Effect of Xuebijing injection on myocardium during cardiopulmonary bypass:A prospective,randomized,double blind trial

BACKGROUND Cardiopulmonary bypass(CPB)is an essential procedure for maintaining the blood supply to vital organs in patients undergoing cardiac surgery.However,perioperative cardiac injury related to CPB remains a severe complication in these patients.Cardiac protection is important for patients undergoing CPB.AIM To evaluate the potential cardioprotective efficacy of the Chinese medicine preparation Xuebijing injection(XBJ)in patients undergoing CPB.METHODS Sixty patients undergoing cardiac surgery with CPB were randomly allocated to the XBJ and control groups(saline).XBJ was administered intravenously three times:12 h prior to surgery,at the beginning of the surgery,and 12 h after the second injection.Cardiac function was evaluated by echocardiography 48 h after surgery.Circulating inflammation-and oxidative-stress-related markers were measured.Clinical outcomes related to intensive care unit(ICU)stay were recorded.RESULTS Compared to control treatment,XBJ was associated with improved PaO2/FiO2 and cardiac systolic function,but reduced troponin I and creatine kinase fraction after surgery(all P<0.05).The circulating concentrations of tumor necrosis factor-α,interleukin(IL)-1βand IL-8 in the XBJ group were significantly lower than those in the control group(all P<0.05),whereas the circulating concentration of IL-10 was significantly higher in the XBJ group(P<0.05).In addition,the lengths of ICU stay and hospitalization after surgery tended to be shorter in the XBJ group than in the control group,although the differences were not significant.CONCLUSION Perioperative administration of XBJ was associated with attenuated cardiac injury during CPB,likely via anti-inflammatory and antioxidative mechanisms.

The protective effects of Xuebijing injection on intestinal injuries of mice exposed to irradiation

Background:Gastrointestinal(GI)injury is one of the most common side effects of radiotherapy.However,there is no ideal therapy method except for symptomatic treatment in the clinic.Xuebijing(XBJ)is a traditional Chinese medicine,used to treat sepsis by injection.In this study,the protective effects of XBJ on radiation-i nduced intestinal injury(RⅢ)and its mechanism were explored.Methods:The effect of XBJ on survival of irradiated C57BL/6 mice was monitored.Histological changes including the number of crypts and the length of villi were evaluated by H&E.The expression of Lgr5^(+)intestinal stem cells(ISCs),Ki67^(+)cells,villin and lysozymes were examined by immunohistochemistry.The expression of cytokines in the intestinal crypt was detected by RT-PCR.DNA damage and apoptosis rates in the small intestine were also evaluated by immunofluorescence.Results:In the present study,XBJ improved the survival rate of the mice after 8.0and 9.0 Gy total body irradiation(TBI).XBJ attenuated structural damage of the small intestine,maintained regenerative ability and promoted proliferation and differentiation of crypt cells,decreased apoptosis rate and reduced DNA damage in the intestine.Elevation of IL-6 and TNF-α was limited,but IL-1,TNF-β and IL-10 levels were increased in XBJ-treated group after irradiation.The expression of Bax and p53 were decreased after XBJ treatment.Conclusions:Taken together,XBJ provides a protective effect on RⅢby inhibiting inflammation and blocking p53-related apoptosis pathway.

Efficacy of Xuebijing injection for the treatment of coronavirus disease 2019 via network pharmacology

Background:To evaluate the mechanism of Chinese patent drug Xuebijing(XBJ)injection in the treatment of a new coronavirus disease 2019(COVID-19)based on network pharmacology and molecular docking technology.Methods:The TCMSP database was employed to collect and screen the active ingredients of the Chinese herb contained in the XBJ injection.The GeneCards database and STRING database were applied to collect and expand the targets of COVID-19 and compare and screen the related targets of COVID-19 by XBJ injection.Cytoscape was employed to build a network connecting Chinese medicine,compounds,targets,disease,and topology analysis was performed via the Network Analyzer to screen the key ingredients and targets.The software of Schrödinger molecular docking was used to verify the binding activity of the key ingredients of XBJ injection and the key targets of COVID-19.Metascape platform and DAVID database were utilized to conduct Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes analysis on the key targets of COVID-19 treated by XBJ injection.Results:Eight key compounds and 15 key targets were screened and verified by molecular docking;these key compounds included luteolin,quercetin,baicalein,and kaempferol.The key targets included DPP4,AR,ESR1,CALM1,and protein kinase 1.Gene Ontology analysis involved an apoptosis and hypoxia reaction and the changes in blood vessel morphology.Kyoto Encyclopedia of Genes and Genomes analysis involved signaling pathways of hypoxia inducible factor-1,VEGF,and PI3K/AKT/NF-κB.Conclusion:The mechanism of XBJ injection when used to treat COVID-19 should be further investigated as the key compounds in XBJ regulated the expression of key targets such as protein kinase 1,VEGF-A,B-cell lymphoma-2,and TNF,which affected the COVID-19 receptors such as angiotensin-converting enzyme 2 and signaling pathways like hypoxia inducible factor-1,PI3K-Akt,and NF-κB,which alleviated the inflammation,respiratory distress,and hypoxia caused by COVID-19 infection.

