Objective: To explore the therapeutic effect of Linggui Zhugan Decoction on nonalcoholic fatty liver disease through in vivo animal experiments, and to explore the mechanism of action of Linggui Zhugan Decoction in th...Objective: To explore the therapeutic effect of Linggui Zhugan Decoction on nonalcoholic fatty liver disease through in vivo animal experiments, and to explore the mechanism of action of Linggui Zhugan Decoction in the intervention of nonalcoholic fatty liver disease through network pharmacology and molecular docking technology. Methods: A rat model of non- alcoholic fatty liver disease was established after 20 weeks of high-fat feeding, and the rats were divided into six groups, normal group, model group, simvastatin group (4 mg/kg), low- dose group of Linggui Zhugan Decoction (2.1 g/kg), medium-dose group of Linggui Zhugan Decoction (4.2 g/kg), and high-dose group of Linggui Zhugan Decoction (8.4 g/kg), and the liver morphological changes of HE staining and oil red O staining after the intervention of Linggui Zhugan Decoction were observed, and the microplate reader detected aspartate aminotransferase, alanine aminotransferase, Four levels of blood lipids. Network pharmacology combined with molecular docking was used to screen the potential mechanism and target of Linggui Zhugan Decoction for the intervention of non-alcoholic fatty liver disease. Results: Linggui Zhugan Decoction significantly improved the levels of alanine aminotransferase and alanine aminotransferase in model rats (P<0.05). HE staining and oil red O staining showed that Linggui Zhugan Decoction significantly reduced liver lipid deposition in rats in the model group. Linggui Zhugan Decoction could significantly reduce the quadruplical levels of blood lipids in model rats (P<0.05). Network pharmacology screened out 10 key targets and 5 key signaling pathways;The molecular docking results showed that the first 20 active ingredients all had good binding ability to the top 10 targets. Conclusion: The results show that Linggui Zhugan Decoction has the effect of regulating blood lipids and improving liver tissue lesions in non-alcoholic fatty liver disease, and preliminarily verifies the regulatory effect of Linggui Zhugan Decoction on lipid metabolism-related genes.展开更多
Background:Xuefu Zhuyu decoction(XFZY)could significantly improve the function of hypertensive vascular endothelial cells,but the targets and mechanism are not clear.This study is to analyze the pharmacological substa...Background:Xuefu Zhuyu decoction(XFZY)could significantly improve the function of hypertensive vascular endothelial cells,but the targets and mechanism are not clear.This study is to analyze the pharmacological substances and targets of Xuefu Zhuyu decoction in hypertensive vascular endothelial cells.Methods:This study used Xuefu Zhuyu decoction to intervene human umbilical vein endothelial cells incubated by hypertensive patients’serum,then detected the function of vascular endothelial cells.The aqueous extract of XFZY was analyzed and validated by liquid chromatography-mass spectrometry technology;Finally,macromolecular docking technology was used to analyze the potential active substances and targets of XFZY in the prevention and treatment of hypertension.Results:Compared with the model group,the XFZY group showed a significant increase in NO expression(P<0.01)and a significant decrease in ET-1 expression(P<0.001);and the expression of BIP,P-JNK,CHOP,and BAX in XFZY group cells was significantly decreased(P<0.001),while the expression of JNK and BCL2 was significantly increased(P<0.001).19 main compounds were identified in XFZY and there were 3 pairs of molecular complexes with high affinity for markers of the endoplasmic reticulum stress,including BIP-Hesperidin complex,BIP-HSYA complex and JNK-Naringin complex.Conclusion:This study analyzed the potential pharmacodynamic substance and targets of Xuefu Zhuyu decoction in improving the function of hypertensive vascular endothelial cells,which could provide a scientific basis for the future molecular mechanism of XFZY in treating hypertension.展开更多
Background:To investigate the mechanism of Xuefu Zhuyu decoction in the treatment of diabetes mellitus erectile dysfunction.Methods:Rats with diabetes mellitus erectile dysfunction were developed using streptozocin an...Background:To investigate the mechanism of Xuefu Zhuyu decoction in the treatment of diabetes mellitus erectile dysfunction.Methods:Rats with diabetes mellitus erectile dysfunction were developed using streptozocin and randomly assigned into model,low-dose herbal,and high-dose herbal groups.All rats were administered normal saline or the corresponding drugs by oral gavage for 4 weeks.The related indices were detected using enzyme-linked immunosorbent assays,immunohistochemistry,western blotting,and transmission electron microscopy.Results:The levels of lectin-like oxidized low-density protein receptor-1,endothelin-1,NADH oxidase,vascular cell adhesion molecule-1,and intercellular adhesion molecule-1 in the model group were significantly higher than they were in the mock group but lower than they were in the herbal treatment group.The level of nitric oxide was lower in the model group than was in the mock group but higher than the level in the herbal treatment group.The calcium-sensitive receptor,phospho-protein kinase Cδ/protein kinase Cδ,phosphorylated c-Jun amino-terminal kinase/c-Jun amino-terminal kinase,and phospho-P38 mitogen-activated protein kinase/P38 mitogen-activated protein kinase expression levels in the model group were higher than were in the mock group but lower than were in the herbal treatment group.The structures of the Corpus cavernosum penis endothelial cells were significantly improved in the herbal treatment group than they did in the model group.Conclusion:Xuefu Zhuyu decoction can decrease injury to the endothelium,improve vascular endothelial diastolic and contractive function,and inhibit vascular fibrosis in rats with diabetes mellitus erectile dysfunction.This mechanism may be related to the CaSR/Gq-PLC-PKC pathway.展开更多
