Xuefu Zhuyu Research Articles

Network Meta-analysis of peroral Chinese patent medicines for activating blood and resolving stasis in treatment of endometriosis

Network Meta-analysis was performed to systematically compare the efficacy of different Chinese patent medicines for activating blood and resolving stasis in the treatment of endometriosis and to provide evidence-based references for clinical medication regimens. The relevant randomized controlled trials(RCTs) involving Chinese patent medicines combined with conventional treatment(experimental group) vs conventional treatment(control group) were retrieved from Chinese and English literature databases. The bias risk assessment tool recommended in Cochrane handbook 5.3 was used to evaluate the quality of the included studies. The result data of each outcome index was extracted for network Meta-analysis in Stata 15.0. A total of 44 RCTs were included in this study, involving 4 345 patients and 9 Chinese patent medicines. The network Meta-analysis revealed the following trends.(1)In terms of reducing the visual analogue scale(VAS) scores, Dan'e Fukang Plaster+conventional treatment>Xuefu Zhuyu Capsules+conventional treatment>Gongliuxiao Capsules+conventional treatment.(2)In terms of reducing cancer antigen CA125, Xiaojin Capsules+conventional treatment>Shaofu Zhuyu Granules+conventional treatment>Dan'e Fukang Plaster+conventional treatment.(3)In terms of reducing estradiol(E_2), Gongliuxiao Capsules+conventional treatment>Xiaojin Capsules+conventional treatment>Sanjie Zhentong Capsules+conventional treatment.(4) In terms of reducing recurrence rate, Guizhi Fuling Capsules+conventional treatment>Xuefu Zhuyu Capsules+conventional treatment>Dan'e Fukang Plaster+conventional treatment. The peroral Chinese patent medicines for activating blood and resolving stasis combined with conventional treatment have better efficacy in the treatment of endometriosis than conventional treatment. However, considering the low quality of the included literature, large-scale high-quality clinical trials are needed in the future research.

Systematic analysis of tRNA-derived small RNAs reveals therapeutic targets of Xuefu Zhuyu decoction in the cortexes of experimental traumatic brain injury

BackgroundXuefu Zhuyu Decoction (XFZYD), a well-known traditional Chinese medicine prescription, has been widely used to treat traumatic brain injury (TBI). However, the underlying mechanisms involved in XFZYD therapy remain unclear. Aim of the studyWe explored new therapeutic targets of XFZYD in TBI by the tsRNA-sequencing (tsRNA-seq) method. Material and methodsHigh-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used to assess the quality of XFZYD. Male Sprague-Dawley rats were randomly categorized into three groups: sham, TBI, and XFZYD. The protective effects of XFZYD were investigated in vivo by using the Morris water maze (MWM), modified neurological severity score (mNSS) tests, hematoxylin-eosin (H&E) staining, and Nissl staining. tsRNA-seq was applied to analyze the expression of tsRNAs in the rat cortex. Four tsRNAs were validated by qRT-PCR. The biological function of putative tsRNAs was investigated using bioinformatics techniques. The functions of tsRNAs targeting mRNAs were verified in vitro. ResultsThe mNSS and MWM indicated that XFZYD notably improved neurological deficits and cognitive function after TBI (p < 0.05). H&E staining and Nissl staining demonstrated that XFZYD suppressed damage and neuronal loss in the TBI rat cortex. We evaluated the dysregulated expression of 732 tsRNAs (128 tsRNAs were significantly altered in the TBI/sham group (fold change > 2 and p < 0.05), and 97 tsRNAs were dysregulated in the XFZYD/TBI group (fold change > 2 and p < 0.05)) in the TBI rat cortex. Interestingly, 41 tsRNAs were distinctly regulated by XFZYD. The qRT-PCR results of the four randomly chosen tsRNAs (tRF-54-75-Glu-TTC-2, tRF-55-75-Gln-CTG-2-M2, tRF-55-76-Val-TAC-1, tRF-64-85-Leu-AAG-1-M4) exhibited trends similar to those of the tsRNA-seq data. We certified the possible targets of tsRNAs and suggested the crosscurrent in the expression trend of the target genes. Bioinformatics analysis showed that XFZYD-related tsRNAs could contribute to regulating insulin resistance, the calcium signaling pathway, autophagy, and axon guidance. ConclusionsThe current research implies that tsRNAs are putative therapeutic targets of XFYZD for TBI treatment. This research provides new insight into the therapeutic targets of XFZYD in treating TBI.

Elucidating the Synergistic Effect of Multiple Chinese Herbal Prescriptions in the Treatment of Post-stroke Neurological Damage.

