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Pub Date : 2025-09-01 Epub Date: 2025-10-22 DOI: 10.1016/S2707-3688(25)00048-2
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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 Epub Date: 2025-05-30 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。
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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 Epub Date: 2025-07-04 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。
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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 Epub Date: 2025-06-17 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。
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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 Epub Date: 2025-06-27 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。
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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 Epub Date: 2025-06-09 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
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 Epub Date: 2025-06-26 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
The ameliorative effects of honeysuckle extract and its major component luteolin on autism-like behaviors in the NDE1 deficiency model 金银花提取物及其主要成分木犀草素对NDE1缺乏模型自闭症样行为的改善作用
Pub Date : 2025-06-01 Epub Date: 2025-07-01 DOI: 10.1016/j.jhip.2025.06.007
Qi Zhang, Shenglan Gou, Jia Lin, Yinglan Zhang, Qiang Li

Objective

To evaluate the effects of honeysuckle extract and its active component, luteolin, on the autistic-like behaviors and neuroinflammatory responses in NDE1-deficient autism spectrum disorder (ASD) zebrafish models. Also, to assess whether differences exist in their behavioral improvement effects and impacts on brain inflammatory factor expression levels.

Methods

Behavioral phenotyping (hyperactivity, stereotypic back-and-forth swimming, and 1VS6 social preference/grouping tests) and molecular analyses (quantification of NF-κB, IL6, TNFα, and IL1β) were performed on NDE1-deficient zebrafish treated with honeysuckle extract or luteolin.

Results

Honeysuckle extract improved two core symptoms of ASD, small circling repetitive stereotyped behavior and 1VS6 social preference behavior. While luteolin enhanced one core symptom, shoaling behavior, and one comorbid symptom, hyperactive locomotor activity. Molecularly, honeysuckle extract normalized IL6 levels, and luteolin reduced IL1β overexpression; their effects on brain inflammation in the NDE1-deficient autism model differed.

Conclusion

Both honeysuckle extract and luteolin demonstrated behavioral rescue and anti-neuroinflammatory effects in NDE1-deficient ASD zebrafish models. The ameliorating effects of luteolin on ASD-related behaviors and neuroinflammation are supported by literature, while the beneficial effects of honeysuckle on ASD-related behaviors represent a novel finding of this study, highlighting medicinal plants and plant-derived compounds as potential ASD therapeutics. Given honeysuckle's traditional Chinese medicinal and food uses, established safety, and superior improvement of core ASD symptoms compared to luteolin, it may offer a safer autism treatment option than luteolin-based small-molecule medication.
目的探讨金银花提取物及其有效成分木犀草素对nde1缺陷型自闭症谱系障碍(ASD)斑马鱼模型的自闭样行为和神经炎症反应的影响。同时,评估它们在行为改善效果和对脑炎症因子表达水平的影响方面是否存在差异。方法采用金银花提取物或木草素处理nde1缺陷斑马鱼,进行行为表型分析(多动、刻板往返游泳、1VS6社会偏好/分组测试)和分子分析(NF-κB、il - 6、TNFα和il - 1β的定量分析)。结果金银花提取物可改善ASD的两大核心症状:小圆重复刻板行为和1VS6社会偏好行为。而木犀草素增强了一个核心症状,即鱼群行为,以及一个共病症状,即过度活跃的运动活动。在分子上,金银花提取物使IL6水平正常化,木犀草素降低了IL1β的过表达;在缺乏nde1的自闭症模型中,它们对脑部炎症的影响有所不同。结论金银花提取物和木犀草素对nde1缺失型ASD斑马鱼均有行为拯救和抗神经炎症作用。木犀草素对ASD相关行为和神经炎症的改善作用已得到文献支持,而金银花对ASD相关行为的有益作用是本研究的新发现,突出了药用植物和植物源性化合物作为潜在的ASD治疗药物。与木犀草素相比,金银花具有传统的中药和食品用途、已建立的安全性以及对核心ASD症状的显著改善,因此它可能是一种比基于木犀草素的小分子药物更安全的自闭症治疗选择。
{"title":"The ameliorative effects of honeysuckle extract and its major component luteolin on autism-like behaviors in the NDE1 deficiency model","authors":"Qi Zhang,&nbsp;Shenglan Gou,&nbsp;Jia Lin,&nbsp;Yinglan Zhang,&nbsp;Qiang Li","doi":"10.1016/j.jhip.2025.06.007","DOIUrl":"10.1016/j.jhip.2025.06.007","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate the effects of honeysuckle extract and its active component, luteolin, on the autistic-like behaviors and neuroinflammatory responses in NDE1-deficient autism spectrum disorder (ASD) zebrafish models. Also, to assess whether differences exist in their behavioral improvement effects and impacts on brain inflammatory factor expression levels.</div></div><div><h3>Methods</h3><div>Behavioral phenotyping (hyperactivity, stereotypic back-and-forth swimming, and 1VS6 social preference/grouping tests) and molecular analyses (quantification of NF-κB, IL6, TNFα, and IL1β) were performed on NDE1-deficient zebrafish treated with honeysuckle extract or luteolin.</div></div><div><h3>Results</h3><div>Honeysuckle extract improved two core symptoms of ASD, small circling repetitive stereotyped behavior and 1VS6 social preference behavior. While luteolin enhanced one core symptom, shoaling behavior, and one comorbid symptom, hyperactive locomotor activity. Molecularly, honeysuckle extract normalized IL6 levels, and luteolin reduced IL1β overexpression; their effects on brain inflammation in the NDE1-deficient autism model differed.</div></div><div><h3>Conclusion</h3><div>Both honeysuckle extract and luteolin demonstrated behavioral rescue and anti-neuroinflammatory effects in NDE1-deficient ASD zebrafish models. The ameliorating effects of luteolin on ASD-related behaviors and neuroinflammation are supported by literature, while the beneficial effects of honeysuckle on ASD-related behaviors represent a novel finding of this study, highlighting medicinal plants and plant-derived compounds as potential ASD therapeutics. Given honeysuckle's traditional Chinese medicinal and food uses, established safety, and superior improvement of core ASD symptoms compared to luteolin, it may offer a safer autism treatment option than luteolin-based small-molecule medication.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"6 2","pages":"Pages 195-203"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144523047","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
Screening of potential markers for vitiligo based on bioinformatics and LASSO regression and prediction of Chinese medicine 基于生物信息学和LASSO回归预测的白癜风潜在标志物筛选
Pub Date : 2025-06-01 Epub Date: 2025-07-14 DOI: 10.1016/j.jhip.2025.06.003
Wei liang , Minni Huang , Yue Sun , Shuyu Guan