Objective To explore the influence of Linggui Zhugan Decoction(LGZGD)on high glucose induced podocyte autophagy Methods LGZGD containing serum were prepared by intragastric administation of 4.2 g·kg^(-1)(low dose...Objective To explore the influence of Linggui Zhugan Decoction(LGZGD)on high glucose induced podocyte autophagy Methods LGZGD containing serum were prepared by intragastric administation of 4.2 g·kg^(-1)(low dose),8.4 g·kg^(-1)(medium dose),and 12.6 g·kg^(-1)(high dose)LGZGD into SD rats respectively.MPC5 and AB8/13 cells were treated with 60 mmol/L glucose to establish diabetic nephropathy podocyte model in vitro.Podocytes,MPC5 and AB8.13,were divided into control group,high glucose group,low dose LGZGD group,medium dose LGZGD group,and high dose LGZGD group,respectively.For the three LGZGD groups,before LGZGD intervention,podocytes were treated with 60 mmol/L glucose for 3 days.After treated with LGZGD containing serum,cells were collected to analyze cell migration using Transwell assay,proliferation using CCK8,apoptosis and cell cycle using flow cytometry,,autophagosome formation using transmission electron microscopy,and expression levels of Beclin-1,Atg5,LC3II/I,and P62 proteins using western blot.Results Compared with the control group,the proliferation and migration of MPC5 and AB8.13 cells in high glucose group showed slightly decreased,whereas these parameters restored after intervention with low and medium concentrations of LGZGD,with the medium dose LGZGD having the best effect.Flow cytometry analysis showed that the medium dose LGZGD group had a lower apoptosis rate(P<0.05)and higher survival rate(P>0.05)compared to the high dose group.High glucose arrested podocytes in G1 phase,whereas LGZGD shifted podocytes from being predominant in G1 phase to increasing into G2.High dose LGZGD significanly reduced increased autophagosome formation due to high glucose in both podocytes(P<0.05).Western blot analysis showed that Beclin-1,Atg5,LC3Ⅱ/Ⅰ,and P62 expressions were increased in MPC5 cells treated with high glucose,and reversed after adminstration of low and medium doses of LGZGD(P<0.05).Conclusion LGZGD reduced apoptosis and enhanced autophagy in high glucose treated podocytes via regulating Beclin-1/LC3II/I/Atg5 expression.展开更多
BACKGROUND The diagnosis and treatment of depression in patients with chronic heart failure(CHF)is challenging,with no ideal treatment at present.AIM To analyze the clinical intervention effect of Xuefu Zhuyu decoctio...BACKGROUND The diagnosis and treatment of depression in patients with chronic heart failure(CHF)is challenging,with no ideal treatment at present.AIM To analyze the clinical intervention effect of Xuefu Zhuyu decoction(XFZYD)on CHF complicated with depression.METHODS The study cohort comprised 116 patients with CHF complicated with depression who received treatment from July 2020 to July 2023,of which 55 received Western medicine(control group)and 61 received XFZYD(research group).Data on clinical effectiveness,traditional Chinese medicine(TCM)syndrome score,cardiac function,negative emotions,and serum inflammatory factors,were collected for comparative analyses.RESULTS Compared with the control group,the research group had an evidently higher total effective rate.Furthermore,there were marked reductions in TCM symptom score,left ventricular end-diastolic diameter,left ventricular end-systolic diameter,Self-Rating Depression Scale,Hamilton Depression Scale,high-sensitivity C-reactive protein,monocyte chemoattractant protein-1,and matrix metalloproteinase-9 in the research group after treatment,and these were lower than the corresponding values in the control group.Left ventricular ejection fraction was increased and higher in the research group compared with the control group after treatment.CONCLUSION Our findings conclusively proved that XFZYD was considerably superior to Western medicine for treating CHF complicated with depression because it significantly alleviated patients’symptoms,improved cardiac function,relieved negative emotions,and reduced the levels of serum inflammatory factors.展开更多
Arrowsmith,a literature retrieval tool,was used to explore the theoretical pharmacological mechanism of action of Xuefu Zhuyu decoction and its single herb against erectile dysfunction.Cytoscape 3.6.1 software was use...Arrowsmith,a literature retrieval tool,was used to explore the theoretical pharmacological mechanism of action of Xuefu Zhuyu decoction and its single herb against erectile dysfunction.Cytoscape 3.6.1 software was used to analyze the correlation between the components of Xuefu Zhuyu decoction and the identified mechanism of action.Different herbs in Xuefu Zhuyu decoction may play a therapeutic role by regulating iNOS,COX-2,mTOR,Wnt,AMPK,Nrf2,TLR4,CYP2D6,BDNF,MAPK,Akt,STAT3,PI3K,ERK1,P38MAPK,JNK,VEGF,and other targets.The treatment of erectile dysfunction with Xuefu Zhuyu decoction embodied the multicomponent,multitarget,and multipathway.The Arrowsmith tool retrieval and analysis provided a scientific basis for further elucidation of the mechanism of Xuefu Zhuyu decoction against erectile dysfunction.展开更多
Objective: To explore the effects of Xuefu Zhuyu Decoction combined with conventional therapy on inflammatory response, oxidative stress, endothelium and related factors in patients with acute cerebral infarction. Met...Objective: To explore the effects of Xuefu Zhuyu Decoction combined with conventional therapy on inflammatory response, oxidative stress, endothelium and related factors in patients with acute cerebral infarction. Methods: A total of 162 patients with acute cerebral infarction admitted to our hospital from November 2016 to January 1818 were selected as subjects. According to the random sampling method, the subjects were divided into 81 cases in the control group and 81 cases in the observation group. The control group was treated with conventional intracranial pressure, anticoagulation, anti-oxidation and lipid-lowering treatment. The observation group was treated with Xuefu Zhuyu Decoction on the basis of the control group. The changes of inflammatory response, oxidative stress, endothelium and related factors were compared and analyzed. Results:Before treatment, the levels of TNF-α, CRP, SOD, MDA, AOPPS, NO, ET-1, MMP-9, PAF and IGF-1 in the two groups were not significantly different, and there was no statistical significance. After treatment, the levels of TNF-α and CRP in the two groups were significantly lower than those before treatment, and the levels of TNF-α and CRP in the observation group were significantly lower than control group;the levels of MDA and AOPPS in the two groups were significantly