Phytomedicine最新文献

{"title":"EGCG inhibits tobacco smoke-promoted proliferation of lung cancer cells through targeting CCL5","authors":"Zhiyuan Dong ,&nbsp;Jinyi Wu ,&nbsp;Liping He ,&nbsp;Chunfeng Xie ,&nbsp;Shanshan Geng ,&nbsp;Jieshu Wu ,&nbsp;Xiaoming Ji ,&nbsp;Xiong Chen ,&nbsp;Caiyun Zhong ,&nbsp;Xiaoting Li","doi":"10.1016/j.phymed.2025.156512","DOIUrl":"10.1016/j.phymed.2025.156512","url":null,"abstract":"<div><h3>Background</h3><div>The occurrence and development of cancer are deeply intertwined with chronic inflammatory processes. Epigallocatechin gallate (EGCG), the most pharmacologically potent catechin derived from tea, has garnered attention for its anti-inflammatory and anti-carcinogenic properties. However, the molecular mechanisms through which EGCG modulates tobacco smoke (TS)-induced inflammatory responses in lung carcinogenesis remain incompletely elucidated.</div></div><div><h3>Purpose</h3><div>To unravel the molecular mechanisms by which EGCG mitigates TS-induced inflammatory processes in lung carcinogenesis.</div></div><div><h3>Methods</h3><div>Network pharmacology analysis was conducted to explore the potential target genes of EGCG involved in the inhibition of TS-induced lung cancer inflammation. <em>In vitro</em> and <em>in vivo</em> experiments were conducted to demonstrate EGCG's chemopreventive potential against lung carcinogenesis.</div></div><div><h3>Results</h3><div>Utilizing data from the US adults, it was uncovered that tea consumption could suppress the inflammatory response in patients with various cancer types. CCL5 (chemokine (C<img>C motif) ligand 5) could function as a core regulator of TS-induced lung cancer cell proliferation, and EGCG exerted beneficial effects. The following experiments revealed that TS upregulated CCL5 expression in H1299 and H226 cells. CCL5 recombinant protein elevated both ROS production and Nrf2 expression to promote lung cancer cell proliferation. EGCG could suppress CCL5-stimulated lung cancer cell proliferation by downregulating Nrf2 expression. In the mouse model, EGCG reduced tumor weight and volume, diminished the levels of CCL5, Ki67, Cyclin D1, PCNA, and Nrf2, and elevated the expression of Keap1 relative to the control group.</div></div><div><h3>Conclusion</h3><div>EGCG targets CCL5 to inhibit the proliferation of TS-induced lung cancer cells and may serve as a new treatment strategy.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156512"},"PeriodicalIF":6.7,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143480481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in bioinformatic methods for the acceleration of the drug discovery from nature","authors":"Magdalena Maciejewska-Turska ,&nbsp;Milen I. Georgiev ,&nbsp;Guoyin Kai ,&nbsp;Elwira Sieniawska","doi":"10.1016/j.phymed.2025.156518","DOIUrl":"10.1016/j.phymed.2025.156518","url":null,"abstract":"<div><h3>Background</h3><div>Drug discovery from nature has a long, ethnopharmacologically-based background. Today, natural resources are undeniably vital reservoirs of active molecules or drug leads. Advances in (bio)informatics and computational biology emphasized the role of herbal medicines in the drug discovery pipeline.</div></div><div><h3>Purpose</h3><div>This review summarizes bioinformatic approaches applied in recent drug discovery from nature.</div></div><div><h3>Study design</h3><div>It examines advancements in molecular networking, pathway analysis, network pharmacology within a systems biology framework and AI for assessing the therapeutic potential of herbal preparations.</div></div><div><h3>Methods</h3><div>A comprehensive literature search was conducted using Pubmed, SciFinder, and Google Database. Obtained data was analyzed and organized in subsections: AI, systems biology integrative approach, network pharmacology, pathway analysis, molecular networking, structure-based virtual screening.</div></div><div><h3>Results</h3><div>Bioinformatic approaches is now essential for high-throughput data analysis in drug target identification, mechanism-based drug discovery, drug repurposing and side-effects prediction. Large datasets obtained from “omics” approaches require bioinformatic calculations to unveil interactions, and patterns in disease-relevant conditions. These tools enable databases annotations, pattern-matching, connections discovery, molecular relationship exploration, and data visualisation.