Frontiers in Pharmacology最新文献

{"title":"Physiologically based pharmacokinetic modeling supports investigation of potential drug-drug interactions in the pre- and early post-hematopoietic stem cell transplantation stages.","authors":"Peile Wang, Jingli Lu, Jing Yang","doi":"10.3389/fphar.2025.1578643","DOIUrl":"10.3389/fphar.2025.1578643","url":null,"abstract":"<p><strong>Introduction: </strong>Drug-drug interactions (DDIs) are an important issue in medication safety and a potential cause of adverse drug events in the pre- and early post-hematopoietic stem cell transplantation (HSCT). This study introduced a physiologically based pharmacokinetic (PBPK) modeling platform to evaluate complex DDIs in these critical stages and to optimize dosing for personalized treatment.</p><p><strong>Methods: </strong>PBPK models were developed using a bottom-up with middle-out approach and executed with PK-Sim^® software. Model validation required that predicted PK values fall within a twofold range of observed data. Then, the validated model was used to simulate alternative dosing regimens to achieve target therapeutic levels.</p><p><strong>Results: </strong>PBPK models were developed and evaluated for 13 drugs commonly used in HSCT, including cyclosporine, tacrolimus, sirolimus, busulfan, phenytoin, voriconazole, posaconazole, itraconazole, fluconazole, letermovir, fosaprepitant, aprepitant, and omeprazole. Simulation results indicated marked DDIs in the pre- and early post-HSCT phases, particularly involving cyclosporine and phenytoin. Several drugs notably increased cyclosporine concentrations, while phenytoin substantially reduced the exposure to other medications.</p><p><strong>Conclusion: </strong>This PBPK modeling platform provides a robust tool for identifying and mitigating DDIs in the pre- and early post-HSCT phases. By enabling the optimization of treatment regimens, this model serves as a valuable tool for improving drug safety and therapeutic outcomes for patients with HSCT.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1578643"},"PeriodicalIF":4.4,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12081248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092339","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 for lupus nephritis: modulation of autoimmune pathogenesis.","authors":"Zhiyan Huang, Xiaolong Li, Qingmiao Zhu, Mengyu Zhu, Yongsheng Fan, Ting Zhao","doi":"10.3389/fphar.2025.1523272","DOIUrl":"10.3389/fphar.2025.1523272","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Lupus nephritis (LN) is an immune complex glomerulonephritis commonly associated with systemic lupus erythematosus. Traditional Chinese medicine (TCM) has emerged as a promising adjuvant therapy for LN, due to its low toxicity and diverse therapeutic effects for long-term management.</p><p><strong>Materials and methods: </strong>A comprehensive search of PubMed and Web of Science was conducted up to 7 June 2024, using keywords related to lupus nephritis, traditional Chinese medicine, immune cells, and kidney resident cells. Study quality were assessed based on Good Automated Manufacturing Practice guidelines, with evaluations jointly conducted by two authors.</p><p><strong>Results: </strong>This review includes 31 research papers and summarizes seven herbal formulas and 18 phytochemicals that modulate the autoimmune pathogenesis of LN. Their mechanisms involve regulating immune cells activation, differentiation, apoptosis, as well as influencing resident kidney cells to support renal protection and immune homeostasis. Since TCM exhibit bidirectional regulation, they activate regulatory immune cells while suppress pathogenic factors. Inconsistent or inconclusive findings are discussed.</p><p><strong>Conclusion: </strong>This review summarizes current research on herbal formulas and phytochemicals in immune cells and kidney resident cells in LN, highlighting the potential and significance of TCM treatment. It also addresses the limitations of existing studies and suggests that future research should focus on exploring the immunosuppressive and kidney-protective effects of herbal formulas and phytochemicals, as well as enhancing the clinical translation and standardization of TCM.