lower than those before treatment, while the level of SOD was significantly higher than before treatment, and the levels of MDA and AOPPS in the observation group were significantly lower than control group, while the level of SOD was significantly higher. In the control group;the level of ET-1 in the two groups was significantly lower than that before treatment, while the level of NO was significantly higher than that before the treatment, and in the observation group the level of ET-1 was significantly lower than the control group, while the level of NO was significantly higher. In the control group;the levels of MMP-9 and PAF in the two groups were significantly lower than those before treatment, while the level of IGF-1 was significantly higher than before treatment, and the levels of MMP-9 and PAF in the observation group were significantly lower than control group, while the level of IGF-1 was significantly higher than control group. Conclusions: Xuefu Zhuyu Decoction combined with conventional treatment of acute cerebral infarction can effectively reduce inflammation and oxidative stress, improve vascular endothelial function and nerve function, and significantly reduce the degree of brain injury, which has clinical significance.展开更多
Objective:Banxia Baizhu Tianma Decoction(半夏白术天麻汤,BBTD)combined with Xuefu Zhuyu Decoction(血府逐瘀汤,XFZYD)is widely used to treat essential hypertension in China,but its efficacy remains largely unexplored.We ...Objective:Banxia Baizhu Tianma Decoction(半夏白术天麻汤,BBTD)combined with Xuefu Zhuyu Decoction(血府逐瘀汤,XFZYD)is widely used to treat essential hypertension in China,but its efficacy remains largely unexplored.We systemically summarized relevant evidence from randomized controlled trials(RCTs)to assess the therapeutic efficacy of BBTD+XFZYD.Methods:This review retrieved 6 databases like Pubmed,Cochrane Library,Embase,CNKI,et al.RCTs of BBTD+XFZYD plus conventional Western drugs(experimental group)and conventional Western drugs alone(control group)for hypertension was collected from the database establishment to August 5,2020.And the outcomes included clinical total effective rate,systolic blood pressure(SBP),diastolic blood pressure(DBP),nitric oxide(NO)and endothelin-1(ET-1).All studies’risk of bias were assessed by the Cochrane Collaboration tool 5.1.0.The data was statistically analyzed by RevMan5.3 Software.Results:Six studies with 608 participants were identified.About duration of treatment,4 studies were 1 month,2 studies were 2 months.The quality presented a high risk of bias.The experimental group showed that clinical total effective rate of the 1-month and 2-month was higher(P<0.00001),the systolic pressure was significantly lower(P<0.05),the NO increased(P<0.00001),and the ET-1 decreased(P<0.00001)compared with the conventional Western drugs used alone.However,DBP was significantly lower(P<0.05)at 2 months of treatment.Conclusion:BBTD+XFZYD plus conventional Western drugs might reduce blood pressure,improve clinical efficacy,repair endothelial function,but still need high-quality RCTs to better assess the outcomes.展开更多
Xuefu Zhuyu decoction has been used for treating traumatic brain injury and improving post-traumatic dysfunction, but its mechanism of action needs further investigation. This study established rat models of traumatic...Xuefu Zhuyu decoction has been used for treating traumatic brain injury and improving post-traumatic dysfunction, but its mechanism of action needs further investigation. This study established rat models of traumatic brain injury by controlled cortical impact. Rat models were intragastrically administered 9 and 18 g/kg Xuefu Zhuyu decoction once a day for 14 or 21 days. Changes in neurological function were assessed by modified neurological severity scores and the Morris water maze. Immunohistochemistry, western blot assay, and re- verse-transcription polymerase chain reaction were used to analyze synapsin protein and mRNA expression at the injury site of rats. Our results showed that Xuefu Zhuyu decoction visibly improved neurological function of rats with traumatic brain injury. These changes were accompanied by increased expression of synaptophysin, synapsin I, and postsynaptic density protein-95 protein and mRNA in a dose-de- pendent manner. These findings indicate that Xuefu Zhuyu decoction increases synapsin expression and improves neurological deficits alder traumatic brain injury.展开更多
Objective:To evaluate the safety and effectiveness of Xuefu Zhuyu Decoction in treating diabetic encephalopathy.Methods:Computer search and manual search of Pub Med,Web of Science,The Cochrane Library,CNKI,WF,VIP and ...Objective:To evaluate the safety and effectiveness of Xuefu Zhuyu Decoction in treating diabetic encephalopathy.Methods:Computer search and manual search of Pub Med,Web of Science,The Cochrane Library,CNKI,WF,VIP and CBM from January 2000 to April 2020 on the treatment of diabetic encephalopathy with Xuefu Zhuyu Decoction In randomized controlled clinical trials,select documents that meet the criteria for analysis using Rev Man 5.3 software.Results:A total of 11 articles and 838 patients were included in the study.Metaanalysis showed that Xuefu Zhuyu Decoction was effective(OR=3.71,95%CI[2.42,5.70],P<0.00001),and the patient’s neurological deficit score(MD=-4.52,95%CI[-5.10,-3.94],P<0.00001),fasting blood glucose(MD=-1.05,95%CI[-1.51,-0.59],P<0.00001),2 hours postprandial blood glucose(MD=-1.31,95%CI[-1.94,-0.69],P<0.00001),glycated hemoglobin(MD=-0.94,95%CI[-1.15,-0.72],P<0.00001),TCM symptom score(MD=-2.44,95%CI[-3.82,-1.06],P=0.0005<0.01),vitality score(MD=12.79,95%CI[8.79,16.79],P<0.00001),the improvement effect is obvious Better than conventional Western medicine treatment.Conclusion:Xuefu Zhuyu Decoction can improve the clinical efficiency of patients with diabetic encephalopathy,reduce brain damage,reduce blood sugar and glycated hemoglobin levels,and has good safety.However,the quality of some of the included literatures is low,and the number of clinical cases is small,which may affect the authenticity of the Meta analysis results.Still need to be further verified by clinical randomized controlled trials with high-quality large samples.展开更多
