首页 > 最新文献

Journal of Holistic Integrative Pharmacy最新文献

英文 中文
Review on clinical diagnosis, pathogenesis and therapeutic strategies of drug-induced liver injury 药物性肝损伤的临床诊断、发病机制及治疗策略综述
Pub Date : 2025-09-01 DOI: 10.1016/j.jhip.2025.09.002
Xinxin Tan , Jiajia Gao , Chao Wang
Drug-induced liver injury (DILI) is a severe adverse reaction caused by various drugs and their metabolites, with complex clinical manifestations, and severe cases may progress to acute liver failure (ALF) or even death. Currently, the pathogenesis of DILI has not been fully elucidated, and specific diagnostic indicators and effective therapeutic strategies are lacking, so it is crucial to deeply analyze its pathogenesis and develop precise intervention strategies. This review explores key pathogenic mechanisms in the development of DILI, with a focus on mitochondrial dysfunction, ferroptosis, immune responses and the gut-liver axis. It further systematically summarizes the clinical diagnostic approaches for DILI, including common diagnostic methods and potential biomarkers. Additionally, the review discusses therapeutic strategies for DILI, encompassing western medical treatments, ethnomedical treatments and non-pharmacological treatments. Although N-acetylcysteine (NAC) remains the FDA-approved standard treatment for acetaminophen (APAP) overdose, superior therapeutic options for DILI need to be explored urgently due to its therapeutic limitations and side effects. In the future, the prevention and treatment strategy of DILI will rely on deeper mechanistic investigations, development of novel biomarkers, and further exploration of multi-targeted traditional Chinese medicine (TCM) therapies.
药物性肝损伤(Drug-induced liver injury, DILI)是由多种药物及其代谢物引起的严重不良反应,临床表现复杂,严重者可发展为急性肝衰竭(acute liver failure, ALF),甚至死亡。目前DILI的发病机制尚未完全阐明,缺乏具体的诊断指标和有效的治疗策略,因此深入分析其发病机制,制定精准的干预策略至关重要。本文从线粒体功能障碍、铁下垂、免疫反应和肠-肝轴等方面探讨了DILI发展的主要致病机制。进一步系统总结了DILI的临床诊断方法,包括常见的诊断方法和潜在的生物标志物。此外,本文还讨论了DILI的治疗策略,包括西医治疗、民族医学治疗和非药物治疗。尽管n -乙酰半胱氨酸(NAC)仍然是fda批准的对乙酰氨基酚(APAP)过量的标准治疗方法,但由于其治疗局限性和副作用,迫切需要探索更好的DILI治疗方案。未来,DILI的防治策略将依赖于更深入的机制研究、新型生物标志物的开发以及多靶点中药治疗方法的进一步探索。
{"title":"Review on clinical diagnosis, pathogenesis and therapeutic strategies of drug-induced liver injury","authors":"Xinxin Tan ,&nbsp;Jiajia Gao ,&nbsp;Chao Wang","doi":"10.1016/j.jhip.2025.09.002","DOIUrl":"10.1016/j.jhip.2025.09.002","url":null,"abstract":"<div><div>Drug-induced liver injury (DILI) is a severe adverse reaction caused by various drugs and their metabolites, with complex clinical manifestations, and severe cases may progress to acute liver failure (ALF) or even death. Currently, the pathogenesis of DILI has not been fully elucidated, and specific diagnostic indicators and effective therapeutic strategies are lacking, so it is crucial to deeply analyze its pathogenesis and develop precise intervention strategies. This review explores key pathogenic mechanisms in the development of DILI, with a focus on mitochondrial dysfunction, ferroptosis, immune responses and the gut-liver axis. It further systematically summarizes the clinical diagnostic approaches for DILI, including common diagnostic methods and potential biomarkers. Additionally, the review discusses therapeutic strategies for DILI, encompassing western medical treatments, ethnomedical treatments and non-pharmacological treatments. Although N-acetylcysteine (NAC) remains the FDA-approved standard treatment for acetaminophen (APAP) overdose, superior therapeutic options for DILI need to be explored urgently due to its therapeutic limitations and side effects. In the future, the prevention and treatment strategy of DILI will rely on deeper mechanistic investigations, development of novel biomarkers, and further exploration of multi-targeted traditional Chinese medicine (TCM) therapies.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"6 3","pages":"Pages 308-321"},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145219993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Potential small-molecule compounds and targets for Alzheimer's disease: Integrating bioinformatics analysis and in vitro verification 阿尔茨海默病潜在的小分子化合物和靶点:整合生物信息学分析和体外验证
Pub Date : 2025-09-01 DOI: 10.1016/j.jhip.2025.09.005
Jiaorong Zheng , Deti Peng , Zhigao Liao , Min Hong , Weiqu Yuan , Danping Huang

Objective

Alzheimer's disease (AD) is a common neurodegenerative disorder characterized by progressive memory decline and cognitive dysfunction. The specific pathogenesis of AD remains unclear. This study aimed to explore the crucial genes and therapeutic small-molecule compounds in AD via integrated bioinformatics analysis, molecular docking, and in vitro verification.

Methods

The gene dataset GSE122063, including 12 samples from patients with AD and 11 non-demented control samples, was downloaded from the Gene Expression Omnibus (GEO) database. The online tool GEO2R was used to analyze differentially expressed genes (DEGs). Functional enrichment analysis of the DEGs was performed using DAVID and ClueGo databases. A protein-protein interaction network was constructed using the STRING database and visualized in Cytoscape. Potential small-molecule compounds for AD therapy were screened using the Connectivity map database. The crucial genes in a rat model of AD were confirmed by RT-PCR. Molecular docking of the screened crucial genes and small-molecule compounds was further performed to identify potential therapeutic drugs for AD.

Results

A total of 1145 DEGs were identified, which were enriched in intracellular protein transport, cell cycle, establishment of protein localization to membrane, and so on. Eight hub genes, including RPS29, CREBBP, ANAPC10, ANAPC4, MAGOHB, TCEB2, RPL10A, and SEC61A1, were identified in the protein-protein interaction network. The MAPK signaling pathway was closely related to AD. Furthermore, increased expression of CREBBP was confirmed in the rat model of AD, and molecular docking revealed that CREBBP exhibited the strongest binding affinity with prochlorperazine.