Efficacy and safety of Xuebijing injection in the treatment of vascular endothelial injury in sepsis patients:A meta-analysis

Objective:To systematically evaluate the efficacy and safety of Xuebijing injection in the treatment of vascular endothelial injury in sepsis,and to provide evidence-based reference for clinical medication.Methods:The randomized controlled trials of Xuebijing injection combined with conventional treatment(experimental group)versus conventional treatment(control group)for sepsis were collected by computer search of Chinese CNKI database,WANFANG database,and VIP database.Literature screening was performed according to the inclusion and exclusion criteria.According to the Cochrane International Collaboration Evaluator Workbook procedure,the quality evaluation and bias analysis were performed for the literatures included in the meta-analysis.Revman 5.3 software was used for systematic meta-analysis.Results:A total of 15 clinical randomized controlled trials with a total of 930 patients were included.Meta-analysis showed that Xuebijing injection combined with conventional therapy could reduce 28-day mortality in sepsis[OR=0.52,95%CI(0.38,0.71),P<0.0001],APACHEⅡintegral[WMD=-2.65,95%CI(-3.23,-2.08),P<0.00001];be effective in decreasing D-dimer[WMD=-0.79,95%CI(-1.17,-0.40),P<0.0001],TNF-α[WMD=-36.71,95%CI(-43.04,-30.39),P<0.00001],vWF[WMD=-15.94,95%CI(-27.60,-4.28),P=0.007],sE-selectin[WMD=-118.30,95%CI(-139.65,-96.95),P<0.00001],ESM-1[WMD=-135.44,95%CI(-186.30,-84.57),P<0.00001],sTM[WMD=-56.46,95%CI(-66.39,-46.53),P<0.00001];can effectively increase platelets[WMD=30.78,95%CI(25.65,35.92),P<0.00001].Conclusion:Xuebijing injection can not only effectively reduce the release of inflammatory factors,thereby improving vascular endothelial injury,reducing coagulation disorders and blocking coagulation-inflammation network;it can also increase the level of platelets,thereby repairing injured vascular endothelial cells,which has a certain value to reduce the condition of sepsis and improve the prognosis.It also provides some basis for the treatment of sepsis secondary to novel coronavirus pneumonia.

Mechanism of Xuebijing injection on hepatic ischemia-reperfusion injury based on network pharmacology

Objective:Using network pharmacology to predict the main active ingredients,targets and signaling pathways of Xuebijing injection in the treatment of hepatic ischemia-reperfusion injury and explore its potential mechanism of action.Methods:Screen the active ingredients and their targets of Danshen,Honghua,Chishao,Chuanxiong,and Danggui in Xuebijing injection through Traditional Chinese Medicine Systems Pharmacology(TCMSP)database and the Hepatic ischemia-reperfusion injury related targets through Online Mendelian Inheritance in Man(OMIM)and GeneCards Suite(The Human Gene Database)database.And acquire drug-disease intersection targets at the same time.The STRING database was used to construct a protein-protein interaction(PPI)network and topologically screen the central targets.Use the R language online search Bioconductor platform to perform GO function enrichment on the target;Database for Annotation,Visualization and Integrated Discovery(DAVID)database was used to perform KEGG channel enrichment analysis on the target.Use Cytoscape 3.7.2 to construct a"ingredient-target-pathway"network diagram and perform a topology analysis.Results:A total of 115 active ingredients were selected from Xuebijing injection,including Quercetin,Luteolin,Kaempferol,Beta-carotene,and Tanshinone IIa,etc.It corresponds to 217 targets.There are 1057 disease-related targets,and 114 drug-disease common targets.PPI topologically screened out 17 target proteins.Topological analysis of the network graph obtained 15 target genes.Thire intersection contains key targets such as JUN,PPARG,PTGS2,AKT1 and MAPK1.A total of 137 related signaling pathways were obtained by GO enrichment analysis.A total of 8 signaling pathways were obtained through KEGG enrichment(P<0.05,FDR<0.05),among which signaling pathways such as Toll-like receptors,T cell receptors,NOD-like receptors,VEGF,and ErbB played an important role in immune regulation,anti-apoptosis,anti-inflammatory,anti-oxidation,and promoting angiogenesis in the treatment.Conclusion:Xuebijing injection can treat hepatic ischemia-reperfusion injury through multiple components,multiple targets and multiple pathways.

