Novel assays for quality evaluation of XueBiJing: Quality variability of a Chinese herbal injection for sepsis management.
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SUBMITTER: Yu X
PROVIDER: S-EPMC9463487 | biostudies-literature | 2022 Aug
REPOSITORIES: biostudies-literature
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Novel assays for quality evaluation of XueBiJing: Quality variability of a Chinese herbal injection for sepsis management.
Yu Xuan X Niu Wei W Wang Ya-Ya YY Olaleye Olajide E OE Wang Jia-Nan JN Duan Meng-Yuan MY Yang Jun-Ling JL He Rong-Rong RR Chu Zi-Xuan ZX Dong Kai K Zhang Gui-Ping GP Liu Chang-Xiao CX Cheng Chen C Li Chuan C
Journal of pharmaceutical analysis 20220126 4
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 herb ...[more]
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Project description:Background: At present, a number of systematic reviews (SRs) on Xuebijing injection (a patent in China) in the treatment of acute pancreatitis (AP) or severe acute pancreatitis (SAP) have been published. However, the quality of evidence is uneven and has not been comprehensively evaluated. Aim: We evaluated the efficacy of Xuebijing injection for AP/SAP through an overview of SR, and to provide a scientific basis for its effectiveness and safety. Methods: We searched Cochrane Library, Embase, PubMed, SinoMed, CNKI, Wanfang, and VIP comprehensively. The retrieval period from inception to 30 November 2021, and the two reviewers independently complete the literature retrieval, data extraction and evaluation. The Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR-2) and the Preferred Reporting Item for Systematic Review and Meta-analysis (PRISMA) were used to evaluate the methodological quality and reporting quality of the SRs, respectively. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool was used to evaluate the quality grading of outcomes and the risk of bias in SRs was evaluated by ROBIS Tool. Finally, the RCTs involved in SRs were synthesized. Stata15.1 was used for quantitative analysis of total effectiveness rate, time until relief of abdominal pain, time until relief of abdominal distension, and serum amylase level. Results: Nine eligible SRs were included, including 92 RCTs and 6,837 participants. The quality of SRs was relatively good, and the manuscript structures were relatively complete. However, the methodological quality of SRs was low or critically low. RoB rated 5 SRs as low risk of bias and 4 SRs as high risk of bias. In GRADE, a total of 47 results were included in the 9 SRs, of which 5 results (10.64%) were moderate quality, 22 results (46.81%) were low quality, and 20 results (42.55%) were very low quality. The results of data synthesis showed that Xuebijing injection combined treatment increased the total effectiveness rate of AP patients (RR = 1.19, 95% CI 1.17–1.23, p < 0.0001), and there was no heterogeneity between studies (I2 = 0.0%, p = 0.589). Compared with the control group, Xuebijing injection group shortened the abdominal pain and distension relief time in AP patients (WMD = −1.69, 95% CI −1.88–−1.50, p < 0.0001; WMD = −1.48, 95% CI −1.74–−1.23, p < 0.0001), with high heterogeneity (I2 = 84.3%, p = 0.000; I2 = 72.2%, p = 0.000). Serum amylase level was also reduced (WMD = −2.06, 95% CI −2.47–−1.64, p < 0.0001), with significant heterogeneity (I2 = 71.6%, p = 0.000). A total of one SR reported adverse drug reaction (ADR), no ADRs were observed in the control group. Conclusion: Although the quality of the evidence is not high, it can still reflect the clinical value of Xuebijing injection as an analgesic and anti-inflammatory traditional Chinese medicine in the treatment of AP/SAP. Therefore, future clinical studies should focus on the long-term efficacy and adverse reactions of drugs. Systematic Review Registration: (website), identifier (registration number).
