Frontiers in Pharmacology最新文献

{"title":"Ferroptosis and hyperoxic lung injury: insights into pathophysiology and treatment approaches.","authors":"Xiaoqiong Zhou, Lei Tian, Wenyan Xiong, Yulan Li, Qian Liu","doi":"10.3389/fphar.2025.1568246","DOIUrl":"https://doi.org/10.3389/fphar.2025.1568246","url":null,"abstract":"<p><p>Hyperoxia therapy is a critical clinical intervention for both acute and chronic illnesses. However, prolonged exposure to high-concentration oxygen can cause lung injury. The mechanisms of hyperoxic lung injury (HLI) remain incompletely understood, and current treatment options are limited. Improving the safety of hyperoxia therapy has thus become an urgent priority. Ferroptosis, a novel form of regulated cell death characterized by iron accumulation and excessive lipid peroxidation, has been implicated in the pathogenesis of HLI, including diffuse alveolar damage, vascular endothelial injury, and bronchopulmonary dysplasia. In this review, we analyze the latest findings on ferroptosis and therapeutic strategies for HLI. Our aim is to provide new insights for the treatment of HLI and to facilitate the translation of these findings from bench to bedside.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1568246"},"PeriodicalIF":4.4,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11958998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763857","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":"Association of rivaroxaban plasma trough concentrations with clinical characteristics and outcomes.","authors":"Huizhen Wu, Qiaoling Yu, Panpan Jin, Lijing Huo, Jing An","doi":"10.3389/fphar.2025.1563745","DOIUrl":"https://doi.org/10.3389/fphar.2025.1563745","url":null,"abstract":"<p><strong>Background: </strong>Rivaroxaban use has increased significantly among older adults; however, no definitive plasma concentration thresholds for bleeding or thrombosis have been established. However, dose adjustments for this population remain controversial.</p><p><strong>Methods: </strong>Between January 2022 and August 2023, we analyzed trough plasma samples from hospitalized patients treated with rivaroxaban for at least three consecutive days. Clinical data, including demographics, comorbidities, and adverse events, were extracted from electronic medical records. The plasma concentrations of rivaroxaban were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Statistical analyses were performed to identify factors influencing rivaroxaban exposure and clinical outcomes.</p><p><strong>Results: </strong>Among 360 plasma samples analyzed (55% male; median age: 72 years), age (P = 0.042) and renal function (P = 0.002) were significant predictors of rivaroxaban concentration-to-dose ratio. Bleeding events were associated with higher trough concentrations (median: 81.85 ng/mL in the bleeding group vs. 26.80 ng/mL in others; P < 0.001) and were more common in patients with malignancies or prior bleeding history. Thrombotic events occurred predominantly in older patients with a history of stroke (P < 0.05). Patients who died were older and had higher CHA2DS2-VASc scores (P < 0.05), prolonged prothrombin times (P < 0.001), and multiple comorbidities.</p><p><strong>Conclusion: </strong>Routine monitoring of rivaroxaban plasma concentrations may improve safety in older adults with multiple comorbidities or impaired hepatic, renal, or coagulation functions. Further research is required to establish specific therapeutic thresholds for bleeding and thrombosis.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1563745"},"PeriodicalIF":4.4,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11958709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763652","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":"Editorial: Education and training in pharmaceutical medicine, medicines development and regulation for scientists worldwide.","authors":"Bernd Rosenkranz, Tomoya Tachi, Rolf Bass","doi":"10.3389/fphar.2025.1544678","DOIUrl":"https://doi.org/10.3389/fphar.2025.1544678","url":null,"abstract":"","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1544678"},"PeriodicalIF":4.4,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763852","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":"Editorial: Preventing and treating liver diseases: medicinal and food plants, their metabolites as potential options.","authors":"Rongrui Wei, Wenmin Liu, Chunsu Yuan, Chunlei Zhang, Zhipei Sang, Qinge Ma","doi":"10.3389/fphar.2025.1577547","DOIUrl":"https://doi.org/10.3389/fphar.2025.1577547","url":null,"abstract":"","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1577547"},"PeriodicalIF":4.4,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763853","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":"Effective doses of remimazolam and esketamine combined with remifentanil for endotracheal intubation without muscle relaxants in pediatric patients.","authors":"Jinming Chen, Ying Mai, Xiaolei Cheng, Hao Sun, Zhihong Chen, Zhongqi Zhang","doi":"10.3389/fphar.2025.1558966","DOIUrl":"https://doi.org/10.3389/fphar.2025.1558966","url":null,"abstract":"<p><strong>Introduction: </strong>The combination of remimazolam and esketamine effectively alleviates adverse hemodynamic effects, such as tachycardia and hypertension, during intubation. However, the dosage for achieving optimal intubation conditions when co-administered with remifentanil remains unestablished. Therefore, this study aimed to determine the effective doses of remimazolam and esketamine for endotracheal intubation without muscle relaxants in pediatric patients using Dixon's up-and-down method.