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1523272"},"PeriodicalIF":4.4,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12083088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092960","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":"Compatibility optimization of the traditional Chinese medicines 'Eczema mixture' based on back-propagation artificial neural network and non-dominated sorting genetic algorithm.","authors":"Xin He, Zhijie Song, Yanqun Yang, Siqi Wu, Shuo Meng, Huanyu E, Hongfei Li, Guoyu Ding","doi":"10.3389/fphar.2025.1593783","DOIUrl":"10.3389/fphar.2025.1593783","url":null,"abstract":"<p><strong>Introduction: </strong>Chinese medicine formulas (CMF) are an important aspect of traditional Chinese medicine (TCM) and are formulated based on strict compatibility proportions guided by TCM theory. Due to the complex chemical constituents of TCM and the diversity of evaluation indicators for a certain disease, the research strategy on how to obtain the optimal combination of these crude extracts, homologous compounds or even the specific compounds mixture becomes the key step in the study of compatibility proportion research. Therefore, in this research, the \"Eczema mixture\" (EM) which includes six kinds of Chinese medicinal materials for the treatment of atopic dermatitis was cited as an example to illustrate the proposed compatibility optimization strategy.</p><p><strong>Methods: </strong>Ultra-performance liquid chromatography-quadrupole/time-of-flight (UPLC-Q/TOF) technology was used to analyze the chemical components in the EM formula, and a total of 136 chemical compounds were identified. 76 formulas with different compatibility ratios were generated with the simplex centroid mixture design (SCMD). Two defined objective functions, the maximum of the anti-inflammatory and anti-allergic activity were used to evaluate the bioactivities of all the formulas. The 6-n-2 three-layers of back-propagation artificial neural network (BP-ANN) was employed to model the two defined objective functions. With the predictive models, the Pareto front was determined by a variant of non-dominated sorting genetic algorithm II(VNSGAII) to provide the optimal prescription set.</p><p><strong>Results: </strong>The 6-n-2 three-layers of artificial neural networks demonstrated a satisfactory fitting effect for the nonlinear activity relationship. In the EM formula, Huangbai and Kushen were identified as the main botanical drugs with anti-inflammatory and anti-allergic roles. The results were consistent with the clinical application of the 113 prescriptions involving 230 botanical drugs for the treatment of AD from the 'Dictionary of Traditional Chinese Medicine Prescription'.</p><p><strong>Conclusion: </strong>The proposed SCMD-ANN-VNSGAII is a powerful approach that may facilitate future compatibility optimization of homologous compounds or specific component mixtures.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1593783"},"PeriodicalIF":4.4,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12082046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093385","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":"1-Nitro-2-phenylethane: a promising phytoconstituent to modulate neuroinflammation and oxidative stress with repercussions on neurological and psychiatric disorders.","authors":"Lucas Villar Pedrosa Silva Pantoja, Emily Christie Maia Fonseca, Fábio José Coelho Souza-Junior, Brenda Costa da Conceição, Sarah Viana Farias, Joyce Kelly R da Silva, José Guilherme Soares Maia, Pedro Iuri Castro Silva, Jofre Jacob Silva Freitas, Rui Daniel Prediger, Daniele Luz Campos, Enéas Andrade Fontes-Júnior, Cristiane Socorro Ferraz Maia","doi":"10.3389/fphar.2025.1552295","DOIUrl":"10.3389/fphar.2025.1552295","url":null,"abstract":"<p><p>Neurologic and neuropsychiatric disorders are complex, with common pathophysiological mechanisms associated with inflammation, oxidative stress, and vascular damage. These shared features have stimulated interest in bioactive compounds with neuropharmacological potential. In this regard, the 1-Nitro-2-Phenylethane (1N2PE) emerges as a promissory compound to act on the multiple via of brain disturbances. However, its neuropharmacological mechanisms of action remain largely unknown. We aim to provide a comprehensive overview of the scarce literature on the effects of 1N2PE in brain disorders to highlight the importance of further research into the mechanisms of action and its potential applications in the field of neurology and psychiatry, focusing on the anti-inflammatory and antioxidant properties. The 1N2PE exhibits neuroprotective properties, including anti-inflammatory, antioxidant, and cholinergic-enhancing effects, which together may underlie its potential therapeutic benefits for various neuropsychiatric and neurological disorders, such as depression, anxiety, seizures, and cognitive impairments. This review compiles literature on 1N2PE potential central nervous system activities, highlighting its therapeutic potential in treating behavioral and neurological disorders. Despite promising findings, further research is essential to fully understand 1N2PE as a novel therapeutic agent.