作者机构：
[Dai, Jie; Huang, Shiyi; Liu, Shi Ao; Zhao, Hongqing; Zou, Ting; He, Xiangchang; He, Weihe; Xu, Guangming] Hunan Univ Chinese Med, Sch Pharm, Changsha, Peoples R China.
通讯机构：
[Xu, GM ] H;Hunan Univ Chinese Med, Sch Pharm, Changsha, Peoples R China.
摘要：
Traditional Chinese Medicine (TCM) holds significant potential as a natural source of medication, providing effective alternatives for preventing and treating thrombotic diseases. Although research on the anticoagulant activity of Agrimonia Pilosa Ledeb (Rosaceae, A. pilosa) has been paid attention to, the monomer component and its mechanism of action have not been studied deeply. Therefore, this study aimed to screen and identify the antithrombotic active components of A. pilosa by affinity ultrafiltration (AUF) combined with ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). The affinity between compounds and thrombin was studied through molecular docking, and the activity of thrombin inhibitors was evaluated from multiple dimensions by the zebrafish thrombus model, chromogenic substrate method, and coagulation factor test. Eleven ligands with potential antithrombotic activity were screened from A. pilosa. Among them, compounds hyperoside, quercitrin, afzelin, baicalin, quercetin, kaempferol, and 3-O-caffeoylquinic acid were shown to have antithrombotic activity. This study is the first to report that kaempferol-3-rhamno-glucoside, tiliroside, and taxifolin exhibit thrombin-inhibitory effects through both in vivo and in vitro experiments. The results of this study indicate that AUF-HPLC and UPLC-Q-TOF-MS can be used for high-throughput screening of active components from TCM, thus laying a groundwork for the discovery of thrombin inhibitors and promoting the research progress of antithrombotic drugs.
摘要：
BACKGROUND AND OBJECTIVES: To explore the mechanism of action of the differential components of medicinal and edible lilies in treating depression by network pharmacology using UPLC-Q-TOF-MS technology. METHODS: The chemical composition of medicinal and edible lilies was analyzed, screening for unique medicinal compounds. Searched for depression-related targets. Constructed PPI networks. Performed GO and KEGG analyses. Built a network of differential components, and conducted molecular docking. In addition, the contents of regaloside before and after lily processing were compared Results: Medicinal lilies and edible lilies have 17 main differences, including regaloside B and regaloside E. There are 179 targets for actives, 2690 for antidepressants, and 98 intersected. Core targets (7) led to 238 GO processes and 107 KEGG pathways. The molecular docking results showed that 17 components, including regaloside B, regaloside E, (25R)-3β,17α-Dihydroxy-5α- spirostan-6-one 3-O-α-L- rhamnopyranosyl-(1→2)-β- D-glucopyranoside (Named: Lilium lancifolium saponin), etc. could act on 7 potential targets such as EGFR, HSP90AA1, STAT3, TNF, etc. to exert antidepressant effects. CONCLUSION: This study employed a network pharmacology combined with a molecular docking approach to compare the active constituents of medicinal and edible lilies in antidepressants, and their pharmacological mechanisms, both theoretically and technically. The phytoconstituents were found to act mainly by inhibiting the inflammatory response in depression. Especially Lilium lancifolium saponin may have a close relationship with antidepressants. These results provide some justification for lilies in the treatment of depression.
期刊：
COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING,2025年27(9):1491-1514 ISSN：1386-2073
作者机构：
[Li, Qing; Li, Xiao Ling; Hou, Chao Wen; Shi, Yuhe; Zhu, Jue; Tong, Qiao Zhen; Liu, Xiang Dan] Department of Hunan University of Chinese Medicine, School of Pharmacy, Changsha 410208, Hunan Province, P.R.China
摘要：
AIMS AND OBJECTIVE: This study aimed to identify the bioactive compounds and explore the multi-target mechanisms of Salvia miltiorrhiza Bunge (SMB) against coronary heart disease (CHD) using an integrated serum pharmacochemistry and network pharmacology approach. MATERIALS AND METHODS: The chemical constituents of SMB were characterized by UPLC-MS. The absorbed ingredients and metabolites after oral SMB administration were identified in rat serum. Therapeutic targets of SMB against CHD were predicted by intersecting the targets of absorbed compounds from databases and CHD-associated genes. Protein-protein interaction network, pathway analysis, molecular docking, and molecular dynamic simulation were performed. RESULTS: A total of 61 SMB-derived compounds were identified in rat serum. Network analysis revealed 111 candidate targets highly related to CHD pathways. Further topological analysis identified 10 hub targets and 20 key active compounds, constructing an informative compoundtarget- pathway network. PTGS2 and TNF were predicted as primary targets of SMB against CHD based on molecular dynamic simulation. CONCLUSION: This integrated approach identified bioactive compounds and multi-target mechanisms of SMB against CHD. The results provide scientific evidence supporting SMB's clinical efficacy and reveal potential anti-CHD targets.
期刊：
Drug Design, Development and Therapy,2025年19:1289-1303 ISSN：1177-8881
通讯作者：
Wang, YL;Hu, Q
作者机构：
[Wang, Yanli; Li, Qi; Peng, Bo; Chen, Ying; Dong, Lijinchuan; Li, Mengting; Hu, Qin; Wang, YL; Xiao, Shuiming; Yang, Qing] China Acad Chinese Med Sci, Inst Chinese Mat Med, 16 Dongzhimen Nei Nanxiao Rd, Beijing 100700, Peoples R China.;[Chen, Tian; Hu, Q; Hu, Qin] Beijing Univ Technol, Coll Chem & Life Sci, 100 Pingleyuan Rd, Beijing 100124, Peoples R China.;[Shi, Zhe] Hunan Univ Chinese Med, Div Stem Cell Regulat & Applicat, Key Lab Qual Evaluat Bulk Herbs Hunan Prov, Changsha 410208, Peoples R China.;[Jiang, Ning; Liu, Xinmin] Peking Union Med Coll & Chinese Acad Med Sci, Inst Med Plant Dev, Beijing 100094, Peoples R China.;[Liu, Xinmin] Ningbo Univ, Inst Drug Discovery Technol, Ningbo 315000, Peoples R China.