Background: Traditional Chinese medicine (TCM) has been widely used in the treatment of human diseases. However, the synergistic effects of multiple TCM prescriptions in the treatment of stroke have not been thoroughly studied. Objective of the study: This study aimed to reveal the mechanisms underlying the synergistic effects of these TCM prescriptions in stroke treatment and identify the active compounds. Methods: Herbs and compounds in the Di-Tan Decoction (DTD), Xue-Fu Zhu-Yu Decoction (XFZYD), and Xiao-Xu-Ming Decoction (XXMD) were acquired from the TCMSP database. SEA, HitPick, and TargetNet web servers were used for target prediction. The compound-target (C-T) networks of three prescriptions were constructed and then filtered using the collaborative filtering algorithm. We combined KEGG enrichment analysis, molecular docking, and network analysis approaches to identify active compounds, followed by verification of these compounds with an oxygen-glucose deprivation and reoxygenation (OGD/R) model. Results: The filtered DTD network contained 39 compounds and 534 targets, the filtered XFZYD network contained 40 compounds and 508 targets, and the filtered XXMD network contained 55 compounds and 599 targets. The filtered C-T networks retained approximately 80% of the biological functions of the original networks. Based on the enriched pathways, molecular docking, and network analysis results, we constructed a complex network containing 3 prescriptions, 14 botanical drugs, 26 compounds, 13 targets, and 5 pathways. By calculating the synergy score, we identified the top 5 candidate compounds. The experimental results showed that quercetin, baicalin, and ginsenoside Rg1 independently and synergistically increased cell viability. Conclusion: By integrating pharmacological and chemoinformatic approaches, our study provides a new method for identifying the effective synergistic compounds of TCM prescriptions. The filtered compounds and their synergistic effects on stroke require further research.

The Material Basis and Mechanism of Xuefu Zhuyu Decoction in Treating Stable Angina Pectoris and Unstable Angina Pectoris.

Methods Firstly, we used a network proximity approach to calculate and compare the effectiveness of the formula with that of Western drugs for each type of angina, including all targets and intersecting targets, from a topological perspective. Secondly, we compared the mechanisms of action of the two angina pectoris at three levels and five aspects, including conventional and modular analysis approaches. Thirdly, based on the unique functions of each angina in the complex heterogeneous network, we designed a reverse process for finding the material basis using dynamic, static, and enriched items as well as a total item. Finally, the designed inverse process, material basis, and mechanism of action were validated. Results The target network of Xuefu Zhuyu decoction is closer to the target network of each type of angina than that of Western drugs, and the intersection targets have a closer proximity. Comparison of the mechanisms of action showed that stable angina and unstable angina had 158 common targets, while the unique targets were 34 and 1, respectively. Modularity analysis showed that the GO similarity of target modules was highly correlated with KEGG similarity. We ended up with 67 compounds upregulated for stable angina and 47 compounds upregulated for unstable angina. Our results were validated by literature mining, high-volume molecular docking, and miRNA enrichment analysis. Conclusions For both types of angina pectoris, Xuefu Zhuyu decoction is superior to Western drugs. A comparison of various aspects led to the unique mechanisms of action, from which the material basis of each type of angina was deduced.

Xuefu Zhuyu Decoction on Heart Failure Patients with Middle-Range Coronary Heart Disease with Ejection Fraction

To investigate the impact of Xuefu Zhuyu decoction on cardiac remodeling and quality of life of patients with heart failure and middle-range coronary heart disease with ejection fraction is the main objective of the study. 116 heart failure patients with coronary heart disease in the middle range of ejection fraction were divided as observation or control group. Clinical efficacy of both groups was observed and changes in traditional Chinese medicine symptom scores, cardiac function classification, exercise tolerance, cardiac ultrasound indexes and quality of life were compared before and after treatment between both groups. Relative to before treatment, left ventricular ejection fraction of two groups enhanced dramatically (p<0.05) and the left ventricular enddiastolic diameter increased significantly (p<0.05). Serum N-terminal pro-B-type natriuretic peptide and left ventricular end-systolic diameter significantly declined (p<0.05). Relative to before treatment, physical limitation, physical condition, emotional change, social limitation score and total score in each dimension of Minnesota living with heart failure questionnaire scale obviously declined in both groups (p<0.05), compared with control group following treatment. The above scores decreased in observation group relative to control group (p<0.05). Xuefu Zhuyu decoction can significantly enhance cardiac function and exercise tolerance of such cases, inhibit or reverse cardiac remodeling, and be beneficial to the improvement of quality of life.