Objective: As a classic prescription in traditional Chinese medicine, Xuefu Zhuyu Decoction(XFZYD) has been widely used in the clinical treatment of cardiovascular and cerebrovascular diseases. In order to unveil the ...Objective: As a classic prescription in traditional Chinese medicine, Xuefu Zhuyu Decoction(XFZYD) has been widely used in the clinical treatment of cardiovascular and cerebrovascular diseases. In order to unveil the potentially effective compounds, a rapid ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS) method was established to identify prototype compounds and their metabolites from XFZYD in rats’ serum.Methods: The serum from rats after intragastric administration of XFZYD aqueous extract was analyzed by UPLC-Q-TOF/MS method. The prototype compounds and their metabolites were identified by comparison with the reference standards and tentatively characterized by comprehensively analyzing the retention time, MS data, characteristic MS fragmentation pattern and retrieving literatures.Results: A total of 175 compounds(24 prototype compounds and 151 metabolites) were identified and tentatively characterized. The metabolic pathways of prototype compounds in vivo were also summarized, including glucuronidation, hydrolyzation, sulfation, demethylation, and hydroxylation, and so on.Conclusion: In this study, a UPLC-Q-TOF/MS technique was developed to analyze prototype compounds and their metabolites from XFZYD in serum, which would provide the evidence for further studying the effective compounds of XFZYD.展开更多
Objective: To study the angiogenesis modulation mechanism of Xuefu Zhuyu Decoction (血府逐瘀汤) on the endothelial cell line ECV304. Methods: ECV304 cells were treated with 2.5% Xuefu Zhuyu Decoction- containing s...Objective: To study the angiogenesis modulation mechanism of Xuefu Zhuyu Decoction (血府逐瘀汤) on the endothelial cell line ECV304. Methods: ECV304 cells were treated with 2.5% Xuefu Zhuyu Decoction- containing serum (XFZYD-CS) for 24 h, 48 h or 72 h. Thiazolyl blue tetrazolium bromide (MTT), fluorescence activating cell sorter (FACS), migration, adhesion and in vitro tube formation assays were conducted to confirm an angiogenesis effect of XFZYD at 3 time points. An analysis of angiogenesis regulator profiles was performed at 3 times with real-time polymerase chain reaction (RT-PCR) superarray. Results: At 48 h, XFZYD-CS induced ECV304 significantly improved cell viability, number in S phase, migration, adhesion and tube formation. At 24 h and 72 h, only cell migration was elevated. Microarray results showed that the expression of 27 angiogenesis-related genes was changed. Conclusion: XFZYD-CS treatment induced angiogenesis on ECV304 cells with significant cellcular changes occurring at 48 h and genetic changes as early as 24 h.展开更多
Objective: To compare the angiogenesis behaviors of vascular endothelial growth factor(VEGF) and Chinese medicine Xuefu Zhuyu Decoction(血府逐瘀汤,XZD) treatments.Methods: Human microvascular endothelial cells(...Objective: To compare the angiogenesis behaviors of vascular endothelial growth factor(VEGF) and Chinese medicine Xuefu Zhuyu Decoction(血府逐瘀汤,XZD) treatments.Methods: Human microvascular endothelial cells(HMEC-1) were treated with various concentrations of either XZD-containing serum(XZD-CS) or VEGF for 24,48,and 72 h,respectively.Cell viability,proliferation,migration,adhesion,and in vitro tube formation assays were used to assess their angiogenic effects.Results: VEGF promoted all cellular phases involved in angiogenesis including cell viability,proliferation,migration,adhesion,and tube formation(P〈0.05 or P〈0.01).Unlike the continuous promotion effects of VEGF at the above stages,XZD inhibited cell viability and proliferation(P〈0.05 or P〈0.01) and only promoted tube formation in the early phase of angiogenesis(P〈0.01).Conclusions: These two medications promote different angiogenesis behaviors,which might be an important reason for their distinct therapeutic profile in clinical usage.展开更多
Objective: To observe the effect of Xuefu Zhuyu Decoction (血府逐瘀汤)-containing serum (XFZYD-CS) on endothelial progenitor cell (EPC) tube formation in vitro. Methods: Mononuclear cells from rat bone marrow ...Objective: To observe the effect of Xuefu Zhuyu Decoction (血府逐瘀汤)-containing serum (XFZYD-CS) on endothelial progenitor cell (EPC) tube formation in vitro. Methods: Mononuclear cells from rat bone marrow were prepared in a Ficoll density gradient centrifuge. EPCs were separated by the differential attachment method, and observed with inverted microscope for the effect of XFZYD-CS on EPC tube formation. Results: After one day, EPCs exposed to the serum containing 5%, 10% and 15% XFZYD-CS formed typical tubes or vessel networks. The tube formation time was two days ahead of the control group and the size of most tubes in the serum groups was smaller than in the control group. Conclusion: XFZYD-CS could induce EPC angiogenesis and hasten tube formation, especially in capillary vessels. The study provides experimental evidence for the plausibility of Xuefu Zhuyu Decoction in the treatment of ischemic diseases.展开更多
Objective:To evaluate the effects of the modified Linggui Zhugan Decoction(加味苓桂术甘汤) combined with short-term very low calorie diets(VLCDs) on glycemic control in newly diagnosed type 2 diabetes mellitus(T2DM) p...Objective:To evaluate the effects of the modified Linggui Zhugan Decoction(加味苓桂术甘汤) combined with short-term very low calorie diets(VLCDs) on glycemic control in newly diagnosed type 2 diabetes mellitus(T2DM) patients.Methods:A total of 20 subjects with newly diagnosed T2DM were treated with the modified Linggui Zhugan Decoction(one-month administration) combined with short-term VLCDs(5 days),and 3-months follow-up.A standard 75-g oral-glucose-tolerance test(OGTT) indexes fasting plasma glucose(FPG),post-prandial 0.5 h and 2 h plasma glucose(P0.5hPG,P2hPG),glycated hemoglobin A1C(GHbA1C),body weight,body mass index(BMI),insulin function,insulin resistance index,incidence of hypoglycemia,and the liver and renal functions were evaluated before and after treatment.Correlations of BMI with insulin function and insulin resistance were also assessed.Results:After the treatment,the patients' plasma glucose decreased steadily,FPG decreased from 5.8±0.9 mmol/L at pre-treatment to 5.0±0.6 mmol/L at 3-months follow-up(P<0.05),and P2hPG decreased from 11.7±3.8 mmol/L at pre-treatment to 6.9±0.9 mmol/L at 3-months follow-up(P<0.01).The level of GHbA1C declined from(6.47±1.24)% at pre-treatment to(6.14±0.99)% at 3-months follow-up(P<0.01).Body weight and BMI also declined significantly.Insulin resistance index was improved obviously and no event of hypoglycemia occurred.Part of the patients companied with fatty liver had a transient increase in hepatic transaminase during the treatment,but it turned to normal after the treatment.Conclusions:The modified Linggui Zhugan Decoction combined with short-term VLCDs can be safely implemented for steady glycemic control in newly diagnosed T2DM patients.展开更多
