Frontiers in Pharmacology最新文献

{"title":"<i>In vitro</i>, <i>in vivo</i>, and <i>in silico</i> approaches for evaluating the preclinical DMPK profiles of ammoxetine, a novel chiral serotonin and norepinephrine reuptake inhibitor.","authors":"Xiuqing Zhu, Yuexin Li, Huan Luo, Yunxia Zhang, Zhenqing Zhang, Jinglai Li","doi":"10.3389/fphar.2024.1486856","DOIUrl":"10.3389/fphar.2024.1486856","url":null,"abstract":"<p><strong>Background and aim: </strong>Ammoxetine, a novel chiral serotonin and norepinephrine reuptake inhibitor, holds promise for major depressive disorder treatment. This study aimed to thoroughly investigate its preclinical drug metabolism and pharmacokinetics (DMPK) profiles.</p><p><strong>Methods: </strong>The preclinical DMPK profiles of ammoxetine were examined through <i>in vitro</i>, <i>in vivo</i>, and <i>in silico</i> methods.</p><p><strong>Results: </strong>Assessment of blood-brain barrier penetration <i>via</i> MDCK-MDR1 cells revealed strong brain permeation by ammoxetine, despite being a probable P-glycoprotein (P-gp) substrate. Molecular docking indicated a robust binding interaction between ammoxetine and P-gp. Ammoxetine was well absorbed orally, with T_max ranging from 0.75 to 3.83 h in rats and 0.75-1.40 h in beagle dogs. At a 2 mg/kg dose in beagle dogs, ammoxetine exhibited an absolute bioavailability of approximately 42%. Plasma protein binding rates were around 50%-60% in beagle dogs, rats, and humans, suggesting moderate binding. Tissue distribution studies displayed rapid and extensive ammoxetine spread in major rat tissues post-gavage, with notable brain exposure and no tissue accumulation. Cumulative excretion rates in rats' urine, feces, and bile accounted for only 1.11% of the total administered drug, indicating extensive transformation into metabolites. Chiral inversion of ammoxetine was absent <i>in vivo</i>. Metabolic stability varied across species using liver microsomes, but beagle dogs showed clearance rates more akin to humans. Metabolic pathways unveiled two key metabolites, M1 and M2. M1, likely generated through methylenedioxyphenyl ring oxidation, involves CYP2C19 and CYP3A4, crucial human cytochrome P450 (CYP) enzymes for liver metabolism, while M2 is M1's glucuronide conjugate. Ammoxetine may exhibit saturation elimination trends with increasing doses in rats and beagle dogs. A high-throughput assay using the cocktail-substrate method indicated weak CYP inhibition by ammoxetine on CYP2D6 and CYP1A2, with minimal effects on other CYP enzymes, suggesting a low likelihood of CYP inhibition-related drug-drug interactions.</p><p><strong>Conclusion: </strong>This study presents encouraging DMPK profiles of ammoxetine, backing its potential as a candidate compound for future clinical assessments.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"15 ","pages":"1486856"},"PeriodicalIF":4.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11579541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686618","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":"Estrogen: the forgotten player in metaflammation.","authors":"Bao-Ting Zhu, Qing-Qing Liao, Hai-Ying Tian, Dao-Jiang Yu, Teng Xie, Xi-Lu Sun, Xin-Meng Zhou, Ying-Xuan Han, Yu-Jie Zhao, Mohamed El-Kassas, Xiu-Xiu Liu, Xiao-Dong Sun, Yuan-Yuan Zhang","doi":"10.3389/fphar.2024.1478819","DOIUrl":"10.3389/fphar.2024.1478819","url":null,"abstract":"<p><p>Metaflammation is low-grade inflammation triggered by chronic metabolic imbalance and caused by dysregulated metabolites in metabolic inflammatory syndrome (MIS), which includes four diseases: obesity, type 2 diabetes mellitus (T2DM), atherosclerosis (AS), and nonalcoholic fatty liver diseases (NAFLD, recently proposed to be replaced by metabolic dysfunction-associated steatotic liver disease, MASLD). These diseases exhibit apparent sex dimorphism as regards MIS. Estrogen not only plays a crucial role in gender differences in adults but also possesses an anti-inflammatory effect on many metabolic diseases. In this study, we present a prediction of the differential proteins and signal transduction of estrogen in MIS through network pharmacology and review the validated studies on obesity, T2DM, AS, and NAFLD. Subsequently, we compared them to obtain valuable targets, identify current gaps, and provide perspectives for future research on the mechanisms of estrogen in metaflammation.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"15 ","pages":"1478819"},"PeriodicalIF":4.