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xuebijing improves intestinal microcirculation dysfunction in septic rats by regulating the VEGF-A/PI3K/Akt signaling pathway

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World Journal of Emergency Medicine 2024年第3期15卷 206-213页

作者： A-ling Tang Yan Li Li-chao Sun Xiao-yu Liu Nan Gao Sheng-tao Yan Guo-qiang Zhang Department of Emergency China-Japan Friendship HospitalBeijing 100029China Graduate School Beijing University of Chinese MedicineBeijing 100105China

BACKGROUND:This study aims to explore whether xuebijing(XBJ) can improve intestinal microcirculation dysfunction in sepsis and its mechanism.METHODS:A rat model of sepsis was established by cecal ligation and puncture(CLP).A total of 30 male SD rats were divided into four groups:sham group,CLP group,XBJ + axitinib group,and XBJ group.XBJ was intraperitoneally injected 2 h before CLP.Hemodynamic data(blood pressure and heart rate) were recorded.The intestinal microcirculation data of the rats were analyzed via microcirculation imaging.Enzyme-linked immunosorbent assay(ELISA) kits were used to detect the serum levels of interleukin-6(IL-6),C-reactive protein(CRP),and tumor necrosis factor-α(TNF-α) in the rats.Histological analysis and transmission electron microscopy were used to analyze the injury of small intestinal microvascular endothelial cells and small intestinal mucosa in rats.The expression of vascular endothelial growth factor A(VEGF-A),phosphoinositide 3-kinase(PI3K),phosphorylated PI3K(p-PI3K),protein kinase B(Akt),and phosphorylated Akt(p-Akt) in the small intestine was analyzed via Western blotting.RESULTS:XBJ improved intestinal microcirculation dysfunction in septic rats,alleviated the injury of small intestinal microvascular endothelial cells and small intestinal mucosa,and reduced the systemic inflammatory response.Moreover,XBJ upregulated the expression of VEGF-A,p-PI3K/total PI3K,and p-Akt/total Akt in the rat small intestine.CONCLUSION:XBJ may improve intestinal microcirculation dysfunction in septic rats possibly through the VEGF-A/PI3K/Akt signaling pathway.

关键词： Sepsis xuebijing Vascular endothelial growth factor A Microcirculation Rat Phosphoinositide 3-kinase Protein kinase B

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Novel assays for quality evaluation of xuebijing:Quality variability of a Chinese herbal injection for sepsis management

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Journal of Pharmaceutical Analysis 2022年第4期12卷 664-682页

作者： Xuan Yu Wei Niu Ya-Ya Wang Olajide E.Olaleye Jia-Nan Wang Meng-Yuan Duan Jun-Ling Yang Rong-Rong He Zi-Xuan Chu Kai Dong Gui-Ping Zhang Chang-Xiao Liu Chen Cheng Chuan Li State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai201203China School of Pharmacy University of Chinese Academy of SciencesBeijing100049China Graduate School Tianjin University of Traditional Chinese MedicineTianjin300193China Research Institute Tianjin Chasesun Pharmaceutical Co.Ltd.Tianjin301700China State Key Laboratory of Drug Delivery Technology and Pharmacokinetics and Tianjin Key Laboratory of Quality-Marker of Traditional Chinese Medicines Tianjin Institute of Pharmaceutical ResearchTianjin300193China

xuebijing is an intravenous five-herb injection used to treat sepsis in China.The study aimed to develop a liquid chromatography-tandem mass spectrometry(LC-MS/MS)-or liquid chromatography-ultraviolet(LC-UV)-based assay for quality evaluation of xuebijing.Assay development involved identifying marker constituents to make the assay therapeutically relevant and building a reliable one-point calibrator for monitoring the various analytes in parallel.Nine marker constituents from the five herbs were selected based on xuebijing's chemical composition,pharmacokinetics,and pharmacodynamics.A selectivity test(for“similarity of response”)was developed to identify and minimize interference by nontarget constituents.Then,an intercept test was developed to fulfill“linearity through zero”for each analyte(absolute ratio of intercept to C response,xuebijing,manufactured over three years,and found small batch-to-batch variability in contents of the marker constituents(4.1%-14.8%),except for senkyunolide I(26.5%).