N6-Methyladenosine Profiling Reveals Xuefu Zhuyu Decoction Upregulates METTL14 and BDNF in a Rat Model of Traumatic Brain Injury

N6-Methyladenosine Profiling Reveals Xuefu Zhuyu Decoction Upregulates METTL14 and BDNF in a Rat Model of Traumatic Brain Injury

Application of a Complex Network Modeling Approach to Explore the Material Basis and Mechanisms of Traditional Chinese Medicine: A Case Study of Xuefu Zhuyu Decoction for the Treatment of Two Types of Angina Pectoris

The complex processes of action of Chinese medicines and their formulations can be studied in terms of complex heterogeneous networks, however multiple diseases are different from one disease. In this study, we proposed a graph neural network-based modelling strategy to explore the material basis and mechanisms of the formulae under multiple disease conditions, exemplified by Xuefu Zhuyu Decoction for stable angina pectoris and unstable angina pectoris. Our modelling approach consists of two parts, a feature part and a model part. In the feature part, we calculated four similarities and their combinations in the similarity network as features of nodes of the heterogeneous network, using a variety of algorithms. In the model part, both the multi-label classification model for compounds and the link prediction model for compounds-targets were performed in six model comparison experiments and four partial ablation experiments. We confirmed that the GraphSAGE-based model was the best performing multi-label classification model while the GAT-based model was the best performing link prediction model, and that the full model with various similarity contents was optimal. Good generalization ability of the model was demonstrated through generalization ability experiments. In the case study, the model was used to predict potential compound-target interactions for marker targets and the reliability of the predictions was demonstrated by molecular docking and literature mining. In conclusion, the model successfully predicted the known material basis and mechanisms and also predicted unknown compound-marker target interactions. The proposed modelling approach can be extended to the study of other formulations.

Identification of active components in Xuefu Zhuyu Decoction based on targets of blood-activating function

As a classic prescription for promoting blood circulation to remove blood stasis, Xuefu Zhuyu Decoction(XFZYD) is widely used in clinical practice and has notable curative effect. Based on the key targets of activating blood circulation, this study identified the active components of XFZYD to reveal the material basis. The components of XFZYD were collected from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The molecular docking models were built for the blood-activating targets obtained from the previous study with the components of XFZYD. The top five active components with measurability for each target were selected as the potential blood-activating components in the prescription. The efficacy of the prescription can embody key pharmacological and high-content components. In this study, anti-platelet aggregation activity was used to characterize the effect of activating blood, and the in vivo experiments were conducted to verify the accuracy of the active components. A total of 210 chemical components of XFZYD were screened out from TCMSP and docked with the key targets with the function of activating blood. Ligustrazine, acteoside, naringin, etc. were selected as the potential active components for activating blood in XFZYD. The anti-platelet aggregation activity of the combination of Chuanxiong Rhizoma, Rehmanniae Radix, Aurantii Fructus, Glycyrrhizae Radix et Rhizoma, and Carthami Flos was 9.82%±5.11%. Compared with that in the control group, the platelet aggregation induced by adenosine diphosphate(ADP) was significantly inhibited in the test group(P&lt;0.01), which verified the accuracy of the active components. This study can guide the research on the material basis of XFZYD and provide insights into the development and utilization of the classical prescription.

The Efficacy and Mechanism of Xuefu Zhuyu Decoction Combined with Tenofovir Dipyrfurate Fumarate Tablets in The Treatment of Liver Depression and Blood Stasis Type Hepatitis B Cirrhosis