通讯机构：
[Hu, Q ] B;[Wang, YL ] C;China Acad Chinese Med Sci, Inst Chinese Mat Med, 16 Dongzhimen Nei Nanxiao Rd, Beijing 100700, Peoples R China.;Beijing Univ Technol, Coll Chem & Life Sci, 100 Pingleyuan Rd, Beijing 100124, Peoples R China.
关键词：
ginseng total saponins;gastrointestinal microbiome;immunity;short-chain fatty acids;weightlessness simulation
摘要：
BACKGROUND: Duringmedium- to long-duration spaceflights, real-time microgravity can increase the health risks of astronauts. In particular, the disruption of intestinal homeostasis is closely related to other health problems, and it is necessary to monitor related treatment strategies. Ginseng is a well-known Chinese herbal medicine often used to maintain health. Ginseng total saponins (GTSs), which are the bioactive components of ginseng, have been reported to regulate immune homeostasis, anti-inflammation, and anti-oxidation. This study focused on the regulation of GTSs in intestinal homeostasis imbalance caused by microgravity. METHODS: A hindlimb suspension (HLS) rat model was established to evaluate the intestinal protective effects of GTSs. Differentially expressed genes (DEGs) were screened using RNA-Seq. RT-PCR was performed to further focus and verify these results. The gut microbiome composition was examined based on 16S rRNA gene amplicon sequencing, and the short-chain fatty acids produced were further analyzed. RESULTS: We found that GTSs intervention effectively improved the intestinal injury caused by simulated weightlessness, including reducing the pathological damage, increasing the expression of tight junction proteins and reducing the levels of inflammatory factors. Moreover, GTSs treatment significantly restored the levels of intestinal immunity-related genes and remodeled the gut microbiota. In particular, GTSs significantly increased the abundance of short-chain fatty acid metabolism-related bacteria, thereby increasing the level of propionic acid, butyric acid, isobutyric acid. CONCLUSION: Our results revealed that GTSs improved intestinal microecological disorders and impaired immune function caused by the weightlessness simulation. The underlying mechanism may be related to the "intestinal immune -microbiota-metabolic" pathway. These findings provide a theoretical basis for the precise design and development of GTSs for space-health products.
作者机构：
[Shunli Ji] Department of Pharmacology, School of Pharmacy, China Pharmaceutical University, Nanjing, China.;State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.;Chongqing Innovation Institute of China Pharmaceutical University, Chongqing, China.;[Yan Duan; Shunxiang Li] School of Pharmacy, Hunan University of Chinese Medicine, Changsha, China.;[Guanglei Li] College of Food Science and Engineering, Nanjing University of Finance and Economics, Nanjing, China.
通讯机构：
[Meiling Lu] S;[Meirong Chen; Yibei Xiao] D;Department of Pharmacology, School of Pharmacy, China Pharmaceutical University, Nanjing, China.<&wdkj&>State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.<&wdkj&>Chongqing Innovation Institute of China Pharmaceutical University, Chongqing, China.<&wdkj&>State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.<&wdkj&>Chongqing Innovation Institute of China Pharmaceutical University, Chongqing, China.<&wdkj&>Department of Biochemistry, School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.
摘要：
Prokaryotes have evolved diverse defense strategies against viral infection, including foreign nucleic acid degradation by CRISPR-Cas systems and DNA and RNA synthesis inhibition through nucleotide pool depletion. Here, we report an antiviral mechanism of type III CRISPR-Cas–regulated adenosine triphosphate (ATP) depletion in which ATP is converted into inosine triphosphate (ITP) by CRISPR-Cas–associated adenosine deaminase (CAAD) upon activation by either cA 4 or cA 6 , followed by hydrolysis into inosine monophosphate (IMP) by Nudix hydrolase, ultimately resulting in cell growth arrest. The cryo–electron microscopy structures of CAAD in its apo and activated forms, together with biochemical evidence, revealed how cA 4 or cA 6 binds to the CRISPR-associated Rossmann fold (CARF) domain and abrogates CAAD autoinhibition, inducing substantial conformational changes that reshape the structure of CAAD and induce its deaminase activity. Our results reveal the mechanism of a CRISPR-Cas–regulated ATP depletion antiviral strategy.
作者：
Si Yan;Guang-Shuai Zhang;Yan Liu;Zi-Wei Du;Qing Min;...
期刊：
Cancer Advances,2025年8:e25001-e25030
作者机构：
[Si Yan; Guang-Shuai Zhang; Yan Liu; Zi-Wei Du; Qing Min] School of Pharmacy, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China.;Research Center for Precision Medication of Chinese Medicine, School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China.;Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing 100039, China.;[Xiao-He Xiao] Research Center for Precision Medication of Chinese Medicine, School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China.<&wdkj&>Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing 100039, China.;[Shuang-Lin Qin] School of Pharmacy, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China.<&wdkj&>Research Center for Precision Medication of Chinese Medicine, School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China.<&wdkj&>Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing 100039, China.