关键词： xuebijing Chinese herbal medicine Quality variability Quality marker One-point calibration

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xuebijing alleviates LPS-induced acute lung injury by downregulating pro-inflammatory cytokine production and inhibiting gasdermin-E-mediated pyroptosis of alveolar epithelial cells

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中国天然药物:英文版 2023年第8期21卷 576-588页

作者： ZHANG Cuiping CHEN Xiaoyan WEI Tianchang SONG Juan TANG Xinjun BI Jing CHEN Cuicui ZHOU Jian SU Xiao SONG Yuanlin Shanghai Key Laboratory of Lung Inflammation and Injury Department of Pulmonary MedicineZhongshan HospitalFudan UniversityShanghai 200032China The Unit of Respiratory Infection and Immunity Institut Pasteur of ShanghaiChinese Academy of SciencesShanghai 200031China Shanghai Institute of Infectious Disease and Biosecurity Shanghai 200032China Shanghai Respiratory Research Institute Shanghai 200032China National Clinical Research Center for Aging and Medicine Huashan HospitalFudan UniversityShanghai 200032China Department of Pulmonary Medicine Jinshan Hospital of Fudan UniversityShanghai 201508China

Acute lung injury/acute respiratory distress syndrome(ALI/ARDS)is characterized by diffuse alveolar injury primarily caused by an excessive inflammatory response.Regrettably,the lack of effective pharmacotherapy currently available contributes to the high mortality rate in patients with this condition.xuebijing(XBJ),a traditional Chinese medicine recognized for its potent anti-inflammatory properties,exhibits promise as a potential therapeutic agent for ALI/ARDS.This study aimed to explore the preventive effects of XBJ on ALI and its underlying mechanism.To this end,we established an LPS-induced ALI model and treated ALI mice with XBJ.Our results demonstrated that pre-treatment with XBJ significantly alleviated lung inflammation and increased the survival rate of ALI mice by 37.5%.Moreover,XBJ substantially suppressed the production of TNF-α,IL-6,and IL-1βin the lung tissue.Subsequently,we performed a network pharmacology analysis and identified identified 109 potential target genes of XBJ that were mainly involved in multiple signaling pathways related to programmed cell death and anti-inflammatory responses.Furthermore,we found that XBJ exerted its inhibitory effect on gasdermin-E-mediated pyroptosis of lung cells by suppressing TNF-αproduction.Therefore,this study not only establishes the preventive efficacy of XBJ in ALI but also reveals its role in protecting alveolar epithelial cells against gasdermin-E-mediated pyroptosis by reducing TNF-αrelease.

关键词： Pyroptosis Gasdermin-E TNF-α xuebijing Acute lung injury

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xuebijing alters tumor necrosis factor-alpha, interleukin-1beta and p38 mitogen activated protein kinase content in a rat model of cardiac arrest following cardiopulmonary resuscitation

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Neural Regeneration Research 2011年第33期6卷 2573-2576页

作者： Haifeng Li Mingli Sun Yaxin Yu Xiaoliang Liu Emernenc.v Medicine. Second Branch of First Hosoital of Jilin University Chanclchun 130031 Jilin Province China

We established a rat model of cardiac arrest by clamping the endotracheal tube of adult rats at expiration. Twenty-four hours after cardiopulmonary resuscitation, nerve cell injury and expression of tumor necrosis factor-α, interleukin-1β, and p38 mitogen activated protein kinase content were increased. Rats injected with xuebijing, a Chinese herb compound preparation, exhibited normal cellular structure and morphology, dense neuronal cytoplasm, and decreased tumor necrosis factor-α, interleukin-1β, and p38 mitogen activated protein kinase expression at 24 hours following cardiopulmonary resuscitation. These data suggest that xuebijing can attenuate neuronal injury induced by hypoxia and reperfusion during cardiopulmonary resuscitation.