| S-EPMC9399720 | biostudies-literature
Project description:IntroductionSepsis patients with diabetes are at a high clinical risk. It is well reported that XueBiJing injection has good clinical benefit in sepsis individuals. However, there is no relevant report about the efficacy and safety of XBJ in sepsis patients with comorbid diabetes.MethodsData of two large randomized controlled clinical trials (XBJ-SAP (ChiCTR-TRC-13003534) and EXIT-SEP (NCT0323874)) were combined, and post hoc analyses were performed. Sepsis patients with diabetes were further divided into the XBJ-treated group and placebo group based on inclusion and exclusion criteria. The primary (28-day mortality) and secondary outcomes (mortality in the ICU and in the post-randomization hospital, acute physiology, and chronic health evaluation II (APACHE II) score and sequential organ failure assessment (SOFA) score) were compared between the XBJ treatment and placebo groups in sepsis patients with the diabetes status at baseline. Moreover, the occurrence of adverse events (AEs) was also assessed.ResultsAt the study baseline, a total of 378 sepsis patients (227 men [60.0%] and 151 women [40.0%]; mean [SD] age, 60.3 [11.1] years) were considered to have diabetes, of which 177 received XBJ and 201 received placebo administration. Among these sepsis patients with diabetes, the mortality at 28 days was significantly lower in the XBJ group than in the placebo group (29 of 173 patients [16.8%] vs. 56 of 198 patients [28.3%], P = 0.01), and the absolute risk difference was 11.5% (95% CI, 3.1%-19.9%). Furthermore, there was no difference in the overall incidence of adverse events (AEs) when XBJ was used (24.4% [42 of 172 patients] vs. 27.7% [54 of 195 patients].DiscussionThe present study underscores the pivotal role of XBJ in modulating the immune response among sepsis patients suffering from diabetes mellitus, exploring the positive effects of XBJ on sepsis patients with diabetes mellitus. The efficacy and safety of XBJ compared with those of the placebo were consistent with the overall trial findings, demonstrating that XBJ is efficacious in sepsis patients with diabetes and suggesting that there is no need for special safety precautions.Trial registration identifierChiCTR-TRC-13003534 and NCT0323874.
| S-EPMC11905295 | biostudies-literature
Project description:Excessive endothelial pro-inflammatory response is an early hallmark in sepsis-induced acute lung injury (ALI). Xuebijing (XBJ) as a Chinese traditional medicine is widely used for treating sepsis in the clinic. However, the molecular mechanism of the beneficial effectiveness of XBJ remains unclear. Our present study showed that XBJ inhibited phosphorylation-dependent activation of ATP citrate lyase (ACLY), thereby suppressing the acetylation-dependent nuclear translocation of transcription factor MYB. Thus, as the downstream target gene of MYB, the expression of retinoic acid inducible gene I (RIG-I) was downregulated, leading to the inhibition of NF-κB signaling and EC pro-inflammatory and coagulation activation, which further alleviated sepsis-associated ALI. Moreover, XBJ compounds Quercetin, Ferulic Acid, Kaempferol and Paeoniflorin all showed inhibitory effects on the activation of the downstream MYB/RIG-I signaling by binding to ACLY protein. Our study revealed the novel regulatory mechanism of XBJ in sepsis-induced EC dysfunction and ALI via ACLY/MYB/RIG-I axis, providing theoretical basis for the clinical application of XBJ and shedding insight into novel therapeutic targets for treating sepsis.
