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VX-509 attenuates the stemness characteristics of colorectal cancer stem-like cells by regulating the epithelial-mesenchymal transition through Nodal/Smad2/3 signaling

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World Journal of Stem Cells 2024年第2期16卷 207-227页

作者： Yun Yuan Xu-Fan Zhang Yu-Chen Li Hong-Qing Chen Tian Wen Jia-Lian Zheng Zi-Yi Zhao Qiong-Ying Hu Department of Laboratory medicine Hospital of Chengdu University of Traditional Chinese MedicineChengdu 610072Sichuan ProvinceChina Department of Nuclear medicine Hospital of Chengdu University of Traditional Chinese MedicineChengdu 610072Sichuan ProvinceChina College of Medical Technology Chengdu University of Traditional Chinese MedicineChengdu 611137Sichuan ProvinceChina Department of Hepatology Affiliated Hospital of Liaoning University of Traditional Chinese MedicineShenyang 110032Liaoning ProvinceChina hospital of Chengdu University of traditional chinese medicine Chengdu 610072Sichuan ProvinceChina traditional chinese medicine Regulating Metabolic Diseases Key Laboratory of Sichuan Province Chengdu 610072Sichuan ProvinceChina

BACKGROUND Colorectal cancer stem cells(CCSCs)are heterogeneous cells that can self-renew and undergo multidirectional differentiation in colorectal cancer(CRC)*** are generally accepted to be important sources of CRC and are responsible for the progression,metastasis,and therapeutic resistance of ***,targeting this specific subpopulation has been recognized as a promising strategy for overcoming *** To investigate the effect of VX-509 on CCSCs and elucidate the underlying *** CCSCs were enriched from CRC cell lines by in conditioned serum-free *** blot,Aldefluor,transwell and tumorigenesis assays were performed to verify the phenotypic characteristics of the *** anticancer efficacy of VX-509 was assessed in HCT116 CCSCs and HT29 CCSCs by performing cell viability analysis,colony formation,sphere formation,flow cytometry,and western blotting assessments in vitro and tumor growth,immunohistochemistry and immunofluorescence assessments in *** Compared with parental cells,sphere cells derived from HCT116 and HT29 cells presented increased expression of stem cell transcription factors and stem cell markers and were more potent at promoting migration and tumori-genesis,demonstrating that the CRC sphere cells displayed CSC ***-509 inhibited the tumor malignant biological behavior of CRC-stem-like cells,as indicated by their proliferation,migration and clonality in vitro,and suppressed the tumor of CCSC-derived xenograft tumors in ***,VX-509 suppressed the CSC character-istics of CRC-stem-like cells and inhibited the progression of epithelial-mesenchymal transition(EMT)signaling in *** was identified as the regulatory factor of VX-509 on CRC stem-like cells through analyses of differen-tially expressed genes and CSC-related database ***-509 markedly downregulated the expression of Nodal and its downstream phosphorylated Smad2/3 to inhibit EMT ***,VX-509 rev

关键词： Colorectal cancer stem cells Stemness VX-509 Epithelial-mesenchymal transition Nodal

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Network Pharmacology and Molecular Docking Analysis of the Mechanisms of Combined Radix Bupleuri(Chai-Hu) and Radix Paeoniae Alba(Bai-Shao) Treatment in the Prevention and Treatment of Alzheimer's Disease

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World Journal of traditional chinese medicine 2024年第2期10卷 254-262页

作者： Zhao-Han Huang Yuan Fang Qi Yu Tong Wang College of traditional chinese medicine Beijing University of Chinese MedicineBeijingChina shanghai Center for Women and Children's Health ShanghaiChina