</div></div><div><h3>Conclusion</h3><div>Despite the complexity of plant metabolites, bioinformatic approaches assist in characterization of herbal preparations and selection of bioactive molecule. It is perceived as powerful tool for uncovering multi-target effects and potential molecular mechanisms of compounds. By integrating multiple networks that connect gene-disease, drug-target and gene-drug-target, drug discovery from natural sources is experiencing a remarkable comeback.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156518"},"PeriodicalIF":6.7,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143480483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Berberine protects against dysentery by targeting both Shigella filamentous temperature sensitive protein Z and host pyroptosis: Resolving in vitro–vivo effect discrepancy","authors":"Xiangyin Chi ,&nbsp;Jinwen Ding ,&nbsp;Yu Zhang,&nbsp;Ying Chen,&nbsp;Yanxing Han,&nbsp;Yuan Lin,&nbsp;Jiandong Jiang","doi":"10.1016/j.phymed.2025.156517","DOIUrl":"10.1016/j.phymed.2025.156517","url":null,"abstract":"<div><h3>Background</h3><div>Berberine (BBR), an isoquinoline alkaloid, has been applied clinically to treat dysentery caused by <em>Shigella</em> for decades. Nevertheless, the precise mechanisms behind its anti-<em>Shigella</em> effect have not been fully elucidated.</div></div><div><h3>Purpose</h3><div>This study aims to investigate the mechanism of BBR on antibacterial activity against <em>S. flexneri</em> infection.</div></div><div><h3>Methods</h3><div>We initially reproduced the mouse model of <em>Shigella flexneri</em>-induced dysentery, and then, assessed the therapeutic effect of BBR. <em>In vitro</em>, we measured the inhibitory effect of BBR against <em>S. flexneri</em> and the GTPase activity of FtsZ (filamentous temperature sensitive protein Z) using the minimum inhibitory concentration (MIC) test and an enzyme activity assay to investigate the bacteria-directed mechanisms. Subsequently, we utilized both the <em>in vivo</em> mouse model of dysentery and the <em>in vitro</em> macrophage infection model with <em>S. flexneri</em> to explore the host-directed anti-<em>Shigella</em> mechanisms of BBR. The canonical pyroptosis pathway mediated by caspase-1 and mitochondrial damage were examined by Western blot, immunofluorescence and RNA interference analysis.</div></div><div><h3>Results</h3><div>Administration of BBR alleviated the symptoms of dysentery induced by <em>S. flexneri</em> infection. <em>In vitro</em>, BBR could inhibit the growth of <em>S. flexneri</em> by targeting the GTPase activity of FtsZ, thereby affecting bacterial cell division. Additionally, our <em>in vivo</em> findings revealed that BBR suppressed macrophage pyroptosis by inhibiting the expression of caspase-1 and subsequently the mitochondrial damage, which in turn reduced the intestinal inflammation and tissue damage.</div></div><div><h3>Conclusions</h3><div>Our results provide a novel mechanism of BBR's action, which targets both the bacterium and the host to exert its antibacterial effects. Furthermore, it also provides an explanation for the discrepancy between BBR's relatively modest antibacterial efficacy <em>in vitro</em> and its enhanced antibacterial effects <em>in vivo</em>, thus, giving support to its clinical use.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156517"},"PeriodicalIF":6.7,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143463537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effects and mechanisms of aqueous Persicaria capitata extract on uropathogenic Escherichia coli adhesion","authors":"Yang Zhou ,&nbsp;Zuying Zhou ,&nbsp;Lin Jin ,&nbsp;Yue Peng ,&nbsp;Jingwen Tang ,&nbsp;Aimin Wang ,&nbsp;Meng Zhou ,&nbsp;Yueting Li ,&nbsp;Lin Zheng ,&nbsp;Yong Huang","doi":"10.1016/j.phymed.2025.156515","DOIUrl":"10.1016/j.phymed.2025.156515","url":null,"abstract":"<div><h3>Background</h3><div>Urinary tract infections (UTIs) in humans are common, with uropathogenic <em>Escherichia coli</em> (UPEC) being the primary pathogen. The adhesive capabilities of UPEC are a substantial pathogenicity factor. Due to limitations of first-line antibiotics, <em>Persicaria capitata</em> (Buch.-Ham. ex D. Don) H. Gross, a traditional Chinese medicinal plant, is frequently used to treat various urological disorders. However, its mechanism regarding bacterial adhesion, remain unclear.</div></div><div><h3>Purpose</h3><div>To investigate the effects and mechanisms of action of aqueous <em>P. capitata</em> extracts (PCE) on UPEC adhesion in T24 cells and rat models.