Effect of Xuebijing injection on hematopoietic homeostasis of LPS induced sepsis in mice

Objective:To explore the effect and mechanism of Xuebijing injection (XBJ) on the hematopoietic homeostasis of bone marrow (BM) in septic mice. Methods:BM cells stimulated with XBJ were analyzed by inverted optical microscope and qPCR, to evaluate the effect of XBJ on differentiation function of BM cells in vitro. Lipopolysaccharide (LPS) 055:B5 at the dose of 20mg/kg was used to establish the sepsis model. To determine the hematopoietic stem cells homeostasis affected by LPS in mice, BM cells were isolated and analyzed by flow cytometry based on the immunophenotypic surface markers. 20ml/kg of XBJ was administered by tail vein once/day after peritoneal injection of LPS. All animals were sacrificed on the fifth day. The frequency of hematopoietic stem cells (HSC) and immune cells in mice were quantified by flow cytometry. The gene expression of transcription factors were detected by qPCR. Results:XBJ promoted myeloid differentiation of BM cells in vitro, which may be related to the mRNA expression of the transcription factors. The results in vivo showed the percentage of BM Lin-SCA-1+c-KIT+(LSK) cells, and Long-term HSCs (LT-HSC) were significantly increased in LPS group. But the percentage of multipotential progenitors (MPPs), granulocyte-monocyte progenitor (GMP) and megakaryocytic-erythroid precursor (MEP) were significantly decreased in LPS group. Whereas, XBJ improved the immune function in sepsis mice by suppression the LSK expansion in vivo. The result of qPCR showed that LSD1 and PU.1 mRNA expression in XBJ group were significantly higher than LPS group and control group respectively. Conclusion:Xuebijing injection can improve immune function in sepsis mice by regulating hematopoietic homeostasis. Its mechanism may be related to the up-regulation of LSD1 and PU.1 gene expressions.

Xuebijing injection,a Chinese patent medicine,against severe pneumonia:Current research progress and future perspectives

Severe pneumonia is one of the most common infectious diseases and the leading cause of sepsis and septic shock.Preventing infection,balancing the patient’s immune status,and anti-coagulation therapy are all important elements in the treatment of severe pneumonia.As multi-target agents,Xuebijing injection(XBJ)has shown unique advantages in targeting complex conditions and saving the lives of patients with severe pneumonia.This review outlines progress in the understanding of XBJ’s anti-inflammatory,endotoxin antagonism,and anticoagulation effects.From the hundreds of publications released over the past few years,the key results from representative clinical studies of XBJ in the treatment of severe pneumonia were selected and summarized.XBJ was observed to effectively suppress the release of pro-inflammatory cytokines,counter the effects of endotoxin,and assert an anticoagulation effect in most clinical trials,which are consistent with experimental studies.Collectively,this evidence suggests that XBJ could play an important and expanding role in clinical medicine,especially for sepsis,septic shock and severe pneumonia.

Effectiveness and safety of Xuebijing injection for patients with coronavirus disease 2019:a systematic review and Meta-analysis