基金Anhui Natural Science Foundat ion General Project(No.2208085MH277)。
文摘Objective: To explore the therapeutic effect of Linggui Zhugan Decoction on nonalcoholic fatty liver disease through in vivo animal experiments, and to explore the mechanism of action of Linggui Zhugan Decoction in the intervention of nonalcoholic fatty liver disease through network pharmacology and molecular docking technology. Methods: A rat model of non- alcoholic fatty liver disease was established after 20 weeks of high-fat feeding, and the rats were divided into six groups, normal group, model group, simvastatin group (4 mg/kg), low- dose group of Linggui Zhugan Decoction (2.1 g/kg), medium-dose group of Linggui Zhugan Decoction (4.2 g/kg), and high-dose group of Linggui Zhugan Decoction (8.4 g/kg), and the liver morphological changes of HE staining and oil red O staining after the intervention of Linggui Zhugan Decoction were observed, and the microplate reader detected aspartate aminotransferase, alanine aminotransferase, Four levels of blood lipids. Network pharmacology combined with molecular docking was used to screen the potential mechanism and target of Linggui Zhugan Decoction for the intervention of non-alcoholic fatty liver disease. Results: Linggui Zhugan Decoction significantly improved the levels of alanine aminotransferase and alanine aminotransferase in model rats (P<0.05). HE staining and oil red O staining showed that Linggui Zhugan Decoction significantly reduced liver lipid deposition in rats in the model group. Linggui Zhugan Decoction could significantly reduce the quadruplical levels of blood lipids in model rats (P<0.05). Network pharmacology screened out 10 key targets and 5 key signaling pathways;The molecular docking results showed that the first 20 active ingredients all had good binding ability to the top 10 targets. Conclusion: The results show that Linggui Zhugan Decoction has the effect of regulating blood lipids and improving liver tissue lesions in non-alcoholic fatty liver disease, and preliminarily verifies the regulatory effect of Linggui Zhugan Decoction on lipid metabolism-related genes.
基金financially supported by Natural Science Foundation of Shandong Province(No.ZR2023QH037)Medical and Health Science and Technology Development Program of Shandong Province(No.202203010622)+1 种基金GuangDong Basic and Applied Basic Research Foundation(No.2020A1515111005)China Postdoctoral Science Foundation(No.2018M643053).
文摘Background:Xuefu Zhuyu decoction(XFZY)could significantly improve the function of hypertensive vascular endothelial cells,but the targets and mechanism are not clear.This study is to analyze the pharmacological substances and targets of Xuefu Zhuyu decoction in hypertensive vascular endothelial cells.Methods:This study used Xuefu Zhuyu decoction to intervene human umbilical vein endothelial cells incubated by hypertensive patients’serum,then detected the function of vascular endothelial cells.The aqueous extract of XFZY was analyzed and validated by liquid chromatography-mass spectrometry technology;Finally,macromolecular docking technology was used to analyze the potential active substances and targets of XFZY in the prevention and treatment of hypertension.Results:Compared with the model group,the XFZY group showed a significant increase in NO expression(P<0.01)and a significant decrease in ET-1 expression(P<0.001);and the expression of BIP,P-JNK,CHOP,and BAX in XFZY group cells was significantly decreased(P<0.001),while the expression of JNK and BCL2 was significantly increased(P<0.001).19 main compounds were identified in XFZY and there were 3 pairs of molecular complexes with high affinity for markers of the endoplasmic reticulum stress,including BIP-Hesperidin complex,BIP-HSYA complex and JNK-Naringin complex.Conclusion:This study analyzed the potential pharmacodynamic substance and targets of Xuefu Zhuyu decoction in improving the function of hypertensive vascular endothelial cells,which could provide a scientific basis for the future molecular mechanism of XFZY in treating hypertension.
基金supported by Fujian Provincial Natural Science Foundation Project(2020J01243).
文摘Background:To investigate the mechanism of Xuefu Zhuyu decoction in the treatment of diabetes mellitus erectile dysfunction.Methods:Rats with diabetes mellitus erectile dysfunction were developed using streptozocin and randomly assigned into model,low-dose herbal,and high-dose herbal groups.All rats were administered normal saline or the corresponding drugs by oral gavage for 4 weeks.The related indices were detected using enzyme-linked immunosorbent assays,immunohistochemistry,western blotting,and transmission electron microscopy.Results:The levels of lectin-like oxidized low-density protein receptor-1,endothelin-1,NADH oxidase,vascular cell adhesion molecule-1,and intercellular adhesion molecule-1 in the model group were significantly higher than they were in the mock group but lower than they were in the herbal treatment group.The level of nitric oxide was lower in the model group than was in the mock group but higher than the level in the herbal treatment group.The calcium-sensitive receptor,phospho-protein kinase Cδ/protein kinase Cδ,phosphorylated c-Jun amino-terminal kinase/c-Jun amino-terminal kinase,and phospho-P38 mitogen-activated protein kinase/P38 mitogen-activated protein kinase expression levels in the model group were higher than were in the mock group but lower than were in the herbal treatment group.The structures of the Corpus cavernosum penis endothelial cells were significantly improved in the herbal treatment group than they did in the model group.Conclusion:Xuefu Zhuyu decoction can decrease injury to the endothelium,improve vascular endothelial diastolic and contractive function,and inhibit vascular fibrosis in rats with diabetes mellitus erectile dysfunction.This mechanism may be related to the CaSR/Gq-PLC-PKC pathway.