</div></div><div><h3>Methods</h3><div>Broth microdilution and growth experiments were used to explore the direct antibacterial effects of PCE on UPEC. Additionally, motility assays were conducted. Different microscopy methods were used to further examine the mechanisms of action. Transcriptomic analysis and RT-qPCR were used to explore mechanisms on a molecular level. Relevant molecules were assessed using western blotting and immunohistochemistry.</div></div><div><h3>Results</h3><div>PCE modulated UPEC motility by disrupting the fimbriae and flagella. UPEC pathways, including those essential for constructing fimbriae and flagella, and bacterial motility, were affected. PCE reduced UPEC adhesion and invasion of T24 cells, altering the protein expression of adhesion-related molecules, by modulating the secretion of extracellular vesicles (EVs). It improved blood and urine parameters, reduced inflammatory markers, and ameliorated pathological changes in the kidneys and bladder of rats. Furthermore, the expression of adhesion-related molecules in bladder tissues decreased in the UTI rat model.</div></div><div><h3>Conclusions</h3><div>This study provides new insights into the mechanisms of herbal medicines in treating UTIs.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156515"},"PeriodicalIF":6.7,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143444799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of standardized lime peel supplement in adults with sleep disturbance: A randomized, double-blind, placebo-controlled, polysomnographic study","authors":"Seonghui Kim ,&nbsp;Min Young Um ,&nbsp;Jin-Kyu Han ,&nbsp;Duhyeon Kim ,&nbsp;Yunjin Choi ,&nbsp;Gibeom Choi ,&nbsp;Chaeyoung Bang ,&nbsp;Youngtaek Oh ,&nbsp;Jang H. Youn ,&nbsp;Suengmok Cho","doi":"10.1016/j.phymed.2025.156510","DOIUrl":"10.1016/j.phymed.2025.156510","url":null,"abstract":"<div><h3>Background</h3><div>Citrus peels are rich in flavonoids with potential sedative-hypnotic effects; however, these effects have not yet been fully explored. We previously demonstrated that, in mice, standardized lime peel supplement (SLPS) induced non-rapid eye movement sleep and shortened sleep latency through GABA_A receptors activation.</div></div><div><h3>Purpose and Study Design</h3><div>This study aimed to evaluate the effects of SLPS in adults experiencing sleep disturbances. The randomized, double-blind, placebo-controlled clinical trial involved 80 subjects who received either SLPS (300 mg/day) or placebo for a 2-week period.</div></div><div><h3>Results</h3><div>SLPS significantly improved polysomnographic outcomes, including a reduction in sleep latency, wake after sleep onset, and total wake time, and enhancement of sleep efficiency, total sleep time, and stage 2 sleep. Daytime sleepiness, assessed via the Epworth Sleepiness Scale, was also decreased by SLPS.</div></div><div><h3>Conclusion</h3><div>No serious adverse effects or side effects were reported among participants in the SLPS group during the intervention period. Our findings support SLPS as a potential natural sleep aid for improving sleep in adults with sleep disturbance.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156510"},"PeriodicalIF":6.7,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143436586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An effective strategy for exploring the taste markers in alum-processed Pinellia ternata tuber based on the analysis of substance and taste by LC-MS and electronic tongue","authors":"Jun-Li Kang ,&nbsp;Jia-Wei Wang ,&nbsp;Xiang-Dong Chen ,&nbsp;Qing Liu ,&nbsp;De-Quan Zhu ,&nbsp;Zhen-Yu Li ,&nbsp;Jing Li ,&nbsp;Xiao-Zhou Jia ,&nbsp;Li-Yuan Qu ,&nbsp;Dong-Mei Sun ,&nbsp;Hui Zhang ,&nbsp;Hua Zhou","doi":"10.1016/j.phymed.2025.156509","DOIUrl":"10.1016/j.phymed.2025.156509","url":null,"abstract":"<div><h3>Objective</h3><div>To explore the taste-related quality markers of Qingbanxia, the alum-processed <em>Pinellia ternata</em> tuber.</div></div><div><h3>Methods</h3><div>Eighteen samples of Banxia and Qingbanxia were analyzed by the Ultra-High Performance Liquid Chromatography coupled with Q-Exactive Orbitrap Mass Spectrometry. Data of all samples were pre-processed by Compound Discoverer 3.3 Software. The discrimination was analyzed by Principal Component Aanalysis, and Orthogonal Partial Least-square Discriminant Analysis. The chemical markers were identified by MS/MS fragments based on the fragment rules. The electronic tongue was utilized to determine the taste traits of Banxia and Qingbanxia. Furthermore, the taste-related material basis was discovered according to correlation analysis and molecular docking.