关键词： cardiac arrest brain tumor necrosis factor-α interleukin-1β p38 mitogen activated protein kinase xuebijing cardiopulmonary resuscitation

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High degree of pharmacokinetic compatibility exists between the five-herb medicine xuebijing and antibiotics comedicated in sepsis care

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Acta Pharmaceutica Sinica B 2019年第5期9卷 1035-1049页

作者： Jian Li Olajide E.Olaleye Xuan Yu Weiwei Jia Junling Yang Chuang Lu Songqiao Liu Jingjing Yu Xiaona Duan Yaya Wanga Kai Dong Rongrong He Chen Cheng Chuan Li State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of Sciences University of Chinese Academy of Sciences Department of DMPK Department of Critical Care Medicine Zhongda HospitalSchool of MedicineSoutheast University School of Pharmacy University of Washington Tianjin Chasesun Pharmaceutical Co.Ltd.

Managing the dysregulated host response to infection remains a major challenge in sepsis care. Chinese treatment guideline recommends adding Xue Bi Jing, a five-herb medicine, to antibioticbased sepsis care. Although adding Xue Bi Jing further reduced 28-day mortality via modulating the host response, pharmacokinetic herbedrug interaction is a widely recognized issue that needs to be studied.Building on our earlier systematic chemical and human pharmacokinetic investigations of Xue Bi Jing, we evaluated the degree of pharmacokinetic compatibility for Xue Bi Jing/antibiotic combination based on mechanistic evidence of interaction risk. Considering both Xue Bi Jing-antibiotic and antibiotic-Xue Bi Jing interaction potential, we integrated informatics-based approach with experimental approach and developed a compound pair-based method for data processing. To reflect clinical reality, we selected for study Xue Bi Jing compounds bioavailable for drug interactions and 45 antibiotics commonly used in sepsis care in China. Based on the data of interacting with drug metabolizing enzymes and transporters, no Xue Bi Jing compound could pair, as perpetrator, with the antibiotics. Although some antibiotics could,due to their inhibition of uridine 50-diphosphoglucuronosyltransferase 2 B15, organic anion transporters1/2 and/or organic anion-transporting polypeptide 1 B3, pair with senkyunolide I, tanshinol and salvianolic acid B, the potential interactions(resulting in increased exposure) are likely desirable due to these Xue Bi Jing compounds’ low baseline exposure levels. Inhibition of aldehyde dehydrogenase by 7 antibiotics probably results in undesirable reduction of exposure to protocatechuic acid from Xue Bi Jing.Collectively, Xue Bi Jing/antibiotic combination exhibited a high degree of pharmacokinetic compatibility at clinically relevant doses. The methodology developed can be applied to investigate other drug combinations.

关键词： xuebijing Antibiotic Combination drug therapy Sepsis Pharmacokinetic compatibility Herb-drug interaction

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Intravenous injection of xuebijing attenuates acute kidney injury in rats with paraquat intoxication

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World Journal of Emergency Medicine 2017年第1期8卷 61-64页

作者： Jia-jun Xu Jian-tao Zhen Li Tang Qing-ming Lin Department of Emergency Medicine Quanzhou First Hospital Affiiated Fujian Medical University Department of Emergency Medicine Fujian Provincial Hospital Shengli Clinical Medical College of Fujian Medical University

BACKGROUND: The study aimed to investigate the therapeutic benefits of intravenous xuebijing on acute kidney injury(AKI) in rats with paraquat intoxication.METHODS: Male Sprague-Dawley rats were randomly divided equally into three groups: sham group(n=8), paraquat group(n=8) and xuebijing-treated group(n=8) using a random number table. The rats were intraperitoneally injected with 50 mg/kg of paraquat. One hour after paraquat administration, the rats were treated intravenously with xuebijing(8 mL /kg). At 12 hours after paraquat administration, serum was collected to evaluate kidney function, then the rats were sacrificed and kidney samples were immediately harvested. AKI scores were evaluated by renal histopathology and pro-in? ammatory cytokines mR NA levels in kidney were assayed using real-time RT-PCR.RESULTS: Serum urea nitrogen, creatinine and AKI scores were significantly higher in the paraquat group, compared with the sham group(Pxuebijing signi? cantly decreased serum urea nitrogen, creatinine, AKI scores and IL-1β, IL-6 and TNF-α m RNA levels, compared with the paraquat group(Pxuebijing attenuates AKI following paraquat poisoning by suppressing in? ammatory response.