</p><p><strong>Methods: </strong>This prospective, non-controlled, non-randomized clinical trial sequentially allocated 41 children aged 3-6 into two phases. All patients underwent tracheal intubation under general anesthesia. Patients received a fixed dose of remifentanil at 2.5 μg/kg via a pump over 90 s. In the first phase, the induction dose of remimazolam was set at 0.2 mg/kg. The first patient received esketamine at a dose of 0.5 mg/kg, administered with a dose gradient of 0.2 mg/kg based on Dixon's up-and-down method. 50% effective dose (ED₅₀) and 95% effective dose (ED₉₅) for esketamine were then measured through probit regression analysis. Similarly, in the second phase, the ED₉₅ of esketamine was fixed. The first patient received remimazolam at a dose of 0.2 mg/kg, administered at a dose gradient of 0.1 mg/kg. ED₅₀ and ED₉₅ for remimazolam were then measured. Intubation conditions were assessed via the Copenhagen scale. Heart rate (HR) and mean arterial pressure (MAP) were recorded at the following time points: Just before intubation (T1) and 1 min after intubation (T2). Adverse events were also recorded during anesthesia induction.</p><p><strong>Results: </strong>At a fixed dose of remifentanil (2.5 μg/kg), the ED₅₀ of esketamine was 0.74 mg/kg (95% confidence interval [CI]: 0.61-0.89 mg/kg), while the ED₉₅ was 0.97 mg/kg (95% CI: 0.85-1.75 mg/kg). The ED₅₀ of remimazolam was 0.39 mg/kg (95% CI: 0.29-0.53 mg/kg), while the ED₉₅ was 0.56 mg/kg (95% CI: 0.46-1.47 mg/kg). Hemodynamic stability was maintained during anesthesia induction, with no significant adverse events observed.</p><p><strong>Conclusion: </strong>The ED₅₀ and ED₉₅ values of remimazolam and esketamine in this study provide initial dosing references for pediatric endotracheal intubation without muscle relaxants. A fixed dose of 2.5 μg/kg remifentanil combined with these agents is safe and effective in children aged 3-6 years, though further multicenter studies are recommended for validation.</p><p><strong>Clinical trial registration: </strong>www.chictr.org.cn, number: ChiCTR2200063847.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1558966"},"PeriodicalIF":4.4,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763854","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":"A real-world disproportionality analysis of ripretinib data mining of the public version of FDA adverse event reporting system.","authors":"Yingkai Feng, Xinyu Fa, Yifei Wang, Tao Zhang, Xuan Sun, Faping Li","doi":"10.3389/fphar.2025.1469597","DOIUrl":"https://doi.org/10.3389/fphar.2025.1469597","url":null,"abstract":"<p><strong>Background: </strong>Tyrosine kinase inhibitors (TKIs) are the preferred targeted therapy for advanced gastrointestinal stromal tumors (GIST). Ripretinib, the first tyrosine kinase switch control inhibitor, has not yet been extensively studied for long-term safety in large populations. This study evaluates Ripretinib-related adverse events (AEs) in real-world applications by analyzing data from the FDA's Adverse Event Reporting System (FAERS).</p><p><strong>Methods: </strong>To quantify signals of AEs, we employed several disproportionality analyses: the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS).</p><p><strong>Results: </strong>In the FAERS database, out of 7,064,646 reports, 3,161 were identified as related to Ripretinib AEs, with 438 significant disproportionality in preferred terms. The most common adverse reactions were tiredness, hair loss, nausea, constipation, diarrhea, loss of appetite, palmar-plantar erythrodysesthesia syndrome, and vomiting. These reactions align with the medication instructions and reports from corresponding clinical trials. Notably, the label includes unexpected and significant AEs such as \"hepatic neoplasm\", \"hair texture abnormal\", \"metastases to liver\" and \"red blood cell count decreased\". The median onset time for Ripretinib-related AEs was 99 days, with an interquartile range of 27-245 days. Most cases (26.74%, n = 165) occurred within the first month of Ripretinib administration.</p><p><strong>Conclusion: </strong>Our findings align with clinical observations. We identified novel and unexpected AEs signatures of Ripretinib, indicating that prospective clinical studies are necessary to confirm these findings and clarify their implications. These results could provide valuable evidence to guide further safety studies on Ripretinib.