Objective

This study aimed to use bioinformatics techniques to screen biomarkers related to vitiligo.

Methods

Firstly, the gene expression profiles of vitiligo were obtained from the GEO database, and differentially expressed genes (DEGs) were identified. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on these differentially expressed genes. Through weighted gene co-expression network analysis (WGCNA), the core genes in the module most closely related to vitiligo were identified, and an intersection analysis was conducted with the DEGs. Next, a protein-protein interaction (PPI) network analysis was carried out on the intersection genes. Key genes were further screened using Cytohubba and least absolute shrinkage and selection operator (LASSO) regression analysis, and the roles of these key genes in immune cell infiltration were explored through single-sample gene set enrichment analysis (ssGSEA). In addition, the diagnostic effectiveness of the key genes was verified by the receiver operating characteristic (ROC) curve, and drugs related to the key genes were predicted using databases. Finally, the expression levels of these key genes were verified through reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot experiments.

Results

A total of 667 DEGs were identified, and the enrichment analysis mainly involved cell adhesion molecules, T cell receptor signaling pathway, etc. Nineteen core genes were screened out from the five algorithms of Cytohubba, and LASSO regression analysis further determined four key genes (IL7R, GZMH, CD3G, and UBD). Immune cell infiltration analysis showed that these four key genes had high expression in immune cells. The prediction results of traditional Chinese medicine showed that 15 traditional Chinese medicines were related to the key genes. The results of RT-qPCR showed that the expressions of IL7R, GZMH, and CD3G were significantly upregulated (P ​< ​0.05, ∗∗P ​< ​0.01, ∗∗∗P ​< ​0.001), and Western blot showed obvious expressions of IL7R, GZMH, CD3G, and UBD.