Conclusion

CREBBP was identified as a crucial hub gene and might serve as a potential target for AD. Prochlorperazine, which exhibited strong binding to CREBBP, showed potential as a therapeutic drug in AD.
目的阿尔茨海默病(AD)是一种常见的神经退行性疾病,以进行性记忆衰退和认知功能障碍为特征。阿尔茨海默病的具体发病机制尚不清楚。本研究旨在通过综合生物信息学分析、分子对接和体外验证,探索AD的关键基因和治疗性小分子化合物。方法从gene Expression Omnibus (GEO)数据库中下载基因数据集GSE122063,包括12例AD患者样本和11例非痴呆对照样本。使用在线工具GEO2R分析差异表达基因(DEGs)。使用DAVID和ClueGo数据库进行deg的功能富集分析。利用STRING数据库构建蛋白-蛋白相互作用网络,并在Cytoscape中可视化。使用Connectivity map数据库筛选潜在的用于阿尔茨海默病治疗的小分子化合物。RT-PCR证实了大鼠AD模型中的关键基因。筛选的关键基因和小分子化合物的分子对接进一步确定潜在的阿尔茨海默病治疗药物。结果共鉴定出1145个基因,富集于细胞内蛋白转运、细胞周期、蛋白向膜定位等方面。在蛋白相互作用网络中鉴定出8个枢纽基因,包括RPS29、CREBBP、ANAPC10、ANAPC4、MAGOHB、TCEB2、RPL10A和SEC61A1。MAPK信号通路与AD密切相关。此外,在AD大鼠模型中证实CREBBP表达增加,分子对接显示CREBBP与丙氯拉嗪的结合亲和力最强。结论crebbp是一个重要的中枢基因,可能是AD的潜在靶点。丙氯哌嗪与CREBBP结合较强,具有治疗AD的潜力。
{"title":"Potential small-molecule compounds and targets for Alzheimer's disease: Integrating bioinformatics analysis and in vitro verification","authors":"Jiaorong Zheng ,&nbsp;Deti Peng ,&nbsp;Zhigao Liao ,&nbsp;Min Hong ,&nbsp;Weiqu Yuan ,&nbsp;Danping Huang","doi":"10.1016/j.jhip.2025.09.005","DOIUrl":"10.1016/j.jhip.2025.09.005","url":null,"abstract":"<div><h3>Objective</h3><div>Alzheimer's disease (AD) is a common neurodegenerative disorder characterized by progressive memory decline and cognitive dysfunction. The specific pathogenesis of AD remains unclear. This study aimed to explore the crucial genes and therapeutic small-molecule compounds in AD via integrated bioinformatics analysis, molecular docking, and <em>in vitro</em> verification.</div></div><div><h3>Methods</h3><div>The gene dataset GSE122063, including 12 samples from patients with AD and 11 non-demented control samples, was downloaded from the Gene Expression Omnibus (GEO) database. The online tool GEO2R was used to analyze differentially expressed genes (DEGs). Functional enrichment analysis of the DEGs was performed using DAVID and ClueGo databases. A protein-protein interaction network was constructed using the STRING database and visualized in Cytoscape. Potential small-molecule compounds for AD therapy were screened using the Connectivity map database. The crucial genes in a rat model of AD were confirmed by RT-PCR. Molecular docking of the screened crucial genes and small-molecule compounds was further performed to identify potential therapeutic drugs for AD.</div></div><div><h3>Results</h3><div>A total of 1145 DEGs were identified, which were enriched in intracellular protein transport, cell cycle, establishment of protein localization to membrane, and so on. Eight hub genes, including <em>RPS29</em>, <em>CREBBP</em>, <em>ANAPC10</em>, <em>ANAPC4</em>, <em>MAGOHB</em>, <em>TCEB2</em>, <em>RPL10A</em>, and <em>SEC61A1</em>, were identified in the protein-protein interaction network. The MAPK signaling pathway was closely related to AD. Furthermore, increased expression of <em>CREBBP</em> was confirmed in the rat model of AD, and molecular docking revealed that CREBBP exhibited the strongest binding affinity with prochlorperazine.</div></div><div><h3>Conclusion</h3><div><em>CREBBP</em> was identified as a crucial hub gene and might serve as a potential target for AD. Prochlorperazine, which exhibited strong binding to CREBBP, showed potential as a therapeutic drug in AD.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"6 3","pages":"Pages 324-332"},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145219992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
ToC ToC
Pub Date : 2025-09-01 DOI: 10.1016/S2707-3688(25)00048-2
{"title":"ToC","authors":"","doi":"10.1016/S2707-3688(25)00048-2","DOIUrl":"10.1016/S2707-3688(25)00048-2","url":null,"abstract":"","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"6 3","pages":"Pages i-ii"},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145361865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Phytochemical profiles, biological activities and medicinal importance of Aloe vera L.: A review 芦荟的植物化学特征、生物活性及其药用价值综述
Pub Date : 2025-08-05 DOI: 10.1016/j.jhip.2025.07.001
Suchhanda Nandi, Golak Majumdar, Shyamapada Mandal
Aloe vera (Av) is revered in Ayurveda as the "wand of heaven" or "heaven's blessing" and precisely the "silent healer". This herbaceous plant belongs to Asphodelaceae family, previously classified as Liliaceae. In Traditional Chinese Medicine (TCM), Av is acknowledged for its abundant bioactive substances that have considerable therapeutic value. Therefore, the objective of this review is to analyze Av's bioactive compounds, highlighting its medicinal potential in drug development. An extensive literature review is performed utilizing databases such as PubMed, Web of Science, SpringerLink, and more until October 2024. The research investigates the bioactive compounds of Av and their in vivo, in vitro, and in silico effects on infections (bacterial, fungal, viral, and protozoan infections), along with their medicinal properties and significance in drug development. The most investigated active constituents of Av are aloin, emodin, acemannan, and aloesin. Av contains more than 100 potentially active components from six different classes: anthraquinone, chromone, phenylpropanoids, coumarins, phenylpyrone, and phytosterols, focusing on its anti-infective, anti-cancer, anti-diabetic, anti-oxidant, anti-inflammatory, immuno-modulatory activity and impact on neural diseases as well, based on peer-reviewed scientific data. By deepening the understanding of Av's medicinal value, this study may provide a reference for its future research and the development of new bioactive drug molecules from Av.
芦荟(Av)在阿育吠陀中被尊为“天堂的魔杖”或“天堂的祝福”,确切地说是“沉默的治疗师”。这种草本植物属于藤科,以前归类为百合科。在传统中医(TCM)中,Av因其丰富的生物活性物质而被公认具有相当的治疗价值。因此,本文对其生物活性成分进行分析,以突出其在药物开发中的应用潜力。在2024年10月之前,将利用PubMed、Web of Science、SpringerLink等数据库进行广泛的文献综述。本研究调查了病毒的生物活性化合物及其体内、体外和体内对感染(细菌、真菌、病毒和原生动物感染)的影响,以及它们的药用特性和在药物开发中的意义。研究最多的Av活性成分是芦荟素,大黄素,紫丁香聚糖和芦荟素。Av含有来自6个不同类别的100多种潜在活性成分:蒽醌、色素、苯丙素、香豆素、苯吡咯酮和植物甾醇,重点是其抗感染、抗癌、抗糖尿病、抗氧化、抗炎、免疫调节活性以及对神经疾病的影响,这是基于同行评审的科学数据。通过加深对Av药用价值的认识,本研究可为Av的进一步研究和从Av中开发新的生物活性药物分子提供参考。
{"title":"Phytochemical profiles, biological activities and medicinal importance of Aloe vera L.: A review","authors":"Suchhanda Nandi,&nbsp;Golak Majumdar,&nbsp;Shyamapada Mandal","doi":"10.1016/j.jhip.2025.07.001","DOIUrl":"10.1016/j.jhip.2025.07.001","url":null,"abstract":"<div><div><em>Aloe vera</em> (Av) is revered in Ayurveda as the \"wand of heaven\" or \"heaven's blessing\" and precisely the \"silent healer\". This herbaceous plant belongs to Asphodelaceae family, previously classified as Liliaceae. In Traditional Chinese Medicine (TCM), Av is acknowledged for its abundant bioactive substances that have considerable therapeutic value. Therefore, the objective of this review is to analyze Av's bioactive compounds, highlighting its medicinal potential in drug development. An extensive literature review is performed utilizing databases such as PubMed, Web of Science, SpringerLink, and more until October 2024. The research investigates the bioactive compounds of Av and their <em>in vivo</em>, <em>in vitro</em>, and <em>in silico</em> effects on infections (bacterial, fungal, viral, and protozoan infections), along with their medicinal properties and significance in drug development. The most investigated active constituents of Av are aloin, emodin, acemannan, and aloesin. Av contains more than 100 potentially active components from six different classes: anthraquinone, chromone, phenylpropanoids, coumarins, phenylpyrone, and phytosterols, focusing on its anti-infective, anti-cancer, anti-diabetic, anti-oxidant, anti-inflammatory, immuno-modulatory activity and impact on neural diseases as well, based on peer-reviewed scientific data. By deepening the understanding of Av's medicinal value, this study may provide a reference for its future research and the development of new bioactive drug molecules from Av.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"6 3","pages":"Pages 251-262"},"PeriodicalIF":0.0,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144771652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Therapeutic effects of raw rhubarb on gastrointestinal complications in ischemic stroke: An integrated analysis of gut microbiota, metabolomics, and network pharmacology 生大黄对缺血性脑卒中胃肠道并发症的治疗作用:肠道微生物群、代谢组学和网络药理学的综合分析
Pub Date : 2025-06-01 DOI: 10.1016/j.jhip.2025.05.002
Zhanhao Ye , Dongmin Cao , Wenxing Ao , Ting Li , Minghua Xian , Shumei Wang

