Phytomedicine最新文献

{"title":"Linarin attenuates hyperuricemic nephropathy by modulating Nrf2/Keap1 and TLR4/NF-κB signaling pathways","authors":"Yongshuai Qian ,&nbsp;Yan Zhang ,&nbsp;Yue Chen ,&nbsp;Xiaofei Wang ,&nbsp;Li Liu ,&nbsp;Huifan Yu ,&nbsp;Zhengkun Wu ,&nbsp;Lili Gui ,&nbsp;Xuelai He ,&nbsp;Linsheng Huang ,&nbsp;Han Luo ,&nbsp;Mao Xu ,&nbsp;Ying Jiang ,&nbsp;Fei Li","doi":"10.1016/j.phymed.2025.156440","DOIUrl":"10.1016/j.phymed.2025.156440","url":null,"abstract":"<div><h3>Background</h3><div>Hyperuricemia (HUA) can lead to hyperuricemic nephropathy (HN) as a result of prolonged uric acid (UA) supersaturation, primarily characterized by excessive inflammation and oxidative stress. In clinical practice, the absence of specific drugs for HN treatment necessitates the use of urate-lowering drugs, despite their lack of reno-protective properties. Linarin, the principal pharmacological constituent of <em>Chrysanthemum indicum</em> L. (<em>C. indicum</em> L.), exhibits diverse bioactivities, including anti-inflammatory, antioxidant, and nephroprotective effects. However, there have been no reports on linarin's ability to mitigate HN, and the underlying mechanisms remain unexplored.</div></div><div><h3>Purpose</h3><div>This study aimed to investigate the mechanisms of linarin on ameliorating HN, with a particular emphasis on oxidative stress and inflammatory pathways.</div></div><div><h3>Methods</h3><div>A HUA mouse model was developed using male ICR mice treated with hypoxanthine and potassium oxonate. Additionally, an adenosine-induced hyperuricemic cell model was established in NRK-52E cells. Following linarin treatment, serum UA levels and renal function parameters were assessed. The expression of proteins associated with UA production and excretion, oxidative stress, inflammation, and apoptosis was evaluated using western blot, immunohistochemical, and immunofluorescence analyses. Furthermore, <em>Nrf2</em> knockout mice and Nrf2 inhibitor ML385 were utilized to investigate the mechanism of linarin on improving HN.</div></div><div><h3>Results</h3><div>Linarin significantly decreased the serum UA levels, inhibited XO activity and regulated UA transporter in the HUA mice. Moreover, linarin reversed the renal index, serum BUN and Cr levels, along with the expression levels of KIM-1, apoptosis-related molecules. Additionally, linarin obviously reduced the levels of TNF-α, IL-1β and IL-6, and alleviated renal inflammatory via suppressing the TLR4, p-NF-κB and p-IκBα levels. Furthermore, linarin was able to reverse the levels of SOD and MDA, and the expression of Nrf2, Keap1, NQO1, and HO-1 to mitigate oxidative stress both <em>in vitro</em> and <em>in vivo</em>. Inhibition of Nrf2 further confirmed that the renoprotective effect of linarin was linked to the activation of Nrf2.</div></div><div><h3>Conclusion</h3><div>This study is the first to propose linarin as a potential natural compound for alleviating HN by modulating the Nrf2/Keap1 and TLR4/NF-κB signaling pathways, providing a promising strategy for HN.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156440"},"PeriodicalIF":6.7,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143099393","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":"Proteomic analysis reveals QiShenYiQi Pills ameliorates ischemia-induced heart failure through inhibition of mitochondrial fission","authors":"Jia Li ,&nbsp;Xinyao Zhang ,&nbsp;Liuqing Hou ,&nbsp;Bo-Yu Liu ,&nbsp;Yuan-Ming Fan ,&nbsp;Yajun Zhang ,&nbsp;Feizuo Wang ,&nbsp;Keke Jia ,&nbsp;Xiang Li ,&nbsp;Zongxiang Tang ,&nbsp;Xiaojian Yin","doi":"10.1016/j.phymed.2025.156435","DOIUrl":"10.1016/j.phymed.2025.156435","url":null,"abstract":"<div><h3>Background</h3><div>QiShenYiQi Pills (QSYQ) has widely used in clinical treatment of cardiovascular diseases; however, the exact mechanism behind its effectiveness still requires further investigation.</div></div><div><h3>Purpose</h3><div>The purpose of the study was to explore the potential mechanism of QSYQ in the treatment of ischemic heart failure from the perspective of proteomics.