Objective: Radix Bupleuri and Radix Paeoniae Alba are referred to as Chai-Hu and Bai-Shao, respectively, in chinese. We used molecular docking and network pharmacological approaches to explore the active components of this chinese herb combination which is commonly used for treating Alzheimer's disease(AD), the Chai-Hu and Bai-Shao pair(CBP). Materials and Methods: The active compounds and action targets of Chai-Hu and Bai-Shao were identified in the traditional chinese medicine Systems Pharmacology database, and the Therapeutic Target Database, Drug Bank, Gen Cards, Dis Ge NET, and Online Mendelian Inheritance in Man databases were used to identify therapeutic targets in patients with AD. To identify a common target of CBP in the treatment of AD, we used the Metascape tool to perform Gene Ontology function enrichment and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. In addition, CBP-AD protein–protein interaction(PPI) and herb-component-target networks were created using Cytoscape 3.8.2. Molecular docking was verified using Auto Dock tools. Results: We identified 20 active compounds of CBP, 202 active targets, 1,323 disease targets, and 117 active compound disease intersection targets;the PPI network showed that the top eight key targets were AKT1, interleukin(IL) 6, JUN, MAPK1, tumor necrosis factor, TP53, vascular endothelial growth factor, and epidermal growth factor. These act mainly on the fluid shear stress, atherosclerosis, IL-17, hypoxia-inducible factor-1, and nonalcoholic fatty liver disease pathways, among others, which control immune inflammation, cell proliferation, and apoptosis. Based on molecular docking results, the active components of CBP bind well to its key targets. Conclusion: Our results indicated that CBP was effective for treating AD by reducing the expression of inflammatory factors, promoting cell proliferation and differentiation, and preventing nerve cell death and anti-neuronal cell apoptosis.

关键词： Alzheimer's disease Bai-Shao Chai-Hu molecular docking network pharmacology

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Effects of anterior sciatic nerve acupuncture on lower limb paralysis after cerebral infarction:study protocol for a randomized controlled trial

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Journal of traditional chinese medicine 2024年第1期44卷 205-211页

作者： LI Menghan WANG Yu RAN Dawei YANG Xinming DENG Shizhe SHI Lei MENG Zhihong Department of Acupuncture First Teaching Hospital of Tianjin University of Traditional Chinese MedicineTianjin 300193China National Clinical Research Center for chinese medicine Acupuncture and Moxibustion Tianjin 300193China Graduate department Tianjin University of Traditional Chinese MedicineTianjin 301617China Department of Massage and Rehabilitation Second Affiliated Hospital of Tianjin University of Traditional Chinese MedicineTianjin 300250China

Stroke is the main cause of disability in the middle and old ***,especially lower limb paralysis,often leads to the loss of self-care ability and a series of secondary *** main method to improve hemiplegic limb movement is exercise therapy,but there are still many patients with disabilities after rehabilitation *** one of the non-pharmacological therapies for stroke,acupuncture has been recognized to improve motor function in ***,we propose a new method,anterior sciatic nerve acupuncture,which can stimulate both the femoral nerve and the sciatic *** designed this study to determine the effect of this method on lower limb motor *** participants recruited with hemiplegia after cerebral infarction will be randomly assigned to the test group or control group in a 1:1 *** control group will receive Xingnao Kaiqiao acupuncture,and the test group will receive anterior sciatic nerve acupuncture on this *** participants will get acupuncture treatment once a day,6 times a week for 2 *** primary outcome is Fugl-Meyer Assessment of Lower Extremity and the secondary outcomes are Modified Ashworth Scale and Modified Barthel *** will be collected before treatment,1week after treatment,and 2 weeks after treatment,and then statistical analysis will be *** study can preliminarily verify the effect of anterior sciatic nerve acupuncture on improving lower limb motor function in patients with cerebral infarction,which may provide an alternative approach for clinical treatment of hemiplegia.

关键词： anterior sciatic nerve acupuncture paralysis cerebral infarction Xingnao Kaiqiao clinical protocols

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Qingchang suppositry(清肠栓)induced remission in patients with mild-to-moderate ulcerative proctitis:a multicenter,prospective,randomized,parallel-controlled clinical trial

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Journal of traditional chinese medicine 2024年第1期44卷 156-162页

作者： DAI Xiaoling ZHANG Anming LIN Hui SHI Bei REN Yi WEN Hongzhu FEI Xiaoyan LIN Jiang Department of Gastroenterology Longhua Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai 200032China Department of Gastroenterology Shanghai Putuo Traditional Chinese Medicine hospitalShanghai 200063China Department of Protocology Shanghai Tianshan Traditional Chinese Medicine hospitalShanghai 200050China

