BackgroundEpigenetics denotes heritable alterations in gene expression patterns independent of changes in DNA sequence. Epigenetic therapy seeks to reprogram malignant cells to a normal phenotype and has been extensively investigated in oncology. This study conducts a bibliometric analysis of epigenetic therapy in cancer, providing a comprehensive overview of current research, identifying trends, and highlighting key areas of investigation.MethodsPublications concerning epigenetic inhibitors in cancer spanning 2004 to 2023 were retrieved from the Web of Science Core Collection (WoSCC). Co-occurrence analysis using VOSviewer assessed current status and focal points. Evolutionary trends and bursts in the knowledge domain were analyzed using CiteSpace. Bibliometrix facilitated topic evolution and revealed trends in keywords. National, institutional, and author affiliations and collaborations were also examined.ResultsA total of 2,153 articles and reviews on epigenetic therapy in oncology were identified, demonstrating a consistent upward trend over time. The United States (745 papers), University of Texas MD Anderson Cancer Center (57 papers), and Stephen B. Baylin (27 papers) emerged as the most productive country, institution, and author, respectively. Keyword co-occurrence analysis identified five primary clusters: tumor, DNA methylation, epigenetic therapy, expression, and immunotherapy. In the past 5 years, newly emerging themes with increased centrality and density include “drug resistance,” “immunotherapy,” and “combination therapy.” The most cited publication reviewed current understanding of potential causes of epigenetic diseases and proposed future therapeutic strategies.ConclusionIn the past two decades, the importance of epigenetic therapy in cancer research has become increasingly prominent. The United States occupies a key position in this field, while China, despite having published a large number of related papers, still has relatively limited influence. Current research focuses on the “combination therapy” of epigenetic drugs. Future studies should further explore the sequencing and scheduling of combination therapies, optimize trial designs and dosing regimens to improve clinical efficacy.
背景表观遗传学指基因表达模式的遗传性改变,与 DNA 序列的变化无关。表观遗传学疗法旨在将恶性细胞重编程为正常表型,已在肿瘤学领域得到广泛研究。本研究对癌症中的表观遗传疗法进行了文献计量分析,全面概述了当前的研究情况,确定了研究趋势,并突出了重点研究领域。方法从科学网核心文献库(WoSCC)中检索了2004年至2023年有关癌症中表观遗传抑制剂的文献。使用 VOSviewer 进行的共现分析评估了现状和焦点。使用 CiteSpace 分析了知识领域的演变趋势和突发情况。Bibliometrix 促进了主题的演变并揭示了关键词的趋势。结果共发现 2,153 篇关于肿瘤学表观遗传疗法的文章和综述,显示出持续上升的趋势。美国(745篇)、德克萨斯大学MD安德森癌症中心(57篇)和Stephen B. Baylin(27篇)分别成为发表论文最多的国家、机构和作者。关键词共现分析确定了五个主要集群:肿瘤、DNA甲基化、表观遗传疗法、表达和免疫疗法。在过去 5 年中,新出现的中心性和密度增加的主题包括 "耐药性"、"免疫疗法 "和 "联合疗法"。被引用次数最多的出版物回顾了目前对表观遗传疾病潜在病因的理解,并提出了未来的治疗策略。美国在这一领域占据重要地位,而中国尽管发表了大量相关论文,但影响力仍相对有限。目前的研究重点是表观遗传药物的 "联合治疗"。未来的研究应进一步探讨联合疗法的排序和时间安排,优化试验设计和给药方案,以提高临床疗效。
{"title":"Research hotspots and trends of epigenetic therapy in oncology: a bibliometric analysis from 2004 to 2023","authors":"Sisi Li, Xinrui Liang, Qing Shao, Guanwen Wang, Yuxin Huang, Ping Wen, Dongping Jiang, Xiaohua Zeng","doi":"10.3389/fphar.2024.1465954","DOIUrl":"https://doi.org/10.3389/fphar.2024.1465954","url":null,"abstract":"BackgroundEpigenetics denotes heritable alterations in gene expression patterns independent of changes in DNA sequence. Epigenetic therapy seeks to reprogram malignant cells to a normal phenotype and has been extensively investigated in oncology. This study conducts a bibliometric analysis of epigenetic therapy in cancer, providing a comprehensive overview of current research, identifying trends, and highlighting key areas of investigation.MethodsPublications concerning epigenetic inhibitors in cancer spanning 2004 to 2023 were retrieved from the Web of Science Core Collection (WoSCC). Co-occurrence analysis using VOSviewer assessed current status and focal points. Evolutionary trends and bursts in the knowledge domain were analyzed using CiteSpace. Bibliometrix facilitated topic evolution and revealed trends in keywords. National, institutional, and author affiliations and collaborations were also examined.ResultsA total of 2,153 articles and reviews on epigenetic therapy in oncology were identified, demonstrating a consistent upward trend over time. The United States (745 papers), University of Texas MD Anderson Cancer Center (57 papers), and Stephen B. Baylin (27 papers) emerged as the most productive country, institution, and author, respectively. Keyword co-occurrence analysis identified five primary clusters: tumor, DNA methylation, epigenetic therapy, expression, and immunotherapy. In the past 5 years, newly emerging themes with increased centrality and density include “drug resistance,” “immunotherapy,” and “combination therapy.” The most cited publication reviewed current understanding of potential causes of epigenetic diseases and proposed future therapeutic strategies.ConclusionIn the past two decades, the importance of epigenetic therapy in cancer research has become increasingly prominent. The United States occupies a key position in this field, while China, despite having published a large number of related papers, still has relatively limited influence. Current research focuses on the “combination therapy” of epigenetic drugs. Future studies should further explore the sequencing and scheduling of combination therapies, optimize trial designs and dosing regimens to improve clinical efficacy.","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142201849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-11eCollection Date: 2024-01-01DOI: 10.3389/fphar.2024.1403147
Adriana Yndart Arias, Kamila Vadell, Arti Vashist, Nagesh Kolishetti, Madepalli K Lakshmana, Madhavan Nair, Juan P Liuzzi
Background: Finding new strategies to treat cognitive disorders is a challenging task. Medication must defeat the blood-brain barrier. Cannabidiol (CBD), a non-intoxicating compound of the cannabis plant, has gained recognition as a nutraceutical for its potential effectiveness in treating anxiety, oxidative stress, convulsions, and inflammation. However, the dose, tolerable upper intake, formulation, administration routes, comorbidities, diet, and demographic factors to reverse cognitive impairments have not been completely explored. Trials using CBD as a primary intervention have been conducted to alleviate cognitive issues. This review evaluates the benefits of CBD supplementation, research design, formulations, and outcomes reported in randomized clinical trials.