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11578702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686496","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 study of adverse drug reactions of two isocitrate dehydrogenase inhibitor based on the US FDA adverse event reporting system and VigiAccess databases.","authors":"Mengmeng Peng, Qian Guo, Zihan Dang, Baiquan Zhang, Manjuan Li, Zixuan Wang, Xuemian Lu, Jie Lin","doi":"10.3389/fphar.2024.1489045","DOIUrl":"10.3389/fphar.2024.1489045","url":null,"abstract":"<p><strong>Background and objectives: </strong>Isocitrate dehydrogenase (IDH) inhibitor drugs (Enasidenib, Ivosidenib) restore normal metabolism and epigenetic regulation in cells, offering a precision-targeted therapeutic option for acute myeloid leukemia (AML) patients with IDH mutations by specifically inhibiting mutated IDH enzymes. This research evaluates the relationship between adverse drug reactions (ADR) and the use of two isocitrate dehydrogenase inhibitors by using the database from the World Health Organization (WHO) VigiAccess and compares the characteristics of ADRs of the two drugs.</p><p><strong>Methods: </strong>This study design used the retrospective descriptive analysis. We calculated the ratio of ADRs recorded in reports to compare the same points and different points in ADRs between two medications. Proportional reporting ratio (PRR) and reported odds ratio were used to evaluate the relationship between these two isocitrate dehydrogenase inhibitor medications and adverse events.</p><p><strong>Results: </strong>Overall, during the search, 4,072 adverse events related to two types of isocitrate dehydrogenase inhibitors were reported in VigiAccess. The results revealed that the top 10 most common AEs were off label use, death, fatigue, nausea, diarrhea, acute myeloid leukemia, drug ineffective, differentiation syndrome, platelet count decreased and decreased appetite. Compared two drugs, enasidinib had the highest adverse reaction reporting rate in general disorders and administration site conditions while ivosidenib had the highest adverse drug reactions reporting rate in injury, poisoning and procedural complications.</p><p><strong>Conclusion: </strong>Based on the current comparative observational studies, the ADR reports received by the World Health Organization, Food and Drug Administration for these drugs list common and specific adverse drug reactions. Clinical doctors should develop individualized treatment plans based on the adverse reactions of different drugs and the specific conditions of patients to promote the rational use of these expensive medications.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"15 ","pages":"1489045"},"PeriodicalIF":4.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11578689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686619","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":"Efficacy analysis of neuroprotective drugs in patients with acute ischemic stroke based on network meta-analysis.","authors":"Mei Li, Xianhao Huo, Qing Chang, Xiaozhuo Liu, Jianning Zhang, Zhiqi Mao","doi":"10.3389/fphar.2024.1475021","DOIUrl":"10.3389/fphar.2024.1475021","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;This network meta-analysis aims to explore the efficacy and safety of neuroprotective agents in patients with ischemic stroke and attempts to identify which drug is the most effective in improving outcomes for patients with acute ischemic stroke (AIS) through a ranking method.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We comprehensively searched the PubMed, Medline, Embase, Web of Science, and Cochrane library databases from their establishment to 30 June 2024. Data were extracted from the studies identified, and their quality was assessed using the Cochrane risk-of-bias tool or the Newcastle-Ottawa Scale (NOS). The outcome measures were for a favorable prognosis, based on the modified Rankin Scale score (mRS) or National Institutes of Health Stroker Scale (NIHSS) score, mortality, and adverse effect with different drug regimens. We utilized Stata version 16.0 and Review Manager (RevMan) version 5.3.0 for statistical analysis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 35 studies were included: 25 randomized control trials, eight retrospective studies, and two prospective studies. The total sample size was 18,423 cases and included nine interventions: citicoline, edaravone (EDV), edaravone dexborneol, cinepazide maleate, cerebrolysin, minocycline, ginkgolide, ginkgo diterpene lactone meglumine (GDLM), and conventional (CON) treatment. Our analysis revealed that, except for edaravone dexborneol, the ginkgolide, EDV, cinepazide maleate, citicoline, cerebrolysin, minocycline, and GDLM treatment schemes reduced the mortality of patients with AIS compared with CON. Each drug regimen significantly improved the neural function of these patients compared with CON, which from highest to lowest was citicoline + vinpocetine, GDLM, citicoline, edaravone dexborneol, cinepazide maleate, ginkgolide, EDV, and CON. Moreover, we also found that, except for citicoline, the ginkgolide, EDV, edaravone dexborneol, GDLM, and cinepazide maleate treatment schemes had a high total treatment effective rate in these patients, the order from highest to lowest being ginkgolide, EDV, edaravone