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1469597"},"PeriodicalIF":4.4,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763562","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 role and impact of the IL-6 mediated JAK2-STAT1/3 signaling pathway in the pathogenesis of gout.","authors":"Zeng Zhang, Peng Wang, Tianyi Lei, Jianwei Guo, Yi Jiang, Yanhui Li, Jianxiong Zheng, Shunbing Wang, Haimuzi Xu, Guilin Jian, Quanbo Zhang, Yufeng Qing","doi":"10.3389/fphar.2025.1480844","DOIUrl":"https://doi.org/10.3389/fphar.2025.1480844","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Interleukin-6 (IL-6) is a pleiotropic cytokine, with specific effects depending on the immune microenvironment. Extensive research has confirmed the pathological roles of the IL-6/JAK2/STAT1/3 signaling pathway in inflammation, autoimmunity, and cancer, as well as its involvement in the pathogenesis of various rheumatic diseases. However, the role and impact of IL-6 as an upstream regulator of the JAK2-STAT1/3 pathway in gout have seldom been reported. This study explores the influence and role of upstream IL-6 in regulating the JAK2-STAT1/3 signaling pathway on gout inflammation, offering new insights for targeted therapeutic interventions and drug development in gout management.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods and results: &lt;/strong&gt;Clinical data and peripheral blood specimens were collected from gout patients and healthy individuals. In vitro and in vivo models of acute gout inflammation were established by stimulating PBMCs, THP-1 cells, and mice with MSU crystals. IL-6 expression was manipulated using IL-6 agonists and IL-6 knockout (KO) mouse technology to investigate the role and impact of the IL-6-mediated JAK2-STAT1/3 signaling pathway in gout models. RT-qPCR, WB, and ELISA were utilized to assess gene and protein expression levels. Paw swelling in mice was measured using a caliper gauge, while HE and IHC staining were conducted to evaluate the inflammatory status of mouse paw pad synovial tissues and detect the positive expression of relevant proteins. Serum IL-6 protein expression levels were significantly elevated in patients with gouty arthritis (GA) compared to healthy individuals, with multifactor logistic regression revealing an odds ratio (OR) of 2.175 for IL-6. In GA patients, mRNA expression of IL-6, JAK2, STAT1/3, and IL-1β was notably lower in the gout group compared to the healthy control (HC) group. Moreover, IL-6, JAK2, STAT1/3, p-JAK2, p-STAT1/3, and IL-1β proteins were markedly higher in the acute gout (AG) group compared to the intercritical gout (IG) and HC groups. Within the IG group, IL-6, JAK2, STAT3, and IL-1β proteins were significantly elevated compared to the HC group, whereas STAT1, p-JAK2, and p-STAT1/3 proteins were significantly lower. The expression of IL-6 protein and JAK2 mRNA showed positive correlations with certain inflammatory markers. In the 2h human blood in vitro gout inflammation model, expressions of IL-1β, IL-6, JAK2 mRNA, and IL-1β, IL-6, JAK2, STAT1/3, p-JAK2, p-STAT1/3 proteins were significantly higher compared to both the blank control and PBS-negative control groups. In the acute gout THP-1 cell model, The 6-hour model group showed significantly higher levels of IL-1β, IL-6, JAK2, STAT1/3 mRNA, and corresponding proteins, including their phosphorylated forms, compared to the blank control group. Additionally, treatment with an IL-6 agonist further increased these expression levels compared to the untreated model group. In the acute gout mouse model, IL-6 KO mice exhibi","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1480844"},"PeriodicalIF":4.4,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763861","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":"Ferulic acid inhibits ox-LDL-induced ferroptosis and apoptosis in RAW 264.7 cells via the HIF-1 signaling pathway.","authors":"Xize Wu, Xue Pan, Jian Kang, Yuxi Huang, Jiaqi Ren, Jiaxiang Pan, Kaifeng Yu, Yue Li","doi":"10.3389/fphar.2025.1524736","DOIUrl":"https://doi.org/10.3389/fphar.2025.1524736","url":null,"abstract":"<p><strong>Objective: </strong>Ferulic acid (FA) has shown potential in treating atherosclerosis (AS) by improving lipid metabolism and exerting anti-hypoxic effects. This study aimed to validate the mechanism of FA in AS through <i>in vitro</i> experiments.</p><p><strong>Methods: </strong>Network analysis was employed to predict the mechanisms underlying the therapeutic effects of FA on AS. An <i>in vitro</i> foam cell model was established using RAW 264.7 cells treated with ox-LDL. Cellular lipid accumulation was detected using Oil Red O staining; cell viability was assessed by cell counting kit-8; mitochondrial morphology and function were evaluated by transmission electron microscopy and JC-1 staining; apoptosis levels were detected by TUNEL and DAPI staining; mitochondrial Fe²⁺ content was measured by Mito-FerroGreen; and Western blot was performed to determine the protein expression levels of HIF-1α, Bax, Bcl2, GPX4, and EGFR.