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1552295"},"PeriodicalIF":4.4,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12082040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093265","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":"Population pharmacokinetic model of high-dose methotrexate in Chinese patients with intracranial germ cell tumors.","authors":"Jiashu Zhao, Ruoyun Wu, Sitian Zhang, Qian Lu, Ruitao Wang, Yingjun He, Zhigang Zhao, Shenghui Mei","doi":"10.3389/fphar.2025.1548203","DOIUrl":"10.3389/fphar.2025.1548203","url":null,"abstract":"<p><p>This study aims to investigate the pharmacokinetics of methotrexate (MTX) in Chinese patients with intracranial germ cell tumors (iGCTs) and to develop a robust population pharmacokinetic (PPK) model. A two-compartment model with an exponential inter-individual variability and a proportional residual model was established using nonlinear mixed-effects modeling. The model was based on 5,470 plasma concentration data points from 505 Chinese iGCT patients, including 370 children. The impact of covariates on model parameters was evaluated using forward addition and backward elimination strategies. Goodness-of-fit plots, bootstrap, visual predictive check and normalized prediction distribution errors were used to assess model performance. In the final model, the clearance of the central compartment (CL) was determined using the following equation <math><mrow><mi>C</mi> <mi>L</mi> <mo>=</mo> <mn>12.88</mn> <mo>×</mo> <msup> <mrow> <mfenced><mrow><mi>e</mi> <mi>G</mi> <mi>F</mi> <mi>R</mi> <mo>/</mo> <mn>102.2</mn></mrow> </mfenced> </mrow> <mn>0.23</mn></msup> <mo>×</mo> <msup> <mrow> <mfenced><mrow><mi>B</mi> <mi>W</mi> <mo>/</mo> <mn>47</mn></mrow> </mfenced> </mrow> <mn>0.39</mn></msup> <mo>×</mo> <msup><mi>e</mi> <mrow><mi>B</mi> <mi>L</mi> <mi>M</mi></mrow> </msup> <mo>×</mo> <msup> <mrow> <mfenced><mrow><mi>T</mi> <mi>B</mi> <mi>I</mi> <mi>L</mi> <mo>/</mo> <mn>15.3</mn></mrow> </mfenced> </mrow> <mrow><mo>-</mo> <mn>0.05</mn></mrow> </msup> <msup><mrow><mo>×</mo> <mrow> <mfenced><mrow><mi>A</mi> <mi>L</mi> <mi>B</mi> <mo>/</mo> <mn>40.9</mn></mrow> </mfenced> </mrow> </mrow> <mrow><mo>-</mo> <mn>0.18</mn></mrow> </msup> </mrow> </math> (BLM = 0.08 when combined with bleomycin, otherwise = 0). The apparent volume of the central compartment (V_c) was <math> <mrow><msub><mi>V</mi> <mi>c</mi></msub> <mo>=</mo> <mn>72.04</mn> <mo>×</mo> <msup> <mrow> <mfenced><mrow><mtext>BW</mtext> <mo>/</mo> <mn>47</mn></mrow> </mfenced> </mrow> <mn>0.31</mn></msup> </mrow> </math> . The apparent volumes of the peripheral compartments (V_p) and the inter-compartmental clearance (Q) were fixed as 94.94 L and 1.08 L/h, respectively. Co-administration with bleomycin could increase MTX CL by a factor of 1.08. Elevated total bilirubin and albumin levels were associated with decreased MTX CL. Goodness-of-fit and model evaluation confirmed the final model's adequacy, stability, and predictive performance. In our study, a PPK model was developed to identify the key factors influencing MTX pharmacokinetics, thereby optimizing and personalizing MTX therapy for Chinese patients with iGCTs.