Background: Cirrhosis is a chronic progressive liver disease. Hepatocyte injury leads to liver dysfunction. At present, antiviral drugs are mainly used to inhibit the replication of hepatitis virus to block liver fibrosis. Tenofovir disoproxil fumarate is a novel nucleotide reverse transcriptase inhibitor, which can eliminate hepatitis B virus and control the deterioration of chronic hepatitis B. Objective To investigate the efficacy and mechanism of Xuefu Zhuyu Decoction combined with tenofovir disoproxil fumarate tablets in the treatment of hepatitis B cirrhosis of liver depression and blood stasis. Methods A total of 150 patients with hepatitis B cirrhosis who were treated in our hospital from January 2019 to June 2021 with the dialectical type of "liver stagnation and blood stasis" were selected and divided into groups according to their treatment plan. 75 cases in the control group were given Fu Tenofovir disoproxil marate tablets were treated, and 75 patients in the observation group were treated with Xuefu Zhuyu Decoction combined with tenofovir disoproxil fumarate tablets. Count the total effective rates and adverse reactions of the two groups, record the scores of TCM syndromes, liver hemodynamics, fibrosis, liver function, hepatitis B virus deoxyribonucleic acid (HBV-DNA), MMP1, TIMP1, TIMP1/MMP1 changes. Results The curative effect of the observation group was higher than that of the control group, which was statistically significant (P&lt;0.05). Compared with before treatment, the portal vein flow rate (PW) and intrahepatic circulation time (HV-HA) of the two groups increased (P&lt;0.05), the portal vein congestion index (PV-CI) decreased (P&lt;0.05), and the portal vein diameter (PVD) Compared with before treatment, the difference was not statistically significant (P&gt;0.05). After treatment, PW and HV-HA in the observation group were higher than those in the control group (P&lt;0.05), and PV&lt;I was lower than that in the control group (P&lt;0.05). Compared with the control group, the difference was not statistically significant (P&gt;0.05). Compared with before treatment, the scores of the two groups of chest and hypothermia distended, abdominal distension, mental fatigue, depression, irritability, and amitrati decreased (P&lt;0.05). The scores of TCM syndromes of the observation group were lower than those of the control group (P&lt;0.05). P&lt;0.05). Compared with before treatment, the two groups of matrix metalloproteinase 1 (MMP1) increased (P&lt;0.05), laminin (LV), type IV collagen (IV-C), type III procollagen (PCIHT, hyaluronic acid (P&lt;0.05) HA), tissue inhibitor of matrix metalloproteinase 1 (TIMP1), TIMP1/MMP1, alanine aminotransferase (ALT), aspartate aminotransferase (AST), HBV-DNA decreased (P&lt;0.05), observe After treatment, MMP1 in the group was higher than that in the control group (P&lt;0.05), and fibrosis indexes, liver function indexes, TIMP1, TIMP1/MMP1, and HBV-DNA were lower than those in the control group (P&lt;0.05). The adverse reactions between the two groups were not statistically significant (P&gt;0.05). Conclusion Xuefu Zhuyu Decoction combined with tenofovir disoproxil fumarate tablets is effective in treating hepatitis B cirrhosis of liver depression and blood stasis, and its mechanism may be related to improving liver hemodynamics, regulating fibrosis, liver function and other indicators related.

Qi-Regulating and Blood Circulation-Promoting Therapy Improves Health Status of Stable Angina Pectoris Patients with Depressive Symptoms

Depressive symptoms have been found to be highly prevalent among patients with coronary heart disease (CHD) and seriously affect the patients' quality of life. However, most psychotropic drugs have warnings about potential side effects. Accordingly, safer effective alternatives are urgently demanded. Angina pectoris of CHD is considered as “chest stuffiness and heartache syndrome” in traditional Chinese medicine, with the major syndrome type named Qi stagnation and blood stasis. Qi-regulating and blood circulation-promoting therapy has increasingly shown unique advantages in CHD patients. This study investigated the efficacy of Xuefu Zhuyu decoction, a representative prescription of Qi-regulating and blood circulation-promoting therapy, on angina pectoris patients with depressive symptoms. Depressive symptoms were stratified at baseline in 30 patients with stable angina pectoris who participated in both baseline and 12-week follow-up studies. After performing a stratified analysis, the angina pectoris-specific health status and traditional Chinese medicine “chest stuffiness and heartache syndrome” were evaluated by self-reports using the associated questionnaire scales, respectively. We measured serum concentrations of serotonin, brain-derived neurotrophic factor, and ATP, which are associated with the development of depression. We found that the Xuefu Zhuyu granule significantly improved the angina pectoris-specific health status in patients after 12 weeks of treatment; specifically, it had a better curative effect on patients with depressive symptoms. Xuefu Zhuyu granule also significantly improved the chest stuffiness and heartache syndrome in patients with depressive symptoms (efficacy index is 61.24%, P < 0.05 versus baseline). Interestingly, Xuefu Zhuyu granule has been found to be more susceptible to improving ATP levels in patients with depressive symptoms, indicating that the improvement in serum ATP levels might account for the better efficacy of Xuefu Zhuyu granule in patients with depressive symptoms. Our data provide prospective evidence that Xuefu Zhuyu granule improves angina pectoris-specific health status through regulating Qi and promoting blood circulation. This trial is registered with ChiCTR-IOR-15006989.

Xuefu Zhuyu decoction improves asthma-induced asthenozoospermia based on network pharmacology and in vivo experiment.