dexborneol, GDLM, cinepazide maleate, CON, and citicoline. In terms of the ineffective rate, we found that, compared with CON, the edaravone dexborneol, EDV, citicoline, GDLM, ginkgolide, and cinepazide maleate treatment schemes all had a lower ineffective rate. Finally, our analysis revealed that, except for cinepazide maleate and ginkgolide, the EDV, minocycline, edaravone dexborneol, GDLM, citicoline, and cerebrolysin schemes all had a higher rate of adverse effect on patients compared to CON. Based on the impact of the adverse effect with different surgical interventions, we further analyzed the effect of these drug treatments by the total treatment effective rate combined with adverse effect, revealing that EDV, ginkgolide, and edaravone dexborneol were the safest and most effective treatments.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;In patients with AIS, ginkgolide,","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"15 ","pages":"1475021"},"PeriodicalIF":4.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11578817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686622","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":"Small molecule inhibitors target multiple neuropathological signaling to exert novel neuroprotection in intracranial aneurysms.","authors":"Acharya Balkrishna, Shalini Mishra, Maneesha Rana, Satyendra Kumar Rajput, Suhrud Pathak, Keyi Liu, Muralikrishnan Dhanasekaran, Vedpriya Arya, Shalini Singh","doi":"10.3389/fphar.2024.1469211","DOIUrl":"10.3389/fphar.2024.1469211","url":null,"abstract":"<p><p>Intracranial aneurysms (IAs) represent a critical health concern due to their potential to rupture, leading to severe morbidity and mortality. Small molecule inhibitors (SMIs) have emerged as promising therapeutic candidates for managing IA progression and rupture risk. The current landscape of SMIs targets various molecular pathways implicated in IA pathogenesis, including inflammation, endothelial dysfunction, and extracellular matrix (ECM) degradation. Among the prominent therapeutic candidates discussed are statins, recognized for their multifaceted effects, anti-inflammatory properties, and enhancement of endothelial stability, which may mitigate IA progression. Matrix metalloproteinase inhibitors are also highlighted for their role in preserving ECM structural integrity, essential for preventing IA wall weakening and rupture. Furthermore, the review evaluates the efficacy of anti-inflammatory agents such as corticosteroids and cytokine inhibitors in attenuating IA growth driven by inflammatory processes. Our findings highlight the possibility of several pharmaceutical therapies that target matrix remodeling, inflammation, and other underlying processes to manage cerebral aneurysms. By precisely delivering therapeutic chemicals, such as antioxidants, gene therapy vectors, or anti-inflammatory medicines, to the aneurysm site, these SMI technologies treat the underlying pathophysiological causes while sparing healthy brain tissue. This review underscores the potential of SMIs as adjunctive or primary therapies in the comprehensive management of IAs, emphasizing the need for further clinical research to optimize their efficacy and safety in clinical practice.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"15 ","pages":"1469211"},"PeriodicalIF":4.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11578703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686665","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":"Scutellarin: pharmacological effects and therapeutic mechanisms in chronic diseases.","authors":"Shanshan Nie, Shan Zhang, Ruipeng Wu, Yuhang Zhao, Yongxia Wang, Xinlu Wang, Mingjun Zhu, Peng Huang","doi":"10.3389/fphar.2024.1470879","DOIUrl":"10.3389/fphar.2024.1470879","url":null,"abstract":"<p><p>Scutellarin (SCU), a flavonoid glucuronide derived from <i>Scutellaria barbata</i> and <i>Erigeron breviscapus</i>, exhibits broad pharmacological effects with promising therapeutic potential in treating various chronic diseases. It has demonstrated efficacy in modulating multiple biological pathways, including antioxidant, anti-inflammatory, anti-apoptotic, and vasodilatory mechanisms. These protective roles make SCU a valuable compound in treating chronic diseases such as cerebrovascular diseases, cardiovascular diseases, neurodegenerative disorders, and metabolic diseases. Despite its multi-targeted effects, SCU faces challenges such as low bioavailability and limited clinical data, which hinder its widespread therapeutic application. Current research supports its potential to prevent oxidative stress, reduce inflammatory responses, and enhance cell survival in cells and rats. However, more comprehensive studies are required to clarify its molecular mechanisms and to develop strategies that enhance its bioavailability for clinical use. SCU could emerge as a potent therapeutic agent for the treatment of chronic diseases with complex pathophysiological mechanisms. This review examines the current literature on Scutellarin to provide a comprehensive understanding of its pharmacological activity, mechanisms of action, and therapeutic potential in treating chronic diseases.