</div></div><div><h3>Methods</h3><div><em>In vivo</em><strong>,</strong> to observe QSYQ actions on the progression of ischemia-induced heart failure, cardiac function and remodeling was analyzed. The heart tissues of mice were used for Tandem Mass Tag (TMT)-based proteomic analysis. Cardiomyocytes were prepared and subjected to oxygen-glucose deprivation injury. QSYQ effects on differential proteins expressions, mitochondrial fission and mitochondrial function were assayed.</div></div><div><h3>Results</h3><div>QSYQ treatment preserved cardiac function, limited cardiac fibrosis and alleviated cardiomyocyte hypertrophy in post-myocardial ischemia mice. Proteomic analysis revealed that QSYQ-responsive proteins were mainly involved in mitochondrial fission, including mitochondrial calcium uniporter (MCU), membrane associated ring-CH-type finger 5 (MARCHF5), and mitochondrial fission process 1 (MTFP1). Protein-protein interaction analysis revealed that MCU, MARCHF5 and MTFP1 commonly interacted with dynamin-related protein 1 (DRP1). Knockdown of MCU, MARCHF5, or MTFP1 attenuated excessive mitochondrial fission in cardiomyocytes through regulating DRP1 phosphorylation and its mitochondrial translocation. QSYQ decreased the phosphorylation of DRP1 at Ser616 and enhanced its inhibitory phosphorylation at Ser637, as well as mitigating the mitochondrial recruitment and oligomerization of DRP1, through downregulation of these three differential proteins. As a result, QSYQ alleviated aberrant mitochondrial fission, ameliorated mitochondrial dysfunction, and protected cardiomyocytes from ischemic injury.</div></div><div><h3>Conclusion</h3><div>The novelty lies in the proteomics-based investigation of the mechanism of QSYQ, uncovering that QSYQ mitigated ischemia-induced heart failure by suppressing MCU/MARCHF5/MTFP1-DRP1-driven mitochondrial fission.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"Article 156435"},"PeriodicalIF":6.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075182","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":"Zhuyu pill attenuates metabolic-associated fatty liver disease by regulating macrophage polarization through TLR4 signaling pathway","authors":"Mei Zhao ,&nbsp;Qingman He ,&nbsp;Xinyao Shu ,&nbsp;Ruitong Xu ,&nbsp;Zhongyi Zhang ,&nbsp;Yu Mou ,&nbsp;Wenhao Liao ,&nbsp;Yong Zhang ,&nbsp;Zubing Zhou ,&nbsp;Tao Shen","doi":"10.1016/j.phymed.2025.156439","DOIUrl":"10.1016/j.phymed.2025.156439","url":null,"abstract":"<div><h3>Background</h3><div>Metabolic-associated fatty liver disease (MAFLD) is the leading chronic liver disease globally, impacting a large segment of the population. The Zhuyu Pill (ZYP), a traditional Chinese remedy, has been clinically used for treating MAFLD, with its effectiveness demonstrated in both human patients and animal models. However, the underlying mechanisms of how ZYP addresses MAFLD still require further investigation.</div></div><div><h3>Objective</h3><div>This study investigated the molecular mechanism of ZYP in treating MAFLD through both <em>in vivo</em> and <em>vitro</em> methods.</div></div><div><h3>Methods</h3><div>A murine MAFLD model was induced by a high-fat, high-fructose diet for 12 weeks. ZYP was administered for 4 weeks, with fenofibrate serving as a positive control. Indicators of lipid metabolism in serum and liver tissue were detected by automatic biochemical analyzer and ELISA, respectively. Histopathological evaluation of liver sections was performed using HE and oil red O staining. Transcriptomics was employed to further investigate the therapeutic mechanism of ZYP in MAFLD. Additionally, macrophages and their polarization in the liver were analyzed using ELISA, flow cytometry, immunohistochemistry, and immunofluorescence (IF). Candidate proteins and pathways were validated <em>in vivo</em> and <em>in vitro</em> by western blotting and IF. Validation of the pathway was performed in <em>vitro</em> using inhibitors and co-culture strategies.