Objective

Gastrointestinal complications (GITC) are a major cause of increased morbidity and mortality in stroke patients, significantly impairing recovery by triggering systemic inflammation and hindering brain healing. Raw Rhubarb (RR) is a commonly used traditional Chinese medicine with significant potential in treating GITC of ischemic stroke (IS). However, its therapeutic mechanisms remain largely unknown. This study aims to investigate the therapeutic effects and potential mechanisms of RR on GITC in IS through an integrated analysis of gut microbiota, metabolomics, and network pharmacology.

Methods

Male Sprague-Dawley rats were subjected to middle cerebral artery occlusion/reperfusion (MCAO/R) to induce IS. The rats were divided into six groups: sham, model, nimodipine-treated, and three different dose groups for RR. Neuroprotective efficacy was assessed using infarct size measurement, neurological scoring, and histopathological analysis. Gut microbiota composition was analyzed through 16S rRNA gene sequencing, while metabolomic profiling of brain and colon tissues was performed using UPLC-Q-Orbitrap HRMS/MS. Multivariate statistical methods were employed to identify the key metabolites and pathways affected by RR treatment. Correlation analysis was conducted to establish links between gut microbiota alterations and differential metabolites. Additionally, network pharmacology, molecular docking analysis, and Western blot assays were utilized to explore the molecular mechanisms underlying RR's treatment of GITC in IS.

Results

RR showed significant neuroprotective effects, reducing infarct volume, improving neurological scores, and restoring intestinal function compared to the model group. In addition, gut microbiota analysis revealed that RR administration reversed gut microbiota dysbiosis in MCAO/R rats by increasing the abundance of Bifidobacterium and Lactobacillus while decreasing the abundance of Escherichia-Shigella. Metabolomics analysis indicated that RR reversed the metabolic disturbances in MCAO/R rats by modulating arachidonic acid (AA) metabolism. Correlation analysis showed that AA and its metabolites, such as PGE2, were closely associated with Bifidobacterium and Lactobacillus. Combining metabolomics, network pharmacology, and molecular docking analysis suggested that RR might regulate AA metabolism through the PI3K/mTOR signaling pathway to treat GITC in IS. Finally, Western blot validation confirmed that RR modulates the PI3K/mTOR signaling pathway.