</p><p><strong>Results: </strong>Network analysis suggested that FA may exert its therapeutic effects on AS through the HIF-1 signaling pathway and is closely associated with the regulation of ferroptosis and apoptosis. FA upregulated the expression of ALOX5, BCL2, ERN1, GPX4, NOS3, and SLC2A1 mRNA and downregulated the expression of BAX, CYCS, EGFR, FLT1, HIF1A, NFKB1, NOS2, PARP1, and STAT3 mRNA. <i>In vitro</i> experiments demonstrated that FA reduces lipid accumulation, increases cell viability, improves mitochondrial function, and decreases reactive oxygen species content. Additionally, FA inhibited ferroptosis and apoptosis by suppressing the HIF-1 signaling pathway, up-regulating the expression of GPX4 and Bcl2, and down-regulating the expression of HIF-1α and Bax protein. HIF-1 agonists reversed these effects by activating the HIF-1 signaling pathway.</p><p><strong>Conclusion: </strong>FA improves mitochondrial function and suppresses ferroptosis and apoptosis by inhibiting the HIF-1 signaling pathway, thereby treating AS.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1524736"},"PeriodicalIF":4.4,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11958962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763858","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":"Onvansertib exhibits anti-proliferative and anti-invasive effects in endometrial cancer.","authors":"Nikita Sinha, Xiaochang Shen, Jennifer Haag, Shuning Chen, Haomeng Zhang, Catherine John, Wenchuan Sun, Michael Emanuele, Chunxiao Zhou, Victoria Bae-Jump","doi":"10.3389/fphar.2025.1545038","DOIUrl":"10.3389/fphar.2025.1545038","url":null,"abstract":"<p><p>Polo-like kinase 1 (Plk1) is widely recognized as an oncogene that promotes cell proliferation by regulating cell division, DNA damage response, and genome stability and has been shown to be overexpressed in many cancers, including endometrial cancer. Targeting Plk1 by onvansertib has been shown to have anti-tumor activity in pre-clinical models of multiple cancers and is currently being evaluated in phase 1 and 2 clinical trials in cancer patients. In this study, we evaluated the potential anti-tumorigenic effects of onvansertib in endometrial cancer cells and the LKB1^fl/fl p53^fl/fl mouse model of endometrial cancer. Onvansertib inhibited cellular proliferation, caused G2 phase arrest, induced cellular stress and apoptosis, and inhibited cellular migration and invasion in endometrial cancer cells. Combined treatment with onvansertib and paclitaxel led to synergistic inhibition of cell proliferation. Onvansertib treatment for 4 weeks significantly reduced tumor growth in LKB1^fl/flp53^fl/fl mice. Given these promising pre-clinical results, further studies are needed to evaluate the clinical translatability of onvansertib combined with paclitaxel as an effective treatment for endometrial cancer.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1545038"},"PeriodicalIF":4.4,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751644","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":"Traditional Chinese Medicine-derived formulations and extracts modulating the PI3K/AKT pathway in Alzheimer's disease.","authors":"Lan Ma, Jing Wang, Rong Zhou, Miao Chen, Zuxiu Huang, Shuyang Lin","doi":"10.3389/fphar.2025.1528919","DOIUrl":"10.3389/fphar.2025.1528919","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a common neurodegenerative disorder characterized by memory decline, cognitive impairment, and behavioral abnormalities. Pathologically, AD is marked by neurofibrillary tangles caused by excessive phosphorylation of Tau protein and abnormal deposition of β-amyloid (Aβ) in the brain. The PI3K/AKT signaling pathway plays a crucial role in the development, survival, and metabolic regulation of the central nervous system, particularly in neuronal growth, differentiation, and apoptosis. However, this pathway is often inhibited in AD patients.In recent years, studies have shown that herbal formulations and extracts derived from Traditional Chinese Medicine (TCM) can regulate the PI3K/AKT signaling pathway, thereby improving AD pathological models. This study reviews fundamental research on both active metabolites and compound formulations from TCM for the treatment of AD, targeting the PI3K/AKT signaling pathway.Keywords include \"Alzheimer's disease\" \"AD\" \"dementia\" \"PI3K\" \"AKT\" \"Traditional Chinese Medicine\" \"Chinese herbology\" \"Chinese medicine\" and \"TCM\".The study is based on relevant literature published over the past 15 years, primarily sourced from electronic databases such as Web of Science, PubMed, CNKI, Wanfang, and VIP databases.The findings indicate that herbal formulations and extracts derived from TCM can mitigate AD pathology by regulating the PI3K/AKT signaling pathway, reducing Tau protein phosphorylation and Aβ deposition, inhibiting inflammatory responses and oxidative stress, and alleviating neuronal apoptosis. This study enhances our understanding of the anti-AD mechanisms of TCM through the PI3K/AKT pathway and offers new insights for the future.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1528919"},"PeriodicalIF":4.4,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752100","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}