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ObjectiveTo explore the material basis and mechanism of Nardostachyos Radix et Rhizoma （NRER）-Agrimoniae Herba （AH）， the herbal pair effective in regulating the liver， invigorating Qi， and calming palpitations， in the treatment of premature ventricular contractions （PVCs） by network pharmacology and molecular docking. MethodThe chemical components and targets of NRER and AH were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） combined with relevant literature. GeneCards，Online Mendelian Inheritance in Man（OMIM），and DrugBank were used to predict the potential targets against PVCs. STRING platform was used for protein-protein interaction （PPI） analysis. Metascape platform was used for Gene Ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analysis. Cytoscape 3.8.0 was used to construct the NRER-AH component-potential target-signaling pathway network. The main target proteins underwent molecular docking to the active components of NRER-AH by AutoDock 4.2.6. ResultThe targets of nine active components in NRER-AH （such as quercetin，kaempferol，and acacetin） against PVCs mainly involved tumor necrosis factor （TNF），mitogen-activated protein kinase 1（MAPK1），and protein kinase B1（Akt1）. The potential targets were mainly enriched in 26 signaling pathways，such as pathways in cancer and the advanced glycosylation end product （AGE）-receptor of advanced glycosylation end product（RAGE） signaling pathway. The results of molecular docking showed that the majority of the active components （92.59%） of NRER-AH had good binding activities with the main target proteins TNF，MAPK1，and Akt1. ConclusionThe active components of NRER-AH can regulate cardiac ion channels，resist inflammation， and combat oxidative stress to treat PVCs through multi-target and multi-pathway interventions. They can also improve symptoms related to depression and anxiety by inhibiting monoamine oxidase activity and protecting nerves from damage. This study is expected to provide research ideas and the theoretical basis for further exploring the material basis and mechanism of NRER-AH in the treatment of PVCs.
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Objective:To investigate the mechanism of Nardostachyos Radix et Rhizoma and Corydalis Rhizoma in treatment of atrial fibrillation by predicting targets and signaling pathways based on network pharmacology.Method:The traditional Chinese medicine system platform (TCMSP) database was used to screen out active components of Nardostachyos Radix et Rhizoma and Corydalis Rhizoma,predict targets,and construct the active component-predicted target network.Through the Online Mendelian Inheritance in Man (OMIM),Therapeutic Target Database (TTD),and Genecards databases,potential target information of atrial fibrillation was retrieved.STRING 11.0 database was used to obtain the protein-protein interaction data of relevant targets,and the results were visualized by Cytoscape 3.7.1 software to construct protein-protein interaction network relating to atrial fibrillation.The predicted targets of Nardostachyos Radix et Rhizoma and Corydalis Rhizoma were mapped to the potential targets of atrial fibrillation.The intersection targets were the potential targets for the treatment of atrial fibrillation with Nardostachyos Radix et Rhizoma and Corydalis Rhizoma.Then,Visualization and Integrated Discovery (DAVID),a database for annotation,was used to analyze biological functions and pathways of the potential targets of Nardostachyos Radix et Rhizoma and Corydalis Rhizoma in the treatment of atrial fibrillation.Finally,Cytoscape3.7.1 software was utilized to construct active component-potential target-signal pathway network of Nardostachyos Radix et Rhizoma and Corydalis Rhizoma in treatment of atrial fibrillation.Result:Totally 51 active components of Nardostachyos Radix et Rhizoma and Corydalis Rhizoma were screened out,and 18 potential targets for the treatment of atrial fibrillation with Nardostachyos Radix et Rhizoma and Corydalis Rhizoma were predicted.The effect was mainly correlated with the regulation of interleukin-6 (IL-6),sodium channel protein type 5 subunit alpha (SCN5A),tumor necrosis factor (TNF),nitric-oxide synthase,endothelial (NOS3),potassium voltage-gated channel subfamily hmember 2 (KCNH2),collagen alpha-1(I) chain (COL1A1),retinoic acid receptor RXR-alpha (RXRA),tissue factor (F3),alpha-1B adrenergic receptor (ADRA1B) and other target proteins,cyclic guanosine monophosphate (cGMP)/cGMP-dependent protein kinase G (PKG) signaling pathway,phosphatidylinositol-3-kinases (PI3K)/protein kinase B (Akt) signaling pathway,transcriptional disorders in cancer,calcium signaling pathways,and adrenergic signals in cardiomyocytes.Conclusion:Nardostachyos Radix et Rhizoma and Corydalis Rhizoma treat atrial fibrillation based on multiple components,multiple targets and multiple channels,and provide a scientific basis for subsequent experimental studies for further explainning its mechanism of action.