Methods: An evidence-based systematic literature review was conducted using PUBMED and the Florida International University Research Library resources. Fourteen randomized trials were selected for review, and their designs and outcomes were compared conceptually and in the form of resume tables.
Results: CBD showed improvement in anxiety and cognitive impairments in 9 out of 16 analyzed trials. However, the variability could be justified due to the diversity of the trial designs, underpowered studies, assayed population, uncontrolled results for comorbidities, medications, severity of drug dependence, compliances, and adherences. Overall, oral single doses of 200 mg-1,500 mg or vaporized 13.75 mg of CBD were shown to be effective at treating anxiety and cognition with a good safety profile and no drug addiction behaviors. Conversely, results that did not have a significant effect on treating cognitive impairments can be explained by various factors such as THC or other abuse drugs masking effect, low dose, and unknown purity of CBD. Furthermore, CBD shows potential properties that can be tested in the future for Alzheimer's disease.
Conclusion: As medical cannabis becomes more accessible, it is essential to understand whether medication rich in CBD exerts a beneficial effect on cognitive disorders. Our study concludes that CBD is a promising candidate for treating neurocognitive disorders; however, more studies are required to define CBD as a therapeutic candidate for managing cognitive disorders.
{"title":"Cannabidiol, a plant-derived compound, is an emerging strategy for treating cognitive impairments: comprehensive review of randomized trials.","authors":"Adriana Yndart Arias, Kamila Vadell, Arti Vashist, Nagesh Kolishetti, Madepalli K Lakshmana, Madhavan Nair, Juan P Liuzzi","doi":"10.3389/fphar.2024.1403147","DOIUrl":"https://doi.org/10.3389/fphar.2024.1403147","url":null,"abstract":"<p><strong>Background: </strong>Finding new strategies to treat cognitive disorders is a challenging task. Medication must defeat the blood-brain barrier. Cannabidiol (CBD), a non-intoxicating compound of the cannabis plant, has gained recognition as a nutraceutical for its potential effectiveness in treating anxiety, oxidative stress, convulsions, and inflammation. However, the dose, tolerable upper intake, formulation, administration routes, comorbidities, diet, and demographic factors to reverse cognitive impairments have not been completely explored. Trials using CBD as a primary intervention have been conducted to alleviate cognitive issues. This review evaluates the benefits of CBD supplementation, research design, formulations, and outcomes reported in randomized clinical trials.</p><p><strong>Methods: </strong>An evidence-based systematic literature review was conducted using PUBMED and the Florida International University Research Library resources. Fourteen randomized trials were selected for review, and their designs and outcomes were compared conceptually and in the form of resume tables.</p><p><strong>Results: </strong>CBD showed improvement in anxiety and cognitive impairments in 9 out of 16 analyzed trials. However, the variability could be justified due to the diversity of the trial designs, underpowered studies, assayed population, uncontrolled results for comorbidities, medications, severity of drug dependence, compliances, and adherences. Overall, oral single doses of 200 mg-1,500 mg or vaporized 13.75 mg of CBD were shown to be effective at treating anxiety and cognition with a good safety profile and no drug addiction behaviors. Conversely, results that did not have a significant effect on treating cognitive impairments can be explained by various factors such as THC or other abuse drugs masking effect, low dose, and unknown purity of CBD. Furthermore, CBD shows potential properties that can be tested in the future for Alzheimer's disease.</p><p><strong>Conclusion: </strong>As medical cannabis becomes more accessible, it is essential to understand whether medication rich in CBD exerts a beneficial effect on cognitive disorders. Our study concludes that CBD is a promising candidate for treating neurocognitive disorders; however, more studies are required to define CBD as a therapeutic candidate for managing cognitive disorders.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11422111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344695","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}
Pub Date : 2024-09-11DOI: 10.3389/fphar.2024.1473019
Dong Wu, Wenjuan Zhou, Jingyi Du, Tiantian Zhao, Naigang Li, Fan Peng, Anna Li, Xinyue Zhang, Meihua Zhang, Aijun Hao
BackgroundWhite matter injury is a predominant form of brain injury in preterm infants. However, effective drugs for its treatment are currently lacking. Previous studies have shown the neuroprotective effects of Isoliquiritigenin (ISL), but its impact on white matter injury in preterm infants remains poorly understood.AimsThis study aimed to investigate the protective effects of ISL against white matter injury caused by infection in preterm infants using a mouse model of lipopolysaccharide-induced white matter injury, integrating network pharmacology as well as in vivo and in vitro experiments.MethodsThis study explores the potential mechanisms of ISL on white matter injury by integrating network pharmacology. Core pathways and biological processes affected by ISL were verified through experiments, and motor coordination, anxiety-like, and depression-like behaviors of mice were evaluated using behavioral experiments. White matter injury was observed using hematoxylin-eosin staining, Luxol Fast Blue staining, and electron microscopy. The development of oligodendrocytes and the activation of microglia in mice were assessed by immunofluorescence. The expression of related proteins was detected by Western blot.ResultsWe constructed a drug-target network, including 336 targets associated with ISL treatment of white matter injury. The biological process of ISL treatment of white matter injury mainly involves microglial inflammation regulation and myelination. Our findings revealed that ISL reduced early nerve reflex barriers and white matter manifestations in mice, leading to decreased activation of microglia and release of proinflammatory cytokines. Additionally, ISL demonstrated the ability to mitigate impairment in oligodendrocyte development and myelination, ultimately improving behavior disorders in adult mice. Mechanistically, we observed that ISL downregulated HDAC3 expression, promoted histone acetylation, enhanced the expression of H3K27ac, and regulated oligodendrocyte pro-differentiation factors.ConclusionThese findings suggest that ISL can have beneficial effects on white matter injury in preterm infants by alleviating inflammation and promoting oligodendrocyte differentiation.