Conclusion

These findings indicate that RR holds significant promise as a therapeutic strategy for addressing GITC of IS. The protective effects mediated by RR are associated with the improvement of gut microbiota dysbiosis and metabolic disturbances.
胃肠道并发症(GITC)是卒中患者发病率和死亡率增加的主要原因,它通过引发全身性炎症和阻碍脑愈合而显著损害康复。生大黄(RR)是一种常用的中药,在治疗缺血性脑卒中(is)的GITC方面具有重要的潜力。然而,其治疗机制在很大程度上仍然未知。本研究旨在通过肠道微生物群、代谢组学和网络药理学的综合分析,探讨RR对IS中GITC的治疗作用及其潜在机制。方法采用大脑中动脉闭塞/再灌注法(MCAO/R)诱导小鼠IS。将大鼠分为假手术组、模型组、尼莫地平组和3个不同剂量的RR组。通过梗死面积测量、神经系统评分和组织病理学分析来评估神经保护效果。通过16S rRNA基因测序分析肠道菌群组成,使用UPLC-Q-Orbitrap HRMS/MS对脑和结肠组织进行代谢组学分析。采用多变量统计方法确定受RR治疗影响的关键代谢物和途径。进行了相关分析,以建立肠道微生物群改变与差异代谢物之间的联系。此外,我们还利用网络药理学、分子对接分析、Western blot等方法探讨了RR治疗IS中GITC的分子机制。结果与模型组比较,tsr具有明显的神经保护作用,可减少梗死面积,改善神经学评分,恢复肠道功能。此外,肠道菌群分析显示,RR通过增加双歧杆菌和乳酸杆菌的丰度而降低埃希氏杆菌-志贺氏菌的丰度,逆转了MCAO/R大鼠肠道菌群失调。代谢组学分析表明,RR通过调节花生四烯酸(AA)代谢逆转MCAO/R大鼠的代谢紊乱。相关性分析表明,AA及其代谢产物PGE2与双歧杆菌和乳杆菌密切相关。结合代谢组学、网络药理学、分子对接分析提示,RR可能通过PI3K/mTOR信号通路调控AA代谢,治疗IS中的GITC。最后,Western blot验证证实RR调节PI3K/mTOR信号通路。结论:这些发现表明,RR作为解决IS GITC的治疗策略具有重要的前景。RR介导的保护作用与改善肠道菌群失调和代谢紊乱有关。
{"title":"Therapeutic effects of raw rhubarb on gastrointestinal complications in ischemic stroke: An integrated analysis of gut microbiota, metabolomics, and network pharmacology","authors":"Zhanhao Ye ,&nbsp;Dongmin Cao ,&nbsp;Wenxing Ao ,&nbsp;Ting Li ,&nbsp;Minghua Xian ,&nbsp;Shumei Wang","doi":"10.1016/j.jhip.2025.05.002","DOIUrl":"10.1016/j.jhip.2025.05.002","url":null,"abstract":"<div><h3>Objective</h3><div>Gastrointestinal complications (GITC) are a major cause of increased morbidity and mortality in stroke patients, significantly impairing recovery by triggering systemic inflammation and hindering brain healing. Raw Rhubarb (RR) is a commonly used traditional Chinese medicine with significant potential in treating GITC of ischemic stroke (IS). However, its therapeutic mechanisms remain largely unknown. This study aims to investigate the therapeutic effects and potential mechanisms of RR on GITC in IS through an integrated analysis of gut microbiota, metabolomics, and network pharmacology.</div></div><div><h3>Methods</h3><div>Male Sprague-Dawley rats were subjected to middle cerebral artery occlusion/reperfusion (MCAO/R) to induce IS. The rats were divided into six groups: sham, model, nimodipine-treated, and three different dose groups for RR. Neuroprotective efficacy was assessed using infarct size measurement, neurological scoring, and histopathological analysis. Gut microbiota composition was analyzed through 16S rRNA gene sequencing, while metabolomic profiling of brain and colon tissues was performed using UPLC-Q-Orbitrap HRMS/MS. Multivariate statistical methods were employed to identify the key metabolites and pathways affected by RR treatment. Correlation analysis was conducted to establish links between gut microbiota alterations and differential metabolites. Additionally, network pharmacology, molecular docking analysis, and Western blot assays were utilized to explore the molecular mechanisms underlying RR's treatment of GITC in IS.</div></div><div><h3>Results</h3><div>RR showed significant neuroprotective effects, reducing infarct volume, improving neurological scores, and restoring intestinal function compared to the model group. In addition, gut microbiota analysis revealed that RR administration reversed gut microbiota dysbiosis in MCAO/R rats by increasing the abundance of <em>Bifidobacterium</em> and <em>Lactobacillus</em> while decreasing the abundance of <em>Escherichia-Shigella</em>. Metabolomics analysis indicated that RR reversed the metabolic disturbances in MCAO/R rats by modulating arachidonic acid (AA) metabolism. Correlation analysis showed that AA and its metabolites, such as PGE2, were closely associated with <em>Bifidobacterium</em> and <em>Lactobacillus</em>. Combining metabolomics, network pharmacology, and molecular docking analysis suggested that RR might regulate AA metabolism through the PI3K/mTOR signaling pathway to treat GITC in IS. Finally, Western blot validation confirmed that RR modulates the PI3K/mTOR signaling pathway.</div></div><div><h3>Conclusion</h3><div>These findings indicate that RR holds significant promise as a therapeutic strategy for addressing GITC of IS. The protective effects mediated by RR are associated with the improvement of gut microbiota dysbiosis and metabolic disturbances.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"6 2","pages":"Pages 136-149"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144178292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A scoping review of five selected underutilized medicinal plants of Sri Lanka: Focusing on ethnobotany, phytochemistry and bioactivities, and evaluation of their potential for novel herbal product development 对斯里兰卡五种未充分利用的药用植物进行范围审查:重点是民族植物学、植物化学和生物活性,以及评估其开发新型草药产品的潜力
Pub Date : 2025-06-01 DOI: 10.1016/j.jhip.2025.06.005
Isuru Sakbo Uyangoda , Mayuri Munasinghe
Ageratum conyzoides L., Artocarpus gomezianus Wall. ex Trécul, Euphorbia hirta L., Plectranthus zeylanicus Benth., and Piper sarmentosum Roxb. have long been utilized in traditional medical practices, particularly across South and Southeast Asia. Despite their significant ethnopharmacological potential to treat various disorders, these plants remain underutilized in Sri Lanka. This review aims to evaluate the habit, propagation, ethnomedicinal uses, phytochemistry, and pharmacological properties of these five underutilized medicinal plants to promote their sustainable utilization in the herbal products industry of Sri Lanka. The plants were selected based on data from pharmacopeias and interviews with traditional medical practitioners. Scientific information on their ethnomedicinal uses, phytochemical compositions, and pharmacological properties was gathered from key scientific databases, including PubMed, Scopus, ScienceDirect, and Google Scholar, as well as web references and books. This information was analyzed to assess the factors