关键词： Paraquat xuebijing Kidney injury Inflammation

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The research idea of xuebijing injection in influencing severe pneumonia-pulmonary fibrosis with blood stasis syndrome evolution by inhibiting inflammation, endotoxin and dispersing blood stasis

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TMR Modern Herbal Medicine 2020年第2期3卷 113-119页

作者： Rui Zheng Chengyu Li Ping Wang Min Li Pengqian Wang Changming Zhong Jianxun Wang Hongcai Shang Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing Dongzhimen HospitalBeijing University of Chinese MedicineBeijingChina Tianjin Chase Sun Pharmaceutical Co. LtdTianjinChina School of Life Sciences Beijing University of Chinese MedicineFangshan DistrictBeijingChina Department of Cardiology Third Affiliated Hospital of Beijing University of Chinese MedicineBeijingChina Institute of Chinese Materia Medica China Academy of Chinese Medical SciencesBeijingChina

Severe pneumonia is one of the most serious infectious diseases.Delayed intervention may lead to pulmonary fibrosis,which greatly threatens people’s life and health.Blood stasis syndrome is an important underlying syndrome throughout the evolution of severe pneumonia-pulmonary fibrosis.xuebijing injection(XBJ)was developed under the theoretical system of“Three syndromes and three methods”,demonstrating a good efficacy in treating severe pneumonia and pulmonary fibrosis due to its effect of removing blood stasis and dispersing toxins.Previous studies have shown that XBJ can protect vascular endothelial function,improve coagulation function and regulate immunity by inhibiting inflammatory.Hence,the research hypothesis is put forward that XBJ treats blood stasis syndrome by removing blood stasis and dredging blood vessels,to inhibit the disease progress of severe pneumonia to pulmonary fibrosis.Further researches are need to confirm the function and explore the mechanism of XBJ.

关键词： xuebijing injection Severe pneumonia Pulmonary fibrosis Blood stasis syndrome Coagulation

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Uncovering the multi-target pharmacological mechanism of xuebijing injection against sepsis by a systems pharmacology approach

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TMR Modern Herbal Medicine 2021年第1期4卷 63-78页

作者： Ping Wang Jingjing Zhu Jie Zhai Xiaorui Li Hongcai Shang Jianxun Wang School of Life Sciences Beijing University of Chinese MedicineBeijing 100029China Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing Dongzhimen HospitalBeijing University of Chinese MedicineBeijing 100700China

Sepsis is a life-threatening organ dysfunction that is associated with a high risk of death.xuebijing(XBJ)injection,a Chinese herbal compound preparation,has been widely used for the treatment of sepsis in China.The purpose of this research is to decipher the underlying multi-target pharmacological mechanism of XBJ in the treatment of sepsis using a systems pharmacology approach.Compounds in XBJ were collected by literature retrieval.The corresponding putative targets of XBJ were screened from the Traditional Chinese Medicine Systems Pharmacology(TCMSP),Swiss Target Prediction(STP),and Search Tool for Interacting Chemicals(STITCH)databases.Sepsis-related targets were summarized using the Genecards,DrugBank,and Online Mendelian Inheritance in Man(OMIM)databases.The intersection targets were obtained with Venny 2.1.Subsequently,protein-protein interaction(PPI)networks were constructed with the STRING database and Cytoscape 3.7.1.Then,degree,betweenness,and closeness were calculated to recognize the core targets in the PPI network.Moreover,the pharmacological mechanism of XBJ against sepsis was predicted via gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment.After the literature review,the 33 most commonly cited chemical ingredients,were screened out as major compounds.Bioinformatics analysis revealed that the major compounds of XBJ modulated 218 common targets associated with sepsis.Through PPI network analysis,41 genes,including IL-6,AKT1,STAT3,TP53,and MAPK1,were identified as core targets.The results of GO and KEGG enrichment revealed that the potential biological functions of XBJ against sepsis were mainly involved in cytokine receptor binding,cytokine activity,growth factor receptor binding,growth factor activity,and chemokine activity.The crucial pathways were closely associated with initial immune activation(CLR/TLR4-NF-κB/MAPK pathway),the acute inflammatory response(TNFMAPK/caspase and IL-MAPK/STAT pathways),and the late inflammation and coagulation process(HMGB1-RAGE and HIF-1 si