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"15 ","pages":"1470879"},"PeriodicalIF":4.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11578714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686623","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":"Rabeprazole suppressed gastric intestinal metaplasia through activation of GPX4-mediated ferroptosis.","authors":"Jing Xie, Xinhua Liang, Fangfang Xie, Canxin Huang, Zijun Lin, Shuping Xie, Fangying Yang, Fengfeng Zheng, Lanlan Geng, Wanfu Xu, Sitang Gong, Li Xiang","doi":"10.3389/fphar.2024.1409001","DOIUrl":"10.3389/fphar.2024.1409001","url":null,"abstract":"<p><strong>Background: </strong>Gastric intestinal metaplasia is a common pathological feature in patients with <i>Helicobacter pylori</i> (<i>H. pylori</i>) infection. Rabeprazole was widely used as the first-line regimen for <i>H. pylori</i> infectious treatment. The objective of this study is to explore the mechanism of rabeprazole in gastric intestinal metaplasia treatment.</p><p><strong>Methods: </strong>Real-time PCR, Western blotting (WB) and ROS analysis were conducted to confirm that rabeprazole could induce ferroptosis to suppress gastric intestinal metaplasia. Cellular fraction, luciferase and chromatin immunoprecipitation (ChIP) were used to identify the mechanism underlying rabeprazole modulated ferroptosis.</p><p><strong>Results: </strong>Herein, we found rabeprazole treatment led to inhibit CDX2 and MUC2 expression, alleviating gastric intestinal metaplasia, which was attributed to enhanced ferroptosis characterized by decreased GPX4 expression. Inhibition of ferroptosis by ferrostatin-1 (Fer-1) could reverse decreased CDX2 and MUC2 expression caused by rabeprazole. Mechanically, Rabeprazole could inhibit CREB phosphorylation and nuclear translocation, which further decreased the binding of CREB to GPX4 promoter, reducing GPX4 transactivity. Moreover, endogenous PKA interacted with CREB, and this interaction was drastically destroyed in response to rabeprazole treatment. Most importantly, enhanced ferroptosis was observed in <i>H. pylori-</i>infected gastric intestinal metaplasia in comparison to HC control.</p><p><strong>Conclusion: </strong>These findings suggested that rabeprazole induced ferroptosis to reduce CDX2 expression in gastric epithelial cells through PKA/CREB cascade signaling, implying that targeting ferroptosis could be a promising strategy in improving gastric intestinal metaplasia during <i>H. pylori</i>-infected patients.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"15 ","pages":"1409001"},"PeriodicalIF":4.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11578692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686551","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 of SIRT1-FXR signaling pathway in valproic acid induced liver injury: a quantitative targeted metabolomic evaluation in epileptic children.","authors":"Mingming Zhao, Guofei Li, Limei Zhao","doi":"10.3389/fphar.2024.1477619","DOIUrl":"10.3389/fphar.2024.1477619","url":null,"abstract":"<p><strong>Aim: </strong>This study aimed to gain deeper insights into the hepatotoxicity mechanisms of valproic acid (VPA), as well as to identify potential risk markers for VPA-induced hepatotoxicity.</p><p><strong>Methods: </strong>Twenty-two children with epilepsy treated with VPA monotherapy were divided into a normal liver function (NLF) group, a mild abnormal liver function (ANLF1) group, and a serious abnormal liver function (ANLF2) group based on their liver function indicator levels. The full quantitative targeted metabolomics technique was used to systematically investigate how the differential endogenous metabolic components change with the development of liver injury.</p><p><strong>Results: </strong>A total of 195 metabolic components were quantitatively analyzed. Nineteen identified metabolites, including five organic acids, four short-chain fatty acids, four amino acids, three fatty acids, and three benzenoids, differed significantly among the three groups, showing a strong association with VPA-induced hepatotoxicity. Only three bile acid metabolites, taurodeoxycholic acid, taurochenodeoxycholic acid, and deoxycholic acid, were significantly different between the ANLF1 and ANLF2 groups, increasing at first and then decreasing with the aggravation of liver injury. The mechanistic evaluation showed that SRT1720 activation could alleviate the severity of liver function abnormalities induced by VPA. Immunocoprecipitation indicated that VPA significantly increased the acetylation level of FXR, and the application of agonist SRT1720 can antagonize the acetylation of FXR by VPA.