contributing to their underutilization and their potential for novel herbal product development in Sri Lanka. All five plants possess a wide range of ethnomedicinal uses and are rich in bioactive compounds, including alkaloids, terpenoids, stilbenoids, and polyphenolic compounds. These bioactive compounds have been scientifically validated for their pharmacological properties, making these plants strong candidates for the development of novel pharmaceuticals and cosmeceuticals. However, their full potential remains largely untapped, primarily due to the lack of detailed phytochemical characterization and bioactive studies specific to Sri Lanka. Further preclinical and clinical research is needed to evaluate their therapeutic outcomes within the local context. The findings of this scoping review will guide future research and encourage broader use of these underutilized plants. Promoting their use will provide a sustainable alternative to the overexploitation of commonly used medicinal plants and support effective biodiversity conservation and resource management.
长尾叶柱,长尾叶柱。extracul, Euphorbia hirta L., Plectranthus zeylanicus Benth。Piper sarmentosum Roxb。长期以来一直用于传统医疗实践,特别是在南亚和东南亚。尽管这些植物具有治疗各种疾病的重大民族药理学潜力,但在斯里兰卡仍未得到充分利用。本综述旨在评估这五种未充分利用的药用植物的习性,繁殖,民族医药用途,植物化学和药理学特性,以促进其在斯里兰卡草药产品工业中的可持续利用。这些植物是根据药典的数据和对传统医生的采访选择的。从PubMed、Scopus、ScienceDirect和b谷歌Scholar等关键科学数据库以及网络参考文献和书籍中收集了有关其民族医学用途、植物化学成分和药理特性的科学信息。对这些信息进行了分析,以评估导致其未充分利用的因素及其在斯里兰卡开发新型草药产品的潜力。这五种植物都具有广泛的民族医药用途,并富含生物活性化合物,包括生物碱、萜类、苯乙烯类和多酚类化合物。这些生物活性化合物的药理特性已经过科学验证,使这些植物成为开发新药和药妆品的有力候选者。然而,它们的全部潜力在很大程度上仍未得到充分开发,这主要是由于缺乏详细的植物化学特性和斯里兰卡特有的生物活性研究。需要进一步的临床前和临床研究来评估它们在当地的治疗效果。这一范围审查的结果将指导未来的研究,并鼓励更广泛地利用这些未充分利用的植物。促进其利用将为常用药用植物的过度开发提供可持续的替代方案,并支持有效的生物多样性保护和资源管理。
{"title":"A scoping review of five selected underutilized medicinal plants of Sri Lanka: Focusing on ethnobotany, phytochemistry and bioactivities, and evaluation of their potential for novel herbal product development","authors":"Isuru Sakbo Uyangoda ,&nbsp;Mayuri Munasinghe","doi":"10.1016/j.jhip.2025.06.005","DOIUrl":"10.1016/j.jhip.2025.06.005","url":null,"abstract":"<div><div><em>Ageratum conyzoides</em> L., <em>Artocarpus gomezianus</em> Wall. ex Trécul, <em>Euphorbia hirta</em> L., <em>Plectranthus zeylanicus</em> Benth., and <em>Piper sarmentosum</em> Roxb. have long been utilized in traditional medical practices, particularly across South and Southeast Asia. Despite their significant ethnopharmacological potential to treat various disorders, these plants remain underutilized in Sri Lanka. This review aims to evaluate the habit, propagation, ethnomedicinal uses, phytochemistry, and pharmacological properties of these five underutilized medicinal plants to promote their sustainable utilization in the herbal products industry of Sri Lanka. The plants were selected based on data from pharmacopeias and interviews with traditional medical practitioners. Scientific information on their ethnomedicinal uses, phytochemical compositions, and pharmacological properties was gathered from key scientific databases, including PubMed, Scopus, ScienceDirect, and Google Scholar, as well as web references and books. This information was analyzed to assess the factors contributing to their underutilization and their potential for novel herbal product development in Sri Lanka. All five plants possess a wide range of ethnomedicinal uses and are rich in bioactive compounds, including alkaloids, terpenoids, stilbenoids, and polyphenolic compounds. These bioactive compounds have been scientifically validated for their pharmacological properties, making these plants strong candidates for the development of novel pharmaceuticals and cosmeceuticals. However, their full potential remains largely untapped, primarily due to the lack of detailed phytochemical characterization and bioactive studies specific to Sri Lanka. Further preclinical and clinical research is needed to evaluate their therapeutic outcomes within the local context. The findings of this scoping review will guide future research and encourage broader use of these underutilized plants. Promoting their use will provide a sustainable alternative to the overexploitation of commonly used medicinal plants and support effective biodiversity conservation and resource management.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"6 2","pages":"Pages 209-223"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144548349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mitochondrial function maintenance and mitochondrial training in ageing and related diseases 老化及相关疾病中的线粒体功能维持和线粒体训练
Pub Date : 2025-06-01 DOI: 10.1016/j.jhip.2025.04.001
Gan Gao , Zhihui Xie , Hongliang Huang
Cellular senescence driven by mitochondrial dysfunction is a key contributor to ageing and related diseases. The decline in the quality and quantity of healthy mitochondria with ageing disrupts energy production, redox homeostasis, and intracellular signaling. Mitochondrial quality control (MQC) is a cellular self-repair mechanism that protects mitochondrial function and maintains a healthy mitochondrial network. Targeted regulation of MQC is expected to moderate the development of cellular senescence and related diseases. We explored the impact of mitochondrial function on cell fate at the molecular and organelle levels, analyzed the role of mitochondria-targeted interventions for delaying cellular senescence and ameliorating age-related diseases, and pointed out the idea of increasing the critical level of healthy mitochondria to cope with internal and external stressful stimuli and to improve the ability of self-repairing by exercising and protecting mitochondria in the long term.
由线粒体功能障碍驱动的细胞衰老是衰老和相关疾病的关键因素。随着年龄的增长,健康线粒体质量和数量的下降会破坏能量产生、氧化还原稳态和细胞内信号传导。线粒体质量控制(MQC)是一种保护线粒体功能和维持线粒体网络健康的细胞自我修复机制。靶向调控MQC有望减缓细胞衰老和相关疾病的发展。我们从分子和细胞器水平探讨了线粒体功能对细胞命运的影响,分析了线粒体靶向干预在延缓细胞衰老和改善年龄相关疾病中的作用,提出了通过长期锻炼和保护线粒体来提高健康线粒体的临界水平,以应对内外应激刺激,提高线粒体的自我修复能力。
