Study on improving hematopoietic function of rats with blood deficiency syndrome by Shengxuebao mixture

Background:Shengxuebao mixture(SXBM)is a novel herbal drug approved by China State Food and Drug Administration for the treatment of Leukopenia and iron deficiency anemia caused by radiotherapy and chemotherapy.Methods:To explore the mechanism of SXBM in treating blood deficiency syndrome(BDS).Firstly,network pharmacology and in vivo experiments were used to screen candidate targets and important signaling pathways of SXBM,GO functional enrichment and KEGG pathway analysis were performed.Secondly,a BDS rat model was established to verify the results of the analysis of network pharmacological enrichment.Histopathology and routine peripheral blood examination were observed.The expressions of tumor necrosis factor-α,interleukin(IL)-6,HIF-1αand NF-κB were detected by Western blot,and the expressions of IL-6,IL-1βwere detected by ELISA.Results:62 bioactive components,66 potential targets and 131 signaling pathways of BDS were successfully identified by network pharmacology.Molecular docking simulation techniques showed that key targets tumor necrosis factor-α,IL-6,IL-1βcan dock well with crucial components,and the BDS-related signaling pathways HIF-1 and JAK-STAT play a vital role.The combined model experiment of acetylphenylhydrazine and cyclophosphamide showed that the model group had obvious blood deficiency,and the histopathology and blood routine were effectively restored after administration.Our findings indicate that SXBM’s therapeutic effect on BDS primarily involves the mediation of the HIF-1α/NF-κB signaling pathway and the regulation of hematopoietic factor expression.Conclusion:This study not only affirmed the protective properties of SXBM against BDS but also provided insights into a potential mechanism for blood replenishment in the treatment of BDS using SXBM.

Exploring the medication pattern and mechanism of action of traditional Chinese medicine in treating polycystic ovary syndrome with kidney deficiency and blood stasis based on data mining and network pharmacology

Background:Using network pharmacology to explore the potential molecular mechanism of traditional Chinese medicine in treating polycystic ovary syndrome(PCOS)with kidney deficiency and blood stasis syndrome.Method:Collect the related literature materials of PCOS with kidney deficiency and blood stasis syndrome treated by traditional Chinese medicine in four databases in recent ten years,extract the information of prescriptions and complete the frequency analysis.Traditional Chinese Medicine Systems Pharmacology Database was used to screen out the effective components.Use Online Mendelian Inheritance in Man and other databases to screen PCOS disease targets.The intersection targets obtained by clustering prescription and PCOS disease targets were submitted to STRING database for protein-protein interaction network analysis,and Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes pathways were analysed by Metascape.Result:There are 155 kinds of traditional Chinese medicines used in the literature.The most commonly utilized ones are Cuscutae Semen,Angelicae Sinensis Radix,and Rehmanniae Radix Praeparata.The results of the cluster analysis indicated that the plants most commonly found throughout the prescription were Leonuri Herba,Lycopi Herba,Dipsaci Radix,etc.GO results show that biological processes include cell reaction to organic nitrogen compounds and cell reaction to nitrogen compounds.The functional display of GO molecule includes cytokine receptor binding,signal receptor regulator activity and so on.Kyoto Encyclopedia of Genes and Genomes results show that the possible mechanisms of action are cancer pathway,an endocrine resistance signal pathway.Conclusion:Through data mining,the cluster prescription for PCOS with kidney deficiency and blood stasis syndrome is Leonuri Herba,Lycopi Herba,Dipsaci Radix,etc.The network pharmacology research of cluster prescription shows that the main drug components for treating PCOS with kidney deficiency and blood stasis syndrome are quercetin,kaempferol,luteolin,tanshinone IIA,etc.,which act on PTGS2,NCOA2,and other targets,and treat PCOS with kidney deficiency and blood stasis syndrome through cancer and endocrine resistance.

