proportion and the markers of Th17 and Treg cells in the spleen and colon were examined. The signal transduction was detected <i>in vivo</i>. <i>In vitro</i>, an activated Notch1-mediated Th17/Treg was modeled, and the effect of PAE on the epithelial cell barrier was examined.</p><p><strong>Results: </strong>PAE mitigated colon inflammation and intestinal barrier damage in UC mice. Network pharmacological analysis showed that the targets of UC intervention by PAE may be closely related to Th17 cell differentiation, the IL-17 signaling pathway, and cytokine-cytokine receptor interaction. Mechanistically, PAE regulated the balance of Th17/Treg and inhibited the Notch1/Math1 pathway in the colon of UC mice. <i>In vitro</i>, PAE intervention alleviated the activated Notch1-mediated Th17/Treg imbalance in Jurkat T cells. After notch1-activated Jurkat T cells were co-cultured with HCoEpic cells, the expressions of Occludin, ZO1 were higher in the HCoEpic cells.</p><p><strong>Conclusion: </strong>PAE could alleviate colon inflammation and mucosal barrier damage in UC, which are related to the inhibition of Notch1 and the regulation of the Th17/Treg balance. PAE might be a potential candidate agent for UC treatment.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"15 ","pages":"1534772"},"PeriodicalIF":4.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255423","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}