This study aimed to verify that Xuefu Zhuyu decoction (XFZYD) can improve asthenozoospermia caused by asthma, and explore its potential mechanism. Ovalbumin solution is used to induce asthma rat models. Sperm concentration and motility are used to evaluate semen quality. Immunohistochemistry (IHC), Western blotting and real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR) are used to detect proteins and mRNA related to rat testis tissue. Haematoxylin and eosin (H&E) staining was used to observe changes in testicular tissues. Through network pharmacology, eriodictyol, 18-β-glycyrrhetinic acid, naringenin, chrysin and Hispidulin were prominent active ingredients of XFZYD. We found that XFZYD regulates the expression levels of albumin (ALB), vascular endothelial growth factor A (VEGFA), interleukin 6 (IL-6) protein and mRNA, thereby improving the histopathological morphology of the testis, increasing the concentration and motility of spermatozoa. We suggest that future research can increase the detection of hormones and oxidative stress and other related indicators, so as to conduct more in-depth exploration.

Facile and label-free fluorescence strategy for evaluating the influence of bioactive ingredients on FMO3 activity via supramolecular host-guest reporter pair

Screening inhibitors of flavin monooxygenase 3 (FMO3) is very important for treating trimethylamine N-oxide (TMAO) derived thrombotic diseases. Herein, focusing on Xuefu Zhuyu decoction (XFZYD) as a Chinese traditional medicine with antithrombotic efficacy, a facile and label-free fluorescence strategy was developed for evaluating the influence of the bioactive ingredients in XFZYD on FMO3 activity through indicator displacement assay. To this end, the optimized supramolecular host-guest (p-sulfonatocalix[4]arene-oxazine 1) reporter pair and FMO3 catalytic system were exploited to determine the influence of the bioactive compounds in XFZYD on the conversion from TMA to TMAO. From the nine compounds tested, naringin, paeoniflorin, β-ecdysterone, 18β-glycyrrhizic acid, amygdalin, albiflorin, and saikosaponin A downregulated FMO3 activity and reduced TMAO biosynthesis. Moreover, molecular docking was successfully applied to simulate the optimal conformation of a receptor-ligand complex between FMO3 and all tested compounds except for β-ecdysterone. Therefore, this approach provides a novel and promising strategy for screening FMO3 inhibitors from Chinese traditional medicine by supramolecular sensing.

1H-NMR-based metabolomics study on coronary heart disease with blood-stasis syndrome and phlegm syndrome.

Coronary heart disease (CHD) is a serious threat to human health because of its high morbidity. It is very urgent to study the pathogenesis of CHD and the effective drug target. The purpose of this paper is using the 1H-nuclear magnetic resonance spectroscopy (1H-NMR) metabolomics technology to establish the metabolic fingerprint and find the potential biomarker metabolites of CHD with blood-stasis syndrome and phlegm syndrome, and to reveal the metabolic mechanism of Xuefu Zhuyu Decoction for the treatment of CHD with blood stasis syndrome. The plasma samples of 69 patients with CHD blood-stasis syndrome, 60 patients with CHD phlegm syndrome, and 40 healthy volunteers were collected in this study. Based on the 1H-NMR metabolomics technology, the metabolic fingerprint of CHD with blood-stasis syndrome and phlegm syndrome was established. Multivariate statistical analysis methods including principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were used to find the potential biomarker metabolites of CHD with blood-stasis syndrome and phlegm syndrome. Xuefu Zhuyu Decoction was used to randomly selected blood-stasis syndrome patient. The plasma samples of pre-treatment and post-treatment were collected. 1H-NMR and multivariate statistical analysis were used to analyze the changes of metabolites in patients with CHD blood-stasis syndrome before and after Xuefu Zhuyu Decoction treatment. A total of 15 potential biomarkers were identified in the plasma of patients with CHD blood-stasis syndrome, including 3-hydroxybutyrate (3-HB), lactate, alanine, glutamate, glutamine, pyruvate,phosphatidylcholine (PC), glycerylphosphorylcholine (GPC), glycine, glucose, phenylalanine, citrate,tyrosine, formate,very low density lipoprotein (VLDL). The levels of glucose, 3-HB, and VLDL increased, while the levels of other 12 metabolites decreased. A total of 16 potential biomarkers were identified in the plasma of patients with CHD phlegm syndrome, including valine, lactate, alanine, N-acetyl-β-glucosaminidase (NAG), glutamate, glutamine, pyruvate, creatine, choline, glycine, glucose, phenylalanine, citrate, histidine, tyrosine, and formate. The levels of glucose and choline increased, while the levels of other 12 metabolites decreased. After treatment with Xuefu Zhuyu Decoction, the levels of choline, phospholipids/glycerolipids, creatine, lipids, and citrate increased, while the level of lactate decreased in patients with CHD blood-stasis syndrome. 1H-NMR combined with multivariate statistical method could effectively establish the diagnostic model for CHD blood-stasis syndrome and CHD phlegm syndrome, and find the metabolites related to the syndrome type. The metabolic mechanism of Xuefu Zhuyu Decoction on CHD blood-stasis syndrome may be associated with regulation of lipid metabolism and energy metabolism.