2025-03-01 | GSE279126 | GEO
Project description:Sepsis is a systemic inflammatory reaction caused by various infectious or noninfectious factors, which can lead to shock, multiple organ dysfunction syndrome, and death. It is one of the common complications and a main cause of death in critically ill patients. At present, the treatments of sepsis are mainly focused on the controlling of inflammatory response and reduction of various organ function damage, including anti-infection, hormones, mechanical ventilation, nutritional support, and traditional Chinese medicine (TCM). Among them, Xuebijing injection (XBJI) is an important derivative of TCM, which is widely used in clinical research. However, the molecular mechanism of XBJI on sepsis is still not clear. The mechanism of treatment of "bacteria, poison and inflammation" and the effects of multi-ingredient, multi-target, and multi-pathway have still not been clarified. For solving this issue, we designed a new systems pharmacology strategy which combines target genes of XBJI and the pathogenetic genes of sepsis to construct functional response space (FRS). The key response proteins in the FRS were determined by using a novel node importance calculation method and were condensed by a dynamic programming strategy to conduct the critical functional ingredients group (CFIG). The results showed that enriched pathways of key response proteins selected from FRS could cover 95.83% of the enriched pathways of reference targets, which were defined as the intersections of ingredient targets and pathogenetic genes. The targets of the optimized CFIG with 60 ingredients could be enriched into 182 pathways which covered 81.58% of 152 pathways of 1,606 pathogenetic genes. The prediction of CFIG targets showed that the CFIG of XBJI could affect sepsis synergistically through genes such as TAK1, TNF-α, IL-1β, and MEK1 in the pathways of MAPK, NF-κB, PI3K-AKT, Toll-like receptor, and tumor necrosis factor signaling. Finally, the effects of apigenin, baicalein, and luteolin were evaluated by in vitro experiments and were proved to be effective in reducing the production of intracellular reactive oxygen species in lipopolysaccharide-stimulated RAW264.7 cells, significantly. These results indicate that the novel integrative model can promote reliability and accuracy on depicting the CFIGs in XBJI and figure out a methodological coordinate for simplicity, mechanism analysis, and secondary development of formulas in TCM.
| S-EPMC8687625 | biostudies-literature
Project description:IntroductionSepsis is a major challenge with high incidence and is associated with high mortality worldwide. Current management of sepsis remains mainly supportive except for treatment with antibiotics. Both basic research and clinical investigation have shown that the Chinese herbal-derived therapeutic Xuebijing (XBJ) injection is beneficial for patients with sepsis. However, the quality of evidence supporting the therapeutic use of XBJ in sepsis is limited. The aim of this trial is to evaluate the Efficacy of Xuebijing Injection for Sepsis, compared with a placebo, on the outcome of patients with sepsis in the intensive care unit (ICU).Methods and analysisIn this multicentre, blinded randomised controlled trial, we are recruiting a total of 1800 subjects who met Sepsis 3.0 criteria. Subjects will be randomised (1:1) to receive XBJ, every 12 hours for 5 days or a matching placebo and usual care. The primary outcome is 28 days all-cause mortality. Secondary outcomes will be the improvement of Sequential Organ Failure Assessment scores, the improvement of the Acute Physiology and Chronic Health Evaluation II score, duration of mechanical ventilation, mortality in ICU and duration of stay in the ICU. Investigators, participants and statisticians will be blinded to the allocated treatment.Ethics and disseminationThis trial has been approved by all ethics committees of the centres that will participate in this trial. The findings of the study will be disseminated in peer-reviewed journals and present at conferences. Once this study is complete, the results of this trial may help provide evidence-based recommendations for complementary therapeutic options for patients with sepsis.Trial registration numberNCT03238742 and ChiCTR-IPR-17012713.
| S-EPMC6720249 | biostudies-literature
Project description:The drug combination of biapenem (BIPM) and xuebijing injection (XBJ) is commonly applied for the treatment of sepsis in China. However, the potential synergistic mechanism is still enigmatic. There have been no studies focused on the plasma metabolome alterations in sepsis after the intervention of this combination. In this work, an untargeted metabolomics approach was performed by liquid chromatography-mass spectrometry coupled with multivariate statistical analysis to provide new insights into the synergistic effect of BIPM in combination with XBJ. We characterized the metabolic phenotype of sepsis and described metabolic footprint changes in septic rats responding to XBJ and BIPM individually and in combination, in addition to histopathological and survival evaluation. A total of 91 potential biomarkers of sepsis were identified and 32 disturbed metabolic pathways were constructed. Among these biomarkers, 36 metabolites were reversely regulated by XBJ, mainly including glycerophospholipids, sphingolipids, free fatty acids (FFAs), bile acids and acylcarnitines; 42 metabolites were regulated by BIPM, mainly including amino acids, glycerophospholipids, and acylcarnitines; 72 metabolites were regulated after XBJ-BIPM combination treatment, including most of the 91 potential biomarkers. The results showed that the interaction between XBJ and BIPM indeed exhibited a synergistic effect by affecting some key endogenous metabolites, 15 metabolites of which could not be regulated when XBJ or BIPM was used alone. Compared with Model group, 13, 22, and 27 metabolic pathways were regulated by XBJ, BIPM, and XBJ-BIPM combination, respectively. It suggested that many more endogenous metabolites and metabolic pathways were significantly regulated after combination treatment compared with XBJ or BIPM monotherapy. Metabolisms of lipids, amino acids, acylcarnitines, and bile acids were common pathways involved in the synergistic action of XBJ and BIPM. This study was the first to employ metabolomics to elucidate the synergistic effect and decipher the underlying mechanisms of BIPM in combination with XBJ against sepsis. The results provide some support for clinical application of antibiotics in combination with traditional Chinese medicines and have important implications for the treatment of sepsis in clinic.