{"title":"Isoliquiritigenin ameliorates abnormal oligodendrocyte development and behavior disorders induced by white matter injury","authors":"Dong Wu, Wenjuan Zhou, Jingyi Du, Tiantian Zhao, Naigang Li, Fan Peng, Anna Li, Xinyue Zhang, Meihua Zhang, Aijun Hao","doi":"10.3389/fphar.2024.1473019","DOIUrl":"https://doi.org/10.3389/fphar.2024.1473019","url":null,"abstract":"BackgroundWhite matter injury is a predominant form of brain injury in preterm infants. However, effective drugs for its treatment are currently lacking. Previous studies have shown the neuroprotective effects of Isoliquiritigenin (ISL), but its impact on white matter injury in preterm infants remains poorly understood.AimsThis study aimed to investigate the protective effects of ISL against white matter injury caused by infection in preterm infants using a mouse model of lipopolysaccharide-induced white matter injury, integrating network pharmacology as well as <jats:italic>in vivo</jats:italic> and <jats:italic>in vitro</jats:italic> experiments.MethodsThis study explores the potential mechanisms of ISL on white matter injury by integrating network pharmacology. Core pathways and biological processes affected by ISL were verified through experiments, and motor coordination, anxiety-like, and depression-like behaviors of mice were evaluated using behavioral experiments. White matter injury was observed using hematoxylin-eosin staining, Luxol Fast Blue staining, and electron microscopy. The development of oligodendrocytes and the activation of microglia in mice were assessed by immunofluorescence. The expression of related proteins was detected by Western blot.ResultsWe constructed a drug-target network, including 336 targets associated with ISL treatment of white matter injury. The biological process of ISL treatment of white matter injury mainly involves microglial inflammation regulation and myelination. Our findings revealed that ISL reduced early nerve reflex barriers and white matter manifestations in mice, leading to decreased activation of microglia and release of proinflammatory cytokines. Additionally, ISL demonstrated the ability to mitigate impairment in oligodendrocyte development and myelination, ultimately improving behavior disorders in adult mice. Mechanistically, we observed that ISL downregulated HDAC3 expression, promoted histone acetylation, enhanced the expression of H3K27ac, and regulated oligodendrocyte pro-differentiation factors.ConclusionThese findings suggest that ISL can have beneficial effects on white matter injury in preterm infants by alleviating inflammation and promoting oligodendrocyte differentiation.","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142201928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kaempferol is a flavonol identified as the most potent activator of chloride (Cl−) secretion among other flavonoids in airway epithelial cells. This study aimed to investigate the cellular mechanisms by which kaempferol stimulates Cl− secretion in the T84 human colon carcinoma cell line by Ussing chambers and voltage clamp technique. Bilateral addition of kaempferol (1–100 µM) increased short-circuit current (Isc) in a concentration-dependent manner. Ion substitution of Cl− or CFTR inhibitors NPPB and glibenclamide or a Na+/K+/2Cl− cotransporter inhibitor bumetanide attenuated kaempferol-induced Isc response. In permeabilized monolayers, selective channel inhibitors CFTRinh-172 and CaCCinh-A01 inhibited kaempferol-induced apical Cl− current (ICl), and K+ blockers BaCl2 and clotrimazole inhibited basolateral K+ current (IKb). The kaempferol-induced ICl showed no additive effects with forskolin or 8cpt-cAMP. The kaempferol-induced ICl was mostly abolished by protein kinase A inhibitor H89, but not by tyrosine kinase inhibitors, AG490 and tyrphostin A23, or tyrosine phosphatase inhibitor vanadate. Treatment with kaempferol for 24 h increased the expression of CFTR protein as determined by the Western blot analysis. These results demonstrated that kaempferol activates Cl− secretion across T84 cells by activating the apical Cl− current and basolateral K+ current. The mechanisms may involve the cAMP/PKA pathway and CFTR expression. Taken together, these findings reveal the beneficial effects of kaempferol to increase fluid secretion which can be used to treat constipation.