Conclusion

This study used bioinformatics methods to explore the biomarkers of vitiligo, and verified the potential of IL7R, GZMH, and CD3G as novel candidate genes through in vitro experiments. These genes may become new targets for the diagnosis, prognosis, and treatment of vitiligo.
目的利用生物信息学技术筛选与白癜风相关的生物标志物。方法首先从GEO数据库中获取白癜风基因表达谱,鉴定差异表达基因(DEGs);随后,对这些差异表达基因进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析。通过加权基因共表达网络分析(weighted gene co-expression network analysis, WGCNA),鉴定出模块中与白癜风关系最密切的核心基因,并与deg进行交叉分析。然后,对交叉基因进行蛋白-蛋白相互作用(PPI)网络分析。通过Cytohubba和least absolute shrinkage and selection operator (LASSO)回归分析进一步筛选关键基因,并通过单样本基因集富集分析(ssGSEA)探讨这些关键基因在免疫细胞浸润中的作用。此外,通过受试者工作特征(ROC)曲线验证关键基因的诊断有效性,并利用数据库预测关键基因相关的药物。最后通过逆转录定量聚合酶链反应(RT-qPCR)和Western blot实验验证这些关键基因的表达水平。结果共鉴定出667个deg,富集分析主要涉及细胞粘附分子、T细胞受体信号通路等。从Cytohubba的5种算法中筛选出19个核心基因,LASSO回归分析进一步确定了4个关键基因(IL7R、GZMH、CD3G和UBD)。免疫细胞浸润分析表明,这四个关键基因在免疫细胞中均有高表达。中药预测结果显示,有15种中药与关键基因相关。RT-qPCR结果显示,IL7R、GZMH和CD3G的表达显著上调(∗P <;0.05, * * P <;0.01, * * * P <;0.001), Western blot显示IL7R、GZMH、CD3G、UBD明显表达。结论本研究采用生物信息学方法探索白癜风的生物标志物,并通过体外实验验证了IL7R、GZMH和CD3G作为新的候选基因的潜力。这些基因可能成为白癜风诊断、预后和治疗的新靶点。
{"title":"Screening of potential markers for vitiligo based on bioinformatics and LASSO regression and prediction of Chinese medicine","authors":"Wei liang ,&nbsp;Minni Huang ,&nbsp;Yue Sun ,&nbsp;Shuyu Guan","doi":"10.1016/j.jhip.2025.06.003","DOIUrl":"10.1016/j.jhip.2025.06.003","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to use bioinformatics techniques to screen biomarkers related to vitiligo.</div></div><div><h3>Methods</h3><div>Firstly, the gene expression profiles of vitiligo were obtained from the GEO database, and differentially expressed genes (DEGs) were identified. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on these differentially expressed genes. Through weighted gene co-expression network analysis (WGCNA), the core genes in the module most closely related to vitiligo were identified, and an intersection analysis was conducted with the DEGs. Next, a protein-protein interaction (PPI) network analysis was carried out on the intersection genes. Key genes were further screened using Cytohubba and least absolute shrinkage and selection operator (LASSO) regression analysis, and the roles of these key genes in immune cell infiltration were explored through single-sample gene set enrichment analysis (ssGSEA). In addition, the diagnostic effectiveness of the key genes was verified by the receiver operating characteristic (ROC) curve, and drugs related to the key genes were predicted using databases. Finally, the expression levels of these key genes were verified through reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot experiments.</div></div><div><h3>Results</h3><div>A total of 667 DEGs were identified, and the enrichment analysis mainly involved cell adhesion molecules, T cell receptor signaling pathway, etc. Nineteen core genes were screened out from the five algorithms of Cytohubba, and LASSO regression analysis further determined four key genes <em>(IL7R, GZMH, CD3G,</em> and <em>UBD</em>). Immune cell infiltration analysis showed that these four key genes had high expression in immune cells. The prediction results of traditional Chinese medicine showed that 15 traditional Chinese medicines were related to the key genes. The results of RT-qPCR showed that the expressions of <em>IL7R</em>, <em>GZMH</em>, and <em>CD3G</em> were significantly upregulated (<sup>∗</sup><em>P</em> ​&lt; ​0.05, <sup>∗∗</sup><em>P</em> ​&lt; ​0.01, <sup>∗∗∗</sup><em>P</em> ​&lt; ​0.001), and Western blot showed obvious expressions of <em>IL7R</em>, <em>GZMH</em>, <em>CD3G</em>, and <em>UBD</em>.</div></div><div><h3>Conclusion</h3><div>This study used bioinformatics methods to explore the biomarkers of vitiligo, and verified the potential of <em>IL7R</em>, <em>GZMH</em>, and <em>CD3G</em> as novel candidate genes through <em>in vitro</em> experiments. These genes may become new targets for the diagnosis, prognosis, and treatment of vitiligo.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"6 2","pages":"Pages 224-234"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144631743","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
Integrating metabolism gene clusters and tumor immune microenvironment in head and neck squamous cell carcinoma 头颈部鳞状细胞癌整合代谢基因簇与肿瘤免疫微环境研究
Pub Date : 2025-06-01 Epub Date: 2025-07-15 DOI: 10.1016/j.jhip.2025.06.006
Meina Lian , Xiaoxia Wang , Zixian Huang , Yudong Wang , Zhiquan Huang

Objective

To investigate the relationship between tumor metabolism and immune cell infiltration in Head and Neck Squamous Cell Carcinoma (HNSCC), aiming to identify novel biomarkers and potential therapeutic targets.

Methods

Seven major metabolic pathways were analyzed using Gene Set Variation Analysis (GSVA) in HNSCC cohorts to assess their correlation with overall survival (OS) and immune microenvironment characteristics. Unsupervised clustering was applied to identify metabolic subtypes, and differentially expressed metabolism-related genes (MRGs) were screened for prognostic relevance. A risk model was constructed based on 16 core MRGs. TNFAIP6 was further evaluated for its functional role through in vitro assays, including proliferation, migration, and invasion analyses.