| S-EPMC7189733 | biostudies-literature
Project description:Sepsis-induced myocardial dysfunction is a major contributor to the poor outcomes of septic shock. As an add-on with conventional sepsis management for over 15 years, the effect of Xuebijing injection (XBJ) on the sepsis-induced myocardial dysfunction was not well understood. The material basis of Xuebijing injection (XBJ) in managing infections and infection-related complications remains to be defined. A murine cecal ligation and puncture (CLP) model and cardiomyocytes in vitro culture were adopted to study the influence of XBJ on infection-induced cardiac dysfunction. XBJ significantly improved the survival of septic-mice and rescued cardiac dysfunction in vivo. RNA-seq revealed XBJ attenuated the expression of proinflammatory cytokines and related signalings in the heart which was further confirmed on the mRNA and protein levels. Xuebijing also protected cardiomyocytes from LPS-induced mitochondrial calcium ion overload and reduced the LPS-induced ROS production in cardiomyocytes. The therapeutic effect of XBJ was mediated by the combination of paeoniflorin and hydroxysafflor yellow A (HSYA) (C0127-2). C0127-2 improved the survival of septic mice, protected their cardiac function and cardiomyocytes while balancing gene expression in cytokine-storm-related signalings, such as TNF-α and NF-κB. In summary, Paeoniflorin and HSYA are key active compounds in XBJ for managing sepsis, protecting cardiac function, and controlling inflammation in the cardiac tissue partially by limiting the production of IL-6, IL-1β, and CXCL2.
| S-EPMC8112230 | biostudies-literature
Project description:A leading cause of death worldwide is sepsis that develops as a dysregulated immune response to infection. Serious infection caused by methicillin-resistant Staphylococcus aureus (MRSA) increases the difficulty of treatment in septic patients. Host-directed therapy (HDT) is an emerging approach to bacterial infections. Xuebijing injection (XBJ), a commercialized injectable prescription from traditional Chinese medicine, has been used as adjuvant therapy for sepsis with a history of 15 years. Whether it plays a protective role in severe infection caused by antibiotic-resistant bacteria is still unknown. In this study, XBJ significantly improved the survival of MRSA-induced sepsis mice. In MRSA-infected mouse model, XBJ down-regulated the expression of inflammatory cytokines interleukin (IL)-6, tumor necrosis factor (TNF)-α, MCP-1, MIP-2, and IL-10 in sera. Besides that, it decreased the bacterial load in spleens, livers, and alleviated tissue damage of lung, liver, and kidney. The combination of XBJ with vancomycin or dexamethasone exhibited a better down-regulatory role of the inflammatory response. Then, the protective mechanism of XBJ was further investigated. XBJ inhibited heat-killed MRSA-induced IL-6 and TNF-α production in mouse macrophages. XBJ also decreased Pam3CSK4 (a synthetic tripalmitoylated lipopeptide mimicking bacterial lipoproteins)-stimulated expression of IL-6, TNF-α, IL-1β, IL-12, etc. in mouse macrophages. Furthermore, XBJ down-regulated the activation of NF-κB, MAPK, and PI3K/Akt pathways in Pam3CSK4-stimulated mouse macrophages. In conclusion, our findings demonstrated that XBJ played a protective role in MRSA-challenged mice and down-regulated the inflammatory response and the activation of signaling pathways initiated by Pam3CSK4. It enlarged the clinical application of XBJ in the treatment of severe bacterial infection, e.g. caused by MRSA.