Serum proteomic approach in patients with Qi deficiency and blood stasis syndrome in coronary heart disease:to explore therapeutic mechanism of Yiqi Huoxue decoction

OBJECTIVE To explore the curative effect and mechanism of Yiqi Huoxue decoction in the treatment of coronary heart disease with Qi deficiency and blood stasis syndrome.METHODS The patients with coronary heart disease of Qi deficiency and blood stasis syndrome were treated with Yiqi Huoxue decoction for 3 months,and the changes of cardiac function were observed.61 serum samples(including 29 cases of disease group and 32 cases of Yiqi Huoxue expression group)were analyzed by non labeled proteomics.The disease group was used as the control group,and the protein with expression level difference of more than 1.2 folds(P<0.05)was screened.The molecular function,biological pathway and protein interaction of the different proteins were analyzed by bioinformatics,so as to identify the molecular and biological pathway of Yiqi Huoxue decoction in the treatment of coronary heart disease with Qi deficiency and blood stasis syndrome.RESULTS Clinical treatment found that Yiqi Huoxue decoction can improve TCM syndrome score and left ventricular ejection fraction,regulate blood glucose and blood lipid levels,prolong thrombin time,and improve heart function.The results of proteomic quantitative analysis showed that there were 69 proteins with different expression levels in the disease group.Bioinformatics analysis results showed that Yiqi Huoxue decoction may regulate ApoA1,alpha-2 and other proteins to act on HDL assembly,platelet degradation,PI3K Akt signaling pathway,and then play a therapeutic role in coronary heart disease with Qi deficiency and blood stasis syndrome.CONCLUSION Yiqi Huoxue decoction can effectively improved the heart function decline caused by Qi deficiency and blood stasis syndrome of coronary heart disease.It mainly act on energy metabolism and platelet activation pathway by activating HDL assembly and platelet degradation signal pathway proteins.This study can provide reference for the follow-up treatment mechanism of Qi deficiency and blood stasis syndrome of coronary heart disease.

Clinical observation on efficacy of compound of warming yang, descending turbidity and dredging collaterals in the treatment of diabetic kidney disease with Yin-Yang deficiency and blood stasis syndrome

Objective:To observe the clinical efficacy of compound of owarming yang,descending turbidity and dredging collaterals in the treatment of diabetic kidney disease with yin-yang deficiency and blood stasis syndrome.Methods:Seventy-six patients of diabetic kidney disease with yin-yang deficiency and blood stasis syndrome were randomly divided into observation group and control group,thirty-eight cases in each group.The control group was given conventional western medicine treatment,while the observation group took compound of owarming yang,descending turbidity and dredging collaterals orally on the basis of conventional western medicine treatment.The course of treatment covered for one month.Before and after treatment,we observed the scores of traditional Chinese medicine symptoms,indicators of renal function[serum creatinine(Scr),blood urea nitrogen(BUN),microalbuminuria(MALB)],indicators of glucose metabolism[fasting plasma glucose(FPG),2-hour postprandial blood glucose(2hPG),glycosylated hemoglobin(HbAlc)],indicators of hemorheology[plasma viscosity(PV),platelet aggregation rate(PAR),fibrinogen(FIB)],Cystatin-C(Cys-C),C-reactive protein(CRP)in the two groups.Results:After treatment,the clinical effect of the observation group was significantly better than the control group(P<0.05).The scores of traditional Chinese medicine symptoms,indicators of renal function(Scr、BUN、UAER),indicators of glucose metabolism(FPG、2hPG、HbAlc),indicators of hemorheology(PV、PAR、FIB),Cys-C and CRP in the two groups were decreased significantly compared with those before treatment(P<0.05),and the decrease in the observation group was superior to that in the control group(P<0.05).Conclusion:Compound of warming yang,descending turbidity and dredging collaterals has remarkable efficacy in treating of diabetic kidney disease patients with yin-yang deficiency and blood stasis syndrome by alleviating clinical symptoms,glucose metabolism,renal function and microcirculatory disturbance,and the mechanism related to alleviation of microinflammation.

Efficacy of Yangyin Yiqi Huoxue Granule (养阴益气活血颗粒) in Treatment of Ischemic Stroke Patients with Qi-Yin Deficiency and Blood Stasis Syndrome: A Randomized, Double-Blind, Multicenter, Phase-2 Clinical Trial