OBJECTIVE:To evaluate the efficacy and safety of Qingchang suppository(清肠栓,QCS),a preparation of chinese herbal medicine,in the induction of remission in patients with mild-to-moderate ulcerative proctitis(UP).METHODS:We performed a multicenter,prospective,randomized,parallel-controlled trial to evaluate the efficacy of QCS induction therapy in 140 adult patients with mild-to-moderate UP and TCM syndrome of dampness-heat in large *** patients were randomized to receive QCS(study group)or Salicylazosulfapyridine(SASP)suppository(control group)one piece each time,twice a day,per anum for 12 *** score and main symptoms score were evaluated at weeks 0,2,4,8 and 12,rectosigmoidscopy was taken at weeks 0,4,8 and 12,Geboes score,erythrocyte sedimentation rate(ESR),C-reactive protein(CRP)and safety indexes were assessed at weeks 0 and *** primary efficacy endpoint is clinical remission rate,the secondary efficacy endpoints are clinical response rate,mucosa healing rate,Geboes score,the remission rates of the main symptoms,the median day to the remission of the symptom,***:There were no statistical difference in the clinical remission rates,the clinical response rates,the mucosa healing rates,Geboes score,ESR and CRP between the two *** remission rates of tenesmus and anal burning sensation of the study group were significantly higher than those of the control group(76.5%vs 25.0%,P=0.009;74.51%vs 29.63%,P=0.003).The median day to the remission of purulent bloody stool of the study group was significantly less than that of control group[11(1,64)vs 19(2,67),P=0.007].The patients receiving QCS had a significantly higher mucosa healing rate at week 4 than the patients receiving SASP suppository(71.42%vs 52.85%,P=0.023).No adverse event occurred in the study group while the adverse events incidence of the control group was 5.7%(P=0.049).CONCLUSIONS:QCS could induce the remission of UP as effectively and safely as SASP suppository,and was superio

关键词： ulcerative proctitis salicylazosulfapyridine suppository Qingchang suppositry randomized controlled trial

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Complement factor Ⅰ knockdown inhibits colon cancer development by affecting Wnt/β-catenin/c-Myc signaling pathway and glycolysis

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2646-2662页

作者： Yong-Jun Du Yue Jiang Yan-Mei Hou Yong-Bo Shi Department of Proctology Hospital of Chengdu University of Traditional Chinese MedicineChengdu 610072Sichuan ProvinceChina School of Clinical medicine Chengdu University of Traditional Chinese MedicineChengdu 610075Sichuan ProvinceChina Department of Proctology Zigong Hospital of Traditional Chinese MedicineZigong 643000Sichuan ProvinceChina

BACKGROUND Colon cancer(CC)occurrence and progression are considerably influenced by the tumor ***,the exact underlying regulatory mechanisms remain *** To investigate immune infiltration-related differentially expressed genes(DEGs)in CC and specifically explored the role and potential molecular mechanisms of complement factor I(CFI).METHODS Immune infiltration-associated DEGs were screened for CC using *** reverse transcription polymerase chain reaction was used to examine hub DEGs expression in the CC cell *** CFI-knockdown HT29 and HCT116 cell lines were constructed,and the diverse roles of CFI in vitro were assessed using CCK-8,5-ethynyl-2’-deoxyuridine,wound healing,and transwell *** and eosin staining and immunohistochemistry staining were employed to evaluate the influence of CFI on the tumorigenesis of CC xenograft models constructed using BALB/c male nude *** proteins associated with glycolysis and the Wnt pathway were measured using western *** Six key immune infiltration-related DEGs were screened,among which the expression of CFI,complement factor B,lymphoid enhancer binding factor 1,and SRY-related high-mobility-group box 4 was upregulated,whereas that of fatty acid-binding protein 1,and bone morphogenic protein-2 was ***,CFI could be used as a diagnostic biomarker for ***,CFI silencing inhibited CC cell proliferation,migration,invasion,and tumor ***,CFI knockdown downregulated the expression of key glycolysis-related proteins(glucose transporter type 1,hexokinase 2,lactate dehydrogenase A,and pyruvate kinase M2)and the Wnt pathway-related proteins(β-catenin and c-Myc).Further investigation indicated that CFI knockdown inhibited glycolysis in CC by blocking the Wnt/β-catenin/c-Myc *** The findings of the present study demonstrate that CFI plays a crucial role in CC development by influencing g

