Current Computer-Aided Drug Design
·
2024
·Vol. 21
·期 4
·503-516
·
IF 1.5
Xiaoyan Meng,Xinming Yan,Peng Xue,Zhaoqing Xi
ObjectiveThis study utilized transcriptomic sequencing combined with cellular and animal models to explore the potential mechanisms of Xuebijing in treating sepsis-induced myocardial dysfunction, also known as sepsis-induced myocardial injury.MethodsWe investigated potential targets and regulatory mechanisms of XBJ injection using network pharmacology and RNA sequencing. The effects of XBJ on oxidative stress and apoptosis levels in human cardiac myocytes (AC16) and C57BL/6 mice exposed to lipopolysaccharide (LPS) were evaluated by Enzyme-Linked Immunosorbent Assay (ELISA), fluorescent probe, Fluorescent Quantitative Polymerase Chain Reaction (qPCR), Western Blot, Transmission Electron Microscopy, oxidative stress-related indicators detection kit, flow cytometry, and Immunohistochemistry (IHC).ResultsFirst, it was verified that XBJ can reduce the deformation of AC16 cardiomyocytes induced by LPS and the production and secretion of ROS (P <0.01). The transcriptome sequencing results showed that the TRIM16 gene was significantly increased after XBJ treatment, and the data of KEGG and GO analyses demonstrated that XBJ could inhibit the pathway expression of oxidative stress damage in AC16 cells, and PCR verified that XBJ could indeed increase the expression level of TRIM16 gene in AC16 cells (P <0.01). Basic animal and cell experiments showed that LPS could inhibit the expression of TRIM16 and NRF2 in cardiomyocytes (P <0.05) and promote the expression of Keap1 (P <0.01), while XBJ could significantly up-regulate the expression levels of TRIM16 and NRF2 (P <0.01) and inhibit the expression of Keap1 (P <0.01), thereby affecting the expression levels of downstream proinflammatory cytokines and alleviating LPS-induced oxidative stress damage. In addition, XBJ also inhibited the expression of the pro-apoptotic proteins Bax and c-caspase3 (P <0.01), promoted the expression of the anti-apoptotic protein Bcl2 (P <0.01), and reduced LPS-induced apoptosis by upregulating TRIM16.ConclusionOur comprehensive data demonstrated that TRIM16 is a key gene in the therapeutic action of Xuebijing in sepsis-induced myocardial dysfunction, protecting myocardial cells from injury through antioxidative stress and anti-apoptotic mechanisms.
研究领域:
医学
·
分子生物学
·
药理学
✓ 已验证
DOI
高影响因子
Frontiers in Pharmacology
·
2018
·
IF 3.831
Zuo Lihua,Zhou Lin,Xu Tanye,Li Zhuolun,Liu Liwei,Shi Yingying,Kang Jian,Gao Guanmin,Du Shuzhang,Sun Zhi,Zhang Xiaojian
Xuebijing (XBJ) injection is an ethnomedicinal formula that has been widely used in the therapy of sepsis in China. However, the underlying theraputic mechanisms remain uninvestigated. In this research, a metabolomic method based on UHPLC-Q-Orbitrap HRMS was applied to make a holistic evaluation of XBJ on septic rats which were induced by the classical cecal ligation and puncture (CLP) operation. The plasma metabolic changes were profiled and evaluated by multivariate analytical (MVA) methods. In the results, a total of 41 differential metabolites were identified between CLP-operated group and sham-operated group, which were mainly involved in amino acid metabolism and lipid metabolism. After pathway analysis, it was finally discovered that the majority of the influenced metabolic pathways caused by sepsis mainly involved in energy metabolism, oxidative stress, and inflammation metabolism. When intervened by XBJ injection, 32 of the 41 disordered metabolites had been adjusted in reverse, which suggested that XBJ could mediate the abnormal metabolic pathways synergistically. In conclusion, the present study systematically investigated the efficacy and its underlying therapeutic mechanisms of XBJ on sepsis, while offering a new insight for the subsequent relevant exploration of other Chinese medicine at the same time.
研究领域:
药理学
·
代谢组学
·
中医药学
✓ 已验证
DOI
PubMed
高影响因子
Analytical Methods
·
2020
·Vol. 12
·期 37
·4562-4571
·
IF 2.596
Wen Liu,Sha Li,Yang Ke Wu,Xiao Yan,Yi Ming Zhu,Fei Ya Jiang,Yu Jiang,Liang Hong Zou,Tong Tong Wang
Xuebijing (XBJ) is a compound Chinese medicine that contains Paeoniae Radix Rubra, ChuanXiong Rhizoma, Salvia Miltiorrhiza Radix et Rhizoma, Carthami Flos, and Angelicae Sinensis Radix. It is widely used in China to treat sepsis. Previous studies have demonstrated that XBJ can decrease mortality in patients with moderate paraquat poisoning. However, the mechanism by which it exerts this effect is not completely clear. In this study, an ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS)-based metabolomics approach was used to perform a metabolic profiling analysis. Principal component analysis (PCA), random forest (RF), and partial least squares discriminant analysis (PLS-DA) were used to identify metabolites to clarify the mechanism of XBJ's activity. XBJ clearly alleviated lung injury in a Sprague Dawley (SD) rat model of paraquat (PQ) poisoning. Seven metabolites related to four pathways, including those involved in sphingolipid and phospholipid metabolism, amino acid metabolism, unsaturated fatty acid metabolism, and pantothenic acid and CoA biosynthesis, were present at different levels in PQ-poisoned rats treated with XBJ compared with untreated rats. XBJ can ameliorate the effects of PQ poisoning in SD rats. Using a metabolomics approach enabled us to gain new insight into the mechanism underlying this effect.