| S-EPMC7047170 | biostudies-literature
Project description:BackgroundXuebijing injection (XBJ) has increasingly been used for sepsis in China. We aimed to evaluate the methodological quality and summarize the evidence regarding the effectiveness of XBJ combined with ulinastatin (UTI) for sepsis from systematic reviews/meta-analyses (SRs/MAs).MethodsFrom the inception to May 23, 2021, eight databases were searched to screen the SRs/MAs of XBJ combined with UTI in the treatment of sepsis. Methodology Quality of Systematic Reviews 2 (AMSTAR-2) was used to evaluate the quality of the methods. Grading of Recommendation,Assessment, Development, and Evaluation (GRADE) was used in the assessment of evidence quality.ResultsSeven SRs/MAs on XBJ combined with UTI treatment for sepsis were included. The AMSTAR-2 showed that the methodological quality of all included SRs/MAs was rated as critically low. According to the evaluation results of GRADE, 30% (13/44), 30% (13/44), and 40% (18/44) were rated to be of moderate, low, and critically low quality, respectively. Descriptive analysis results showed that XBJ combined with UTI was an effective treatment modality for sepsis.ConclusionsAll included SRs/MAs showed that XBJ combined with UTI was more effective than UTI alone in the treatment of sepsis on the basis of conventional treatment, but the reliability of the results was limited due to the disadvantages of lower methodological quality and higher risk of bias in the included SRs/MAs. Further high-quality clinical studies and SRs/MAs are recommended to verify whether XBJ combined with UTI is more effective than UTI alone.
| S-EPMC9592478 | biostudies-literature
Project description:Background: Viral myocarditis (VMC) is a common emergency of cardiovascular disease. Current treatment for VMC includes the prohibition of exercise plus supportive and symptomatic treatment, given the lack of specific antiviral therapeutic options and insufficient evidence for the use of novel immunosuppressive therapies. Trimetazidine, a drug used to improve myocardial energy metabolism, is frequently used for the treatment of viral myocarditis. In China, Chinese herbal injections (CHIs) are often used in combination with trimetazidine. Therefore, we evaluate the efficacy and safety of CHI combined with trimetazidine in the treatment of VMC through the method of network meta-analysis. Methods: We searched PubMed, the Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Database, Chinese Scientific Journals Full-text Database (VIP), and China Biology Medicine Database (CBM) databases from inception to September 1, 2020, to identify eligible randomized controlled trials. The Cochrane risk of bias tool was used to assess the risk of bias among selected studies and the Stata 16.0 software was used to perform the network meta-analysis. Results: A total of 29 studies were included, representing data from 2,687 patients. The effectiveness rate, level of myocardial injury marker, and the adverse reaction rate were evaluated. Compared with conventional treatment or conventional treatment combined with trimetazidine, CHIs combined with trimetazidine appeared to have a better therapeutic effect, with higher effectiveness rate and better reduction of the levels of creatine kinase, creatine kinase-MB, and lactate dehydrogenase. Based on surface under the cumulative ranking, Shenmai injection combined with trimetazidine appeared to be superior in terms of effective rate, while Astragalus injection or Salviae miltiorrhizae and ligustrazine hydrochloride injection combined with trimetazidine appeared most effective in reducing myocardial injury markers. There was no significant difference in safety between the interventions. However, a lack of safety monitoring in some selected studies meant that the safety of some interventions could not be fully evaluated. Conclusion: CHIs combined with trimetazidine may have therapeutic value in the treatment of viral myocarditis, and Shenmai injection, Astragalus injection, and Salviae miltiorrhizae and ligustrazine hydrochloride injection may represent the most effective CHIs. Further clinical investigation is required to confirm these results.
| S-EPMC8117092 | biostudies-literature