Effect of the Chinese Herbal Medicine SS-1 on a Sjögren's Syndrome-Like Disease in Mice.

Sjögren’s syndrome (SS) is an inflammatory autoimmune disease primarily affecting the exocrine glands; it has a major impact on patients’ lives. The Chinese herbal formula SS-1 is composed of Gan Lu Yin, Sang Ju Yin, and Xuefu Zhuyu decoction, which exerts anti-inflammatory, immunomodulatory, and antifibrotic effects. Our previous study demonstrated that SS-1 alleviates clinical SS. This study aimed to evaluate the efficacy and mechanism of the Chinese herbal formula SS-1 for salivary gland protein-induced experimental Sjögren’s syndrome (ESS). These results showed that ESS treatment with the Chinese herbal formula SS-1 (1500 mg/kg) significantly alleviated the severity of ESS. We found that SS-1 substantially improved saliva flow rates in SS mice and ameliorated lymphocytic infiltrations in submandibular glands. In addition, salivary gland protein-induced SS in mice treated with SS-1 significantly lowered proinflammatory cytokines (including IFN-γ, IL-6, and IL-17A) in mouse salivary glands and decreased serum anti-M3R autoantibody levels. In addition, we found that CD4+ T cells isolated from SS-1-treated SS mice significantly reduced the percentages of IFN-γ-producing CD4+ T cells (Th1) and IL-17A-producing CD4+ T cells (Th17). Our data show that SS-1 alleviates ESS through anti-inflammatory and immunomodulatory effects, which provides new insight into the clinical treatment of SS.

Comparison of mechanisms and efficacies of five formulas for improving blood circulation and removing blood stasis

ObjectiveThis study aimed to compare the mechanisms and efficacies of five formulas that improve blood circulation and remove blood stasis. Methods(1) A network pharmacology method was used to determine the targets of five formulas that promote circulation and remove blood stasis. Compounds of the five formulas, namely Danshen Yin (丹参饮, DSY), Huoluo Xiaoling Dan (活络效灵丹, HLXLD), Shixiao San (失笑散, SXS), Taohong Siwu Tang (桃红四物汤, THSWT), and Xuefu Zhuyu Tang (血府逐瘀汤, XFZYT), were retrieved from the Traditonal Chinese Medicine System Pharmacology Database (TCMSP), the Shanghai Institute of Organic Chemistry of CAS, and the TCM Integrated Database. Drug target network was constructed by searching the Swiss Target Prediction database and the STITCH database. The target network of stasis was extracted from the PharmGKB database, the Online Mendelian Inheritance in Man (OMIM) database, the Genetic Association Database (GAD), and the Therapeutic Target Database (TTD). Candidate targets were determined using protein–protein interaction (PPI) network extension and topology selection. Thereafter, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was used to determine the differentiation of the mechanism of the five formulas. (2) Animal experiments were conducted to explore the efficacies of the five formulas in treating blood stasis. Seventy New Zealand rabbits were exposed to high-fat feeding + epinephrine injection to construct a blood stasis syndrome model. The rabbits were evenly divided into control, model, DSY, HLXLD, SXS, THSWT, and XFZYT groups. The latter five groups were orally administered the corresponding formulas [DSY: 3.92 g/(kg·d), XFZYT: 7.10 g/(kg·d), SXS: 1.12 g/(kg·d), HLXLD: 5.60 g/(kg·d), THSWT: 4.48 g/(kg·d)]. Serum lipid and blood rheology were analyzed, and pathology slices were observed. Results(1) A total of 269, 358, 288, 370, and 376 candidate targets of DSY, HLXLD, SXS, THSWT, and XFZYT were obtained among which were 232 shared candidate targets. Fluid shear stress and atherosclerosis were the biological processes common to the five formulas. HLXLD, SXS, DSY, and THSWT regulated lipolysis in adipocytes, and XFZYT, HLXLD, SXS, and THSWT regulated the AGE-RAGE signaling pathway and complement and coagulation cascades. HLXLD, SXS, and XFZYT regulated the HIF-1 signaling pathway, DSY regulated the cGMP-PKG signaling pathway, HLXLD reduced platelet activation, SXS regulated the calcium signaling pathway, and XFZYT regulated the PPAR signaling pathway. (2) In the animal experiments, the values of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), TC/HDL, and TG/HDL in each group decreased, among which the ones seen in XFZYT, HLXLD, and SXS groups were statistically significant (P < 0.05). XFZYT presented the best effect, followed by HLXLD and SXS. XFZYT and HLXLD decreased apolipoprotein B100 (apoB100) and increased apolipoprotein A1/apoB100 (P < 0.05). XFZYT decreased all the values of hematocrit (HCT), plasma viscosity, whole blood viscosity (WBV); HLXLD and SXS affected HCT; and DSY and THSWT regulated WBV (P < 0.05). All the five formulas decreased the values of optical density and area of plaque, among which XFZYT and HLXLD showed statistical significance (P < 0.05). ConclusionAdjusting fluid shear stress and alleviating the injury of endothelial cells might be the common mechanisms by which the five formulas promote blood circulation and remove blood stasis. Different formulas also have unique targets, which may provide guidance for clinical drug selection. By regulating different indices, the five formulas can regulate blood lipid and hemorheology, improve the state of blood stasis, and decrease the degree of aortic plaque in the blood stasis model rabbits. XFZYT and HLXLD had higher efficacies than DSY, THSWT, and SXS.