</div></div><div><h3>Results</h3><div>ZYP significantly improved obesity and hepatic steatosis in MAFLD mice, reducing body/liver weight and regulating lipid metabolism indicators in serum and liver tissue. Bioinformatics analysis of transcriptomic data highlighted lipid metabolism regulation and inflammation control as key effects of ZYP in treating MAFLD. The <em>in vivo</em> experimental results showed that ZYP inhibited M1 polarization of macrophages (pro-inflammatory) and promoted M2 polarization of macrophages (anti-inflammatory) in MAFLD mice. Further <em>in vivo</em> and <em>vitro</em> experiments indicated that ZYP competes with LPS to bind to Toll-like receptor 4 (TLR4), suppressing M1 polarization in liver macrophages, and improving MAFLD. The <em>in vitro</em> co-culture system also confirmed that ZYP reduces liver lipid deposition by modulating M1 macrophage polarization.</div></div><div><h3>Conclusions</h3><div>ZYP alleviates MAFLD by inhibiting M1 polarization of liver macrophages, indicating that ZYP may be a promising treatment for MAFLD. Its mechanism of action is to inhibit the TLR4/MyD88/TRAF6 signaling pathway, modulate macrophage polarization, and improve inflammatory response.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"Article 156439"},"PeriodicalIF":6.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075195","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":"AMP1-1 alleviates bone loss in weightless rats by reducing peripheral 5-HT content via the microbiota-gut-bone axis","authors":"Fan Yang ,&nbsp;Qiuxin Yan ,&nbsp;Yunhao Wang,&nbsp;Qiao Li,&nbsp;Jinpeng Wang,&nbsp;Xiangyin Zeng,&nbsp;Yaning Pi,&nbsp;Manrui Zhang,&nbsp;Lijun Wei","doi":"10.1016/j.phymed.2025.156447","DOIUrl":"10.1016/j.phymed.2025.156447","url":null,"abstract":"<div><h3>Background</h3><div>Weightlessness-induced bone loss (WIBL) refers to the reduction of bone mass and the decline of bone resistance to load in a weightless environment. However, current treatment strategies aimed at increasing bone mass are associated with various limitations and side effects, highlighting the urgent need for safer and more effective therapeutic options to address WIBL.</div></div><div><h3>Purpose</h3><div>We aimed to further explore the potential mechanism of the anti-WIBL effect of <em>Atractylodes macrocephalon</em> polysaccharide1-1(AMP1-1). To find a better way to treat WIBL and provide new insights for the development of therapeutic drugs for this condition.</div></div><div><h3>Methods</h3><div>Firstly, the anti-weightlessness bone loss of AMP1-1 was verified by micro‐computed tomography (Micro-CT), three-point mechanical bending test and Western Blot (WB). Subsequently, the intestinal barrier was examined using histopathology, immunohistochemistry (IHC), and WB. Finally, validation experiments were performed using fecal microbiota transplantation (FMT). After FMT, 16S rDNA sequencing was used to analyze the gut microbiota composition in the rat feces.</div></div><div><h3>Results</h3><div>AMP1-1 was able to inhibit WIBL by enhancing bone mass, improving toughness, and increasing osteogenic activity. Meanwhile, AMP1-1 reduced peripheral 5-HT content by restoring enterochromaffin cell function through gut microbiota regulation and tight junction repair. FMT of rat fecal microbiota after gavage of AMP1-1 into tail suspension rats still has the effects of regulating gut microbiota, repairing intestinal barrier and reducing bone loss.</div></div><div><h3>Conclusion</h3><div>Our results demonstrate that AMP1-1 exerts a protective effect against WIBL in rats, potentially by modulating 5-HT content and 5-HT-related metabolism in bone tissue through microbiota-gut-bone axis. This study is the first to elucidate the mechanism of AMP1-1 in mitigating WIBL through the perspective of the microbiota-gut-bone axis. Moreover, this research integrates plant extract research with the issue of bone loss induced by microgravity (aerospace medicine), thereby opening new avenues for natural drug research.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156447"},"PeriodicalIF":6.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143350492","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":"Corrigendum to \"Jiawei Buzhong Yiqi Decoction attenuates polycystic ovary syndrome through regulating kisspeptin-GPR54-AKT-SHBG system\" [Phytomedicine 133C (2024) 155931 Online ahead of print].","authors":"Runan Hu, Yuli Geng, Yanjing Huang, Zhuo Liu, Fan Li, Kunkun Song, Wenwen Ma, Haoxu Dong, Mingmin Zhang, Ting Lei, Yufan Song, Zhuo Zhang","doi":"10.1016/j.phymed.2025.156415","DOIUrl":"https://doi.org/10.1016/j.phymed.2025.156415","url":null,"abstract":"","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":" ","pages":"156415"},"PeriodicalIF":6.