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1548203"},"PeriodicalIF":4.4,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12081364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092949","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":"Randomized, double-blind, placebo-controlled pilot study of metformin as an adjunctive therapy in Parkinson's disease.","authors":"Hayam Ali AlRasheed, Mostafa M Bahaa, Thanaa A Elmasry, Eman I Elberri, Fedaa A Kotkata, Ramy M El Sabaa, Yasmine M Elmorsi, Mostafa M Kamel, Walaa A Negm, Amir O Hamouda, Khlood Mohammad Aldossary, Muhammed M Salahuddin, Mohamed Yasser, Mamdouh Eldesouqui, Manal A Hamouda, Nashwa Eltantawy, Mirna E Elawady, Mahmoud S Abdallah","doi":"10.3389/fphar.2025.1497261","DOIUrl":"10.3389/fphar.2025.1497261","url":null,"abstract":"<p><strong>Background: </strong>Parkinson's disease (PD) is caused by the progressive loss of dopaminergic neurons in the substantia nigra. Neuroinflammation is considered a key factor contributing to the pathophysiology of PD. Current gold-standard therapies for PD provide only symptomatic relief without slowing disease progression, highlighting the need to develop new disease-modifying treatments. Metformin has been demonstrated to exert a neuroprotective role in several neurodegenerative disorders including PD.</p><p><strong>Aim: </strong>This study aimed to clarify the role of metformin as adjuvant therapy in patients with PD.</p><p><strong>Methods: </strong>Sixty patients with PD were divided into 2 groups (n = 30). Patients in group 1 received levodopa/carbidopa (250/25 mg) three times daily for 3 months plus placebo (Control group), while those in group 2 received levodopa/carbidopa (250/25 mg) three times daily and 500 mg metformin two times daily (Metformin group). Patients were assessed via Unified Parkinson's Disease Rating Scale (UPDRS). The serum concentrations of toll like receptor 4 (TLR-4), α-synuclein, brain derived neurotropic factor (BDNF), and high mobility group box 1 (HMGB-1) were measured before and after treatment.</p><p><strong>Primary outcome: </strong>The improvement in UPDRS from baseline to 3 months.</p><p><strong>Secondary outcome: </strong>Change in the level of biological markers.</p><p><strong>Results: </strong>The control group did not show significant difference in UPDRS when compared to their baseline value by Wilcoxon test (<i>P</i> > 0.05), meanwhile the metformin group showed significant difference when compared to before treatment by Wilcoxon test (<i>P</i> < 0.05). There were no significant differences between the two groups in UPDRS after treatment (<i>P</i> > 0.05) by Man Whitney test. However, the metformin group showed a significant decrease in TLR-4, HMGB-1, and α-synuclein along with a statistically significant increase in BDNF (<i>P</i> < 0.05) when compared to its baseline and control group. The control group did not show any significant changes in all markers when compared to their baseline.</p><p><strong>Conclusion: </strong>While no significant differences in UPDRS scores were observed between the metformin and control groups, trends in biomarker changes suggest a potential impact of adjunctive metformin use on the underlying pathophysiology of PD. Further studies are needed to assess its effects on motor symptoms over a longer duration.</p><p><strong>Clinical trial registration: </strong>identifier NCT05781711.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1497261"},"PeriodicalIF":4.4,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12081955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092921","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":"Advances in the study of Ophiopogon japonicus polysaccharides: structural characterization, bioactivity and gut microbiota modulation regulation.","authors":"Jiani Li, LiQuan Zhou, ZuoWei Xiao","doi":"10.3389/fphar.2025.1583711","DOIUrl":"10.3389/fphar.2025.1583711","url":null,"abstract":"<p><p>Ophiopogon japonicus polysaccharides (OJPS), the principal bioactive constituents isolated from Ophiopogon japonicus, demonstrate substantial physiological efficacy. OJPS is characterized by a high molecular weight, typically ranging from 2.48 to 324.7 kDa. Emerging evidence indicates that OJPS modulates the composition and structural organization of the gut microbiota, thereby maintaining intestinal barrier integrity and enhancing both gastrointestinal and systemic homeostasis. Moreover, OJPS and its metabolic derivatives engage in dynamic interactions with microbial communities, mediating cellular signaling cascades and endocrine regulation to elicit hypoglycemic effects. Despite these findings, comprehensive analyses of OJPS extraction and purification methodologies, structural elucidation, biological functionalities, and mechanistic insights into its crosstalk with the gut microbiota remain scarce. This review systematically synthesizes contemporary knowledge pertaining to the preparation, structural attributes, bioactivity, and mechanistic underpinnings of OJPS, with particular emphasis on its dual regulatory role in host physiology and gut microbial ecology.