Xuefu Zhuyu decoction for nonalcoholic fatty liver disease: A protocol for systematic review and meta-analysis.

Background:Nonalcoholic fatty liver disease (NAFLD) includes nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH), which ranks only second to viral hepatitis and poses an increasingly serious challenge to global public health and economy. NAFLD has attracted more and more attention, but there is no drugs with exact curative effects are available. The commonly used drugs for the treatment of NAFLD in clinical practice are statins, such drugs, inevitably increase the burden on the live. Compared to statins, traditional Chinese medicines are believed to be “all natural” with fewer side effects, are associated with strong patient compliance. Accordingly, a great deal of clinical studies have shown that Xuefu Zhuyu decoction (XFZYD) can significantly improve the clinical symptoms and enhance the therapeutic effect. Meanwhile, a system review and meta-analysis are conducted by us to further clarify the effectiveness and safety of XFZYD for NAFLD.Methods:We will apply to database mainly range from the English literature searches Cochrane Library, PubMed, excerpt medica database, and Web of Science to the Chinese literature China national knowledge infrastructure, Chinese biomedical literature database, VIP, and Wanfang database, randomized controlled trials (RCTs) are enrolled to evaluate the effectiveness and safety of XFZYD in the treatment of NAFLD, the enrollment of RCTs is from the establishment of the database to February 01, 2021. Simultaneously we will retrieval clinical registration tests and grey literatures. The 2 researchers worked independently on literature selection, data extraction, and quality assessment. The dichotomous data is expressed in terms of relative risk, the continuous is represented by mean difference or standard mean difference, whether there is heterogeneity is the factor that determines the synthesis of data in fixed effect model or random effect model. Alanine aminotransferase (ALT) or Aspartic acid aminotransferase (AST) coupled with Glutamyltransferase (GGT) is considered as one of the main indicators of the NAFLD, while the pathology, imaging and diagnosis of metabolic syndrome are also auxiliary results. The last, meta-analysis was conducted by RevMan software version 5.3.Results:This study will provide evidence for treatment of NAFLD with XFZYD in terms of effectiveness and safety.Conclusion:This systematic review aims to confirm the efficacy and safety of XFZYD in the treatment of NAFLD.OSF registration number:DOI 10.17605/OSF.IO/7CWRK.

Quantitative Mass Spectrometry Imaging of Metabolomes and Lipidomes for Tracking Changes and Therapeutic Response in Traumatic Brain Injury Surrounding Injured Area at Chronic Phase.

Traumatic brain injury (TBI) is a complex disease process that may contribute to temporary or permanent disability. Tracking spatial changes of lipids and metabolites in the brain helps unveil the underlying mechanisms of the disease procession and therapeutic response. Here, the liquid microjunction surface sampling technique was used for mass spectrometry imaging of both lipids and metabolites in rat models of controlled cortical impact with and without XueFu ZhuYu decoction treatment, and the work was focused on the diffuse changes outside the injured area at chronic phase (14 days after injury). Quantitative information was provided for phosphotidylcholines and cerebrosides by adding internal standards in the sampling solvent. With principal component analysis for the imaging data, the midbrain was found to be the region with the largest diffuse changes following TBI outside the injured area. In detail, several phosphatidylcholines, phosphatidylethanolamines, phosphatidic acids, and diacylglycerols were found to be significantly up-regulated particularly in midbrain and thalamus after TBI and XFZY treatment. It is associated with the reported "self-repair" mechanisms at the chronic phase of TBI activated by neuroinflammation. Several glycosphingolipids were found to be increased in most of brain regions after TBI, which was inferred to be associated with neuroinflammation and oxidative stress triggered by TBI. Moreover, different classes of small matabolites were significantly changed after TBI, including fatty acids, amino acids, and purines. All these compounds were involved in 10 metabolic pathway networks, and 6 target proteins of XFZY were found related to the impacted pathways. These results shed light on the molecular mechanisms of TBI pathologic processes and therapeutic response.