OBJECTIVE:To evaluate the effectiveness and safety of Xuebijing injection(XBJ)on coronavirus disease 2019(COVID-19)in patients.METHODS:Related studies on multiple biological databases and websites were searched up to December 11,2021 without language and publication time restrictions.Review Manager V.5.3 and Stata 14 software were used for data analysis.RESULTS:Seven studies were finally included.The Meta-analysis showed that compared with the routine treatment alone,XBJ combined with the routine treatment can reduce the 28-day mortality(OR=0.3,95%CI:0.12,0.74),C-reactive protein(MD=-12.8,95%CI:-23.13,-3.46),erythrocyte sedimentation rate(MD=-9.32,95%CI:-14.66,-3.98)and interleukin-6(SMD=-0.6,95%CI:-1.04,-0.17)levels and increase the leukocyte(MD=0.73,95%CI:0.42,1.04)and lymphocyte count(MD=0.18,95%CI:0.07,0.29)in peripheral blood;additionally,it has no obvious side effects(OR=1.11,95%CI:0.65,1.9).There was no evidence that the XBJ combined therapy can improve the nucleic acid conversion rate and computed tomography improvement rate of COVID-19 patients.CONCLUSIONS:Preliminary evidence suggests that XBJ combined with routine treatment seems to be more effective than routine treatment for patients with COVID-19.Limited by the number and quality of included papers,this finding still needs further validation by more studies.

Molecular mechanism of Xuebijing in treating pyogenic liver abscess complicated with sepsis

BACKGROUND:Xuebijing(XBJ)can alleviate the inflammatory response,improve organ function,and shorten the intensive care unit(ICU)stay in patients with pyogenic liver abscess(PLA)complicated with sepsis,but the molecular mechanisms have not been elucidated.This study aimed to explore the molecular mechanism of XBJ in treating PLA complicated with sepsis using a network pharmacology approach.METHODS:The active ingredients and targets of XBJ were retrieved from the ETCM database.Potential targets related to PLA and sepsis were retrieved from the GeneCards,PharmGKB,DisGeNet,Online Mendelian Inheritance in Man(OMIM),Therapeutic Targets Database(TTD),and DrugBank databases.The targets of PLA complicated with sepsis were mapped to the targets of XBJ to identify potential treatment targets.Protein-protein interaction networks were analyzed using the STRING database.Potential treatment targets were imported into the Metascape platform for Gene Ontology(GO)functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses.Molecular docking was performed to validate the interactions between active ingredients and core targets.RESULTS:XBJ was found to have 54 potential treatment targets for PLA complicated with sepsis.Interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor(TNF)were identifi ed as core targets.KEGG enrichment analysis revealed important pathways,including the interleukin-17(IL-17)signaling pathway,the TNF signaling pathway,the nuclear factor-kappa B(NF-κB)signaling pathway,and the Toll-like receptor(TLR)signaling pathway.Molecular docking experiments indicated stable binding between XBJ active ingredients and core targets.CONCLUSION:XBJ may exert therapeutic eff ects on PLA complicated with sepsis by modulating signaling pathways,such as the IL-17,TNF,NF-κB,and TLR pathways,and targeting IL-1β,IL-6,and TNF.

A Clinical Study on the Effects and Mechanism of Xuebijing Injection (血必净注射液) in Severe Pneumonia Patients

Objective: To observe the effects of Xuebijing Injection (血必净注射液) in patients with severe pneumonia, and to explore the mechanism. Methods: Eighty cases of severe pneumonia are randomly assigned to the Xuebijing treatment (forty cases) and the control group (forty cases), with the same routine therapy provided in both groups. Clinical effective rates, inflammatory factors and organ function were observed in both groups. Results: The effective rate was higher in Xuebijing group than that of the control group (80.0% vs. 67.5%, P<0.05). As compared with the control group, the LDH, α1-AG, α1-AT levels and the peak body temperature decreased markedly with the Xuebijing treatment going, and the secretion of TNF-α, IL-6, IL-8 was suppressed in Xuebijing group; but no significant difference was found in leptin level. Conclusion: Xuebijing Injection may show a protective effect in patients with severe pneumonia. The mechanism is possibly with the decreased secretion of TNF-α, IL-6, and IL-8.

Efficacy of Xuebijing Injection(血必净注射液)on Cardiopulmonary Bypass-Associated Pulmonary Injury:A Prospective,Single-center,Double Blinded,Randomized Controlled Trial