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1583711"},"PeriodicalIF":4.4,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12081266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093297","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 compound combinations from <i>Rhodiola tangutica</i> alleviate pulmonary vascular remodeling in high-altitude pulmonary hypertension rats through the PI3K-AKT pathway.","authors":"Na Yang, Meiduo Huayu, Shanshan Su, Bin Hou, Zhanting Yang, Xingmei Nan, Zhanqiang Li","doi":"10.3389/fphar.2025.1582677","DOIUrl":"10.3389/fphar.2025.1582677","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Hypoxia-induced pulmonary vascular remodeling is central to the development of high-altitude pulmonary hypertension (HAPH). &lt;i&gt;Rhodiola tangutica&lt;/i&gt; has traditionally been used to prevent chronic mountain sickness. Although its active fraction (ACRT) shows therapeutic potential for HAPH, the main pharmacodynamic substances remain unclear due to its complex composition.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Aims: &lt;/strong&gt;This study aimed to identify bioactive equivalent combinatorial components (BECCs) of ACRT that alleviate pulmonary vascular remodeling in HAPH rats and explore the underlying pharmacological mechanisms.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Seventy adult Sprague-Dawley rats were divided into control, hypoxia, hypoxia + ACRT (150 mg/kg), hypoxia + BECCs (25, 50, and 100 mg/kg), and hypoxia + sildenafil (30 mg/kg) groups. An HAPH rat model was induced using a hypobaric hypoxia chamber simulating an altitude of 5,000 m. The effects of BECCs on pulmonary vascular remodeling in HAPH rats were evaluated based on hemodynamic indexes and histopathological changes, alongside antioxidant properties. Phosphoproteomics and Western blotting were performed to analyze AKT1-related protein expression in lung tissues. &lt;i&gt;In vitro&lt;/i&gt;, 3% O&lt;sub&gt;2&lt;/sub&gt;-induced pulmonary artery smooth muscle cell (PASMC) models were used to evaluate the anti-proliferative effects of BECCs and identify the dominant components. The underlying mechanisms were explored using Western blotting and a drug affinity responsive target stability (DARTS) assay to assess binding affinity.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;HAPH rat models were successfully established, as evidenced by changes in physiological parameters. BECCs showed comparable efficacy to ACRT in restoring hemodynamic indexes and histopathological changes. Mechanistically, BECCs modulated AKT phosphorylation and related protein expression. &lt;i&gt;In vitro&lt;/i&gt;, BECCs inhibited hypoxia-induced PASMC proliferation. Particularly, flavonoids (FLAs) within BECCs exhibited stronger anti-proliferative activity than other components, acting as the dominant contributors by regulating phosphatidylinositol-3 kinase (PI3K) rather than phosphoinositide-dependent protein kinase (PDPK) or mammalian target of rapamycin (mTOR) pathways to inhibit AKT phosphorylation. Among FLAs, eriodictyol and quercetin were found to inhibit PASMC proliferation by targeting PI3K.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;BECCs demonstrated comparable efficacy to ACRT in alleviating HAPH progression, reversing hypoxia-induced vascular remodeling, and inhibiting oxidative stress and PASMC proliferation by targeting the AKT protein. Flavonoids were identified as the key bioactive components contributing to the holistic effects of BECCs by regulating phosphatidylinositol-3 kinase/protein kinase B (PI3K/AKT) pathways. These findings could be extended to improve quality control and clarify the bioactive components of &lt;i&gt;R. tangutica&lt;/i&gt; while inspiring develo","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1582677"},"PeriodicalIF":4.4,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12081410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093380","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":"Shenmai Injection enhances short-term outcomes in ischemic stroke patients after thrombolysis via AMPKα1.","authors":"Jing Wu, Zhonghao Li, Xiaoke Dong, Jinmin Liu, Le Wang","doi":"10.3389/fphar.2025.1552493","DOIUrl":"https://doi.org/10.3389/fphar.2025.1552493","url":null,"abstract":"<p><strong>Background: </strong>Shenmai Injection (SMI), a traditional Chinese medicine with nourishing properties, has been explored for its therapeutic effects in ischemic stroke (IS). This study aimed to evaluate the protective effects of SMI in patients with IS who received intravenous thrombolysis and to elucidate its potential molecular mechanisms through laboratory investigations.