摘要：
<strong>Background: </strong>Liver cancer (LC) remains a leading cause of cancer-related mortality worldwide, with current treatments often limited by suboptimal efficacy and adverse effects. Banxia Houpu Decoction (BHD), a traditional Chinese herbal formula, has demonstrated potential anti-tumor properties in clinical practice. However, its precise mechanisms against LC remain unclear. This study employs network pharmacology (NP) and molecular docking (MD) approaches to systematically identify BHD’s active components and their molecular targets, aiming to elucidate its anti-LC mechanisms and provide a scientific basis for further investigation.<strong> Methods: </strong>We utilized Liquid Chromatography-Mass Spectrometry alongside the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) to identify the constituents of BHD. We identified potential targets through the utilization of TCMSP, SwissTargetPrediction, Comparative Toxicogenomics Database, and SuperPred Database. Targets linked to LC were obtained from GeneCards, OMIM, the Therapeutic Target Database, and DrugBank. A Venn diagram illustrated the intersection between component and disease targets, while a protein-protein interaction (PPI) network was developed utilizing Cytoscape 3.9.1. Primary targets were discerned through the analysis of centrality metrics, including “Degree,” “Betweenness,” and “Closeness.” The study encompassed analyses of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways to clarify the biological roles and pathways associated with these proteins. The essential interactions between the active constituents of BHD and the principal LC targets were investigated through MD using AutoDock software. <strong>Results:</strong> We identified 34 active components in BHD. The PPI network revealed 212 interaction targets relevant to drug-disease correlations, emphasizing key proteins including Epidermal Growth Factor Receptor (EGFR), Signal Transducer and Activator of Transcription 3 (STAT3), Steroid Receptor Coactivator (SRC), Heat Shock Protein 90 Alpha Family Class A Member 1 (HSP90AA1), and AKT Serine/Threonine Protein Kinase 1 (AKT1). The GO analysis revealed a total of 443 biological processes, 94 cellular components, and 182 molecular functions. The KEGG analysis revealed a total of 169 pathways that are involved. The results from MD revealed that the majority of binding energies fell below −7 kcal/mol, indicating strong interactions between the active compounds and their target proteins. <strong>Conclusion:</strong> Evidence suggests that BHD effectively manages LC through a synergistic mechanism encompassing various components (Magnolol, Chrysoeriol, Cerevisterol, etc.), targets (EGFR, STAT3, SRC, HSP90AA1, AKT1, etc.), and pathways (PI3K-Akt, FoxO, and Ras signaling pathways, etc.). This analysis offers a comprehensive theoretical framework for further investigative and clinical exploration.
摘要：
Poly(ADP-ribose)polymerase-1 (PARP1) could be activated by binding to nucleic acids with specific sequences, thus catalyzing the poly-ADP-ribosylation (PARylation) of target proteins including PARP1 itself. Most of the previously reported electrochemical methods for the determination of PARP1 were relied on the electrostatic interactions, which required the pre-immobilization of DNA on an electrode for the capture of PARP1. Herein, we reported an "immobilization-free" electrochemical strategy for the assays of PARP1 on the basic of avidin-biotin interaction. Once PARP1 was activated by binding with the specific double-stranded DNA (dsDNA) in a homogeneous solution, the biotinylated nicotinamide adenine dinucleotide (biotin-NAD(+)) was transferred onto PARP1, resulting in the formation of biotinylated PAR polymers. The resulting biotinylated PAR polymers were then captured by a neutravidin (NA)-modified electrode through avidin-biotin interactions. The rich biotin moieties in the PAR polymers allowed for the capture of NA-modified silver nanoparticles (NA-AgNPs) through the avidin-biotin interactions. The surface-tethered AgNPs produced a well-defined electrochemical signal due to the characteristic solid-state Ag/AgCl process. The "immobilization-free", electrostatic interaction-independent electrochemical biosensor exhibited low background current, high sensitivity, and good stability. It has achieved the determination of PARP1 with a detection limit down to 0.7 mU. The biosensor was further applied to determine the inhibition efficiency of potential inhibitors with a satisfactory result. This method shows promising potential applications in PARP1-related clinical diagnosis and drug discovery.
期刊：
Frontiers in Oral Health,2025年6:1568252 ISSN：2673-4842
通讯作者：
Liu, HY;Liao, RY;Hu, C
作者机构：
[Tang, Feng; He, Yinghui; Liu, Hongyu] Hunan Univ Chinese Med, Hosp 1, Dept Pharm, Changsha, Peoples R China.;[Liao, Ruoyi; Liao, RY; He, Yinghui] Hunan Univ Chinese Med, Hosp 1, Dept Nursing, Changsha, Peoples R China.;[Hu, Chun; Hu, C] Hunan Univ Chinese Med, Hosp 1, Dept Stomatol, Changsha, Peoples R China.
通讯机构：
[Liao, RY ; Liu, HY ; Hu, C ] H;Hunan Univ Chinese Med, Hosp 1, Dept Pharm, Changsha, Peoples R China.;Hunan Univ Chinese Med, Hosp 1, Dept Nursing, Changsha, Peoples R China.;Hunan Univ Chinese Med, Hosp 1, Dept Stomatol, Changsha, Peoples R China.
摘要：
OBJECTIVES: This randomized controlled trial aimed to investigate the impact of different telephone follow-up frequencies on periodontal clinical parameters after non-surgical periodontal therapy. MATERIALS AND METHODS: Patients with Stage II-IV periodontitis were enrolled and randomly assigned to high-frequency (once every 2 weeks), medium-frequency (once a month), and low-frequency (once in 3 months) follow-up groups. All patients received standard non-surgical periodontal treatment. The full mouth probing depth (PD), clinical attachment loss (CAL), gingival index (GI), and plaque index (PI) were evaluated at baseline, after treatment (T1) and post treatment 3 months (T2). RESULTS: From T1 to T2, the high-frequency follow-up group had significant reduced in PD (p = 0.03), improved in GI (p = 0.04) and PI (p = 0.03) compared with the medium and low-frequency groups. There was no significant difference in PD, GI, and PI between the medium-frequency group and the low-frequency group. No statistical difference was found in CAL among the three groups. CONCLUSION: More frequent telephone follow-up helps maintain and enhance non-surgical periodontal therapy effects.