研究领域:
药理学
·
毒理学
·
代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2017
·Vol. 7
·期 1
·1-15
·
IF 4.259
Sun Zhi,Zuo Lihua,Sun Tongwen,Tang Jinfa,Ding Daling,Zhou Lin,Kang Jian,Zhang Xiaojian
To clarify and quantify the chemical profiling of XueBiJing injection (XBJ) rapidly, a feasible and accurate strategy was developed by applying ultra high performance liquid chromatography-Q Exactive hybrid quadrupole-orbitrap high resolution accurate mass spectrometry (UHPLC-Q-Orbitrap HRMS). A total of 162 components were characterized, including 19 phenanthrenequinones, 33 lactones, 28 flavonoids and 12 phenolic acids and 51 other compounds. Among them, 38 major compounds were unambiguously quantified by comparing with reference standards. Meanwhile, 38 representative compounds were simultaneously detected in XBJ samples by Q-Orbitrap HRMS. Satisfactory linearity and correlation coefficient were achieved with wide linear range. The precisions, repeatability, stability and recovery were meeting requirements. The validated method was successfully applied for simultaneous determination of 38 bioactive compounds in 10 batches XBJ samples. In addition, the similarity evaluation of fingerprintings was applied to assess the quality of XBJ. And the results were evaluated by multiple statistical strategies and five compounds might be the most important chemical markers for chemical quality control of XBJ. Finally, a rapid and simple UPLC-MS/MS method was developed for determination of five markers in XBJ sample. This research established a high sensitive and efficient strategy for integrating quality control, including identification and quantification of XBJ.
研究领域:
药学
·
分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2020
·
IF 4.225
Liu Li-Wei,Shi Ying-Ying,Li Zhuo-Lun,Zuo Li-Hua,Tang Meng,Jing Zi-Wei,Zhao Hong-Yu,Xue Peng,Zhou Lin,Du Qiu-Zheng,Zhang Xiao-Jian,Sun Zhi
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.
研究领域:
医学
·
药理学
·
代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOCHEMISTRY
·
2018
·Vol. 164
·期 6
·427-435
·
IF 2.35
Xu Tanye,Zhou Lin,Shi Yingying,Liu Liwei,Zuo Lihua,Jia Qingquan,Du Shuzhang,Kang Jian,Zhang Xiaojian,Sun Zhi
Sepsis is the dysregulated host response to an infection which leads to life-threatening organ dysfunction. Metabolomic profiling in bio-fluid or tissue is vital for elucidating the pathogenesis of sepsis and evaluating therapeutic effects of medication. In this study, an untargeted metabolomics approach was applied to study the metabolic changes in lung tissue of septic rats induced by cecal ligation and puncture (CLP) and investigate the treatment effects of Xubijing injection (XBJ). Metabolomics analyses were performed on ultra-high performance liquid chromatography-Q Exactive hybrid quadrupole-orbitrap high-resolution accurate mass spectrometry (UHPLC-Q-Orbitrap-HRMS) together with multivariate statistical analysis. A total of 26 differential metabolites between CLP and sham-operated group were identified. The altered metabolic pathways included energy metabolism, amino metabolism, lipid metabolism, fatty acid metabolism and hormone metabolism. Among the 26-varied metabolites, 15 were significantly regulated after XBJ treatment. The metabolic pathway network of sepsis was drawn to interpret the pathological feature of lung damage caused by sepsis and the underlying regulating mechanism of XBJ on the molecular levels. Our findings display that LC-MS-based metabolomics is a useful tool for uncovering the underlying molecular mechanism of sepsis, and XBJ may exert therapeutic effect by regulating multiple metabolic pathways.