</div></div><div><h3>Results</h3><div>Sixteen potential chemical markers of Banxia and Qingbanxia were identified. Lauryldiethanolamine is a unique bitter component. The taste spectrum of bitterness, sourness and umami changes significantly during the processing of Banxia, with sourness increasing and bitterness and umami decreasing.</div></div><div><h3>Conclusion</h3><div>A new approach to explore the taste-related quality markers in alum-processed Banxia was established for the first time based on the Orbitrap MS technology and electronic tongue technology. The bitterness chemical markers were identified for the first time. The mechanism of the sourness of Qingbanxia was clarified. The identification of taste-related quality markers and the generation of comprehensive taste profiles offer an objective and reproducible method for assessing processing efficacy, overcoming the limitations of traditional subjective taste tests. These findings have significant implications for the quality control of Banxia and other traditional Chinese medicine.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156509"},"PeriodicalIF":6.7,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143463539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gastrodin targets the system Xc-/GPX4 axis to inhibit abnormal proliferation of fibroblast-like synoviocytes and improve rheumatoid arthritis","authors":"Yanlu Li ,&nbsp;Aoyun Li ,&nbsp;Yanchao Xing ,&nbsp;Yingshan Jiang ,&nbsp;Hongyan Pei ,&nbsp;Zhongmei He ,&nbsp;Jianming Li ,&nbsp;Yan Zhao ,&nbsp;Kun Shi ,&nbsp;Ying Zong ,&nbsp;Rui Du","doi":"10.1016/j.phymed.2025.156493","DOIUrl":"10.1016/j.phymed.2025.156493","url":null,"abstract":"<div><h3>Background</h3><div>Rheumatoid Arthritis (RA) is a chronic autoimmune disease characterized by the abnormal proliferation of Fibroblast-like Synoviocytes (FLS), leading to synovial hyperplasia and progressive joint destruction in an inflammatory environment. Gastrodin (GAS), the main active ingredient of Gastrodia elata, is also the basis for its anti-inflammatory, anti-tumor, and other pharmacological effects. However, GAS's effects on RA and its specific molecular mechanisms remain to be thoroughly explored.</div></div><div><h3>Purpose</h3><div>This study combines transcriptomics and modern pharmacological methods to explore the molecular mechanism of GAS to ameliorate RA and provide a theoretical basis for the development of new therapeutic strategies for rheumatoid arthritis.</div></div><div><h3>Methods</h3><div>A rat adjuvant arthritis (AA) model was established to further determine the molecular mechanism by which GAS affects RA based on transcriptomics and molecular docking. The pharmacological activity of GAS against RA was evaluated by in vivo experiments such as micro-CT, histopathological examination, transmission electron microscopy and Elisa. Primary FLS cells were also extracted from AA rats for in vitro experiments to reveal the potential of GAS in treating RA.</div></div><div><h3>Results</h3><div>Transcriptomic and molecular docking analyses suggested ferroptosis as a potential mechanism for GAS to ameliorate RA. In vitro and in vivo studies demonstrated that GAS downregulates SLC7A11, impacts the antioxidant system, and inhibits GPX4. It facilitates lipopolysaccharide-induced ferroptosis in RA-FLS (rheumatoid arthritis fibroblast-like synoviocytes) cells, suppresses synovial proliferation, and ameliorates rheumatoid arthritis.</div></div><div><h3>Conclusion</h3><div>This study reveals the molecular mechanism of the anti-RA action of GAS from a novel perspective, suggesting that GAS is a promising drug candidate for the treatment of RA.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156493"},"PeriodicalIF":6.7,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143436489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sclareol improves the pathology of Alzheimer's disease by inhibiting microglial inflammation via interacting with CDK9","authors":"Hao Tang ,&nbsp;Luyao Li ,&nbsp;Qin Yu ,&nbsp;Linjie Chen ,&nbsp;Xiaoxia Xu ,&nbsp;Ziyao Meng ,&nbsp;Yuqing Zeng ,&nbsp;Fan Chen ,&nbsp;Hammad Muzaffar ,&nbsp;Wei Wang ,&nbsp;Xia Zhao ,&nbsp;Guang Liang","doi":"10.1016/j.phymed.2025.156504","DOIUrl":"10.1016/j.phymed.2025.156504","url":null,"abstract":"<div><h3>Background</h3><div>Excessive activation of microglia triggers pro-inflammatory responses, exacerbating neuronal damage and accelerating the progression of Alzheimer's disease (AD). Thus, targeting abnormal microglial activation represents a promising therapeutic strategy for AD. In this study, we identified sclareol (SCL) through compound library screening as a potent anti-inflammatory agent capable of crossing the blood-brain barrier. However, there are currently no reports on whether SCL modulates microglial inflammation or ameliorates AD pathology.