摘要：
Despite extensive research into nanozymes, developing highly active catalysts with broad application potential remains a significant challenge. In this study, we synthesized hollow FeNi Prussian blue analog (H-FeNi PBA) nanocages through a straightforward chemical etching method, using FeNi PBA nanocubes as precursors. The resulting H-FeNi PBA nanocages exhibited enhanced peroxidase-mimetic activity, attributed to their increased specific surface area, pore volume, and Fe 2+ content. Leveraging this activity, we developed a novel colorimetric sensing platform for the detection of mercury ions (Hg 2+ ) and L-cysteine (Cys). The platform operates based on the peroxidase-mimetic activity of H-FeNi PBA nanocages, the inhibitory effect of Cys on this activity, and the restoration of activity through the specific complexation between Cys and Hg 2+ . After optimization, the platform demonstrated wide linear detection ranges (0.1–42 μM for Hg 2+ and 1–64 μM for Cys) and low detection limits (0.035 μM for Hg 2+ and 0.24 μM for Cys). The method was successfully applied to detect Hg 2+ and Cys in real samples, showcasing its potential for environmental monitoring and biomedical applications. This work not only provides a simple strategy for synthesizing highly active nanozymes but also highlights their potential in biosensing and catalysis.
Despite extensive research into nanozymes, developing highly active catalysts with broad application potential remains a significant challenge. In this study, we synthesized hollow FeNi Prussian blue analog (H-FeNi PBA) nanocages through a straightforward chemical etching method, using FeNi PBA nanocubes as precursors. The resulting H-FeNi PBA nanocages exhibited enhanced peroxidase-mimetic activity, attributed to their increased specific surface area, pore volume, and Fe 2+ content. Leveraging this activity, we developed a novel colorimetric sensing platform for the detection of mercury ions (Hg 2+ ) and L-cysteine (Cys). The platform operates based on the peroxidase-mimetic activity of H-FeNi PBA nanocages, the inhibitory effect of Cys on this activity, and the restoration of activity through the specific complexation between Cys and Hg 2+ . After optimization, the platform demonstrated wide linear detection ranges (0.1–42 μM for Hg 2+ and 1–64 μM for Cys) and low detection limits (0.035 μM for Hg 2+ and 0.24 μM for Cys). The method was successfully applied to detect Hg 2+ and Cys in real samples, showcasing its potential for environmental monitoring and biomedical applications. This work not only provides a simple strategy for synthesizing highly active nanozymes but also highlights their potential in biosensing and catalysis.
作者：
Tao Zheng;Yong Yang;Hui Zheng;Fan Jia;Yao Xu;...
期刊：
Foods,2025年14(11):1869- ISSN：2304-8158
通讯作者：
Yong Yang<&wdkj&>Hui Zheng
作者机构：
[Yong Yang] Authors to whom correspondence should be addressed.;[Tao Zheng; Fan Jia; Yao Xu; Yuhang Wu; Jiani Jiang] College of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China;[Hui Zheng] Authors to whom correspondence should be addressed.<&wdkj&>College of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China
通讯机构：
[Yong Yang; Hui Zheng] A;Authors to whom correspondence should be addressed.<&wdkj&>Authors to whom correspondence should be addressed.<&wdkj&>College of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China
关键词：
extrusion cooking;natural medicinal and edible plants;functional components;pharmacological activities;physical properties
摘要：
Extrusion cooking is an innovative, advanced processing technology widely used in the food and feed industries. With growing concerns over the health attributes of food, the effects of extrusion cooking on the functional characteristics of natural medicinal and edible plants (NMEPs) have attracted increasing attention from researchers. This review, based on recent literature on extrusion cooking, systematically summarizes its impact on the physical properties; functional components, such as total polyphenols, total flavonoids, total polysaccharides, and total saponins; and pharmacological activities, including antioxidant, hypoglycemic, hypolipidemic, and anti-inflammatory effects, of NMEPs. The aim is to provide a scientific basis for the application of extrusion cooking technology in the advanced processing of these resources.
摘要：
Water pollution has become an urgent issue around the world, antibiotic residues in water result in health or environmental problems worldwide. In order to address the key issues of low catalytic efficiency, poor stability, and low visible light utilization in the current photocatalytic treatment of recalcitrant organic pollutants in water, bimetallic CuFe 2 O 4 /ABC was successfully obtained from extracted Astragalus residue and used for degradation of tetracycline under visible light. First, the bimetallic active centers (Fe and Cu) enhanced the separation of charge carriers under visible light. Then, Fe and Cu active centers activated and enhanced the production of persistent free radicals (PFRs) in biochar. Fe 2+ and Cu + in the bimetallic active centers transferred e - to O 2 to promote the formation of •O 2 - , which efficiently degraded tetracycline (94.89%) without H 2 O 2 . Notably, the persistent free radicals (PFRs) served as intrinsic electron reservoirs. By donating electrons derived from oxidized C-C bonds to Fe/Cu centers.
Water pollution has become an urgent issue around the world, antibiotic residues in water result in health or environmental problems worldwide. In order to address the key issues of low catalytic efficiency, poor stability, and low visible light utilization in the current photocatalytic treatment of recalcitrant organic pollutants in water, bimetallic CuFe 2 O 4 /ABC was successfully obtained from extracted Astragalus residue and used for degradation of tetracycline under visible light. First, the bimetallic active centers (Fe and Cu) enhanced the separation of charge carriers under visible light. Then, Fe and Cu active centers activated and enhanced the production of persistent free radicals (PFRs) in biochar. Fe 2+ and Cu + in the bimetallic active centers transferred e - to O 2 to promote the formation of •O 2 - , which efficiently degraded tetracycline (94.89%) without H 2 O 2 . Notably, the persistent free radicals (PFRs) served as intrinsic electron reservoirs. By donating electrons derived from oxidized C-C bonds to Fe/Cu centers.