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This study aims to observe the intervention effects of Chinese herbal medicine of supplementing Qi and activating blood circulation on chronic intermittent hypoxia(CIH) composite insulin resistance(IR) mediated atherosclerosis(AS) mice model,and to observe the mechanism of SREBP-1 c signaling molecule.IR Apo E-/-mice model was induced by high-fat diet combined with STZ injection.Then the mice were treated with hypoxic animal incubator for 8 h per day and 8 weeks to establish a CIH+IR-ApoE-/-mouse model.Model mice were randomly and averagely divided into normoxic control group(NC),model group(CIH) and SREBPs inhibitor group(betulin),atorvastatin group(WM),TCM low-dose group(TCM-L),TCM middle-dose group(TCM-M) and TCM high-dose group(TCM-H) group.Chinese herbal medicine of supplementing Qi and activating blood circulation including ginsenosides combined with ligustrazine(TMP) were used as intervention drugs.The study observed the effect of drugs on IR,serum lipid,inflammation,stress,AS and SREBP-1 c related molecules.The results showed that fasting blood glucose in TCM-H group decreased compared with other experimental groups(P<0.05).HDL-C level in betulin group,WM group,TCM-H group was higher than that in CIH group(P<0.05).LDL-C level in TCM-M group,TCM-H group is lower than that in CIH group(P<0.05).The level of CRP in CIH group was higher than that in other groups(P<0.05).The level of SOD in TCM-H group was higher than that in CIH group(P<0.05).NC group and CIH group showed obvious AS aortic plaque,while betulin group,WM group,TCM-H group showed reduction in AS plaque(P<0.05).For descending aorta,AS plaque in CIH group was multiple and large,while less and smaller in WM group and TCM-H(P<0.05).The expression of SREBP-1 c and FAS in aorta and skeletal muscle in TCM-H group was lower than that in CIH group(P<0.05).In aorta,the expression of TNF-α and CD106(VCAM-1) was lower in TCM-H group than that in CIH group(P<0.05).In aorta,skeletal muscle and liver,the level of p-IRS-1 in TCM-H group was significantly higher than that in CIH group(P<0.05).In aorta and liver,the expression of HIF-1α in TCM-H group was lower than that in CIH group(P<0.05).The study demonstrated that combination ginsenosides with TMP could improve IR and serum lipid level and inhibit inflammation and oxidative stress as well as ultimately alleviate AS to some extent.And the mechanism of its interventional effects might be related to the inhibition of CIH-induced upregulation of SREBP-1 c related molecules.
Subject(s)
Animals , Mice , Atherosclerosis , Drug Therapy , Blood Circulation , Drugs, Chinese Herbal , Pharmacology , Ginsenosides , Pharmacology , Hypoxia , Pathology , Insulin Resistance , Mice, Knockout, ApoE , Pyrazines , Pharmacology , Qi , Random AllocationABSTRACT
This study aims to explore the intervention effect of Chinese medicine of nourishing kidney and clearing liver on intermittent hypoxia(IH) induced injury model of HUVECs through p38MAPK/NF-κB signaling pathway in vitro. HUVECs injury model was induced by modified IH treatment. The effective components of Chinese medicine of nourishing kidney and clearing liver including isochteroside, aucubin and ligustrazine were used as intervention drugs. The optimal compatibility concentration of them was screened in vitro, and then the optimal compatibility concentration was selected as the intervention dose to observe the effect on p38MAPK/NF-κB signaling pathway in IH induced injury model of HUVECs. The results showed that isochnae, aucubin and ligustrazine had the best anti-inflammatory effect at concentration of 0.01 mg•L-1. NF-κB p65 and p-IκB in the nucleus in IH group were significantly higher than those in the normal control(N) group and the other groups. Immunofluorescence staining showed significant translocation of NF-κB p65 nucleus in IH group, and HUVECs adhesion capacity in IH group was increased significantly. As compared with IH group, the expression levels of p-p38MAPK, NF-κB p65 and p-IκB in p38MAPK inhibitor(INH) group and Chinese medicine of nourishing kidney and clearing liver(GDC) group were significantly decreased, and HUVECs adhesion capacity in INH group and GDC group was significantly inhibited as well. The optimal concentration of Chinese medicine of nourishing kidney and clearing liver can inhibit the phosphorylation of p38MAPK, and then inhibit the nuclear translocation and transcription function of NF-κB. This may be the mechanism of the protective effect of Chinese medicine on IH induced injury model of HUVECs.
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In recent years a huge amount of clinical studies have proved that fluctuant hypertension could aggravate the damage of target organs and increase the incidence of acute cardio-/cerebrovascular events, when compared with stable hypertension [increased mean artery blood pressure (MBP)]. How to prevent and treat fluctuant hypertension and its damage of target organs has become one of the hot and difficult problems in the field of hypertension studies all over the world. Hypertensive patients often suffer from thromboembolic target organ damage. Platelet activation plays a key role in this progress, but its concrete mechanisms have not been clearly clarified. Based on the in-depth discussions on progress of fluctuant hypertension, its relationship with platelet activation and blood stasis syndrome of Chinese medicine (CM) in recent three years, we proposed, under the fluctuant hypertensive state, the prethrombotic state has occurred in the organisms, i.e., a pathological state featured by platelet activation, liable to have vulnerable thrombopoiesis, and accompanied by endothelial dysfunction. Blood stasis syndrome might occupy an important position in CM syndrome typing of fluctuant hypertension. Herbs for activating blood circulation and removing stasis might have an extensive application prospect.