Objective： To evaluate the efficacy of Xuebijing Injection（血必净注射液, XBJ） on the lung injury induced by cardiopulmonary bypass（CPB）. Methods： Fifty patients undergoing CPB were randomized to either the saline group or XBJ group according to a random number table（25 cases in each group）. The patients in the saline group received saline and patients in XBJ group received XBJ at 12 h prior to the operation, at the beginning of the operation, and at 12 h after the second injection. The PaO_2/Fi O2 at extubation 3 days post-operation, duration of ventilation in the intensive care unit（ICU）, and lengths of stay in the ICU and hospital were recorded. The levels of inflammatory mediators including interleukin（IL）-1β, IL-8, IL-10, and C-reactive protein（CRP） in bronchoalveolar lavage fluid（BALF） and plasma were measured. The neutrophil count and elastase neutrophil elastase in BALF were also measured. In addition, adverse events were monitored. Results： The PaO-2/FiO_2 in the XBJ group was higher than that in the saline group from 12 to 72 h post-operation（all P〈0.05）. The blood levels of IL-1β, IL-8, and CRP in the XBJ group from 12 to 72 h were all significantly lower than those in the saline group（all P〈0.05）. In contrast, the level of the anti-inflammatory cytokine IL-10 was significantly higher in the XBJ group than in the saline group（P〈0.05）. In addition, 4 patients presented with atelectasis in the saline group and none in the XBJ group. Ten patients experienced mild acute respiratory distress syndrome（ARDS） during hospitalization, and 5 patients with mild ARDS were in the XBJ group（P〈0.05）. Conclusion： XBJ shows protective potential against lung injury in patients who undergo CPB surgery, possibly through the downregulation of inflammatory mediators, reduction in neutrophil infiltration, and upregulation of IL-10（Trial registry： Chi CTR-TRC-14004628）.

Traditional Chinese medicine network pharmacology study on exploring the mechanism of Xuebijing Injection in the treatment of coronavirus disease 2019

As a representative drug for the treatment of severe community-acquired pneumonia and sepsis,Xuebijing(XBJ)injection is also one of the recommended drugs for the prevention and treatment of coronavirus disease 2019(COVID-19),but its treatment mechanism for COVID-19 is still unclear.Therefore,this study aims to explore the potential mechanism of XBJ injection in the treatment of COVID-19 employing network pharmacology and molecular docking methods.The corresponding target genes of 45 main active ingredients in XBJ injection and COVID-19 were obtained by using multiple database retrieval and literature mining.102 overlapping targets of them were screened as the core targets for analysis.Then built the PPI network,TCM-compound-target-disease,and disease-target-pathway networks with the help of Cytoscape 3.6.1 software.After that,utilized DAVID to perform gene ontology(GO)function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis to predict the action mechanism of overlapping targets.Finally,by applying molecular docking technology,all compounds were docked with COVID-193 CL protease(3 CLpro),spike protein(S protein),and angiotensin-converting enzyme II(ACE2).The results indicated that quercetin,luteolin,apigenin and other compounds in XBJ injection could affect TNF,MAPK1,IL6 and other overlapping targets.Meanwhile,anhydrosafflor yellow B(AHSYB),salvianolic acid B(SAB),and rutin could combine with COVID-19 crucial proteins,and then played the role of anti-inflammatory,antiviral and immune response to treat COVID-19.This study revealed the multiple active components,multiple targets,and multiple pathways of XBJ injection in the treatment of COVID-19,which provided a new perspective for the study of the mechanism of traditional Chinese medicine(TCM)in the treatment of COVID-19.

Xuebijing Injection(血必净注射液)and Resolvin D1 Synergize Regulate Leukocyte Adhesion and Improve Survival Rate in Mice with Sepsis-Induced Lung Injury

Objective： To investigate the effect of combined application of Xuebijing Injection（血必净注射液, XBJ） and resolvin D1（RvD1） on survival rate and the underlying mechanisms in mice with sepsisinduced lung injury. Methods： The cecal ligation and puncture（CLP） method was used to develop a mouse sepsis model. Specific pathogen free male C57 BL/6 mice were randomly divided into 5 groups（n=20 each）： sham, CLP, CLP＋XBJ, CLP＋RvD1 and CLP＋XBJ＋RvD1. After surgery, mice in the CLP＋XBJ, CLP＋RvD1 and CLP＋XBJ＋RvD1 groups were given XBJ（25 μL/g body weight）, RvD1（10 ng/g body weight）, and their combination（the same dose of XBJ and RvD1）, respectively. In each group, 12 mice were used to observe 1-week survival rate, while the rest were executed at 12 h. Whole blood was collected for flow cytometric analysis of leukocyte adhesion molecules CD18, lung tissues were harvested for observing pathological changes, and testing the activity of myeloperoxidase（MPO） and the expression of intercellular cell adhesion molecule 1（ICAM-1）. Results： Compared with the CLP group, the histopathological damage of the lung tissues was mitigated, MPO activity was decreased in the CLP＋XBJ and CLP＋RvD1 groups（P〈0.05）. In addition, the 1-week survival rate was improved, proportion of CD18-expressing cells in whole blood and ICAM-1 protein expression in lung tissue were decreased in the CLP＋XBJ＋RvD1 group（P〈0.05 or P〈0.01）. Conclusion： XBJ together with RvD1 could effectively inhibit leukocyte adhesion, reduce lung injury, and improve the survival rate of mice with sepsis.