摘要：
Both varietal attributes and geographical indications are crucial for the quality and medicinal efficacy of Zanthoxylum nitidum (Roxb.) DC, therefore, its variety identification and origin tracing are of considerable importance. In this study, an integrating strategy, UHPLC-Q/TOF-MS based metabolomics coupled with molecular network strategy, was proposed to firstly differentiate Z. nitidum from two counterfeits, and trace three geographic origins of Z. nitidum . A total of 167 components were annotated in metabolomics of Z. nitidum using the molecular networking method metabolomics. Principal component analysis showed distinct metabolic phenotype variation between Z. nitidum and its adulterants, as well as among three origins produced -Z. nitidum samples. Furthermore, orthogonal partial least squares discriminant analysis (OPLS-DA) revealed 15 biomarkers for variety discrimination, and 12 biomarkers for geographic origin discrimination of Z. nitidum . The OPLS-DA models established by these 15 biomarkers and 12 biomarkers could differentiate Z. nitidum from adulterants samples, and distinguish Z. nitidum samples from three geographical origins, respectively. This study demonstrated that our proposed comparative metabolomics coupled with molecular networks strategy has analyzing potential for identifying and determining the varieties and geographic origins of Z. nitidum , providing a useful reference for its quality control in the marketplace and clinical.
Both varietal attributes and geographical indications are crucial for the quality and medicinal efficacy of Zanthoxylum nitidum (Roxb.) DC, therefore, its variety identification and origin tracing are of considerable importance. In this study, an integrating strategy, UHPLC-Q/TOF-MS based metabolomics coupled with molecular network strategy, was proposed to firstly differentiate Z. nitidum from two counterfeits, and trace three geographic origins of Z. nitidum . A total of 167 components were annotated in metabolomics of Z. nitidum using the molecular networking method metabolomics. Principal component analysis showed distinct metabolic phenotype variation between Z. nitidum and its adulterants, as well as among three origins produced -Z. nitidum samples. Furthermore, orthogonal partial least squares discriminant analysis (OPLS-DA) revealed 15 biomarkers for variety discrimination, and 12 biomarkers for geographic origin discrimination of Z. nitidum . The OPLS-DA models established by these 15 biomarkers and 12 biomarkers could differentiate Z. nitidum from adulterants samples, and distinguish Z. nitidum samples from three geographical origins, respectively. This study demonstrated that our proposed comparative metabolomics coupled with molecular networks strategy has analyzing potential for identifying and determining the varieties and geographic origins of Z. nitidum , providing a useful reference for its quality control in the marketplace and clinical.
摘要：
Ethnopharmacological relevance Lonicerae Japonicae Flos (Caprifoliaceae) (LJF), an herb with the homology of medicine and food, is traditionally utilized for its heat-clearing, detoxifying, and anticancer properties. Yet, the mechanism by which LJF may assist in the treatment of non-small cell lung cancer (NSCLC) remains unclear.
Lonicerae Japonicae Flos (Caprifoliaceae) (LJF), an herb with the homology of medicine and food, is traditionally utilized for its heat-clearing, detoxifying, and anticancer properties. Yet, the mechanism by which LJF may assist in the treatment of non-small cell lung cancer (NSCLC) remains unclear.
Aim of the study To elucidate the potential mechanisms of LJF in the treatment of NSCLC through phytochemical analysis, network pharmacology, machine learning, and in vitro experimental validation.
To elucidate the potential mechanisms of LJF in the treatment of NSCLC through phytochemical analysis, network pharmacology, machine learning, and in vitro experimental validation.
Materials and methods LJF was analyzed for its components using ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). The active compounds and targets of LJF were identified from TCMSP, and NSCLC-related targets were retrieved from GeneCards, DisGeNET and OMIM. Network pharmacology and multi-machine learning algorithms predicted key features, and GSEA/GSVA assessed pathway enrichment. Immune infiltration analysis evaluated immune cell composition in the NSCLC microenvironment, and molecular docking was performed with AlphaFold. In vitro experiments assessed LJF’s effects on A549 cells, and western blot analyzed protein expression.
LJF was analyzed for its components using ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). The active compounds and targets of LJF were identified from TCMSP, and NSCLC-related targets were retrieved from GeneCards, DisGeNET and OMIM. Network pharmacology and multi-machine learning algorithms predicted key features, and GSEA/GSVA assessed pathway enrichment. Immune infiltration analysis evaluated immune cell composition in the NSCLC microenvironment, and molecular docking was performed with AlphaFold. In vitro experiments assessed LJF’s effects on A549 cells, and western blot analyzed protein expression.
Results Network pharmacology and multi-machine learning indicated that PECAM1 and SPP1 are potential targets for LJF in the treatment of NSCLC. GSEA and immune infiltration analysis suggested PECAM1 and SPP1 influence NSCLC progression and immune evasion. In vitro experiments showed that LJF significantly inhibited A549 cells proliferation, migration, and invasion. Western blot results indicated upregulation of PECAM1 and SPP1 expression under LJF treatment.
Network pharmacology and multi-machine learning indicated that PECAM1 and SPP1 are potential targets for LJF in the treatment of NSCLC. GSEA and immune infiltration analysis suggested PECAM1 and SPP1 influence NSCLC progression and immune evasion. In vitro experiments showed that LJF significantly inhibited A549 cells proliferation, migration, and invasion. Western blot results indicated upregulation of PECAM1 and SPP1 expression under LJF treatment.
Conclusion LJF has an adjunctive therapeutic effect on NSCLC by regulating PECAM1 and SPP1 targets and their associated signaling pathways.
LJF has an adjunctive therapeutic effect on NSCLC by regulating PECAM1 and SPP1 targets and their associated signaling pathways.
摘要：
Hepatic fibrosis is a late-stage process of many chronic liver diseases. Blocking the fibrosis process will be beneficial to the treatment and recovery of the disease. Hepatic macrophages are a remarkably heterogeneous population of immune cells that play multiple functions in homeostasis and are central to liver fibrosis. Glycolysis-mediated macrophage metabolic reprogramming leads to an increase in the proportion of M1 macrophages and the release of pro-inflammatory cytokines. The present study aimed to investigate the therapeutic effect and mechanism of Astragaloside IV (AS-IV) against carbon tetrachloride (CCl 4 )-induced liver fibrosis. The study found that AS-IV is an effective agent for reducing the production of inflammatory factors in CCl 4 -induced liver fibrosis. It was also found that AS-IV blocks macrophage M1 polarization and relieves liver fibrosis. Mechanistically, AS-IV reduces the methylation level of the FoxO1 promoter region and then upregulates its expression. FoxO1 can inhibit the expression of key enzymes in the glycolysis pathway and block glycolysis-mediated macrophage M1 polarization. Our findings indicate that AS-IV is an attractive option for treating liver fibrosis.