关键词： Colon cancer Immune infiltration Complement factor I Glycolysis Wnt/β-catenin/c-Myc pathway

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Melittin analog p5RHH enhances recombinant adeno-associated virus transduction efficiency

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Journal of Integrative medicine 2024年第1期22卷 72-82页

作者： Jing-shun Meng Yun He Heng-bin Yang Li-ping Zhou Si-yuan Wang Xi-lin Feng Omar Yahya Al-shargi Xiao-min Yu Li-qing Zhu Chang-quan Ling shanghai University of traditional chinese medicine Shanghai 201203China Oncology Department of traditional chinese medicine Changhai HospitalNaval Medical UniversityShanghai 200433China Faculty of traditional chinese medicine Naval Medical UniversityShanghai 200043China State Key Laboratory of Genetic Engineering and Engineering Research Center of Gene Technology(Ministry of Education) School of Life SciencesZhongshan HospitalFudan UniversityShanghai 200438China Yantai Fuheng Biological Technology Co. Ltd.YantaiShandong Province 264006China. Department of Clinical Laboratory the First Affiliated Hospital of Wenzhou Medical UniversityWenzhou 325000Zhejiang ProvinceChina

Objective Melittin and its derivatives have been characterized to establish effective gene delivery *** capability of facilitating endosomal release enhances the nanoparticles-based gene ***,little investigation has been conducted to explore its potential application in the context of viral *** Various melittin-derived peptides were inserted into the loop VIII of the capsid proteins of recombinant adeno-associated virus *** vectors carrying either gfp or fluc genes were subjected to qPCR assays and transduction assays of HEK293T cells to investigate the efficiency of vector production and gene *** addition,the ability of a specific p5RHH-rAAV vector to deliver genes was examined through in vitro transduction of different cultured cells and in vivo tail vein administration to C57BL/6 ***,the intricate details of the vector-mediated transduction mechanisms were revealed by specific pharmacological inhibitors of every stage of the rAAV2 intracellular life *** A total of 76 melittin-related peptides were compiled from existing *** them,cMA2,Melt13,p5RHH and aAR3 were found to significantly enhance the gene delivery efficiency of rAAV2 *** p5RHH-rAAV2 vectors efficiently transduced not only rAAV-potent cell lines but also cell lines previously considered resistant to ***,bafilomycin A1,a vacuolar endosome acidification inhibitor,completely inhibited the transgene expression mediated by the p5RHH-rAAV2 *** importantly,p5RHH-rAAV8 vectors also demonstrated increased hepatic transduction in vivo in C57BL/6 *** The incorporation of melittin analogues into the rAAV capsids results in a significant improvement in rAAV-mediated transgene *** further modifications remain an area of interest,our studies have substantially broadened the pharmacological prospects of melittin in the context of viral vector-mediated gene delivery.

关键词： Melittin Recombinant adeno-associated virus Capsid engineering Transduction efficiency

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Cholecystokinin and cholecystokinin-A receptor: An attractive treatment strategy for biliary dyskinesia?

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World Journal of Gastroenterology 2024年第3期30卷 283-285页

作者： Jun Chang Yan Liu Ting-Can Jiang Lan Zhao Jian-Wei Liu Tianjin Institute of Acupuncture and Moxibustion The First Teaching Hospital of Tianjin University of Traditional Chinese MedicineTianjin 300381China Department of Gastroenterology Tianjin Hospital of Integrated Traditional Chinese and Western Medicine Nankai HospitalTianjin 300100China State Key Laboratory of Component-Based chinese medicine Tianjin University of Traditional Chinese MedicineTianjin 301617China School of Integrative medicine Tianjin University of Traditional Chinese MedicineTianjin 301617China