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067419","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":"Unveiling polysaccharides of Houttuynia cordata Thunb.: Extraction, purification, structure, bioactivities, and structure–activity relationships","authors":"Shiyong Gao ,&nbsp;Weiya Wang ,&nbsp;Jianwen Li ,&nbsp;Yue Wang ,&nbsp;Yanmin Shan ,&nbsp;Huixin Tan","doi":"10.1016/j.phymed.2025.156436","DOIUrl":"10.1016/j.phymed.2025.156436","url":null,"abstract":"<div><h3>Background</h3><div><em>Houttuynia cordata</em> Thunb. is a plant valued for both its culinary and medicinal properties, utilized in the prevention and treatment of various ailments. <em>Houttuynia cordata</em> Thunb. polysaccharides (HCP) exhibit a range of biological activities, including antioxidant, immune modulation, anti-inflammatory, antiviral, maintenance of gut homeostasis, and antibacterial effects, rendering them significant for research in ethnopharmacology.</div></div><div><h3>Purpose</h3><div>This review consolidates recent advancements in the extraction, isolation, purification, structural characteristics, and biological activities of <em>Houttuynia cordata</em> Thunb. polysaccharides, while exploring the structure-activity relationships of HCP and the prospects for future research, thereby providing valuable insights for its drug development.</div></div><div><h3>Methods</h3><div>Relevant literature regarding the extraction, isolation, purification, structural analysis, and biological activities of <em>Houttuynia cordata</em> Thunb. polysaccharides was sourced from databases such as PubMed, ScienceDirect, Web of Science, and CNKI.</div></div><div><h3>Results</h3><div><em>Houttuynia cordata</em> Thunb. is a perennial herbaceous plant that thrives in shady, humid environments and exhibits a semi-prostrate growth form. As a traditional herb used for heat-clearing and detoxification, it is effective against various conditions, including cholera, dysentery, and hemorrhoids. <em>Houttuynia cordata</em> Thunb. polysaccharides are key active components that can be extracted through various methods, including water extraction, enzymatic extraction, ultrasonic-assisted extraction, acid extraction, and alkali extraction. Structural analyses of the extracted and purified polysaccharides were conducted, focusing on their monosaccharide composition, molecular weight, and glycosidic bond structure. Additionally, pharmacological investigations reveal that <em>Houttuynia cordata</em> Thunb. polysaccharides possess a variety of biological activities, including antioxidant, immune modulation, antiviral, anti-inflammatory, maintenance of gut homeostasis, and antibacterial effects.</div></div><div><h3>Conclusions</h3><div>Research on HCP has established a solid foundation regarding its monosaccharide composition, molecular weight, and glycosidic linkages, with substantial documentation of its biological activities, including antioxidant, immune-regulating, and antiviral properties. However, investigations into the structural modification of HCP and the correlation between its structure and biological activity remain relatively underexplored. Additionally, the extraction yield of HCP is significantly affected by the choice of extraction and purification methods, highlighting the necessity for further optimization of extraction protocols.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"Article 156436"},"PeriodicalIF":6.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143101724","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":"Glycyrol alleviates osteoporosis through dual modulation on osteoclastogenesis and osteogenesis by targeting Syk signaling pathway","authors":"Lihua Tan ,&nbsp;Yanbei Tu ,&nbsp;Zhimin Miao ,&nbsp;Yuxin Zhao ,&nbsp;Yongkai Liang ,&nbsp;Jinmiao Zhong ,&nbsp;Ruting Zhong ,&nbsp;Nan Xu ,&nbsp;Xin Chen ,&nbsp;Chengwei He","doi":"10.1016/j.phymed.2025.156429","DOIUrl":"10.1016/j.phymed.2025.156429","url":null,"abstract":"<div><h3>Background</h3><div>Osteoporosis, characterized by an imbalance between osteoclast-mediated bone resorption and osteoblast-mediated bone formation, has become a serious public health challenge worldwide. Glycyrol (GC) is a representative natural coumestan isolated from licorice that shows multiple pharmacological activities, but its anti-osteoporotic effect and underlying mechanisms remain unclear.