Results

The activity of key metabolic pathways, such as glycolysis, oxidative phosphorylation, and fatty acid metabolism, significantly correlated with OS and immune infiltration patterns. Two distinct metabolic clusters (C1 and C2) were identified, with C1 associated with a more immune-enriched microenvironment. A total of 698 MRGs were linked to immune modulation and tumor progression. The risk model based on 16 MRGs effectively stratified patients by prognosis and immune infiltration status. TNFAIP6 was highly expressed in malignant cells and associated with immunosuppression, poor survival, and tumor progression. Functional experiments confirmed that TNFAIP6 knockdown inhibited tumor cell proliferation, migration, and invasion.

Conclusion

Metabolic reprogramming plays a critical role in shaping the immune landscape of HNSCC. TNFAIP6 represents a promising prognostic biomarker and potential therapeutic target for improving personalized treatment in HNSCC patients.
目的探讨头颈部鳞状细胞癌(HNSCC)肿瘤代谢与免疫细胞浸润的关系,寻找新的生物标志物和潜在的治疗靶点。方法采用基因集变异分析(GSVA)分析HNSCC队列中7条主要代谢途径与总生存期(OS)和免疫微环境特征的相关性。应用无监督聚类来鉴定代谢亚型,并筛选差异表达的代谢相关基因(MRGs)以确定与预后的相关性。基于16个核心mrg构建风险模型。通过体外实验进一步评估TNFAIP6的功能作用,包括增殖、迁移和侵袭分析。结果糖酵解、氧化磷酸化和脂肪酸代谢等关键代谢途径的活性与OS和免疫浸润模式显著相关。鉴定出两个不同的代谢簇(C1和C2),其中C1与更免疫富集的微环境相关。共有698个MRGs与免疫调节和肿瘤进展有关。基于16个MRGs的风险模型根据预后和免疫浸润情况对患者进行了有效的分层。TNFAIP6在恶性细胞中高表达,与免疫抑制、生存差和肿瘤进展相关。功能实验证实,敲低TNFAIP6可抑制肿瘤细胞的增殖、迁移和侵袭。结论代谢重编程在HNSCC免疫景观的形成中起关键作用。TNFAIP6是一种有前景的预后生物标志物,也是改善HNSCC患者个性化治疗的潜在治疗靶点。
{"title":"Integrating metabolism gene clusters and tumor immune microenvironment in head and neck squamous cell carcinoma","authors":"Meina Lian ,&nbsp;Xiaoxia Wang ,&nbsp;Zixian Huang ,&nbsp;Yudong Wang ,&nbsp;Zhiquan Huang","doi":"10.1016/j.jhip.2025.06.006","DOIUrl":"10.1016/j.jhip.2025.06.006","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the relationship between tumor metabolism and immune cell infiltration in Head and Neck Squamous Cell Carcinoma (HNSCC), aiming to identify novel biomarkers and potential therapeutic targets.</div></div><div><h3>Methods</h3><div>Seven major metabolic pathways were analyzed using Gene Set Variation Analysis (GSVA) in HNSCC cohorts to assess their correlation with overall survival (OS) and immune microenvironment characteristics. Unsupervised clustering was applied to identify metabolic subtypes, and differentially expressed metabolism-related genes (MRGs) were screened for prognostic relevance. A risk model was constructed based on 16 core MRGs. TNFAIP6 was further evaluated for its functional role through <em>in vitro</em> assays, including proliferation, migration, and invasion analyses.</div></div><div><h3>Results</h3><div>The activity of key metabolic pathways, such as glycolysis, oxidative phosphorylation, and fatty acid metabolism, significantly correlated with OS and immune infiltration patterns. Two distinct metabolic clusters (C1 and C2) were identified, with C1 associated with a more immune-enriched microenvironment. A total of 698 MRGs were linked to immune modulation and tumor progression. The risk model based on 16 MRGs effectively stratified patients by prognosis and immune infiltration status. TNFAIP6 was highly expressed in malignant cells and associated with immunosuppression, poor survival, and tumor progression. Functional experiments confirmed that TNFAIP6 knockdown inhibited tumor cell proliferation, migration, and invasion.</div></div><div><h3>Conclusion</h3><div>Metabolic reprogramming plays a critical role in shaping the immune landscape of HNSCC. TNFAIP6 represents a promising prognostic biomarker and potential therapeutic target for improving personalized treatment in HNSCC patients.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"6 2","pages":"Pages 235-248"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144631749","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
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Journal of Holistic Integrative Pharmacy
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