</p><p><strong>Conclusion: </strong>Nineteen identified metabolites showed a strong association with hepatotoxicity and three bile acid metabolites changed with the development of liver injury. The SIRT1-FXR pathway was firstly proposed to participate in VPA-induced hepatotoxicity.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"15 ","pages":"1477619"},"PeriodicalIF":4.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11578826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686666","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":"Investigation of the therapeutic effects and mechanisms of Houpo Mahuang Decoction on a mouse model of chronic obstructive pulmonary disease.","authors":"Shanlan Li, Ziqi Dai, Tong Zhang, Zhuoqian Guo, Feng Gao, Xuehao Cheng, Jin An, Yixuan Lin, Xiaomin Xiong, Nan Wang, Guanghui Jiang, Bing Xu, Haimin Lei","doi":"10.3389/fphar.2024.1448069","DOIUrl":"10.3389/fphar.2024.1448069","url":null,"abstract":"<p><strong>Background: </strong>With a growing global population affected by Chronic Obstructive Pulmonary Disease (COPD), the traditional Chinese herbal formula Houpo Mahuang Decoction (HPMHD) has been used for centuries to address respiratory ailments. While studies have demonstrated the therapeutic benefits of HPMHD in COPD, the effective active ingredients, potential targets, and molecular mechanisms underlying its effectiveness remained unclear.</p><p><strong>Methods: </strong>The mechanisms of action of certain HPMHD components, targets, and pathways for the treatment of COPD were predicted using a network pharmacology method. We induced a COPD mouse model using porcine pancreatic elastase and evaluated the pathological changes and healing processes through HE and Masson staining. Immunofluorescence was used to assess the levels of IL-6 and TNF-ɑ. RNA-Seq analysis was conducted to identify differentially expressed genes (DEGs) in the lungs of normal, control, and treated mice, revealing the biological pathways enriched by HPMHD in COPD treatment. Finally, the expression of DEGs was verified using Western blotting and RT-qPCR.</p><p><strong>Results: </strong>HPMHD effectively alleviated pathological symptoms and improved COPD in mice by modulating the IL-17 signaling pathway. Treatment with HPMHD improved lung morphology and structure, reduced inflammatory cell infiltration, and inhibited IL-6 and TNF-ɑ levels. Network pharmacology and transcriptomics further revealed the mechanism, indicating that the IL-17 signaling pathway might been instrumental in the inhibitory effect of HPMHD on mouse model of COPD. Subsequent experiments, including protein blotting and RT-qPCR analysis, confirmed the activation of the IL-17 signaling pathway by HPMHD in the COPD mouse model, further supporting the initial findings.</p><p><strong>Conclusion: </strong>HPMHD was shown to alleviate COPD and reduce lung inflammation in mice, potentially through the activation of the IL-17 signaling pathway. This study provides a novel direction for the development of COPD drugs.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"15 ","pages":"1448069"},"PeriodicalIF":4.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11578825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686546","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":"Inspired by an ancient Chinese Medicine prescription: the modern significance and potential of Yiyi Fuzi Baijiang San in treating diseases.","authors":"Yuli Zhang, Lu Zhang, Ni Chai, ZhiQiang Wan, Hua Sui","doi":"10.3389/fphar.2024.1465387","DOIUrl":"10.3389/fphar.2024.1465387","url":null,"abstract":"<p><p>Classic Formulas (Jing fang) are considered the essence and authority of Traditional Chinese Medicine (TCM) due to their long history and proven efficacy. These formulas play a pivotal role in all kinds of different disease prevention and therapeutic strategies. Yiyi Fuzi Baijiang San (YYFZBJS), one of the Classic Formulas, was originally developed for the treatment of chronic intestinal abscess. With the accumulation of clinical experience and the exploration of modern pharmacological research in recent years, YYFZBJS has been extensively employed to address a broad spectrum of conditions such as colorectal cancer. Although numerous studies have explored the clinical efficacy and underlying mechanisms of YYFZBJS, no comprehensive review summarizing these findings exists to date. This study aims to systematically review and critically assess the current clinical and mechanistic research on YYFZBJS, with the objective of providing valuable insights and guidance for TCM research in the future.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"15 ","pages":"1465387"},"PeriodicalIF":4.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11578754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686527","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}