{"title":"Mitochondrial function maintenance and mitochondrial training in ageing and related diseases","authors":"Gan Gao ,&nbsp;Zhihui Xie ,&nbsp;Hongliang Huang","doi":"10.1016/j.jhip.2025.04.001","DOIUrl":"10.1016/j.jhip.2025.04.001","url":null,"abstract":"<div><div>Cellular senescence driven by mitochondrial dysfunction is a key contributor to ageing and related diseases. The decline in the quality and quantity of healthy mitochondria with ageing disrupts energy production, redox homeostasis, and intracellular signaling. Mitochondrial quality control (MQC) is a cellular self-repair mechanism that protects mitochondrial function and maintains a healthy mitochondrial network. Targeted regulation of MQC is expected to moderate the development of cellular senescence and related diseases. We explored the impact of mitochondrial function on cell fate at the molecular and organelle levels, analyzed the role of mitochondria-targeted interventions for delaying cellular senescence and ameliorating age-related diseases, and pointed out the idea of increasing the critical level of healthy mitochondria to cope with internal and external stressful stimuli and to improve the ability of self-repairing by exercising and protecting mitochondria in the long term.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"6 2","pages":"Pages 159-174"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144298541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Research advances in the role of selenium in reversing tumor multidrug resistance 硒在逆转肿瘤多药耐药中的作用研究进展
Pub Date : 2025-06-01 DOI: 10.1016/j.jhip.2025.06.004
Haoqiang Hu , Yunjun Chen , Hongtao Xu , Wei Hou
Multidrug resistance (MDR) is a significant challenge in the cancer therapy, with mechanisms primarily involving increased drug efflux mediated by ABC transporters, leading to reduced intracellular drug concentrations. In recent years, various selenium-containing compounds have demonstrated extensive biological activities, including chemoprevention, antioxidant or pro-oxidant effects, and regulation of the nervous and immune system activities. One of the most prominent physiological characteristics of selenium is its antioxidant capacity, which can regulate the levels of reactive oxygen species (ROS) in the body, making it a promising group for reversing MDR activity. Furthermore, research has shown that natural selenium compounds, including selenate, selenite, selenomethionine, and selenocystein, can inhibit the activity of drug resistance proteins and increase the intracellular accumulation of chemotherapeutic drugs by regulating intracellular ROS levels. For instance, sodium selenite has been shown to markedly increase the sensitivity of drug-resistant cell lines to doxorubicin, exhibiting significant antitumor efficacy and potential for reversing MDR. These findings suggest that selenium compounds hold considerable promise in addressing multidrug resistance. Consequently, this review focuses on elucidating the mechanisms of MDR and the chemical properties of selenium compounds, with particular emphasis on their activities in reversing MDR, thereby providing novel strategies for overcoming MDR in tumor cells.
多药耐药(MDR)是癌症治疗中的一个重大挑战,其机制主要涉及ABC转运体介导的药物外排增加,导致细胞内药物浓度降低。近年来,各种含硒化合物已显示出广泛的生物活性,包括化学预防、抗氧化或促氧化作用,以及调节神经和免疫系统活性。硒最突出的生理特性之一是其抗氧化能力,它可以调节体内活性氧(ROS)的水平,使其成为逆转MDR活性的有希望的群体。此外,研究表明,硒酸盐、亚硒酸盐、硒代蛋氨酸和硒半胱氨酸等天然硒化合物可通过调节细胞内ROS水平抑制耐药蛋白的活性,增加化疗药物在细胞内的蓄积。例如,亚硒酸钠已被证明可显著增加耐药细胞系对阿霉素的敏感性,显示出显著的抗肿瘤功效和逆转耐多药的潜力。这些发现表明硒化合物在解决多药耐药方面具有相当大的前景。因此,本文将重点阐述MDR的机制和硒化合物的化学性质,重点研究其在逆转MDR中的作用,从而为克服肿瘤细胞中的MDR提供新的策略。
{"title":"Research advances in the role of selenium in reversing tumor multidrug resistance","authors":"Haoqiang Hu ,&nbsp;Yunjun Chen ,&nbsp;Hongtao Xu ,&nbsp;Wei Hou","doi":"10.1016/j.jhip.2025.06.004","DOIUrl":"10.1016/j.jhip.2025.06.004","url":null,"abstract":"<div><div>Multidrug resistance (MDR) is a significant challenge in the cancer therapy, with mechanisms primarily involving increased drug efflux mediated by ABC transporters, leading to reduced intracellular drug concentrations. In recent years, various selenium-containing compounds have demonstrated extensive biological activities, including chemoprevention, antioxidant or pro-oxidant effects, and regulation of the nervous and immune system activities. One of the most prominent physiological characteristics of selenium is its antioxidant capacity, which can regulate the levels of reactive oxygen species (ROS) in the body, making it a promising group for reversing MDR activity. Furthermore, research has shown that natural selenium compounds, including selenate, selenite, selenomethionine, and selenocystein, can inhibit the activity of drug resistance proteins and increase the intracellular accumulation of chemotherapeutic drugs by regulating intracellular ROS levels. For instance, sodium selenite has been shown to markedly increase the sensitivity of drug-resistant cell lines to doxorubicin, exhibiting significant antitumor efficacy and potential for reversing MDR. These findings suggest that selenium compounds hold considerable promise in addressing multidrug resistance. Consequently, this review focuses on elucidating the mechanisms of MDR and the chemical properties of selenium compounds, with particular emphasis on their activities in reversing MDR, thereby providing novel strategies for overcoming MDR in tumor cells.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"6 2","pages":"Pages 184-194"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144490083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Development and ex vivo / in vitro evaluation of sodium alginate/ hydroxypropyl methylcellulose films for dermal and/or transdermal delivery of p-hydroxycinnamic acid 海藻酸钠/羟丙基甲基纤维素膜用于对羟基肉桂酸真皮和/或透皮给药的研制和离体/体外评价
Pub Date : 2025-06-01 DOI: 10.1016/j.jhip.2025.06.002
Ayşe Pınar Yağcılar , Gökçe Karaotmarlı Güven , Emre Şefik Çağlar , Neslihan Üstündağ Okur , Panoraia I. Siafaka