Hepatic fibrosis is a late-stage process of many chronic liver diseases. Blocking the fibrosis process will be beneficial to the treatment and recovery of the disease. Hepatic macrophages are a remarkably heterogeneous population of immune cells that play multiple functions in homeostasis and are central to liver fibrosis. Glycolysis-mediated macrophage metabolic reprogramming leads to an increase in the proportion of M1 macrophages and the release of pro-inflammatory cytokines. The present study aimed to investigate the therapeutic effect and mechanism of Astragaloside IV (AS-IV) against carbon tetrachloride (CCl 4 )-induced liver fibrosis. The study found that AS-IV is an effective agent for reducing the production of inflammatory factors in CCl 4 -induced liver fibrosis. It was also found that AS-IV blocks macrophage M1 polarization and relieves liver fibrosis. Mechanistically, AS-IV reduces the methylation level of the FoxO1 promoter region and then upregulates its expression. FoxO1 can inhibit the expression of key enzymes in the glycolysis pathway and block glycolysis-mediated macrophage M1 polarization. Our findings indicate that AS-IV is an attractive option for treating liver fibrosis.
作者机构：
[宁露云; Zeng, Jiang; 徐媛菽; Tan, Chen-Si; 王炜; 肖倩; 符天昊] School of Pharmacy, Hunan University of Chinese Medicine Changsha 410208, China Traditional Chinese Medicine and Ethnomedicine Innovation & Development International Laboratory,Hunan University of Chinese Medicine Changsha 410208, China
期刊：
CELL DEATH AND DIFFERENTIATION,2025年:1-19 ISSN：1350-9047
通讯作者：
Chen, NH;Chu, Shi-feng;Zhang, Zhao
作者机构：
[Lai, Hua-qing; Chen, Nai-hong; Fan, Ping-long; Chen, NH] Guangzhou Univ Chinese Med, Shenzhen Hosp Integrated Tradit Chinese & Western, Shenzhen Clin Coll Integrated Chinese & Western Me, Shenzhen, Peoples R China.;[Ye, Jun-rui; Ruan, Yuan; Yan, Xu; Chen, Nai-hong; Chu, Shi-feng; Zhang, Zhao; Chen, NH; Zhang, Z; Wang, Hong-yun; Hu, Kai-chao] Chinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, State Key Lab Bioact Subst & Funct Nat Med, Beijing, Peoples R China.;Chinese Acad Med Sci & Peking Union Med Coll, Neurosci Ctr, Beijing, Peoples R China.;[Peng, Ye; Chen, Nai-hong; Chen, NH; Wang, Sha-sha] Hunan Univ Chinese Med, Coll Pharm, Hunan Engn Technol Ctr Standardizat & Funct Chines, Changsha, Peoples R China.;[He, Wen-bin] Shanxi Univ Chinese Med, Natl Int Joint Res Ctr Mol Chinese Med, Taiyuan, Peoples R China.
通讯机构：
[Chu, SF; Zhang, Z] C;[Chen, NH ] G;Guangzhou Univ Chinese Med, Shenzhen Hosp Integrated Tradit Chinese & Western, Shenzhen Clin Coll Integrated Chinese & Western Me, Shenzhen, Peoples R China.;Chinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, State Key Lab Bioact Subst & Funct Nat Med, Beijing, Peoples R China.;Hunan Univ Chinese Med, Coll Pharm, Hunan Engn Technol Ctr Standardizat & Funct Chines, Changsha, Peoples R China.
摘要：
Efferocytosis is crucial for the clearance of apoptotic cells (ACs) following acute ischemic stroke (AIS), however, its mechanism remains unclear. This study reveals that chemokine-like factor 1 (CKLF1) disrupts efferocytosis by promoting AC finding and internalization while impairing AC degradation in microglia. CKLF1 deficiency reduced the proportion of ACs and lowered levels of damage-associated molecular patterns. Mechanistically, CKLF1 binds to phosphatidylserine on apoptotic neurons/blebs, recruiting microglia to the ischemic penumbra via a C-C chemokine receptor 4 (CCR4)-dependent pathway. Apoptotic blebs with CKLF1 are engulfed into microglia, triggering the rapid production of interleukin-6 (IL6). IL6 enhances AC internalization through the signal transducer and activator of transcription 3 (STAT3)-vav guanine nucleotide exchange factor 1 (VAV1)-ras-related C3 botulinum toxin substrate 1 (RAC1) signaling cascade but simultaneously inhibits transcription factor EB (TFEB) nuclear translocation, leading to lysosomal dysfunction. This effect results in AC accumulation, compromising microglial efferocytosis efficiency and integrity. These findings uncover a novel regulatory axis induced by CKLF1, emphasizing the complex balance between AC internalization and degradation in microglial efferocytosis.
通讯机构：
[Zhu, YZ ] M;[Xiao, WJ ] H;Macau Univ Sci & Technol, Sch Pharm, Taipa 999078, Macao, Peoples R China.;Hunan Agr Univ, Natl Res Ctr Engn Technol Utilizat Bot Funct Ingre, Changsha 410128, Hunan, Peoples R China.