Biliary dyskinesia is a relatively common gastrointestinal disease that is increas-ing in incidence as living standards ***,its underlying pathogenesis remains unclear,hindering the development of therapeutic ***,“Expression and functional study of cholecystokinin-A receptors on the interstitial Cajal-like cells of the guinea pig common bile duct”demonstrated that cholecystokinin(CCK)regulates the contractile function of the common bile duct through interaction with the CCK-A receptor in interstitial Cajal-like cells,contributing to improving the academic understanding of biliary tract dynamics and providing emerging directions for the pathogenesis and clinical management of biliary *** letter provides a brief overview of the role of CCK and CCK-A receptors in biliary dyskinesia from the perspective of animal experiments and clinical studies,and discusses prospects and challenges for the clinical application of CCK and CCK-A receptors as potential therapeutic targets.

关键词： Cholecystokinin Cholecystokinin-A receptor Biliary dyskinesia Interstitial Cajal-like cell Therapeutic target

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Caveolin‑1 is critical for hepatic iron storage capacity in the development of nonalcoholic fatty liver disease

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Military Medical Research 2024年第2期11卷 206-227页

作者： Guang-Hui Deng Chao-Feng Wu Yun-Jia Li Hao Shi Wei-Chao Zhong Mu-Keng Hong Jun-Jie Li Jia-Min Zhao Chang Liu Meng-Chen Qin Zhi-Yun Zeng Wei-Min Zhang Ken Kin Lam Yung Zhi-Ping Lv Lei Gao Department of Gastroenterology Integrated Hospital of Traditional Chinese MedicineSouthern Medical UniversityGuangzhou 510315China School of traditional chinese medicine Southern Medical UniversityGuangzhou 510515China Department of Hepatology Cancer CenterIntegrated Hospital of Traditional Chinese MedicineSouthern Medical UniversityGuangzhou 510315China Shenzhen traditional chinese medicine hospital Shenzhen 518033GuangdongChina Department of Biology Hong Kong Baptist UniversityKowloon TongKowloonHong Kong SAR 999077China

Background:Nonalcoholic fatty liver disease(NAFLD)is associated with disordered lipid and iron *** previous study has substantiated the pivotal role of Caveolin-1(Cav-1)in protecting hepatocytes and mediating iron metabolism in the *** study aimed to explore the specific mechanisms underlying the regulation of iron metabolism by Cav-1 in ***:Hepatocyte-specific Cav-1 overexpression mice and knockout mice were used in this ***-1-knockdown of RAW264.7 cells and mouse primary hepatocytes were performed to verify the changes in ***,a high-fat diet and palmitic acid plus oleic acid treatment were utilized to construct a NAFLD model in vivo and in vitro,respectively,while a high-iron diet was used to construct an in vivo iron overload ***,iron concentration,the expression of Cav-1 and iron metabolism-related proteins in liver tissue or serum were detected using iron assay kit,Prussian blue staining,Western blotting,immunofluorescence staining,immunohistochemical staining and *** related indicators of lipid metabolism and oxidative stress were evaluated by the corresponding reagent kit and ***:Significant disorder of lipid and iron metabolism occurred in *** expression of Cav-1 was decreased in NAFLD hepatocytes(P<0.05),accompanied by iron metabolism ***-1 enhanced the iron storage capacity of hepatocytes by activating the ferritin light chain/ferritin heavy chain pathway in NAFLD,subsequently alleviating the oxidative stress induced by excess ferrous ions in the ***,CD68^(+) CD163^(+) macrophages expressing Cav-1 were found to accelerate iron accumulation in the liver,which was contrary to the effect of Cav-1 in *** correlations were also observed between the serum Cav-1 concentration and the serum iron-related protein levels in NAFLD patients and healthy volunteers(P<0.05).Conclusions:These findings confirm that Cav-1 is an essential target protein that reg

关键词： Caveolin-1 Nonalcoholic fatty liver disease Iron metabolism Ferritin Oxidative stress

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Reduced expression of semaphorin 3A in osteoclasts causes lymphatic expansion in a Gorham-Stout disease(GSD)mouse model