</p><p><strong>Methods: </strong>Patients with IS were randomized to receive either SMI or a placebo for 10 days within 12 h post-intravenous thrombolysis. Clinical efficacy and safety were assessed. An IS cell model was induced using H2O2, followed by treatment with SMI to explore its therapeutic effects and underlying mechanisms.</p><p><strong>Results: </strong>The modified Rankin Scale (mRS) score at 30 days was significantly lower in the SMI group (n = 35) compared to the placebo group (n = 35), indicating improved functional outcomes. No significant difference was observed in NIHSS scores between the groups. Adverse events and biochemical indices showed no significant differences, confirming the safety of SMI. In the H2O2-induced cell model, SMI enhanced cell viability, reduced apoptosis, and decreased the levels of malondialdehyde (MDA) and reactive oxygen species (ROS). It also improved ATP content and mitochondrial membrane potential. Mechanistic studies revealed that these protective effects were partially mediated through the AMPKα1.</p><p><strong>Conclusion: </strong>SMI significantly improves short-term outcomes in IS patients treated with rt-PA thrombolysis. Its protective effects are likely mediated through the AMPKα1, highlighting its potential as an adjunctive therapy for IS.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1552493"},"PeriodicalIF":4.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144077236","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":"Camrelizumab plus rivoceranib versus sorafenib as first-line therapy for patients with unresectable hepatocellular carcinoma: a cost-utility analysis in China and the United States.","authors":"Qiuling Zhao, Yimin He, Zilin Nian, Yongjian Huang, Ruyi Huang, Lijun Lai, Lin Yang","doi":"10.3389/fphar.2025.1404389","DOIUrl":"https://doi.org/10.3389/fphar.2025.1404389","url":null,"abstract":"<p><strong>Objective: </strong>Camrelizumab plus rivoceranib (camr-rivo) has been shown to significantly improve overall survival (OS) in patients with unresectable or advanced hepatocellular carcinoma (HCC) in the CARES-310 trial. However, the cost-utility of this treatment remains unclear. Therefore, this study evaluated the cost-utility of camr-rivo versus sorafenib as a first-line systemic therapy for patients with unresectable or advanced HCC from the perspectives of the Chinese healthcare system and the United States (US) payers.</p><p><strong>Methods: </strong>Based on the CARES-310 trial, a partitioned survival model was constructed to estimate economic costs and health outcomes over a 10-year lifetime horizon. Drug costs were obtained from the public database, Red Book, and relevant literature. Health utility values were derived from the literature. One-way and probabilistic sensitivity analyses were performed. The willingness-to-pay (WTP) threshold was $36,627.25/QALY in China and $150,000.00/QALY in the United States.</p><p><strong>Results: </strong>Camr-rivo yielded an additional 0.34 quality-adjusted life years (QALY) compared to sorafenib for patients with unresectable or advanced HCC. The incremental costs in China and the United States were $4,762.10 and $92,700.49, respectively, and the incremental cost-utility ratios (ICURs) were $14,174.40/QALY and $272,852.59/QALY, respectively. Sensitivity analyses indicated that the cost of rivoceranib and camrelizumab had the greatest impact on the ICUR in China and the United States. Scenario analyses showed that a price reduction of approximately 30% for camrelizumab and rivoceranib could make camr-rivo a cost-utility option in the United States.</p><p><strong>Conclusion: </strong>At the set WTP threshold, camr-rivo is a cost-utility treatment strategy compared to sorafenib as a first-line therapy for patients with unresectable or advanced HCC in China but not in the United States.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1404389"},"PeriodicalIF":4.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144077250","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}