关键词：
Erythritol;Glucose;Lipid and protein metabolism;Mogroside V;Stevioside;Sucralose;Sugar substitute;T2DM
摘要：
Sugar substitutes that maintain the homeostasis of glucose, lipid, and protein metabolism are important for nutritional intervention in type 2 diabetes mellitus (T2DM). However, the specific metabolic effects remain unclear. The aim of this study was to systematically compare the effects of four common sugar substitutes on a high-fat diet (HFD) combined with a streptozotocin (STZ)-induced T2DM mouse model from the perspective of hepatic glucose, lipid, and protein metabolism. In this study, based on the establishment of a T2DM mouse model induced by an HFD combined with STZ and nontargeted metabolomics, the effects of four sugar substitutes on regulating and improving sugar, lipid, and protein metabolism were systematically evaluated. The results showed that mogroside V (MOG), stevioside (ST), and erythritol (ERT) enhanced protein synthesis via the mammalian target of the rapamycin/p-P70S6K pathway. MOG and ST also improved glucose and lipid metabolism by activating the phosphor-AMP-activated protein kinase (p-AMPK) pathway and upregulating peroxisome proliferator-activated receptor alpha/carnitine palmitoyltransferase 1. Sucralose primarily improves lipid metabolism by downregulating sterol regulatory element-binding protein 1, whereas ERT increases lipid droplet accumulation in the liver. These findings provide a foundation for the application of sugar substitutes in T2DM nutritional interventions.
Sugar substitutes that maintain the homeostasis of glucose, lipid, and protein metabolism are important for nutritional intervention in type 2 diabetes mellitus (T2DM). However, the specific metabolic effects remain unclear. The aim of this study was to systematically compare the effects of four common sugar substitutes on a high-fat diet (HFD) combined with a streptozotocin (STZ)-induced T2DM mouse model from the perspective of hepatic glucose, lipid, and protein metabolism. In this study, based on the establishment of a T2DM mouse model induced by an HFD combined with STZ and nontargeted metabolomics, the effects of four sugar substitutes on regulating and improving sugar, lipid, and protein metabolism were systematically evaluated. The results showed that mogroside V (MOG), stevioside (ST), and erythritol (ERT) enhanced protein synthesis via the mammalian target of the rapamycin/p-P70S6K pathway. MOG and ST also improved glucose and lipid metabolism by activating the phosphor-AMP-activated protein kinase (p-AMPK) pathway and upregulating peroxisome proliferator-activated receptor alpha/carnitine palmitoyltransferase 1. Sucralose primarily improves lipid metabolism by downregulating sterol regulatory element-binding protein 1, whereas ERT increases lipid droplet accumulation in the liver. These findings provide a foundation for the application of sugar substitutes in T2DM nutritional interventions.
摘要：
Introduction The phenotypic transition of vascular smooth muscle cells (VSMCs) from a quiescent, contractile type to a secretory phenotype with high proliferation and mobility is a key event in vascular remodeling. PF-477736 is an ATP-competitive inhibitor of Chk1 which induces the accumulation of DNA damage by increasing the level of replicative stress, and ultimately inhibiting cell proliferation or causing cell death. Although this compound has been utilized as an anti-tumor drug, its role in vascular remodeling remains unclear.
The phenotypic transition of vascular smooth muscle cells (VSMCs) from a quiescent, contractile type to a secretory phenotype with high proliferation and mobility is a key event in vascular remodeling. PF-477736 is an ATP-competitive inhibitor of Chk1 which induces the accumulation of DNA damage by increasing the level of replicative stress, and ultimately inhibiting cell proliferation or causing cell death. Although this compound has been utilized as an anti-tumor drug, its role in vascular remodeling remains unclear.
Methods In vitro, Human aortic smooth muscle cell line (HAVSMC) and primary rat aortic smooth muscle cells were used to establish phenotype transformation model with PDGF-bb; Western blot was used to detect the expression of VSMCs phenotype marker α-SMA, Vimentin; MTT and EdU assays were used to evaluate the proliferation ability of VSMCs; wound healing assay was used to evaluate the migration ability of VSMCs. In vivo, we established ballon injury of carotid artery in rats, and the function of the PF-477736 was evaluated by several histological stainings.
In vitro, Human aortic smooth muscle cell line (HAVSMC) and primary rat aortic smooth muscle cells were used to establish phenotype transformation model with PDGF-bb; Western blot was used to detect the expression of VSMCs phenotype marker α-SMA, Vimentin; MTT and EdU assays were used to evaluate the proliferation ability of VSMCs; wound healing assay was used to evaluate the migration ability of VSMCs. In vivo, we established ballon injury of carotid artery in rats, and the function of the PF-477736 was evaluated by several histological stainings.
Results The results exhibit that PF-477736 effectively inhibited VSMCs phenotypic transition, resulting in G1/S phase arrest and decreased proliferation and migration ability of VSMCs. Furthermore, while PDGF-bb down-regulated p53 protein and up-regulated CD44 expression, PF-477736 significantly countered these effects. Pretreatment of VSMCs with p53 siRNA blocked the effect of PF-477736, up-regulated the expression of CD44, and promoted VSMCs' proliferation and migration. Conversely, CD44 silencing through siRNA mitigated the phenotypic transition of VSMCs. In addition, the H&E, Masson’ staining and the immunohistochemistry of PCNA, p53 and CD44 showed that PF-477736 substantially inhibits vascular remodeling in the balloon injury model.
The results exhibit that PF-477736 effectively inhibited VSMCs phenotypic transition, resulting in G1/S phase arrest and decreased proliferation and migration ability of VSMCs. Furthermore, while PDGF-bb down-regulated p53 protein and up-regulated CD44 expression, PF-477736 significantly countered these effects. Pretreatment of VSMCs with p53 siRNA blocked the effect of PF-477736, up-regulated the expression of CD44, and promoted VSMCs' proliferation and migration. Conversely, CD44 silencing through siRNA mitigated the phenotypic transition of VSMCs. In addition, the H&E, Masson’ staining and the immunohistochemistry of PCNA, p53 and CD44 showed that PF-477736 substantially inhibits vascular remodeling in the balloon injury model.