关键词： xuebijing Sepsis Multi-target Mechanism Systems pharmacology

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The effect on immune function and inflammatory factors of adjuvant antibiotic therapy through xuebijing combined with thymopentin in elderly patients with severe pneumonian

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Journal of Hainan Medical University 2017年第11期23卷 26-29页

作者： Yi-Ya Jiang Tie-Feng Qiu Zhi-Fang Zhuang Respiration Medicine of Changzhou Wujin People's Hospital Changzhou Jiangsu213000

Objective:To investigate the effect on immune function and inflammatory factors of adjuvant antibiotic therapy through xuebijing combined with thymopentin in elderly patients with severe pneumonia.Methods:Divided 100 cases of elderly patients with severe pneumonia into the observation group and the treatment group according to odevity of serial number. Fifty patients in each group. Gave control group severe pneumonia conventional treatment, such as mechanical ventilation, antifebrile, removing phlegm and anti-infection, and gave xuebijing by intravenous drop simultaneously;observation group was given xuebijing combined with thymopentin by intravenous drop on the base of conventional treatment. Then compared the T lymphocyte subpopulation and serum inflammatory factors level including CRP, IL-6, IL-1 and TNF-α of two groups before treatment and 7 d, 14 d of treatment respectively.Result:(1) There was significant difference in the level of CD3+, CD4+, CD8+, CD4+/CD8+ in this two groups at different time points, and that the level of CD3+, CD4+, CD4+/CD8+: T2>T1>T0, CD8+ level: T2xuebijing combined with thymopentin in elderly patients with severe pneumonia could improve the immune function and lower the inflammatory factors level.

关键词： Elderly patient with severe pneumonia xuebijing thymopentin Immune function Inflammatory factors

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Effects of xuebijing Combined with Ulinastatin on Coagulation Function of Sepsis Patients

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Medicinal Plant 2019年第3期10卷 90-92页

作者： Yongping ZHANG Xuhong TAN Qin LI Hanlin TANG Zaiqun WANG Li XU The Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine

[Objectives] To study the effects of xuebijing combined with ulinastatin on coagulation function of sepsis patients. [Methods]Fifty six patients conforming to the diagnosis criteria for sepsis and receiving the treatment from May 2015 to January 2019 were selected. They were randomly divided into treatment group and control group according to the order of treatment. The two groups were treated according to the International Guidelines for Management of Severe Sepsis and Septic Shock( 2012),in which ulinastatin and xuebijing were added to the treatment group. Before the treatment and on the seventh day after the treatment,both groups of patients were measured for the activated partial thromboplastin time( APTT),fibrinogen( Fi B),platelet( PLT),and prothrombin time( PT) were measured;the treatment status of the both groups was continuously observed for 7 d,and the mechanical ventilation time,ICU hospitalization time,and 30-day survival rate were recorded. [Results] Both FIB and PLT of the treatment group were significantly increased,and both APTT and PT were significantly shortened.Compared with the control group,the difference was statistically significant( P xuebijing combined with ulinastatin can improve coagulation disorders of sepsis patients.

关键词： Sepsis xuebijing Ulinastatin Coagulation function

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