{"title":"Kaempferol activates chloride secretion via the cAMP/PKA signaling pathway and expression of CFTR in T84 cells","authors":"Janjira Thaweewattanodom, Chatsri Deachapunya, Sutthasinee Poonyachoti","doi":"10.3389/fphar.2024.1401273","DOIUrl":"https://doi.org/10.3389/fphar.2024.1401273","url":null,"abstract":"Kaempferol is a flavonol identified as the most potent activator of chloride (Cl<jats:sup>−</jats:sup>) secretion among other flavonoids in airway epithelial cells. This study aimed to investigate the cellular mechanisms by which kaempferol stimulates Cl<jats:sup>−</jats:sup> secretion in the T84 human colon carcinoma cell line by Ussing chambers and voltage clamp technique. Bilateral addition of kaempferol (1–100 µM) increased short-circuit current (<jats:italic>I</jats:italic><jats:sub><jats:italic>sc</jats:italic></jats:sub>) in a concentration-dependent manner. Ion substitution of Cl<jats:sup>−</jats:sup> or CFTR inhibitors NPPB and glibenclamide or a Na<jats:sup>+</jats:sup>/K<jats:sup>+</jats:sup>/2Cl<jats:sup>−</jats:sup> cotransporter inhibitor bumetanide attenuated kaempferol-induced <jats:italic>I</jats:italic><jats:sub><jats:italic>sc</jats:italic></jats:sub> response. In permeabilized monolayers, selective channel inhibitors CFTRinh-172 and CaCCinh-A01 inhibited kaempferol-induced apical Cl<jats:sup>−</jats:sup> current (<jats:italic>I</jats:italic><jats:sub><jats:italic>Cl</jats:italic></jats:sub>), and K<jats:sup>+</jats:sup> blockers BaCl<jats:sub>2</jats:sub> and clotrimazole inhibited basolateral K<jats:sup>+</jats:sup> current (<jats:italic>I</jats:italic><jats:sub><jats:italic>Kb</jats:italic></jats:sub>). The kaempferol-induced <jats:italic>I</jats:italic><jats:sub><jats:italic>Cl</jats:italic></jats:sub> showed no additive effects with forskolin or 8cpt-cAMP. The kaempferol-induced <jats:italic>I</jats:italic><jats:sub><jats:italic>Cl</jats:italic></jats:sub> was mostly abolished by protein kinase A inhibitor H89, but not by tyrosine kinase inhibitors, AG490 and tyrphostin A23, or tyrosine phosphatase inhibitor vanadate. Treatment with kaempferol for 24 h increased the expression of CFTR protein as determined by the Western blot analysis. These results demonstrated that kaempferol activates Cl<jats:sup>−</jats:sup> secretion across T84 cells by activating the apical Cl<jats:sup>−</jats:sup> current and basolateral K<jats:sup>+</jats:sup> current. The mechanisms may involve the cAMP/PKA pathway and CFTR expression. Taken together, these findings reveal the beneficial effects of kaempferol to increase fluid secretion which can be used to treat constipation.","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142201932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
IntroductionAs a widely used traditional Chinese medicine with hot property, aconite can significantly promote energy metabolism. However, it is unclear whether the gut microbiota and bile acids contribute to the energy metabolism-promoting properties of aconite. The aim of this experiment was to verify whether the energy metabolism-promoting effect of aconite aqueous extract (AA) is related to gut microbiota and bile acid (BA) metabolism.MethodsThe effect of AA on energy metabolism in rats was detected based on body weight, body temperature, and adipose tissue by HE staining and immunohistochemistry. In addition, 16S rRNA high-throughput sequencing and targeted metabolomics were used to detect changes in gut microbiota and BA concentrations, respectively. Antibiotic treatment and fecal microbiota transplantation (FMT) were also performed to demonstrate the importance of gut microbiota.ResultsRats given AA experienced an increase in body temperature, a decrease in body weight, and an increase in BAT (brown adipose tissue) activity and browning of WAT (white adipose tissue). Sequencing analysis and targeted metabolomics indicated that AA modulated gut microbiota and BA metabolism. The energy metabolism promotion of AA was found to be mediated by gut microbiota, as demonstrated through antibiotic treatment and FMT. Moreover, the energy metabolism-promoting effect of aconite is associated with the bile acid receptor TGR5 (Takeda G-protein-coupled receptor 5)-UCP1 (uncoupling protein 1) signaling pathway.ConclusionThe energy metabolism-promoting effect of aconite is associated with gut microbiota and bile acid receptor TGR5-UCP1 signaling.
引言 作为一种广泛使用的热性传统中药,乌头能显著促进能量代谢。然而,目前尚不清楚肠道微生物群和胆汁酸是否对乌头的能量代谢促进作用做出了贡献。本实验的目的是验证乌头水提取物(AA)促进能量代谢的作用是否与肠道微生物群和胆汁酸(BA)代谢有关。方法通过 HE 染色和免疫组织化学方法检测 AA 对大鼠体重、体温和脂肪组织能量代谢的影响。此外,16S rRNA 高通量测序和靶向代谢组学分别用于检测肠道微生物群和 BA 浓度的变化。结果给予 AA 的大鼠体温升高,体重下降,BAT(棕色脂肪组织)活性增加,WAT(白色脂肪组织)褐变。测序分析和靶向代谢组学表明,AA 可调节肠道微生物群和 BA 代谢。通过抗生素治疗和 FMT,发现 AA 对能量代谢的促进作用是由肠道微生物群介导的。此外,乌头碱对能量代谢的促进作用与胆汁酸受体 TGR5(武田 G 蛋白偶联受体 5)-UCP1(解偶联蛋白 1)信号通路有关。
{"title":"The energy metabolism-promoting effect of aconite is associated with gut microbiota and bile acid receptor TGR5-UCP1 signaling","authors":"Dandan Zhang, Hao Cheng, Jing Wu, Yaochuan Zhou, Fei Tang, Juan Liu, Wuwen Feng, Cheng Peng","doi":"10.3389/fphar.2024.1392385","DOIUrl":"https://doi.org/10.3389/fphar.2024.1392385","url":null,"abstract":"IntroductionAs a widely used traditional Chinese medicine with hot property, aconite can significantly promote energy metabolism. However, it is unclear whether the gut microbiota and bile acids contribute to the energy metabolism-promoting properties of aconite. The aim of this experiment was to verify whether the energy metabolism-promoting effect of aconite aqueous extract (AA) is related to gut microbiota and bile acid (BA) metabolism.MethodsThe effect of AA on energy metabolism in rats was detected based on body weight, body temperature, and adipose tissue by HE staining and immunohistochemistry. In addition, 16S rRNA high-throughput sequencing and targeted metabolomics were used to detect changes in gut microbiota and BA concentrations, respectively. Antibiotic treatment and fecal microbiota transplantation (FMT) were also performed to demonstrate the importance of gut