文摘Objective To explore the influence of Linggui Zhugan Decoction(LGZGD)on high glucose induced podocyte autophagy Methods LGZGD containing serum were prepared by intragastric administation of 4.2 g·kg^(-1)(low dose),8.4 g·kg^(-1)(medium dose),and 12.6 g·kg^(-1)(high dose)LGZGD into SD rats respectively.MPC5 and AB8/13 cells were treated with 60 mmol/L glucose to establish diabetic nephropathy podocyte model in vitro.Podocytes,MPC5 and AB8.13,were divided into control group,high glucose group,low dose LGZGD group,medium dose LGZGD group,and high dose LGZGD group,respectively.For the three LGZGD groups,before LGZGD intervention,podocytes were treated with 60 mmol/L glucose for 3 days.After treated with LGZGD containing serum,cells were collected to analyze cell migration using Transwell assay,proliferation using CCK8,apoptosis and cell cycle using flow cytometry,,autophagosome formation using transmission electron microscopy,and expression levels of Beclin-1,Atg5,LC3II/I,and P62 proteins using western blot.Results Compared with the control group,the proliferation and migration of MPC5 and AB8.13 cells in high glucose group showed slightly decreased,whereas these parameters restored after intervention with low and medium concentrations of LGZGD,with the medium dose LGZGD having the best effect.Flow cytometry analysis showed that the medium dose LGZGD group had a lower apoptosis rate(P<0.05)and higher survival rate(P>0.05)compared to the high dose group.High glucose arrested podocytes in G1 phase,whereas LGZGD shifted podocytes from being predominant in G1 phase to increasing into G2.High dose LGZGD significanly reduced increased autophagosome formation due to high glucose in both podocytes(P<0.05).Western blot analysis showed that Beclin-1,Atg5,LC3Ⅱ/Ⅰ,and P62 expressions were increased in MPC5 cells treated with high glucose,and reversed after adminstration of low and medium doses of LGZGD(P<0.05).Conclusion LGZGD reduced apoptosis and enhanced autophagy in high glucose treated podocytes via regulating Beclin-1/LC3II/I/Atg5 expression.
基金Supported by Scientific Research Plan Project of Hebei Provincial Administration of Traditional Chinese Medicine,No.2018507.
文摘BACKGROUND The diagnosis and treatment of depression in patients with chronic heart failure(CHF)is challenging,with no ideal treatment at present.AIM To analyze the clinical intervention effect of Xuefu Zhuyu decoction(XFZYD)on CHF complicated with depression.METHODS The study cohort comprised 116 patients with CHF complicated with depression who received treatment from July 2020 to July 2023,of which 55 received Western medicine(control group)and 61 received XFZYD(research group).Data on clinical effectiveness,traditional Chinese medicine(TCM)syndrome score,cardiac function,negative emotions,and serum inflammatory factors,were collected for comparative analyses.RESULTS Compared with the control group,the research group had an evidently higher total effective rate.Furthermore,there were marked reductions in TCM symptom score,left ventricular end-diastolic diameter,left ventricular end-systolic diameter,Self-Rating Depression Scale,Hamilton Depression Scale,high-sensitivity C-reactive protein,monocyte chemoattractant protein-1,and matrix metalloproteinase-9 in the research group after treatment,and these were lower than the corresponding values in the control group.Left ventricular ejection fraction was increased and higher in the research group compared with the control group after treatment.CONCLUSION Our findings conclusively proved that XFZYD was considerably superior to Western medicine for treating CHF complicated with depression because it significantly alleviated patients’symptoms,improved cardiac function,relieved negative emotions,and reduced the levels of serum inflammatory factors.
文摘Arrowsmith,a literature retrieval tool,was used to explore the theoretical pharmacological mechanism of action of Xuefu Zhuyu decoction and its single herb against erectile dysfunction.Cytoscape 3.6.1 software was used to analyze the correlation between the components of Xuefu Zhuyu decoction and the identified mechanism of action.Different herbs in Xuefu Zhuyu decoction may play a therapeutic role by regulating iNOS,COX-2,mTOR,Wnt,AMPK,Nrf2,TLR4,CYP2D6,BDNF,MAPK,Akt,STAT3,PI3K,ERK1,P38MAPK,JNK,VEGF,and other targets.The treatment of erectile dysfunction with Xuefu Zhuyu decoction embodied the multicomponent,multitarget,and multipathway.The Arrowsmith tool retrieval and analysis provided a scientific basis for further elucidation of the mechanism of Xuefu Zhuyu decoction against erectile dysfunction.
文摘Objective: To explore the effects of Xuefu Zhuyu Decoction combined with conventional therapy on inflammatory response, oxidative stress, endothelium and related factors in patients with acute cerebral infarction. Methods: A total of 162 patients with acute cerebral infarction admitted to our hospital from November 2016 to January 1818 were selected as subjects. According to the random sampling method, the subjects were divided into 81 cases in the control group and 81 cases in the observation group. The control group was treated with conventional intracranial pressure, anticoagulation, anti-oxidation and lipid-lowering treatment. The observation group was treated with Xuefu Zhuyu Decoction on the basis of the control group. The changes of inflammatory response, oxidative stress, endothelium and related factors were compared and analyzed. Results:Before treatment, the levels of TNF-α, CRP, SOD, MDA, AOPPS, NO, ET-1, MMP-9, PAF and IGF-1 in the two groups were not significantly different, and there was no statistical significance. After treatment, the levels of TNF-α and CRP in the two groups were significantly lower than those before treatment, and the levels of TNF-α and CRP in the observation group were significantly lower than control group;the levels of MDA and AOPPS in the two groups were significantly lower than those before treatment, while the level of SOD was significantly higher than before treatment, and the levels of MDA and AOPPS in the observation group were significantly lower than control group, while the level of SOD was significantly higher. In the control group;the level of ET-1 in the two groups was significantly lower than that before treatment, while the level of NO was significantly higher than that before the treatment, and in the observation group the level of ET-1 was significantly lower than the control group, while the level of NO was significantly higher. In the control group;the levels of MMP-9 and PAF in the two groups were significantly lower than those before treatment, while the level of IGF-1 was significantly higher than before treatment, and the levels of MMP-9 and PAF in the observation group were significantly lower than control group, while the level of IGF-1 was significantly higher than control group. Conclusions: Xuefu Zhuyu Decoction combined with conventional treatment of acute cerebral infarction can effectively reduce inflammation and oxidative stress, improve vascular endothelial function and nerve function, and significantly reduce the degree of brain injury, which has clinical significance.