</div></div><div><h3>Results</h3><div>GC significantly suppressed lipopolysaccharide-induced mouse bone loss and dexamethasone-induced zebrafish bone formation deficiency. Meanwhile, GC exhibited dual effects of inhibiting osteoclast formation and bone resorption, and stimulating osteoblast differentiation and mineralization. By combining kinomic screening assay, bioinformatics analysis and cellular target engagement validation, spleen tyrosine kinase (Syk) was identified as a key kinase target of GC. Subsequently, Syk was determined to play important roles in promoting osteoclast formation and impeding osteoblast differentiation. Interestingly, GC directly bound to the active cavity of Syk through hydrogen bonds and significantly inhibited its activity. Moreover, GC remarkably inhibited RANKL-induced activation of Syk/PLCγ2/Ca²⁺/NFATc1 and MAPK pathways in macrophages undergoing differentiation into osteoclasts.</div></div><div><h3>Conclusion</h3><div>These results demonstrated that GC exerted a dual regulation on osteoclastogenesis and osteogenesis and consequently alleviated osteoporosis through targeting Syk and its downstream signaling pathways. In addition, the current study emphasizes the key roles of Syk in bone resorption and formation, suggesting the application potential of Syk inhibitors for the management of bone diseases. Meanwhile, this study provides evidence supporting the development of GC or its derivatives as effective anti-resorptive and bone anabolic agents for the prevention or treatment of osteoporosis and other bone diseases.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"Article 156429"},"PeriodicalIF":6.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143101385","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":"Zyxin—a novel detrimental target, is inhibited by Saikosaponin A during allergic asthma","authors":"Haoyun Bai ,&nbsp;Yongjing Zhang ,&nbsp;Xinping Zhang ,&nbsp;Chenjia Li ,&nbsp;Mengyang Ma ,&nbsp;Jie Gao ,&nbsp;Tingting Deng ,&nbsp;Chang Gao ,&nbsp;Nan Wang","doi":"10.1016/j.phymed.2025.156434","DOIUrl":"10.1016/j.phymed.2025.156434","url":null,"abstract":"<div><h3>Background</h3><div>Allergic asthma is a heterogeneous disease involving numerous inflammatory cells. Mast cell (MC) plays a key role during allergic asthma. Saikosaponin A (SSA) inhibits MC activation and ameliorates allergic asthma, however, its underlying mechanism remains unclear. This study aims to identify SSA-binding proteins and reveal their functions.</div></div><div><h3>Methods</h3><div>C57BL/6J mice were used to establish allergic asthma models to evaluate therapeutic effect of SSA. Protein microarray, RNA-seq, surface plasmon resonance (SPR), and pull-down assay were used to explore and validate the binding proteins of SSA. The functions of Zyxin were explored by knockdown and overexpression in LAD2. Zyxin knockout mice were constructed to investigate the role of Zyxin in allergic asthma.</div></div><div><h3>Results</h3><div>SSA alleviates allergic asthma and inhibits MC activation. Zyxin was confirmed as a binding protein of SSA. <em>In vitro</em> experiments proved the crucial role of Zyxin in mast cell exocytosis. Zyxin Ser142/143 is phosphorylated during MC activation, which can be inhibited by SSA. <em>In vivo</em> studies showed that Zyxin expression in MC has detrimental effects, while its deficiency ameliorates allergic asthma.</div></div><div><h3>Conclusion</h3><div>Our results verified the detrimental effect of Zyxin in allergic asthma for the first time. We also innovatively demonstrated that SSA exerts inhibitory effects on MC activation and allergic asthma by directly binding to and inhibiting Zyxin phosphorylation.