</div></div><div><h3>Objective</h3><div>To evaluate the anti-inflammatory effects and underlying molecular mechanism of SCL on microglial-mediated inflammation and neuronal damage in AD.</div></div><div><h3>Methods</h3><div>Drug Affinity Responsive Target Stability (DARTS), Liquid Chromatography-Tandem Mass Spectrometry (LC-MS), protein interaction assays, Biolayer Interferometry (BLI), and molecular docking were used to explore the interaction between SCL and cyclin-dependent kinase 9 (CDK9). Behavioral tests and immunofluorescent (IF) staining were performed to assess the effects of SCL on microglial activation and AD pathology. The molecular mechanism of the anti-inflammatory effect of SCL was analyzed by interfering with CDK9.</div></div><div><h3>Results</h3><div>SCL significantly inhibited the release of proinflammatory mediators, reduced neuronal damage, and alleviated cognitive deficits in AD model mice. Notably, SCL demonstrated the ability to cross the blood-brain barrier (BBB), highlighting its therapeutic potential. Mechanistically, SCL binds directly to CDK9, which contributes to the inflammatory response through its interaction with NF-κB. Knockdown of CDK9 reduced the NF-κB-mediated inflammatory response, but did not have an additive effect on SCL, indicating that SCL's efficacy is mediated by CDK9 inhibition and subsequent suppression of the NF-κB signaling pathway.</div></div><div><h3>Conclusion</h3><div>This study demonstrates that SCL exerts neuroprotective effects in AD mice by targeting CDK9 and downstream NF-κB signaling pathway to reduce the inflammatory activation of microglia. These findings suggest that SCL is a promising candidate for the treatment of AD, offering a novel therapeutic approach to mitigate disease progression through modulation of microglial activation.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156504"},"PeriodicalIF":6.7,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143429206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"6′-O-caffeoylarbutin of Vaccinium dunalianum alleviated ischemic stroke through the PI3K/AKT/NF-κB pathway","authors":"Zhuo-Qi Shi ,&nbsp;Xi Wen ,&nbsp;Xian-Run Wu ,&nbsp;Hui-Zhen Peng ,&nbsp;Yan-Ling Qian ,&nbsp;Yun-Li Zhao ,&nbsp;Xiao-Dong Luo","doi":"10.1016/j.phymed.2025.156505","DOIUrl":"10.1016/j.phymed.2025.156505","url":null,"abstract":"<div><h3>Background</h3><div><em>Vaccinium dunalianum</em> (“Que Zui Tea”) has been traditionally consumed as a tea substitute in Yunnan, China, for its health benefits, <em>i.e.</em>, improving vascular health. 6′-O-caffeoylarbutin (CA) is its major bioactive compound (∼20 %). However, the potential of CA against ischemic stroke remains unknown.</div></div><div><h3>Purpose</h3><div>This study explores the protective properties of CA in ischemic stroke, providing empirical support for the folk use of the plant and further drug development.</div></div><div><h3>Methods</h3><div>An oxygen-glucose deprivation/reoxygenation (OGD/R)-induced BV2 cells were utilized to identify potential bioactive compounds. Moreover, the pathway and targets were predicted and further verified in OGD/R-induced microglia, nerve cells and in mice of middle cerebral artery occlusion.</div></div><div><h3>Results</h3><div>CA effectively reduced nitric oxide (NO) release and transcript-level expression of inflammatory factors in OGD/R-stimulated BV2 cells. NF-κB1, IL-6, AKT1, CASP3, and MMP9 were identified as key CA targets for ischemic stroke treatment. In silico predictions suggested that phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PI3K/AKT), mitogen-activated protein kinase (MAPK), and tumor necrosis factor (TNF) were the relevant pathways. These predictions were supported <em>in vitro</em> by an observed decrease in NO, reactive oxygen species, lactate dehydrogenase, and inflammatory cytokines (IL-6, IL-1β, and TNF-α) levels following CA treatment<em>.