研究领域:
医学
·
药理学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2018
·Vol. 33
·期 2
·e4400
·
IF 1.688
Lihua Zuo,Zhi Sun,Zhenhui Wang,Daling Ding,Tanye Xu,Liwei Liu,Li Gao,Shuzhang Du,Jian Kang,Xiaojian Zhang
Xuebijing injection (XBJI) is a traditional Chinese medicine prescription extracted from five Chinese herbs. Hydroxysafflor yellow A, oxypaeoniflorin, ferulic acid and benzoylpaeoniflorin are the main bioactive ingredients of XBJI. This paper presents an application of ultra-high-performance liquid chromatography–Q–exactive hybrid quadrupole–Orbitrap high-resolution mass spectrometry (UHPLC–Q–Orbitrap HRMS) to quantify four compounds of XBJI in rats various tissues for tissue distribution studies. The analytes were separated on a Waters Acquity UHPLC ® BEH C 18 column with a gradient mobile phase consisting of acetonitrile–water (containing 0.1% formic acid) at a flow rate of 0.2 mL/min. Mass spectrometric detection was performed by parallel reaction monitoring via a heated electrospray ionization source under the negative ionization mode. The method was validated in various tissue samples, and has demonstrated great performance for rapidity, accuracy, high sensitivity and selectivity. It was successfully applied to the tissue distribution studies of XBJI after intravenous administration to rats. It was also the first study to investigate the tissue distribution of XBJI in rats and we found that the concentrations of four compounds were high in kidney, liver, stomach and intestine. The clinical use of XBJI should focus on its pharmacodynamics and safety studies in these tissues.
研究领域:
药理学
·
分析化学
·
中药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2017
·
IF 3.255
Lihua Zuo,Qiuyue Zhong,Zhenhui Wang,Zhi Sun,Lin Zhou,Zhuolun Li,Tanye Xu,Yingying Shi,Jinfa Tang,Shuzhang Du,Xiaojian Zhang
Xuebijing injection (XBJ) is a traditional Chinese herbal prescription widely used in the treatment of sepsis. Extensive studies revealed that the major bioactive constituents of XBJ injection, including phenolic acids, flavonoids, monoterpene glycosides, lactones and organic acids, play an important role in the treatment. In this study, a rapid, sensitive and accurate ultra high performance liquid chromatography – Q Exactive hybrid quadrupole – orbitrap high-resolution accurate mass spectrometry (UHPLC-Q-Orbitrap HRMS) method was developed for simultaneous determination of twelve bioactive compounds in rat plasma after intravenous administration of XBJ injection. A gradient elution for separation was achieved on a waters ACQUITY UHPLC ® BEH C 18 column (2.1 mm × 50 mm, 1.7 μm) column with acetonitrile-water (containing 0.1% formic acid) as mobile phase at a flow rate of 0.2 mL/min. All compounds and IS were monitored by parallel reaction monitoring assay both in positive and negative ion mode. The developed method was validated for intra-day and inter-day accuracy and precision whose values fell in the acceptable limits. Extraction recoveries at three levels of QC concentrations were all more than 80% for all compounds and IS, and matrix effects were found in the range of 80.0–120.0%. Stability results showed that all analytes were stable at the investigated conditions. The validated method was successfully applied to a pharmacokinetic study of Xuebijing injection following intravenous administration of 2.5, 5.0, 10.0 mL/kg to rats respectively. And the result indicated that the pharmacokinetic behavior of XBJ injection is positively related to dosage at the range of 2.5–10 mg/kg. This study will provide a meaningful basis for evaluating the rationality of XBJ injection for clinical application.
研究领域:
中药学
·
分析化学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2017
·
IF 3.255
Lihua Zuo,Zhi Sun,Yurong Hu,Ya Sun,Wenhua Xue,Lin Zhou,Jun Zhang,Xiaoyue Bao,Zhenfeng Zhu,Guanglu Suo,Xiaojian Zhang
Xuebijing injection (XBJ) is a traditional Chinese herbal prescription widely used in the treatment of sepsis. Extensive chemical studies revealed that XBJ injection contains amino acids, phenolic acids, flavonoid glycosides, terpeneglycosides and phthalides. In this study, the applicability of ultra high performance liquid chromatography coupled with high resolution hybrid quadruple-orbitrap mass spectrometry (UHPLC-Q-Orbitrap MS) for the simultaneous quantitative analysis of 30 bioactive constituents in XueBiJing injection (XBJ) was investigated. The mass spectrometer was operated in full MS scan mode. The use of 70,000 FWHM mass resolution and narrow mass windows (5 ppm) could effectively improve the selectivity of the method. Separation was achieved on a Waters ACQUITY UPLC ® HSS C 18 column (2.1 mm × 100 mm, 1.8 μm) with a gradient mobile phase consisting of acetonitrile-water (containing 10 mM ammonium acetate) at a flow rate of 0.2 mL/min. Satisfactory linearity was achieved within wide linear range and all correlation coefficients (r) of analytes were more than 0.9996. The limits of detection (LODs) were in the range of 0.1180–27.82 ng/mL for different analytes. The relative standard deviations (RSDs) of inter- and intra-day precisions were less than 3.0% and the recoveries of the assay were in the range of 98.5%–101.5%. The validated method was successfully applied for simultaneous determination of 30 bioactive compounds in XueBiJing injection from 10 batches samples by UHPLC-Q-Orbitrap MS within 10 min. Moreover, the results were evaluated principal component analysis and two compounds might be the most important chemical markers for chemical quality control of XBJ injection. The novel Q-Orbitrap mass spectrometry has been proved to be a very promising and powerful tool for routine screening of bioactive compounds in traditional Chinese medicine injection, ensuring drug safety and public health.
研究领域:
药物分析
·
中药化学
·
质谱技术
·
药物质量控制
·
代谢组学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）