Study on Xuefu Zhuyu Decoction on changes of serum cytokines MMP-13 and TNF-α in rats with knee osteoarthritis

Study on Xuefu Zhuyu Decoction on changes of serum cytokines MMP-13 and TNF-α in rats with knee osteoarthritis

Research on Effect and Mechanism of Xuefu Zhuyu Decoction on CHD Based on Meta-Analysis and Network Pharmacology.

Xuefu Zhuyu Decoction (XFZY) is an ancient compound widely used in the treatment of coronary heart disease. However, its efficacy evaluation is not complete and its mechanism of action is not clear enough. In an attempt to address these problems, the efficacy was evaluated by meta-analysis and the mechanism was elucidated by the network pharmacology method. We systematically searched relevant studies in PubMed, Chinese National Knowledge Infrastructure Database (CNKI), Cochrane Library, Wanfang Data, and other databases from 2007 to 2019. The association between XFZY treatment and CHD was estimated by risk ratio (RR) and corresponding 95% confidence intervals (95% CIs). The compounds and the potential protein targets of XFZY were obtained from TCMSP, and active compounds were selected according to their oral bioavailability and drug similarity. The potential genes of coronary heart disease were obtained from TTD, OMIM, and GeneCards. The potential pathways related to genes were determined by GO and KEGG pathway enrichment analyses. The compound-target and compound-target-pathway networks were constructed. Molecular docking validates the component and the target. A total of 21 studies including 1844 patients were enrolled in the present meta-analysis, indicating that XFZY has a greater beneficial on total effect (fixed effect RR = 1.30; 95% Cl: 1.24–1.36; P=0.82; I2 = 0.0%) and electrocardiogram efficacy (fixed effect RR = 1.40; 95% Cl: 1.26–1.56; P=0.96; I2 = 0.0%) compared with the control group. A total of 1342 components in XFZY were obtained, among which, 241 were chosen as bioactive components. GO and KEGG analyses got top 10 significantly enriched terms and 10 enriched pathways. The C-T network included 192 compounds and 3085 targets, whereas the C-T-P network included 10 compounds, 109 targets, and 5 pathways. There was a good binding activity between the components and the targets. XFZY has the curative effect on coronary heart disease, and its mechanism is related to 10 compounds, 10 core targets, and 5 pathways.

Mechanism of Xuefu Zhuyu Decoction in treatment of myocardial infarction based on network pharmacology and molecular docking

To explore the action mechanism of Xuefu Zhuyu Decoction in treating myocardial infarction based on network pharmaco-logy and molecular docking. Active components and corresponding targets of Xuefu Zhuyu Decoction were obtained through Traditional Chinese Medicine Systems Pharmacology Database(TCMSP), and related targets of myocardial infarction were obtained through GeneCards, DisGeNET, and OMIM databases. Then the intersection targets were obtained by integrating the drug targets and disease targets. The &quot;active component-target&quot; network was constructed by Cytoscape software, and protein-protein interaction(PPI) network was drawn using STRING platform. Protein cluster analysis was carried out using MCODE. GO enrichment analysis and KEGG pathway analysis were carried out using DAVID database and ClueGO, and molecular docking was carried out using Autodock Vina and Pymol. Finally, 226 active components of Xuefu Zhuyu Decoction were obtained, 257 corresponding targets, 1 340 targets of myocardial infarction, and 109 drug and disease intersection targets were obtained. From GO enrichment analysis, 208 biological process terms, 38 molecular function terms, and 33 cellular component terms were obtained. From KEGG pathway analysis, NF-κB signaling pathway, IL-17 signaling pathway, HIF-1 signaling pathway, and other related pathways were obtained. The molecular docking results showed that the main active components(quercetin, kaempferol, β-sitosterol, luteolin, stigmasterol and baicalein) of Xuefu Zhuyu Decoction in the treatment of myocardial infarction had good binding properties with the core proteins IL6, ALB, VEGFA, TNF, MAPK3 and CASP3. The results suggested that Xuefu Zhuyu Decoction may play a role in the treatment of myocardial infarction by reducing the inflammatory response, reducing oxidative stress, inhibiting cell apoptosis, and promoting angiogenesis.