Objective To evaluate the efficacy and safety of Yangyin Yiqi Huoxue Granule(养阴益气活血颗粒,YYHG)in the treatment of ischemic stroke(IS)patients with qi-yin deficiency and blood stasis syndrome(QYDBSS),and to explore its effective dosage.Methods The total of 288 patients were randomly assigned to the YYHG high-dose,YYHG low-dose,positive control(administered Xiaoshuantong Granule,XSTG,消栓通颗粒),or placebo control(administered inert granule)groups(72 cases per group)by software-drived competitive block randomization.The trial was conducted for a 28-day period,with a 180-day follow-up period.The primary outcome was the comprehensive curative evaluation,and secondary outcomes were the National Institute of Health Stroke Scale(NIHSS)score,Barthel activities of daily living(ADL)index score,the quality of life index(QLI)score,and the Chinese medicine syndrome(CMS)score.All analyses were done on an intention-to-treat basis.The clinical safety was also assessed.Results The total of 288 participants were recruited between June 1,2008 and September 30,2009,and 287 patients received intervention;the treatment groups were well balanced at baseline.The comprehensive cure rates of YYHG high-dose,low-dose,positive and placebo control groups were 63.38%,31.94%,36.11%and 6.14%,respectively;there was a statistical difference between the two groups(P<0.01),while the high-dose YYHG treatment group was significantly higher than the other 3 groups(P<0.01).The improvement of NIHSS,ADL,QLI and CMS scores of the YYHG high-dose and low-dose groups was significantly better than that of the positive control group and the placebo control group(P<0.05).In terms of improving the classification of the NIHSS scale and the assessment of the ADL scale,the YYHG high-dose group was significantly better than the other three groups(P<0.05),and the YYHG low-dose group was better than the placebo control group(P<0.01).At the same time,except for the QLI score,the high-dose group was better than the low-dose group(P<0.05).In terms of safety,adverse reactions after YYHG treatment were generally mild(3.78%),and no serious adverse reactions have been reported.Conclusion YYHG is safe and effective in the treatment of IS patients with QYDBSS.

Energy Metabolism Disorder and Myocardial Injury in Chronic Myocardial Ischemia with Qi Deficiency and Blood Stasis Syndrome Based on 2-DE Proteomics

Objective： To inquire the characteristic proteins in chronic myocardial ischemia by testing twodimensional electrophoresis （2-DE） map to explore the possible inherent pathological mechanism and the therapeutic intervention of qi deficiency and blood stasis syndrome. Methods： Ameroid constrictor ring was placed on the first interval of left anterior descending coronary artery to prepare chronic myocardial ischemia model on Chinese miniature swine. Animals were randomly divided into sham group and model group with 10 animals in each group, respectively. The dynamic symptoms observation of the four diagnostic information was collected from 0 to 12 weeks. Echocardiography was employed to evaluate cardiac function and the degree of myocardial ischemia, 2-DE and matrix-assisted laser desorption/ionization-time of flight mass spectrometry （MALDI-TOF-MS） were used to carry out proteomics research on animals. Enzyme-linked immunosorbent assay was applied to identify the relevant differential proteins on chronic myocardial ischemia with qi deficiency and blood stasis syndrome. Results： The preliminary study found that at the 12th week, chronic myocardial ischemia with qi deficiency and blood stasis syndrome model was established stably. Compared with the sham group, there were 8 different proteins down-regulated, 22 proteins up-regulated significantly. After validated by MALDI- TOF-MS/MS, 11 protein spots were identified. Distinct proteins were mainly associated with energy metabolism and myocardial structural injury, including isocitrate dehydrogenase 3 （NAD＋） alpha, NADH dehydrogenase （NAD） Fe-S protein 1, chain A （crystal structure of aidose reductase by binding domain reveals a new Nadph）, heat shock protein 27 （HSP27）, oxidoreductase （NAD-binding protein）, antioxidant protein isoform, cardiac troponin T （cTnT）, myosin （myosin light polypeptide）, cardiac alpha tropomyosin, apolipoprotein A- I and albumin. Conclusion： Down-regulated energy metabolism disorder mediated by NADH respiratory chain and myocardial injury may be the pathogenesis of myocardial ischemia with qi deficiency and blood stasis syndrome. These proteins may be the potential diagnostic marker（s） for qi deficiency and blood stasis syndrome, finally provided new clues for new therapeutic drug target of Chinese medicine

Hepatic metabolomics combined with network pharmacology to reveal the correlation between the anti-depression effect and nourishing blood effect of Angelicae Sinensis Radix