Conclusion Our findings show that PF-477736 exerts anti-vascular remodeling effect by inhibiting phenotypic transition through the Chk1/p53/CD44 pathway in VSMCs, providing novel therapeutic strategies for preventing and treating vascular remodeling.
Our findings show that PF-477736 exerts anti-vascular remodeling effect by inhibiting phenotypic transition through the Chk1/p53/CD44 pathway in VSMCs, providing novel therapeutic strategies for preventing and treating vascular remodeling.
作者机构：
["Chen, Simin; Xiao, Chang; Liu, Bin"] College of Biology, Hunan University, Changsha, 410082, China;[Wang, Wei] TCM and Ethnomedicine Innovation & Development International Laboratory, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410208, China;[Xie, Hailong] Hunan Province Key Laboratory of Tumor Cellular & Molecular Pathology, Institute of Cancer Research, School of Medicine, University of South China, Hengyang, 421001, China;Hunan Provincial Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, Changsha Medical University, Changsha, 410219, China;[Xie, Qian] Hunan Provincial Maternal and Child Health Care Hospital, Hunan Province, Changsha 410008, China
通讯机构：
[Wei Wang] T;TCM and Ethnomedicine Innovation & Development International Laboratory, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410208, China
关键词：
Bufotalin;Cancer;Chlorin e6;Combination therapy;Prussian blue nanoparticles
摘要：
The combination of chemotherapy and photodynamic therapy (PDT) for enhancing cancer therapeutic efficiency has attracted tremendous attention recently. However, limitations, such as low local concentration and uncontrollable release of therapeutic agents, reduce combined treatment efficacy. In the present study, we engineered a biomimetic nanodrug employing hollow Prussian blue nanoparticles (HPB NPs) to co-load the chemical agent bufotalin (CS-5) and the photosensitizer chlorin e6 (Ce6) for combined chemo/PDT therapy against cancer. HPB NPs with catalase (CAT)-mimetic activity significantly improved the efficacy of PDT by catalyzing the decomposition of H 2 O 2 into O 2 , thus alleviating hypoxia, which conversely amplified the efficiency of combination therapy. In vivo assay demonstrated that the encapsulation of a hybrid membrane on the HPB NPs prolonged blood circulation life 3.4-fold compared to free drug. Additionally, this strategy of combinational chemo/PDT therapy exhibits a remarkable cytotoxic effect against gastric cancer (BGC-823) and breast cancer (4T1) through the induction of ferroptosis and pyroptosis while simultaneously activating the immune response, with minimal adverse effects on normal organs. Thus, the co-delivery system based on biomimetic nanocarriers appears to be a promising platform for combined chemo/PDT therapy in tumor treatment.
The combination of chemotherapy and photodynamic therapy (PDT) for enhancing cancer therapeutic efficiency has attracted tremendous attention recently. However, limitations, such as low local concentration and uncontrollable release of therapeutic agents, reduce combined treatment efficacy. In the present study, we engineered a biomimetic nanodrug employing hollow Prussian blue nanoparticles (HPB NPs) to co-load the chemical agent bufotalin (CS-5) and the photosensitizer chlorin e6 (Ce6) for combined chemo/PDT therapy against cancer. HPB NPs with catalase (CAT)-mimetic activity significantly improved the efficacy of PDT by catalyzing the decomposition of H 2 O 2 into O 2 , thus alleviating hypoxia, which conversely amplified the efficiency of combination therapy. In vivo assay demonstrated that the encapsulation of a hybrid membrane on the HPB NPs prolonged blood circulation life 3.4-fold compared to free drug. Additionally, this strategy of combinational chemo/PDT therapy exhibits a remarkable cytotoxic effect against gastric cancer (BGC-823) and breast cancer (4T1) through the induction of ferroptosis and pyroptosis while simultaneously activating the immune response, with minimal adverse effects on normal organs. Thus, the co-delivery system based on biomimetic nanocarriers appears to be a promising platform for combined chemo/PDT therapy in tumor treatment.
通讯机构：
[Xia, BH ; Liao, DF] H;Hunan Univ Chinese Med, Sch Pharm, Key Lab Qual Evaluat Bulk Herbs Hunan Prov, Changsha 410208, Peoples R China.
关键词：
IL-24/CXCL12/CXCR4 signaling axis;PTP1B/PI3K/AKT/mTOR pathway;triple-negative breast cancer;triterpenes of Prunella vulgaris (PVT)
摘要：
Triple-negative breast cancer (TNBC) is a type of breast cancer characterized by high molecular heterogeneity. Owing to the lack of effective therapeutic strategies, patients with TNBC have a poor prognosis. Prunella vulgaris L. has the effects of reducing swelling, dissolving knots and treating breast carbuncles and mammary rocks. Modern pharmacological studies have reported that it can effectively inhibit the growth of breast cancer. The main active antitumor components of Prunella vulgaris are triterpenoids (PVT); however, the role and potential mechanism of PVT in TNBC remain unexplored. Our study aimed to further explore the inhibitory effects of PVT on TNBC and the associated mechanism. The results showed that 19 compounds associated with PVT were identified, 9 of which were triterpenoids. The percentages of ursolic acid and oleanolic acid in PVT were 34.51% and 11.32%, respectively. Triterpenes of Prunella vulgaris significantly inhibited the proliferation, migration and invasion of MDA-MB-231 cells and promoted their apoptosis in a concentration-dependent manner. PVT could also effectively downregulate the mRNA and protein expression levels of Ptp1b, Pi3k, Akt and mtor and upregulate the mRNA and protein expression levels of Il-24 in MDA-MB-231 cells. In mice with tumors of TNBC, PVT significantly reduced tumor growth and the expression levels of PTP1B, CXCL12, CXCR4, PI3K, AKT, mTOR and other proteins in TNBC tumor tissue and upregulated the expression of IL-24. This study showed that PVT played an anti-TNBC role by regulating the PTP1B/PI3K/AKT/mTOR signaling pathway and the IL-24/CXCL12/CXCR4 signaling axis.