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第1期25卷 38-50页

作者： Dongfang ZHANG Hao XU Chi QIN Kangming CAI Jing ZHANG Xinqiu XIA Jingwen BI Li ZHANG Lianping XING Qianqian LIANG Wensheng WANG Laboratory of Molecular medicine College of Life Science and State Key Laboratory of Cell Differentiation and RegulationHenan Normal UniversityXinxiang453007China Longhua hospital&Spine Institute Shanghai University of Traditional Chinese MedicineShanghai200032China Key Laboratory of Theory and Therapy of Muscles and Bones Ministry of Education(Shanghai University of Traditional Chinese Medicine)Shanghai201203China Department of Pathology and Laboratory medicine University of Rochester Medical CenterRochester14642USA

Gorham-Stout disease(GSD)is a sporadic chronic disease characterized by progressive bone dissolution,absorption,and disappearance along with lymphatic vessel infiltration in bone-marrow *** the osteolytic mechanism of GSD has been widely studied,the cause of lymphatic hyperplasia in GSD is rarely *** this study,by comparing the RNA expression profile of osteoclasts(OCs)with that of OC precursors(OCPs)by RNA sequencing,we identified a new factor,semaphorin 3A(Sema3A),which is an osteoprotective factor involved in the lymphatic expansion of *** to OCPs,OCs enhanced the growth,migration,and tube formation of lymphatic endothelial cells(LECs),in which the expression of Sema3A is low compared to that in *** the presence of recombinant Sema3A,the growth,migration,and tube formation of LECs were inhibited,further confirming the inhibitory effect of Sema3A on LECs in *** an LEC-induced GSD mouse model,the effect of Sema3A was examined by injecting lentivirus-expressing Sema3A into the tibiae in *** found that the overexpression of Sema3A in tibiae suppressed the expansion of LECs and alleviated bone loss,whereas the injection of lentivirus expressing Sema3A short hairpin RNA(shRNA)into the tibiae caused GSD-like *** staining further demonstrated that OCs decreased and osteocalcin increased after Sema3A lentiviral treatment,compared with the *** on the above results,we propose that reduced Sema3A in OCs is one of the mechanisms contributing to the pathogeneses of GSD and that expressing Sema3A represents a new approach for the treatment of GSD.

关键词： Semaphorin 3A Gorham-Stout disease Osteoclast Osteolysis Lymphatic endothelial cell

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Evaluating the Compatibility Mechanism of Shengxian Decoction Based on an Excretion Study of 18 Bioactive Constituents in Rat Biosamples

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World Journal of traditional chinese medicine 2024年第1期10卷 40-52页

作者： Tao Pang Nan Weng Yong Chen Cui-Yun Huang Mei Sun Feng Zhang Wan-Sheng Chen Department of Pharmacy Changzheng HospitalNaval Medical University(Second Military Medical University)ShanghaiChina Department of Pharmacognosy Shenyang Pharmaceutical University ShenyangLiaoning ProvinceChina traditional chinese medicine Resource and Technology Center Shanghai University of Traditional Chinese MedicineShanghaiChina

Introduction:The Shengxian decoction(SXT),a chinese herbal medication used to treat heart failure,is composed of Astragali Radix,Anemarrhenae Rhizoma,Bupleuri Radix,Cimicifuage Rhizoma,and Platycodonis *** of the excretion of the active compounds in this herbal medication is vital for investigating the underlying mechanisms behind its ***,this remains ***:Liquid chromatography coupled with mass spectrometry was performed in both positive and negative modes to assay 18 constituents of SXT from rat urinary,fecal,and biliary ***:The methodology was validated and showed good linearity(r≥0.9),precision,stability,repeatability,and *** relative standard deviations and relative errors for the precision and accuracy did not exceed 15%.The recoveries of all the compounds ranged from 77.37%to 114.82%,and the matrix effect was between 82.53%and 105.71%.The results suggested that,when combined with Platycodonis Radix,the levels of 14 constituents from the four herbs were reduced in the urine,while the levels of six constituents were reduced in the ***:The comparative excretion results indicated that Platycodonis Radix reduced the excretion of compounds in SXT,demonstrating the compatibility mechanism and holistic properties of these compounds,favoring the pharmacological effects of SXT.

关键词： Compatibility excretion liquid chromatography coupled with mass spectrometry Platycodonis Radix Shengxian decoction

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