microbiota.ResultsRats given AA experienced an increase in body temperature, a decrease in body weight, and an increase in BAT (brown adipose tissue) activity and browning of WAT (white adipose tissue). Sequencing analysis and targeted metabolomics indicated that AA modulated gut microbiota and BA metabolism. The energy metabolism promotion of AA was found to be mediated by gut microbiota, as demonstrated through antibiotic treatment and FMT. Moreover, the energy metabolism-promoting effect of aconite is associated with the bile acid receptor TGR5 (Takeda G-protein-coupled receptor 5)-UCP1 (uncoupling protein 1) signaling pathway.ConclusionThe energy metabolism-promoting effect of aconite is associated with gut microbiota and bile acid receptor TGR5-UCP1 signaling.","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142201923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The main bioactive components of agarwood, derived from Aquilaria sinensis, include sesquiterpenes, 2-(2-phenethyl) chromone derivatives, aromatic compounds, and fatty acids, which typically exert anti-inflammatory, antioxidant, immune-modulating, hypoglycemic, and antitumor pharmacological effects in the form of essential oils. Agarwood tree leaves, rich in flavonoids, 2-(2-phenethyl) chromone compounds, and flavonoid compounds, also exhibit significant anti-inflammatory, antioxidant, and immune-modulating effects. These properties are particularly relevant to the treatment of periodontitis, given that inflammatory responses, oxidative stress, and immune dysregulation are key pathological mechanisms of the disease, highlighting the substantial potential of agarwood and agarwood tree leaves in this therapeutic area. However, the low solubility and poor bioavailability of essential oils present challenges that necessitate the development of improved active formulations. In this review, we will introduce the bioactive components, extraction methods, pharmacological actions, and clinical applications of agarwood and agarwood tree leaves, analyzing its prospects for the treatment of periodontitis.
{"title":"Pharmacology and therapeutic potential of agarwood and agarwood tree leaves in periodontitis","authors":"Chen Xie, Jing-Zhe Dong, Bing-Shuai Lu, Peng-Yao Yan, Yun-Shan Zhao, Xin-Yue Ding, Cheng-En Lv, Xu Zheng","doi":"10.3389/fphar.2024.1468393","DOIUrl":"https://doi.org/10.3389/fphar.2024.1468393","url":null,"abstract":"The main bioactive components of agarwood, derived from Aquilaria sinensis, include sesquiterpenes, 2-(2-phenethyl) chromone derivatives, aromatic compounds, and fatty acids, which typically exert anti-inflammatory, antioxidant, immune-modulating, hypoglycemic, and antitumor pharmacological effects in the form of essential oils. Agarwood tree leaves, rich in flavonoids, 2-(2-phenethyl) chromone compounds, and flavonoid compounds, also exhibit significant anti-inflammatory, antioxidant, and immune-modulating effects. These properties are particularly relevant to the treatment of periodontitis, given that inflammatory responses, oxidative stress, and immune dysregulation are key pathological mechanisms of the disease, highlighting the substantial potential of agarwood and agarwood tree leaves in this therapeutic area. However, the low solubility and poor bioavailability of essential oils present challenges that necessitate the development of improved active formulations. In this review, we will introduce the bioactive components, extraction methods, pharmacological actions, and clinical applications of agarwood and agarwood tree leaves, analyzing its prospects for the treatment of periodontitis.","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142201900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-11DOI: 10.3389/fphar.2024.1452545
Yuhan Yang, Ziyi Sun, Xiaoning Sun, Jin Zhang, Tong Tong, Xiaoxiao Zhang, Kuiwu Yao
BackgroundSalvianolic acid B is the most abundant water-soluble component in the traditional Chinese medicine Danshen and can reduce myocardial ischemia-reperfusion (MI/R) injury through multiple targets and pathways. However, the role of SalB in protecting the myocardium from ischemia/reperfusion injury remains unclear.PurposeTo perform a preclinical systematic review and meta-analysis to assess the efficacy of Sal B in an animal model of myocardial infarction/reperfusion (MI/R) and to summarize the potential mechanisms of Sal B against MI/R.MethodsStudies published from inception to March 2024 were systematically searched in PubMed, Web of Science, Embase, China National Knowledge Infrastructure Wanfang, and VIP databases. The methodological quality was determined using the SYRCLE RoB tool. The R software was used to analyze the data. The potential mechanisms are categorized and summarized.Results32 studies containing 732 animals were included. The results of the meta-analysis showed that Sal B reduced myocardial infarct size (p < 0.01), and the cardiological indices of CK-MB (p < 0.01), CK (p < 0.01), LDH (p < 0.01), and cTnI (p < 0.01) compared to the control group. In addition, Sal B increased cardiac function indices, such as LVFS (p < 0.01), -dp/dt max (p < 0.01), +dp/dt max (p < 0.01), and cardiac output (p < 0.01). The protective effects of Sal B on the myocardium after I/R may be mediated by attenuating oxidative stress and inflammation, promoting neovascularization, regulating vascular function, and attenuating cardiac myocyte apoptosis. Publication bias was observed in all the included studies. Further studies are required to elucidate the extent of the cardioprotective effects of SalB and the safety of its use.ConclusionTo the best of our knowledge, this is the first meta-analysis of Sal B in the treatment of MI/R injury, and Sal B demonstrated a positive effect on MI/R injury through the modulation of key pathological indicators and multiple signaling pathways. Further studies are needed to elucidate the extent to which SalB exerts its cardioprotective effects and the safety of its use.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/.