Protective effect of Xuebijing injection on myocardial injury in patients with sepsis: a randomized clinical trial

OBJECTIVE: To investigate the protective effect and possible mechanism of Xuebijing Injection on myocardial injury in patients with sepsis, and to evaluate its prognostic implications.METHODS: Patients with septic myocardial injury were recruited, and were randomly divided into two groups: treatment group and control group. All patients in two groups received conventional cluster treatment, the patients in treatment group additional received Xuebijing injection dissolved in0.9% sodium chloride injection, and the patients in control group received the same amount of 0.9%sodium chloride injection. At the beginning of treatment and 3, 7 and 10-day after treatment, lab-oratory indicators of cardiac troponin Ⅰ(cTnI),N-terminal pro B-type natriuretic peptide(NT-pro BNP) and procalcitonin(PCT) were respectively tested in venous blood. The patient's length of stay in Intensive Care Unit(ICU) and the mortality in 28 days were recorded.RESULTS: At 3, 7 and 10-day after treatment, the improvements of c Tn I, NT-pro BNP and PCT in treatment group were better than those in control group, and the differences were statistically significant(P < 0.05). The mortality of treatment group in28 days was not significantly different from that of control group(P > 0.05). The ICU length of stay of treatment group was shorter than that of control group(P > 0.05).CONCLUSION: Xuebijing injection could improve the levels of c Tn I, NT-pro BNP and PCT in patients with septic myocardial injury.and it had a protective effect on myocardial injury.

Xuebijing Injection(血必净注射液)Increases Early Survival Rate by Alleviating Pulmonary Vasopermeability in Rats Subjected to Severe Burns

Objective： To investigate the effects of Xuebijing Injection（血必净注射液, XBJ） on survival rate and pulmonary vasopermeability in a rat model of severe scald injury. Methods： Rats were divided into two experiments： experiment 1 was monitored for 12 h post-injury for survival analysis after severe burns; in experiment 2, rats were killed for determination of pulmonary vascular permeability and pro-inflammatory mediators. In both experiments, rats were subject to third-degree 50% total body surface area（TBSA） burns or sham injury followed by XBJ or normal saline（NS） treatment. In addition, rat pulmonary microvascular endothelium cells（PMECs） were pretreated with either XBJ or phosphate buffer saline（PBS）, and then subjected to sham serum or scald serum stimulation for 2 or 6 h, followed by transwell examination for the permeability of PMECs. Meanwhile, pro-inflammatory mediators in PMECs culture supernatant were also investigated. Results： The average survival time in the scald＋XBJ group was 582.1±21.2 min, which was significantly longer than that in the scald ＋ NS group（345.8±25.4 min, P〈0.01）. Plasma levels of tumor necrosis factor-alpha（TNF-α）, E-selectin, interleukin-6（IL-6）, vascular permeability and water content of lung tissues were significantly increased in animals after severe burns（P〈0.01）. However, administration of XBJ significantly decreased these levels in plasma and lung tissue. In in vitro cell experiments, XBJ markedly attenuated permeability in PMECs monolayer and reduced the levels of TNF-α, IL-6 and soluble E-selectin after stimulation with scald serum（P〈0.01）. Conclusions： XBJ increases early survival rate by alleviating pulmonary vasopermeability and inhibiting pro-inflammatory mediators in rats subjected to lethal scald injury. XBJ may be a potent drug in treatment of severe burns.