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"Article 156434"},"PeriodicalIF":6.7,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067389","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":"Screening effective-component compatibility from Jinshui Chenfei formula for silicosis treatment by serum-pharmacochemistry and feedback system control","authors":"Xinguang Liu ,&nbsp;Peng Zhao ,&nbsp;Liming Wang ,&nbsp;Jinyan Wu ,&nbsp;Wenrui He ,&nbsp;Yu Wei ,&nbsp;Hongrui Chen ,&nbsp;Jiansheng Li","doi":"10.1016/j.phymed.2025.156419","DOIUrl":"10.1016/j.phymed.2025.156419","url":null,"abstract":"<div><h3>Background</h3><div>The unclear chemical composition and mechanisms of action pose challenges for new drug development and quality control of traditional Chinese medicine (TCM) formulas. To address this, the concept of effective-component compatibility (ECC) was proposed to represent drug combination with equivalent efficacy to TCM formulas, along with clear composition and dosage. However, previous strategies for screening ECC have often overlooked the synergistic effects of its components.</div></div><div><h3>Purpose</h3><div>This study proposed a strategy integrating serum pharmacochemistry and feedback system control (FSC) to identify synergistic combinations as ECC of TCM formulas. The strategy was applied to identify the ECC of Jinshui Chenfei formula (JCF) for silicosis treatment.</div></div><div><h3>Methods</h3><div>A chemical library of JCF was constructed using ultra-high-performance liquid chromatography-quadrupole extractive orbitrap mass spectrometry (UHPLC-Q-Extractive Orbitrap MS). The library was then used to identify absorbed prototype compounds of JCF, and the serum levels of its main components were analyzed. Based on the primary absorbed prototypes, FSC was employed to screen the most effective synergistic combinations from JCF for inhibiting LPS- and IL-4-induced macrophage polarization. The pharmacological effects of ECC-JCF were further validated using a silica-induced silicosis mouse model, and its synergistic mechanisms were investigated through transcriptomics and molecular dynamic simulations.</div></div><div><h3>Results</h3><div>A total of 437 compounds were identified in JCF, with 203 absorbed prototypes detected following oral administration. After three rounds of FSC iterative screening, a synergistic combination of isoliquiritin (180 μg/ml/0.43 mM), glycyrrhizic acid (180 μg/ml/0.22 mM), and gallic acid (3.75 μg/ml/0.02 mM) significantly inhibited the expression of TNF-α, IL-1β, IL-6, CD206, and Arg-1 mRNA in mouse alveolar macrophages. This combination also protected lung tissues from alveolar collapse, inflammatory cell infiltration, fibroblast proliferation, and fibrous nodule formation. In addition, the combination improved alveolitis and fibrosis scores in silicosis mice, outperforming both the original JCF formula and the sum of individual components. The synergistic effects of these compounds may regulate targets in inflammation and fibrosis formation pathways.</div></div><div><h3>Conclusion</h3><div>This study identified an ECC of JCF with a well-defined composition and mechanism of action, facilitating the future development of JCF as a new drug. Compared with traditional ECC screening methods, this strategy reduces experimental workload while accounting for synergistic effects.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"Article 156419"},"PeriodicalIF":6.7,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067334","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":"Corrigendum to \"Z-Ligustilide Alleviates Atherosclerosis by Reconstructing Gut Microbiota and Sustaining Gut Barrier Integrity through Activation of Cannabinoid Receptor 2\" [Phytomedicine. 135(2024)156117].","authors":"Si-Jing Liu, Jiao-Jiao Fu, Zhen-Yue Liao, Yi-Xin Liu, Jing He, Li-Ying He, Jing Bai, Jing-Yan Yang, Shu-Qi Niu, Jin-Lin Guo","doi":"10.1016/j.phymed.2025.156414","DOIUrl":"https://doi.org/10.1016/j.phymed.2025.156414","url":null,"abstract":"","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":" ","pages":"156414"},"PeriodicalIF":6.7,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143060381","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}