背景丹参酚酸 B 是中药丹参中含量最高的水溶性成分,可通过多种靶点和途径减轻心肌缺血再灌注损伤。目的 进行临床前系统综述和荟萃分析,评估丹参在心肌梗死/再灌注(MI/R)动物模型中的疗效,并总结丹参抗心肌梗死/再灌注的潜在机制。方法 在PubMed、Web of Science、Embase、中国国家知识基础设施万方和VIP数据库中系统检索了从开始到2024年3月发表的研究。使用 SYRCLE RoB 工具确定研究方法的质量。使用 R 软件对数据进行分析。结果共纳入 32 项研究,包含 732 只动物。荟萃分析结果表明,与对照组相比,萨尔乙能缩小心肌梗死面积(p< 0.01),降低CK-MB(p< 0.01)、CK(p< 0.01)、LDH(p< 0.01)和cTnI(p< 0.01)等心脏病学指标。此外,盐 B 还能增加心功能指数,如 LVFS(p < 0.01)、-dp/dt max(p < 0.01)、+dp/dt max(p < 0.01)和心输出量(p < 0.01)。盐 B 对 I/R 后心肌的保护作用可能是通过减轻氧化应激和炎症、促进血管新生、调节血管功能和减轻心肌细胞凋亡来实现的。所有纳入的研究均存在发表偏倚。结论 据我们所知,这是第一份关于 Sal B 治疗 MI/R 损伤的荟萃分析,Sal B 通过调节关键病理指标和多种信号通路对 MI/R 损伤有积极作用。还需要进一步的研究来阐明 Sal B 发挥心脏保护作用的程度及其使用的安全性。系统综述注册https://www.crd.york.ac.uk/PROSPERO/。
{"title":"Protective effect of salvianolic acid B against myocardial ischemia/reperfusion injury: preclinical systematic evaluation and meta-analysis","authors":"Yuhan Yang, Ziyi Sun, Xiaoning Sun, Jin Zhang, Tong Tong, Xiaoxiao Zhang, Kuiwu Yao","doi":"10.3389/fphar.2024.1452545","DOIUrl":"https://doi.org/10.3389/fphar.2024.1452545","url":null,"abstract":"BackgroundSalvianolic acid B is the most abundant water-soluble component in the traditional Chinese medicine Danshen and can reduce myocardial ischemia-reperfusion (MI/R) injury through multiple targets and pathways. However, the role of SalB in protecting the myocardium from ischemia/reperfusion injury remains unclear.PurposeTo perform a preclinical systematic review and meta-analysis to assess the efficacy of Sal B in an animal model of myocardial infarction/reperfusion (MI/R) and to summarize the potential mechanisms of Sal B against MI/R.MethodsStudies published from inception to March 2024 were systematically searched in PubMed, Web of Science, Embase, China National Knowledge Infrastructure Wanfang, and VIP databases. The methodological quality was determined using the SYRCLE RoB tool. The R software was used to analyze the data. The potential mechanisms are categorized and summarized.Results32 studies containing 732 animals were included. The results of the meta-analysis showed that Sal B reduced myocardial infarct size (<jats:italic>p</jats:italic> &lt; 0.01), and the cardiological indices of CK-MB (<jats:italic>p</jats:italic> &lt; 0.01), CK (<jats:italic>p</jats:italic> &lt; 0.01), LDH (<jats:italic>p</jats:italic> &lt; 0.01), and cTnI (<jats:italic>p</jats:italic> &lt; 0.01) compared to the control group. In addition, Sal B increased cardiac function indices, such as LVFS (<jats:italic>p</jats:italic> &lt; 0.01), -dp/dt max (<jats:italic>p</jats:italic> &lt; 0.01), +dp/dt max (<jats:italic>p</jats:italic> &lt; 0.01), and cardiac output (<jats:italic>p</jats:italic> &lt; 0.01). The protective effects of Sal B on the myocardium after I/R may be mediated by attenuating oxidative stress and inflammation, promoting neovascularization, regulating vascular function, and attenuating cardiac myocyte apoptosis. Publication bias was observed in all the included studies. Further studies are required to elucidate the extent of the cardioprotective effects of SalB and the safety of its use.ConclusionTo the best of our knowledge, this is the first meta-analysis of Sal B in the treatment of MI/R injury, and Sal B demonstrated a positive effect on MI/R injury through the modulation of key pathological indicators and multiple signaling pathways. Further studies are needed to elucidate the extent to which SalB exerts its cardioprotective effects and the safety of its use.Systematic Review Registration<jats:ext-link>https://www.crd.york.ac.uk/PROSPERO/</jats:ext-link>.","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142201901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-11DOI: 10.3389/fphar.2024.1382876
Akshaya Simha N., Shashank M. Patil, Jayanthi M. K., Chaitra N., Ling Shing Wong, Jureerat Kijsomporn, Ranjith Raj, Ramith Ramu
IntroductionLectins are carbohydrate-binding proteins that are extremely selective for sugar groups in the other molecules. As a result, they perform a variety of roles in biological processes involving cell, carbohydrate, and protein recognition at the cellular and molecular levels. Because lectins can bind to carbohydrates, they may play a role in determining the rate of carbohydrate digestion. They also bind to some proteins involved in diabetes mellitus (DM) pathophysiology. The present review aims to summarize the efficiency of lectins from different sources as potential antihyperglycemic agents.MethodsThe Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were employed for the drafting. In this regard, published scientific articles on the effects of different lectins on blood glucose (BG), glucose tolerance, hormonal effects, carbohydrate-digesting enzymes, oxidative stress, and insulin production process were collected from reputed journals using electronic databases. Furthermore, the toxicity effects of lectins from different sources were collected. A specific keyword search was completed to collect numerous articles with unique experimental designs and significant results. This was followed by the selection of the requisite articles based on the criteria designed by the authors. Data extraction was based on the common research elements included in the articles.Results and DiscussionOf 13 identified studies, 11 studies were considered after double screening based on the inclusion criteria. All 11 pharmacological investigations were considered for review. Subsequent studies reflected on the pharmacological properties of lectins on the levels of BG, oxidative stress, β-cell proliferation, insulin resistance, inhibition of carbohydrate digesting enzymes, body weight, food and water intake, lipid profile, and other parameters. This review highlights lectins as potential anti-diabetic agents.ConclusionHowever, due to limited research, systematic evaluation is recommended for their development and promotion as effective potential antihyperglycemic agents. The clinical efficacy and safety of lectins against diabetes mellitus must also be evaluated.