文摘Objective:Banxia Baizhu Tianma Decoction(半夏白术天麻汤,BBTD)combined with Xuefu Zhuyu Decoction(血府逐瘀汤,XFZYD)is widely used to treat essential hypertension in China,but its efficacy remains largely unexplored.We systemically summarized relevant evidence from randomized controlled trials(RCTs)to assess the therapeutic efficacy of BBTD+XFZYD.Methods:This review retrieved 6 databases like Pubmed,Cochrane Library,Embase,CNKI,et al.RCTs of BBTD+XFZYD plus conventional Western drugs(experimental group)and conventional Western drugs alone(control group)for hypertension was collected from the database establishment to August 5,2020.And the outcomes included clinical total effective rate,systolic blood pressure(SBP),diastolic blood pressure(DBP),nitric oxide(NO)and endothelin-1(ET-1).All studies’risk of bias were assessed by the Cochrane Collaboration tool 5.1.0.The data was statistically analyzed by RevMan5.3 Software.Results:Six studies with 608 participants were identified.About duration of treatment,4 studies were 1 month,2 studies were 2 months.The quality presented a high risk of bias.The experimental group showed that clinical total effective rate of the 1-month and 2-month was higher(P<0.00001),the systolic pressure was significantly lower(P<0.05),the NO increased(P<0.00001),and the ET-1 decreased(P<0.00001)compared with the conventional Western drugs used alone.However,DBP was significantly lower(P<0.05)at 2 months of treatment.Conclusion:BBTD+XFZYD plus conventional Western drugs might reduce blood pressure,improve clinical efficacy,repair endothelial function,but still need high-quality RCTs to better assess the outcomes.
基金supported by the National Natural Science Foundation of China,No.81673719,81173175 and 81303074a grant from China Postdoctoral Science Foundation,No.2016M600639 and 2017T100614
文摘Xuefu Zhuyu decoction has been used for treating traumatic brain injury and improving post-traumatic dysfunction, but its mechanism of action needs further investigation. This study established rat models of traumatic brain injury by controlled cortical impact. Rat models were intragastrically administered 9 and 18 g/kg Xuefu Zhuyu decoction once a day for 14 or 21 days. Changes in neurological function were assessed by modified neurological severity scores and the Morris water maze. Immunohistochemistry, western blot assay, and re- verse-transcription polymerase chain reaction were used to analyze synapsin protein and mRNA expression at the injury site of rats. Our results showed that Xuefu Zhuyu decoction visibly improved neurological function of rats with traumatic brain injury. These changes were accompanied by increased expression of synaptophysin, synapsin I, and postsynaptic density protein-95 protein and mRNA in a dose-de- pendent manner. These findings indicate that Xuefu Zhuyu decoction increases synapsin expression and improves neurological deficits alder traumatic brain injury.
基金National natural science foundation of China(No.81973796)。
文摘Objective:To evaluate the safety and effectiveness of Xuefu Zhuyu Decoction in treating diabetic encephalopathy.Methods:Computer search and manual search of Pub Med,Web of Science,The Cochrane Library,CNKI,WF,VIP and CBM from January 2000 to April 2020 on the treatment of diabetic encephalopathy with Xuefu Zhuyu Decoction In randomized controlled clinical trials,select documents that meet the criteria for analysis using Rev Man 5.3 software.Results:A total of 11 articles and 838 patients were included in the study.Metaanalysis showed that Xuefu Zhuyu Decoction was effective(OR=3.71,95%CI[2.42,5.70],P<0.00001),and the patient’s neurological deficit score(MD=-4.52,95%CI[-5.10,-3.94],P<0.00001),fasting blood glucose(MD=-1.05,95%CI[-1.51,-0.59],P<0.00001),2 hours postprandial blood glucose(MD=-1.31,95%CI[-1.94,-0.69],P<0.00001),glycated hemoglobin(MD=-0.94,95%CI[-1.15,-0.72],P<0.00001),TCM symptom score(MD=-2.44,95%CI[-3.82,-1.06],P=0.0005<0.01),vitality score(MD=12.79,95%CI[8.79,16.79],P<0.00001),the improvement effect is obvious Better than conventional Western medicine treatment.Conclusion:Xuefu Zhuyu Decoction can improve the clinical efficiency of patients with diabetic encephalopathy,reduce brain damage,reduce blood sugar and glycated hemoglobin levels,and has good safety.However,the quality of some of the included literatures is low,and the number of clinical cases is small,which may affect the authenticity of the Meta analysis results.Still need to be further verified by clinical randomized controlled trials with high-quality large samples.
基金supported by National Natural Science Foundation of China (No. 81873192 and 81202877)Postgraduate Research and Innovation Project of Tianjin (No. 2019YJSS197)。
文摘Objective: As a classic prescription in traditional Chinese medicine, Xuefu Zhuyu Decoction(XFZYD) has been widely used in the clinical treatment of cardiovascular and cerebrovascular diseases. In order to unveil the potentially effective compounds, a rapid ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS) method was established to identify prototype compounds and their metabolites from XFZYD in rats’ serum.Methods: The serum from rats after intragastric administration of XFZYD aqueous extract was analyzed by UPLC-Q-TOF/MS method. The prototype compounds and their metabolites were identified by comparison with the reference standards and tentatively characterized by comprehensively analyzing the retention time, MS data, characteristic MS fragmentation pattern and retrieving literatures.Results: A total of 175 compounds(24 prototype compounds and 151 metabolites) were identified and tentatively characterized. The metabolic pathways of prototype compounds in vivo were also summarized, including glucuronidation, hydrolyzation, sulfation, demethylation, and hydroxylation, and so on.Conclusion: In this study, a UPLC-Q-TOF/MS technique was developed to analyze prototype compounds and their metabolites from XFZYD in serum, which would provide the evidence for further studying the effective compounds of XFZYD.