Objective

Skin diseases and chronic wounds are health problems that require solutions for health systems due to their high costs and difficulties in effective and rapid treatment. Hydroxycinnamic acid and its derivatives are powerful antioxidant molecules with widespread applications in medicine, cosmetics, and food industry. In this study, p-hydroxycinnamic acid was used as a potent agent for the management of skin diseases and other disorders.

Method

Herein, sodium alginate and hydroxypropylmethylcellulose-based films loaded with p-hydroxycinnamic acid at various concentrations were prepared by solvent-casting method and characterized in terms of mechanical, physicochemical, bioadhesive properties, and in vitro release kinetic modelling.

Results

The masses of the films were found to be between 16.933 ​± ​1.108 ​mg and 15.200 ​± ​0.432 mg and thicknesses between 135 ​± ​4 μm and 163 ​± ​6 μm. F1 formulation with higher sodium alginate concentration exhibited higher moisture absorption and moisture loss percentages (18.373% ​± ​2.610% and 8.281% ​± ​1.834%). In terms of water absorption, it was observed that F3 had up to 100% and F1 had the lowest absorption capacity. However, F1 degraded in a shorter time compared to other films. In terms of mechanical properties, F1 has shown that it has higher tensile strength, reaches 100% by providing continuous release with in vitro release studies, and has the highest bioadhesion. In addition, as a result of FTIR analysis and ex vivo permeation and penetration studies, the formulation F1 proved that it is suitable for dermal applications.

Conclusion

The developed formulations exhibited desired dermal film properties, making it a promising treatment option for dermal applications.
目的皮肤疾病和慢性伤口是卫生系统需要解决的健康问题,因其成本高,难以有效和快速治疗。羟基肉桂酸及其衍生物是一种强大的抗氧化分子,在医药、化妆品和食品工业中有着广泛的应用。在这项研究中,对羟基肉桂酸被用作治疗皮肤病和其他疾病的有效药物。方法采用溶剂铸造法制备不同浓度海藻酸钠和羟丙基甲基纤维素基对羟基肉桂酸膜,并对其进行力学、物理化学、生物粘附性能和体外释放动力学模拟表征。结果膜的质量为16.933±1.108 mg ~ 15.200±0.432 mg,膜的厚度为135±4 μm ~ 163±6 μm。海藻酸钠浓度越高,F1配方吸湿率和失湿率越高(分别为18.373%±2.610%和8.281%±1.834%)。吸水率方面,F3吸水率最高达100%,F1吸水率最低。然而,与其他薄膜相比,F1在较短的时间内退化。在力学性能方面,F1表明其具有较高的抗拉强度,体外释放研究提供连续释放达到100%,具有最高的生物粘附性。此外,FTIR分析和体外渗透渗透研究表明,配方F1适合皮肤应用。结论该制剂具有良好的真皮膜性能,是一种很有前途的真皮治疗选择。
{"title":"Development and ex vivo / in vitro evaluation of sodium alginate/ hydroxypropyl methylcellulose films for dermal and/or transdermal delivery of p-hydroxycinnamic acid","authors":"Ayşe Pınar Yağcılar ,&nbsp;Gökçe Karaotmarlı Güven ,&nbsp;Emre Şefik Çağlar ,&nbsp;Neslihan Üstündağ Okur ,&nbsp;Panoraia I. Siafaka","doi":"10.1016/j.jhip.2025.06.002","DOIUrl":"10.1016/j.jhip.2025.06.002","url":null,"abstract":"<div><h3>Objective</h3><div>Skin diseases and chronic wounds are health problems that require solutions for health systems due to their high costs and difficulties in effective and rapid treatment. Hydroxycinnamic acid and its derivatives are powerful antioxidant molecules with widespread applications in medicine, cosmetics, and food industry. In this study, <em>p</em>-hydroxycinnamic acid was used as a potent agent for the management of skin diseases and other disorders.</div></div><div><h3>Method</h3><div>Herein, sodium alginate and hydroxypropylmethylcellulose-based films loaded with <em>p</em>-hydroxycinnamic acid at various concentrations were prepared by solvent-casting method and characterized in terms of mechanical, physicochemical, bioadhesive properties, and <em>in vitro</em> release kinetic modelling.</div></div><div><h3>Results</h3><div>The masses of the films were found to be between 16.933 ​± ​1.108 ​mg and 15.200 ​± ​0.432 mg and thicknesses between 135 ​± ​4 μm and 163 ​± ​6 μm. F1 formulation with higher sodium alginate concentration exhibited higher moisture absorption and moisture loss percentages (18.373% ​± ​2.610% and 8.281% ​± ​1.834%). In terms of water absorption, it was observed that F3 had up to 100% and F1 had the lowest absorption capacity. However, F1 degraded in a shorter time compared to other films. In terms of mechanical properties, F1 has shown that it has higher tensile strength, reaches 100% by providing continuous release with <em>in vitro</em> release studies, and has the highest bioadhesion. In addition, as a result of FTIR analysis and <em>ex vivo</em> permeation and penetration studies, the formulation F1 proved that it is suitable for dermal applications.</div></div><div><h3>Conclusion</h3><div>The developed formulations exhibited desired dermal film properties, making it a promising treatment option for dermal applications.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"6 2","pages":"Pages 175-183"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144490077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Baicalin induces apoptosis and autophagy in resistant human hepatocellular carcinoma cell line Bel-7402/5-FU cells via PI3K/AKT pathway 黄芩苷通过PI3K/AKT通路诱导耐药人肝癌Bel-7402/5-FU细胞凋亡和自噬
Pub Date : 2025-06-01 DOI: 10.1016/j.jhip.2025.05.001
Fei Li , Zilin Lan , Weiwei Jiang , Jianheng Zhou , Jiumao Lin , Jinyan Zhao

Objective

Multidrug resistance (MDR) is one main cause of chemotherapy failure. Baicalin is an important active ingredient with anticancer potential in many Chinese herbal medicines. In order to understand the function of baicalin reversing MDR in hepatocellular carcinoma (HCC) and the molecular mechanisms that underlie it, the current study was designed.