{"title":"From sugar binders to diabetes fighters: the lectin saga of antihyperglycemic activity through systematic review and meta-analysis","authors":"Akshaya Simha N., Shashank M. Patil, Jayanthi M. K., Chaitra N., Ling Shing Wong, Jureerat Kijsomporn, Ranjith Raj, Ramith Ramu","doi":"10.3389/fphar.2024.1382876","DOIUrl":"https://doi.org/10.3389/fphar.2024.1382876","url":null,"abstract":"IntroductionLectins are carbohydrate-binding proteins that are extremely selective for sugar groups in the other molecules. As a result, they perform a variety of roles in biological processes involving cell, carbohydrate, and protein recognition at the cellular and molecular levels. Because lectins can bind to carbohydrates, they may play a role in determining the rate of carbohydrate digestion. They also bind to some proteins involved in diabetes mellitus (DM) pathophysiology. The present review aims to summarize the efficiency of lectins from different sources as potential antihyperglycemic agents.MethodsThe Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were employed for the drafting. In this regard, published scientific articles on the effects of different lectins on blood glucose (BG), glucose tolerance, hormonal effects, carbohydrate-digesting enzymes, oxidative stress, and insulin production process were collected from reputed journals using electronic databases. Furthermore, the toxicity effects of lectins from different sources were collected. A specific keyword search was completed to collect numerous articles with unique experimental designs and significant results. This was followed by the selection of the requisite articles based on the criteria designed by the authors. Data extraction was based on the common research elements included in the articles.Results and DiscussionOf 13 identified studies, 11 studies were considered after double screening based on the inclusion criteria. All 11 pharmacological investigations were considered for review. Subsequent studies reflected on the pharmacological properties of lectins on the levels of BG, oxidative stress, β-cell proliferation, insulin resistance, inhibition of carbohydrate digesting enzymes, body weight, food and water intake, lipid profile, and other parameters. This review highlights lectins as potential anti-diabetic agents.ConclusionHowever, due to limited research, systematic evaluation is recommended for their development and promotion as effective potential antihyperglycemic agents. The clinical efficacy and safety of lectins against diabetes mellitus must also be evaluated.","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142201927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-11DOI: 10.3389/fphar.2024.1433186
Xiaoshu Guo, Kai Xu, Lan Wang, Linke Ding, Wenwen Li, Xinsheng Zhang, Weiming Zhao, Ningdan Wang, Gaiping Wang, Wenyu Zhao, Ivan Rosas, Guoying Yu
BackgroundIdiopathic pulmonary fibrosis (IPF) is the result of multiple cycles of epithelial cell injury and fibroblast activation; currently, there is no clear etiology. Increasing evidence suggests that protein metabolism and amino acids play a crucial role in IPF, but the role of D-amino acids is not yet clear. The aim of this study was to identify novel mediators in order to test the hypothesis that D-amino acid oxidase (DAO) plays a significant role in the pathogenesis of IPF.MethodsWe analyzed DAO gene expression in patients with IPF and mice with bleomycin (BLM)-induced lung fibrosis. We performed in vitro and in vivo assays to determine the effect of DAO on primary type II alveolar epithelial cells from mice and A549 cells.ResultsDAO expression was downregulated in the lungs of IPF patients and BLM-induced fibrotic mice. Treatment with D-serine (D-Ser) or drug inhibition of DAO promoted cell senescence through the p53/p21 pathway. Dao−/− mice showed an intensified fibrotic response, and the anti-fibrotic role of T3 was abolished.ConclusionWe concluded that the DAO-p53/p21 axis might be a key anti-fibrotic pathway regulating the progress of fibrosis and facilitating the therapeutic role of T3.