Effect of Xuebijing Injection(血必净注射液) on Systemic Lupus Erythematosus in Mice

Objective： To observe the effects of Xuebijing Injection （血必净注射液） on dendritic cells （DCs） and T lymphocytes, and the potential mechanisms of its therapeutic effect on systemic lupus erythematosus （SLE）. Methods： A widely used mouse model, SLE-prone BLLF1 mice aged 8-10 weeks, was employed. Mice were randomly divided into 4 groups： a normal group, a model group and two treatment groups treated with Xuebijing Injection with a dose of 6.4 mL/kg via intraperitoneal administration for SLE-prone BLLF1 mice aged 8 weeks （treatment A group） and 10 weeks （treatment B group）. Renal tissue sections were stained with Masson＇s trichrome and periodic acid-silver methenamine. Histopathological changes in the kidney were evaluated by a light microscopy. The capacity of the DCs isolated from the spleen to stimulate the T cell proliferation in response to concanavalin A （Con A） was determined. Results： Compared with the model group, levels of anti-dsDNA antibodies in the two treatment groups decreased remarkablely （P〈0.01, P〈0.05）, and levels of serum creatinine and blood urea nitrogen increased （P〈0.01, P〈0.05）. Pathological changes were found in the kidney in the model group. Histopathological abnormalities were alleviated in the two treatment groups. Treatment with Xuebijing injection also significantly upregulated the expression of CD80, CD86 and major histocompatibility class Ⅱ by DCs compared with the model group （P〈0.05）. When splenic T lymphocytes from BLLF1 mice were co-cultured with DCs at ratios of 1：100, 1：150 and 1：200 for 3 and 5 days, the proliferation of T lymphocytes was suppressed compared with the normal group （P〈0.05）, but this was restored by Xuebijing Injection under the same conditions. In the model group, levels of tumor necrosis factor （TNF）-α in supernatants were significantly elevated compared with the normal group （P〈0.01）, interleukin-2 levels decreased （P〈0.05）, while these changes were significantly alleviated in the Xuebijing treatment groups. Conclusions： Xuebijing Injection alleviated renal injury in SLE-prone BLLF-1 mice. The mechanism might be through influencing T cell polarization mediated by DCs, and Xuebijing Injection might be a potential drug that suppresses immune dysfunction in patients with SLE.

Xuebijing Injection Ameliorates H_(2)S-Induced Acute Respiratory Distress Syndrome by Promoting Claudin-5 Expression

Objective:To investigate the protective effects and underlying mechanisms of Xuebijing Injection(XBJ)on the lung endothelial barrier in hydrogen sulfide(H2S)-induced acute respiratory distress syndrome(ARDS).Methods:Sprague-Dawley rats were exposed to H2S(300 ppm)to establish ARDS model,while human pulmonary microvascular endothelial cells(HPMECs)were incubated with NaHS(a H2S donor,500μmol/L)to establish cell model.H2S and XBJ were concurrently administered to the rat and cell models.Lung hematoxylin and eosin staining,immunohistochemistry,transmission electron microscopy and wet/dry ratio measurement were used to confirm ARDS induced by H2S in vivo.The expression levels of claudin-5,phosphorylated protein kinase B(p-AKT)/t-AKT and p-forkhead box transcription factor O1(FoxO1)/t-FoxO1 in vivo and in vitro were also assessed.Paracellular permeability and transepithelial electrical resistance(TEER)were measured to evaluate endothelial barrier function in the cell model.Results:The morphological investigation showed that XBJ attenuated H2S-induced ARDS in rats.XBJ significantly ameliorated both the reduction in TEER and the increased paracellular permeability observed in NaHS-treated HPMECs(P<0.05).The protective effects of XBJ were blocked by LY294002,a phosphatidylinositol 3-kinase(PI3K)/AKT/FoxO1 pathway antagonist(P<0.05).Furthermore,XBJ promoted the expression of claudin-5 and increased the levels of p-AKT and p-FoxO1 in vivo and in vitro(P<0.05).Conclusion:XBJ ameliorated H2S-induced ARDS by promoting claudin-5 expression via the PI3K/AKT/FoxO1 signaling pathway.