基金Supported by the National Natural Science Foundation of China (No.81072933 and No.81173431)Fujian Natural Science Foundation(No.2007J0101)+1 种基金Fujian Academy of Integrative Medicine Foundation(No.CKJ2008001)National Institutes of Health-The National Center for Complementary and Alternative Medicine Foundation of US(NIH-NCCAM No.K24 AT004095)
文摘Objective: To study the angiogenesis modulation mechanism of Xuefu Zhuyu Decoction (血府逐瘀汤) on the endothelial cell line ECV304. Methods: ECV304 cells were treated with 2.5% Xuefu Zhuyu Decoction- containing serum (XFZYD-CS) for 24 h, 48 h or 72 h. Thiazolyl blue tetrazolium bromide (MTT), fluorescence activating cell sorter (FACS), migration, adhesion and in vitro tube formation assays were conducted to confirm an angiogenesis effect of XFZYD at 3 time points. An analysis of angiogenesis regulator profiles was performed at 3 times with real-time polymerase chain reaction (RT-PCR) superarray. Results: At 48 h, XFZYD-CS induced ECV304 significantly improved cell viability, number in S phase, migration, adhesion and tube formation. At 24 h and 72 h, only cell migration was elevated. Microarray results showed that the expression of 27 angiogenesis-related genes was changed. Conclusion: XFZYD-CS treatment induced angiogenesis on ECV304 cells with significant cellcular changes occurring at 48 h and genetic changes as early as 24 h.
基金Supported by the National Natural Science Foundation of China(Nos.81072933,81173431 and 81102844)T.J.Kaptchuk was partially supported by National Center for Complementary and Alternative Medicine,National Institutes of Health,USA(No.2K24 AT004095)
文摘Objective: To compare the angiogenesis behaviors of vascular endothelial growth factor(VEGF) and Chinese medicine Xuefu Zhuyu Decoction(血府逐瘀汤,XZD) treatments.Methods: Human microvascular endothelial cells(HMEC-1) were treated with various concentrations of either XZD-containing serum(XZD-CS) or VEGF for 24,48,and 72 h,respectively.Cell viability,proliferation,migration,adhesion,and in vitro tube formation assays were used to assess their angiogenic effects.Results: VEGF promoted all cellular phases involved in angiogenesis including cell viability,proliferation,migration,adhesion,and tube formation(P〈0.05 or P〈0.01).Unlike the continuous promotion effects of VEGF at the above stages,XZD inhibited cell viability and proliferation(P〈0.05 or P〈0.01) and only promoted tube formation in the early phase of angiogenesis(P〈0.01).Conclusions: These two medications promote different angiogenesis behaviors,which might be an important reason for their distinct therapeutic profile in clinical usage.
基金Supported by the National Natural Science Foundation of China (No.30772877)Basic Research Fund of China Academy of Chinese Medical Sciences(No.ZZ2006039)Fujian Academy of Integrative Medicine Foundation(No.3000-905010805)
文摘Objective: To observe the effect of Xuefu Zhuyu Decoction (血府逐瘀汤)-containing serum (XFZYD-CS) on endothelial progenitor cell (EPC) tube formation in vitro. Methods: Mononuclear cells from rat bone marrow were prepared in a Ficoll density gradient centrifuge. EPCs were separated by the differential attachment method, and observed with inverted microscope for the effect of XFZYD-CS on EPC tube formation. Results: After one day, EPCs exposed to the serum containing 5%, 10% and 15% XFZYD-CS formed typical tubes or vessel networks. The tube formation time was two days ahead of the control group and the size of most tubes in the serum groups was smaller than in the control group. Conclusion: XFZYD-CS could induce EPC angiogenesis and hasten tube formation, especially in capillary vessels. The study provides experimental evidence for the plausibility of Xuefu Zhuyu Decoction in the treatment of ischemic diseases.
基金supported by International Science and Technology Cooperation Program of Guangdong Province (No. 2009B050700022)
文摘Objective:To evaluate the effects of the modified Linggui Zhugan Decoction(加味苓桂术甘汤) combined with short-term very low calorie diets(VLCDs) on glycemic control in newly diagnosed type 2 diabetes mellitus(T2DM) patients.Methods:A total of 20 subjects with newly diagnosed T2DM were treated with the modified Linggui Zhugan Decoction(one-month administration) combined with short-term VLCDs(5 days),and 3-months follow-up.A standard 75-g oral-glucose-tolerance test(OGTT) indexes fasting plasma glucose(FPG),post-prandial 0.5 h and 2 h plasma glucose(P0.5hPG,P2hPG),glycated hemoglobin A1C(GHbA1C),body weight,body mass index(BMI),insulin function,insulin resistance index,incidence of hypoglycemia,and the liver and renal functions were evaluated before and after treatment.Correlations of BMI with insulin function and insulin resistance were also assessed.Results:After the treatment,the patients' plasma glucose decreased steadily,FPG decreased from 5.8±0.9 mmol/L at pre-treatment to 5.0±0.6 mmol/L at 3-months follow-up(P<0.05),and P2hPG decreased from 11.7±3.8 mmol/L at pre-treatment to 6.9±0.9 mmol/L at 3-months follow-up(P<0.01).The level of GHbA1C declined from(6.47±1.24)% at pre-treatment to(6.14±0.99)% at 3-months follow-up(P<0.01).Body weight and BMI also declined significantly.Insulin resistance index was improved obviously and no event of hypoglycemia occurred.Part of the patients companied with fatty liver had a transient increase in hepatic transaminase during the treatment,but it turned to normal after the treatment.Conclusions:The modified Linggui Zhugan Decoction combined with short-term VLCDs can be safely implemented for steady glycemic control in newly diagnosed T2DM patients.