{"title":"Triiodothyronine acts on DAO to regulate pulmonary fibrosis progression by facilitating cell senescence through the p53/p21 signaling pathway","authors":"Xiaoshu Guo, Kai Xu, Lan Wang, Linke Ding, Wenwen Li, Xinsheng Zhang, Weiming Zhao, Ningdan Wang, Gaiping Wang, Wenyu Zhao, Ivan Rosas, Guoying Yu","doi":"10.3389/fphar.2024.1433186","DOIUrl":"https://doi.org/10.3389/fphar.2024.1433186","url":null,"abstract":"BackgroundIdiopathic pulmonary fibrosis (IPF) is the result of multiple cycles of epithelial cell injury and fibroblast activation; currently, there is no clear etiology. Increasing evidence suggests that protein metabolism and amino acids play a crucial role in IPF, but the role of D-amino acids is not yet clear. The aim of this study was to identify novel mediators in order to test the hypothesis that D-amino acid oxidase (DAO) plays a significant role in the pathogenesis of IPF.MethodsWe analyzed DAO gene expression in patients with IPF and mice with bleomycin (BLM)-induced lung fibrosis. We performed <jats:italic>in vitro</jats:italic> and <jats:italic>in vivo</jats:italic> assays to determine the effect of DAO on primary type II alveolar epithelial cells from mice and A549 cells.ResultsDAO expression was downregulated in the lungs of IPF patients and BLM-induced fibrotic mice. Treatment with D-serine (D-Ser) or drug inhibition of DAO promoted cell senescence through the p53/p21 pathway. <jats:italic>Dao</jats:italic><jats:sup>−/−</jats:sup> mice showed an intensified fibrotic response, and the anti-fibrotic role of T<jats:sub>3</jats:sub> was abolished.ConclusionWe concluded that the DAO-p53/p21 axis might be a key anti-fibrotic pathway regulating the progress of fibrosis and facilitating the therapeutic role of T<jats:sub>3</jats:sub>.","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142201926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BackgroundFFBZL is composed of three herbs: <jats:italic>Scutellaria barbata D. Don</jats:italic> (SBD), <jats:italic>Astragali Radix</jats:italic> (AR), and <jats:italic>Ligusticum chuanxiong Hort</jats:italic> (CX). FFBZL has been reported to be effective in the treatment of oral squamous cell carcinoma (OSCC). However, the molecular mechanism involved remains unclear. Based on network pharmacology combined with bioinformatics and molecular docking, the effect and molecular mechanism of action of FFBZL in treating OSCC were explored.Materials and methodsThis study employed an integrated approach using various databases and literature sources to identify the effective components of FFBZL, with a specific emphasis on screening active ingredients that align with traditional Chinese medicine principles. The TCMSP, ETCM, and SymMap databases were utilized to collect information on the active constituents and targets of FFBZL, while the PharmMapper database was used to predict targets. Key components were selected based on the degree value of the ‘active component−target’ network. Transcriptome data for OSCC samples were obtained from the TCGA and GEO databases. Differential gene expression analysis was conducted to identify targets associated with OSCC, and these targets were subsequently aligned with targets of the effective components of FFBZL to identify common targets. Subsequently, the STRING database was utilized to construct a protein‒protein interaction (PPI) network of these common targets, which was subsequently visualized using Cytoscape. Next, 71 targets were rescreened using the PPI network, and GO and KEGG enrichment analyses were performed; the PI3K-Akt signaling pathway was the top-ranking pathway related to cell apoptosis. Next, the expression of 19 genes enriched in the PI3K-Akt signaling pathway was analyzed using OSCC transcriptome data from the TCGA and GEO databases. The targets were subsequently mapped to the PI3K-Akt signaling pathway using the KEGG database, and the GSEA algorithm was used to assess the overall expression trend of the genes in this pathway. The 71 common targets were subsequently imported into the STRING database and visualized using Cytoscape. The DEGREE and MCC algorithms were used to select the corresponding targets within the PPI network. The intersection of these targets and the 19 targets mapped to the PI3K-Akt signaling pathway led to the identification of 6 key targets associated with cell apoptosis: GSK3B, PIK3CA, FN1, MET, SPP1, and MAPK3. Subsequently, the UALCAN database was utilized to analyze the expression levels and survival associations of the key genes related to cell apoptosis, and the transcriptome data from the GEO database were used to assess the correlations among the 6 key genes. Finally, molecular docking studies were conducted to explore the relationships between these targets and the active components with predicted associations.ResultsThis study identified six key components of FF
{"title":"Network pharmacology and transcriptomics reveal the mechanisms of FFBZL in the treatment of oral squamous cell carcinoma","authors":"Shiyang Zhao, Shudong Xiao, Wanting Wang, Xinyue Dong, Xichen Liu, Qingsen Wang, Yourong Jiang, Wen Wu","doi":"10.3389/fphar.2024.1405596","DOIUrl":"https://doi.org/10.3389/fphar.2024.1405596","url":null,"abstract":"BackgroundFFBZL is composed of three herbs: <jats:italic>Scutellaria barbata D. Don</jats:italic> (SBD), <jats:italic>Astragali Radix</jats:italic> (AR), and <jats:italic>Ligusticum chuanxiong Hort</jats:italic> (CX). FFBZL has been reported to be effective in the treatment of oral squamous cell carcinoma (OSCC). However, the molecular mechanism involved remains unclear. Based on network pharmacology combined with bioinformatics and molecular docking, the effect and molecular mechanism of action of FFBZL in treating OSCC were explored.Materials and methodsThis study employed an integrated approach using various databases and literature sources to identify the effective components of FFBZL, with a specific emphasis on screening active ingredients that align with traditional Chinese medicine principles. The TCMSP, ETCM, and SymMap databases were utilized to collect information on the active constituents and targets of FFBZL, while the PharmMapper database was used to predict targets. Key components were selected based on the degree value of the ‘active component−target’ network. Transcriptome data for OSCC samples were obtained from the TCGA and GEO databases. Differential gene expression analysis was conducted to identify targets associated with OSCC, and these targets were subsequently aligned with targets of the effective components of FFBZL to identify common targets. Subsequently, the STRING database was utilized to construct a protein‒protein interaction (PPI) network of these common targets, which was subsequently visualized using Cytoscape. Next, 71 targets were rescreened using the PPI network, and GO and KEGG enrichment analyses were performed; the PI3K-Akt signaling pathway was the top-ranking pathway related to cell apoptosis. Next, the expression of 19 genes enriched in the PI3K-Akt signaling pathway was analyzed using OSCC transcriptome data from the TCGA and GEO databases. The targets were subsequently mapped to the PI3K-Akt signaling pathway using the KEGG database, and the GSEA algorithm was used to assess the overall expression trend of the genes in this pathway. The 71 common targets were subsequently imported into the STRING database and visualized using Cytoscape. The DEGREE and MCC algorithms were used to select the corresponding targets within the PPI network. The intersection of these targets and the 19 targets mapped to the PI3K-Akt signaling pathway led to the identification of 6 key targets associated with cell apoptosis: GSK3B, PIK3CA, FN1, MET, SPP1, and MAPK3. Subsequently, the UALCAN database was utilized to analyze the expression levels and survival associations of the key genes related to cell apoptosis, and the transcriptome data from the GEO database were used to assess the correlations among the 6 key genes. Finally, molecular docking studies were conducted to explore the relationships between these targets and the active components with predicted associations.ResultsThis study identified six key components of FF","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142201974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}