Angelicae Sinensis Radix(AS)is reproted to exert anti-depression effect(ADE)and nourishing blood effect(NBE)in a rat model of depression.The correlation between the two therapeutic effects and its underlying mechanisms deserves further study.The current study is designed to explore the underlying mechanisms of correlation between the ADE and NBE of AS based on hepatic metabonomics,network pharmacology and molecular docking.According to metabolomics analysis,30 metabolites involved in 11 metabolic pathways were identified as the potential metabolites for depression.Furthermore,principal component analysis and correlation analysis showed that glutathione,sphinganine,and ornithine were related to pharmacodynamics indicators including behavioral indicators and hematological indicators,indicating that metabolic pathways such as sphingolipid metabolism were involved in the ADE and NBE of AS.Then,a target-pathway network of depression and blood deficiency syndrome was constructed by network pharmacology analysis,where a total of 107 pathways were collected.Moreover,37 active components obtained from Ultra Performance Liquid Chromatography-Triple-Time of Flight Mass Spectrometer(UPLC-Triple-TOF/MS)in AS extract that passed the filtering criteria were used for network pharmacology,where 46 targets were associated with the ADE and NBE of AS.Pathway enrichment analysis further indicated the involvement of sphingolipid metabolism in the ADE and NBE of AS.Molecular docking analysis indciated that E-ligustilide in AS extract exhibited strong binding activity with target proteins(PIK3CA and PIK3CD)in sphingolipid metabolism.Further analysis by Western blot verified that AS regulated the expression of PIK3CA and PIK3CD on sphingolipid metabolism.Our results demonstrated that sphingolipid metabolic pathway was the core mechanism of the correlation between the ADE and NBE of AS.

Relationship between Two Blood Stasis Syndromes and Inflammatory Factors in Patients with Acute Coronary Syndrome

Objective： To investigate the relationship between inflammatory factors and two Chinese medicine（CM） syndrome types of qi stagnation and blood stasis（QSBS） and qi deficiency and blood stasis（QDBS） in patients with acute coronary syndrome（ACS）. Methods： Sixty subjects with ACS, whose pathogenesis changes belongs to qi disturbance blood stasis syndrome, were divided into 2 groups： 30 in the QSBS group and 30 in the QDBS group. The comparative analysis on them was carried out through comparing general information, coronary angiography and inflammatory factors including intracellular adhesion molecule-1（ICAM-1）, chitinase-3-like protein 1（YKL-40） and lipoprotein-associated phospholipase A2（Lp-PLA2）. Results： Compared with the QSBS group, Lp-PLA2 and YKL-40 levels in the QDBS group showed no-significant difference（P〉0.05）; ICAM-1 was significantly higher in the QDBS group than in the QSBS group in the pathological processes of qi disturbance and blood stasis syndrome of ACS（P〈0.05）. Conclusion： Inflammatory factor ICAM-1 may be an objective basis for syndrome typing of QSBS and QDBS, which provides a research direction for standardization research of CM syndrome types.

Serum Low-Density Lipoprotein and Heart Rate Related to the Effectiveness in the Treatment of Angina Pectoris with Two Similar Chinese Medicine Herbal Formulae

Objective： To explore the effectiveness related indicators which might help identify the indications of Tongxinluo Capsule （通心络胶囊） and Kangxin Capsule （康欣胶囊） targeting on qi deficiency and blood stasis pattern in Chinese medicine （CM） in the treatment of angina pectoris. Methods： The data from a multicenter, randomized and double-blinded study conducted at 5 centers in China were obtained for the analysis. A total of 239 patients with angina pectoris and CM syndrome of qi deficiency and blood stasis were randomly assigned in a 1：1 ratio to Tongxinluo Capsule group （119 cases） and Kangxin Capsule group （120 cases）. Angina effectiveness and electrocardiogram （ECG） improvement were selected as the therapeutic outcomes. Results： After a 4-week treatment, the effective rates of Tongxinluo Capsule and Kangxin Capsule were 43.70% and 25.00%, respectively （P〈0.05）. Serum low-density lipoprotein （LDL） level was found to influence the effectiveness of Tongxinluo Capsule which had higher effective rate in the patients with lower level of LDL. Heart rate was found to influence the effectiveness in the patients treated with Kangxin Capsule which had higher effective rate in the patients with heart rate ≤80 beats/min. Conclusion： LDL level and heart rate were the indicators which help indentify the indications of Tongxinluo Capsule and Kangxin Capsule, respectively, in the treatment of angina pectoris with CM syndrome of qi deficiency and blood stasis.