Molecular Insight into the Therapeutic Promise of Xuebijing Injection against Coronavirus Disease 2019

Background:The potential human-to-human transmission of the coronavirus pneumonia(coronavirus disease 2019[COVID-19])has caused an outbreak of acute respiratory illness.Xuebijing injection is recommended as first-line treatment for the severe and critical patients with COVID-19.The aim of present study is to interpret the pharmacological mechanisms and molecular connections of Xuebijing injection against COVID-19 by utilizing the approaches of network pharmacology and molecular docking.Materials and Methods:Active ingredients of Xuebijing injection were collected by Traditional Chinese Medicine Systems Pharmacology(TCMSP)database,and putative therapeutic targets were screened from TCMSP,Swiss Target Prediction,and STITCH databases.Moreover,the protein–protein interactions,topological analysis,and pathway enrichment were established to distinguish the hub targets and pathways by employing STRING database,Cytoscape software,DAVID database,respectively.In addition,the potential interaction and binding activity of candidate ingredients in Xuebijing injection with core targets were revealed by molecular docking simulation(Auto Dock software).Results:A total of 115 bioactive components in Xuebijing injection were collected,and416 targets including AKT1,TP53,VEGFA,ALB,TNF and so on were responsible for treating COVID-19.Bioinformatics analysis revealed that matching core targets were closely associated with the inhibition of cytokine storm for its clinical beneficial effects in severe cases.The results of enrichment analysis indicated that PI3 K-Akt signaling pathway,human T-cell leukemia virus type 1 infection,mitogen-activated protein kinase signaling pathway,tuberculosis,focal adhesion,TNF signaling pathway,and small-cell lung cancer were represented pathways of Xuebijing injection against COVID-19 in terms of lung inflammation,virus infection,and lung injury.Meanwhile,the active ingredients of Xuebijing injection exerted superior binding activities with 3 CLpro and angiotensin-converting enzyme 2 as observed via molecular docking simulation.Conclusions:Through the comprehensive analysis of network pharmacology,the current research preliminarily elaborated the molecular regulation of therapeutic mechanisms for Xuebijing injection against COVID-19 and binding activity between active components and core targets,which provided scientific evidence to facilitate the development of Xuebijing injection and clinical treatment for COVID-19.

Effect of traditional Chinese preparation Xuebijing on inflammatory markers in patients with ventilator-associated pneumonia

Objective:To observe the effect of Xuebijing,a complex traditional Chinese preparation,on inflammation and prognosis of patients with pneumonia.Methods:The patients with ventilator-associated pneumonia in the intensive care unit(ICU)were randomly divided into the control group and the treatment group with 35 cases in each group.Both groups were given routine treatment such as anti-inflammatory drugs,rehydration,expectorant,and nutritional support,while the treatment group was additionally given Xuebijing injection.Serum C-reactive protein(CRP),clinical pulmonary infection score(CPIS),acute physiology,and chronic health scoreⅡ(APACHEⅡ)were recorded before treatment,the 3rd and 7th day after treatment.The duration of antibiotic use,mechanical ventilation,ICU stay,and mortality during 28 days was recorded.Results:There was no significant difference in CRP,CPIS,and APACHEⅡbetween the two groups before treatment(P>0.05).The improvement of CRP,CPIS,and APACHEⅡin the treatment group was better than those in the control group on the 3 and 7 days after treatment,and the differences were statistically significant(P<0.05).The duration of antibiotic use,mechanical ventilation,and ICU stay in the treatment group were less than those in the control group(P<0.05).The 28-day mortality of the treatment group was lower than that of the control group,but the difference was not statistically significant(P>0.05).Conclusions:Xuebijing injection can improve the inflammatory indexes of patients with ventilator-associated pneumonia,and can partly improve the prognosis.

New insights for infection mechanism and potential targets of COVID-19:Three Chinese patent medicines and three Chinese medicine formulas as promising therapeutic approaches

The coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)with high pathogenicity and infectiousness has become a sudden and lethal pandemic worldwide.Currently,there is no accepted specific drug for COVID-19 treatment.Therefore,it is extremely urgent to clarify the pathogenic mechanism and develop effective therapies for patients with COVID-19.According to several reliable reports from China,traditional Chinese medicine(TCM),especially for three Chinese patent medicines and three Chinese medicine formulas,has been demonstrated to effectively alleviate the symptoms of COVID-19 either used alone or in combination with Western medicines.In this review,we systematically summarized and analyzed the pathogenesis of COVID-19,the detailed clinical practice,active ingredients investigation,network pharmacology prediction and underlying mechanism verification of three Chinese patent medicines and three Chinese medicine formulas in the COVID-19 combat.Additionally,we summarized some promising and high-frequency drugs of these prescriptions and discussed their regulatory mechanism,which provides guidance for the development of new drugs against COVID-19.Collectively,by addressing critical challenges,for example,unclear targets and complicated active ingredients of these medicines and formulas,we believe that TCM will represent promising and efficient strategies for curing COVID-19 and related pandemics.