</em> Western blotting confirmed the regulation of p-IκBα, P65, AKT, and apoptosis-related proteins (further confirmed by PI3K inhibitor LY294002 treatment). These findings were further supported <em>in vivo</em>, with CA ameliorating neurological functions and deficits in ischemic mice. This amelioration correlated with increased cerebral blood flow, and alleviated neuron wrinkling, necrosis, and cell shrinkage. CA also increased brain superoxide dismutase, catalase, and glutathione peroxidase levels.</div></div><div><h3>Conclusion</h3><div>CA exerts neuroprotective effects in ischemic stroke by inhibiting inflammation and oxidative stress through the PI3K/AKT/NF-κB pathway, suggesting its therapeutic potential for cerebral ischemia and supporting the traditional use of <em>V. dunalianum</em>.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156505"},"PeriodicalIF":6.7,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143444798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Panax notoginseng saponins ameliorate LPS-induced acute lung injury by promoting STAT6-mediated M2-like macrophage polarization","authors":"Xunjiang Wang ,&nbsp;Hanyang Zhao ,&nbsp;Wenyuan Lin ,&nbsp;Wenxiang Fan ,&nbsp;Tongxi Zhuang ,&nbsp;Xu Wang ,&nbsp;Qi Li ,&nbsp;Xiaohui Wei ,&nbsp;Zhengtao Wang ,&nbsp;Kaixian Chen ,&nbsp;Li Yang ,&nbsp;Lili Ding","doi":"10.1016/j.phymed.2025.156513","DOIUrl":"10.1016/j.phymed.2025.156513","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Acute lung injury (ALI) is a severe inflammatory condition characterized by dysregulated immune responses and high mortality rates, with limited effective therapeutic options currently available. Panax notoginseng saponins (PNS), bioactive compounds derived from &lt;em&gt;Panax notoginseng&lt;/em&gt;, have shown promise in mitigating lipopolysaccharide (LPS)-induced ALI. However, the molecular mechanisms underlying their therapeutic effects remain poorly understood. Given the critical role of M2-like macrophage polarization in resolving inflammation and promoting tissue repair, we investigated whether PNS exerts its protective effects in ALI by modulating this process. Furthermore, we explored the specific involvement of the signal transducer and activator of transcription 6 (STAT6) pathway in mediating these effects.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Chemical profiling of PNS was performed using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS), followed by quantitative analysis of its major bioactive components &lt;em&gt;via&lt;/em&gt; high-performance liquid chromatography (HPLC). To evaluate the therapeutic efficacy of PNS and its principal constituents, we established an ALI mouse model through intratracheal administration of LPS. Comprehensive assessments included lung field shadowing, oxygen saturation levels, pulmonary function, and systematic histopathological examination. The regulatory effects of PNS on macrophage polarization were examined in THP-1 cells and bone marrow-derived macrophages (BMDMs), with cellular phenotypes analyzed by flow cytometry. To elucidate the mechanistic role of STAT6 in PNS-mediated protection, experiments were conducted using &lt;em&gt;Stat6&lt;/em&gt;-deficient BMDMs and &lt;em&gt;Stat6&lt;/em&gt; knockout mice.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;UPLC-Q-TOF-MS and HPLC identified and quantified the principal components of PNS: Notoginsenoside R1, Ginsenoside Rg&lt;sub&gt;1&lt;/sub&gt;, Ginsenoside Re, and Ginsenoside Rb&lt;sub&gt;1&lt;/sub&gt;. PNS treatment dose-dependently reduced inflammatory responses in LPS-induced ALI mice, as evidenced by decreased cytokine levels. Each of the four major PNS components independently alleviated ALI symptoms in mice. Pathway analysis revealed 56 potential ALI-related targets, with Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment suggesting that PNS exerts its protective effects by modulating inflammatory signaling pathways. &lt;em&gt;In vitro&lt;/em&gt; studies demonstrated that PNS promoted STAT6 phosphorylation and nuclear translocation, enhancing M2-like macrophage polarization and interleukin-10 (IL-10) secretion in a STAT6-dependent manner. Genetic ablation of &lt;em&gt;Stat6&lt;/em&gt; partially reversed the protective effects of PNS on ALI, macrophage polarization, and IL-10 production, confirming the pivotal role of STAT6 in mediating PNS activity.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;This study demonstrates that PNS alleviates LPS-induced ALI by promoting STAT","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156513"},"PeriodicalIF":6.7,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143480482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}