Methods

Bel-7402 and Bel-7402/5-FU cells were cultured, and MTT assay was applied to detect cell viability and the cross-resistance of Bel-7402/5-FU cells. The pump function, apoptosis, and autophagy were detected by flow cytometry. The related proteins were detected by Western blot assay. The PI3K agonist (740Y-P) was used to verify whether baicalin overcomes the drug resistance of HCC cells by blocking the PI3K/AKT pathway.

Results

The findings showed that Bel-7402/5-FU cells were cross-resistant to different chemotherapeutic drugs. Baicalin inhibited cell viability in both Bel-7402/5-FU and Bel-7402 ​cells, and baicalin increased sensitivity of Bel-7402/5-FU cells to 5-FU in time- and dose-dependent manners. Baicalin increased the accumulation of doxorubicin and rhodamine-123 in Bel-7402/5-FU cells and inhibited the protein expression of ABCG2, ABCB1, and ABCC1, associated with pump function. In addition, baicalin induced apoptosis of Bel-7402/5-FU cells via up-regulating Bax expression. Furthermore, baicalin increased autophagy through regulating LC3-Ⅱ, p62, and Beclin-1. Baicalin reversed drug resistance in Bel-7402/5-FU cells by inhibiting the PI3K/AKT pathway, which promoted autophagy and apoptosis to restore chemosensitivity.

Conclusion

Baicalin increased accumulation of chemotherapy drugs and induced apoptosis and autophagy in Bel-7402/5-FU cells by inhibiting the PI3K/AKT signaling pathway, that may be the important mechanism by which baicalin reverses the MDR of HCC.
目的耐多药(MDR)是化疗失败的主要原因之一。黄芩苷是许多中草药中具有抗癌作用的重要活性成分。为了了解黄芩苷在肝细胞癌(HCC)中逆转MDR的作用及其分子机制,本研究进行了设计。方法培养bel -7402和Bel-7402/5-FU细胞,采用MTT法检测Bel-7402/5-FU细胞活力和交叉抗性。流式细胞术检测泵功能、细胞凋亡和细胞自噬。Western blot法检测相关蛋白。使用PI3K激动剂(740Y-P)验证黄芩苷是否通过阻断PI3K/AKT通路来克服HCC细胞的耐药。结果Bel-7402/5-FU细胞对不同化疗药物有交叉耐药。黄芩苷对Bel-7402/5-FU和Bel-7402细胞的活性均有抑制作用,且黄芩苷增加Bel-7402/5-FU细胞对5-FU的敏感性呈时间和剂量依赖性。黄芩苷增加了Bel-7402/5-FU细胞中阿霉素和罗丹明-123的积累,抑制了与泵功能相关的ABCG2、ABCB1和ABCC1蛋白的表达。黄芩苷通过上调Bax表达诱导Bel-7402/5-FU细胞凋亡。此外,黄芩苷通过调节LC3-Ⅱ、p62和Beclin-1来增加自噬。黄芩苷通过抑制PI3K/AKT通路逆转Bel-7402/5-FU细胞耐药,促进细胞自噬和凋亡,恢复化疗敏感性。结论黄芩苷通过抑制PI3K/AKT信号通路,增加Bel-7402/5-FU细胞化疗药物积累,诱导细胞凋亡和自噬,这可能是黄芩苷逆转肝癌多药耐药的重要机制。
{"title":"Baicalin induces apoptosis and autophagy in resistant human hepatocellular carcinoma cell line Bel-7402/5-FU cells via PI3K/AKT pathway","authors":"Fei Li ,&nbsp;Zilin Lan ,&nbsp;Weiwei Jiang ,&nbsp;Jianheng Zhou ,&nbsp;Jiumao Lin ,&nbsp;Jinyan Zhao","doi":"10.1016/j.jhip.2025.05.001","DOIUrl":"10.1016/j.jhip.2025.05.001","url":null,"abstract":"<div><h3>Objective</h3><div>Multidrug resistance (MDR) is one main cause of chemotherapy failure. Baicalin is an important active ingredient with anticancer potential in many Chinese herbal medicines. In order to understand the function of baicalin reversing MDR in hepatocellular carcinoma (HCC) and the molecular mechanisms that underlie it, the current study was designed.</div></div><div><h3>Methods</h3><div>Bel-7402 and Bel-7402/5-FU cells were cultured, and MTT assay was applied to detect cell viability and the cross-resistance of Bel-7402/5-FU cells. The pump function, apoptosis, and autophagy were detected by flow cytometry. The related proteins were detected by Western blot assay. The PI3K agonist (740Y-P) was used to verify whether baicalin overcomes the drug resistance of HCC cells by blocking the PI3K/AKT pathway.</div></div><div><h3>Results</h3><div>The findings showed that Bel-7402/5-FU cells were cross-resistant to different chemotherapeutic drugs. Baicalin inhibited cell viability in both Bel-7402/5-FU and Bel-7402 ​cells, and baicalin increased sensitivity of Bel-7402/5-FU cells to 5-FU in time- and dose-dependent manners. Baicalin increased the accumulation of doxorubicin and rhodamine-123 in Bel-7402/5-FU cells and inhibited the protein expression of ABCG2, ABCB1, and ABCC1, associated with pump function. In addition, baicalin induced apoptosis of Bel-7402/5-FU cells via up-regulating Bax expression. Furthermore, baicalin increased autophagy through regulating LC3-Ⅱ, p62, and Beclin-1. Baicalin reversed drug resistance in Bel-7402/5-FU cells by inhibiting the PI3K/AKT pathway, which promoted autophagy and apoptosis to restore chemosensitivity.</div></div><div><h3>Conclusion</h3><div>Baicalin increased accumulation of chemotherapy drugs and induced apoptosis and autophagy in Bel-7402/5-FU cells by inhibiting the PI3K/AKT signaling pathway, that may be the important mechanism by which baicalin reverses the MDR of HCC.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"6 2","pages":"Pages 150-158"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144239602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Journal of Holistic Integrative Pharmacy
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1