Subject(s)
Humans , Hypertension , Blood , Integrative Medicine , Platelet ActivationABSTRACT
Obstructive sleep apnea syndrome (OSAS) and hypertension commonly coexist. Clinical studies indicate that OSAS plays a key role in increasing the risk of prevalent hypertension. Chronic intermittent hypoxia (CIH) is the core pathological mechanism of OSAS, and has a close relationship with systemic inflammation. Growing evidence shows that CIH and hypertension are strongly related, involving markers or pathways indicative of systemic inflammation, such as high-sensitivity C-reactive protein (hs-CRP), interleukin-6, nuclear factor-kappa B, tumor necrosis factor-α, interleukin-8 and p38 mitogen-activated protein kinase (MAPK)-dependent pathways. Oxidative stress also plays an important role in this process, including in the activation of polymorphonuclear neutrophils. However, the pathophysiological and clinical significance of systemic inflammation in CIH and hypertension is not proven. This review article highlights the relationship between CIH and hypertension through systemic inflammation and the current interventions available in Chinese medicine, to offer a background for the future treatment of OSAS-related hypertension with integrative medicine.
Subject(s)
Humans , Clinical Trials as Topic , Hypertension , Drug Therapy , Pathology , Hypoxia , Drug Therapy , Pathology , Inflammation , Drug Therapy , Pathology , Medicine, Chinese Traditional , Oxidative StressABSTRACT
The inflammation factors and roles of them in acute coronary syndrome (ACS) were explored. The similarity between the theory of pathogenic toxin in Chinese Medicine and the inflammation response theory in ACS was discussed. The exploration of new inflammatory factors may be helpful for Chinese Medicine in the research of ACS.
Subject(s)
Humans , Acute Coronary Syndrome , Diagnosis , Therapeutics , Inflammation , Pathology , Therapeutics , Inflammation Mediators , Physiology , Medicine, Chinese Traditional , Prognosis , Toxins, BiologicalABSTRACT
<p><b>OBJECTIVE</b>To observe the regulatory effect of assorted use of Chinese drugs for detoxifying and activating blood circulation on serum high sensitive C-reactive protein (hs-CRP) in apolipoprotein E gene knock-out [ApoE (-/-)] mice.</p><p><b>METHODS</b>ApoE (-/-) mice of 13-week old were devided into two groups, 12 in Group A fed with common forage and 98 in Group B with high lipid forage. Besides, 12 C57 BL/6J mice, 13-week old, were set as Group C fed with common forage. After being fed for 19 weeks, and the formation of vulnerable plaque had been confirmed in 2 mice of Group B, the other 96 mice were sub-divided into 8 groups, 12 in each group. Except that 0.4 mL normal saline was infused to the Group B1 as well as Group A and C, the other 7 sub-groups of Group B were respectively medicated with various drugs as follows: B2, Polydatin (PD, an extract from giant knotweed rhizome for detoxicating) 26. 6 mg/kg; B3, Xiongshao Capsule (XS, a Chinese herbal preparation for activating blood circulation), 110 mg/kg; B4, PD 53.2 mg/kg + XS 220 mg/kg; B5, PD 26. 6 mg/kg + XS 110 mg/kg; B6, PD 13.3 mg/kg + XS 55 mg/kg; B7, Lovastatin 3.3 mg/kg; and B8, Xuezhikang (XZK, a Chinese patent drug) 0.2 g/kg, all were administered by dissolving in 0.4 mL of distilled water for gastrogavage. The serum contents of hs-CRP were detected, with blood sample drawing from inferior vena cava, using enzyme-linked immunosorbent assay 17 weeks after medication.</p><p><b>RESULTS</b>The hs-CRP level was significantly higher in Group B1 than in Groups A and C (P <0.05, P <0.01). Comparisons between various sub-groups of Group B in hs-CRP content showed that hs-CRP in Group B2, B4 and B7 was lower than that in B1 (P <0.01), hs-CRP in Group B4 was the lowest, and hs-CRP was lower in Group B2 than in Group B3.</p><p><b>CONCLUSION</b>Assorted use of Chinese drugs for detoxifying and activating blood circulation could reduce serum hs-CRP level in ApoE (-/-) mice.</p>
Subject(s)
Animals , Female , Humans , Male , Mice , Apolipoproteins E , Genetics , Metabolism , Atherosclerosis , Drug Therapy , Genetics , Metabolism , Blood Circulation , C-Reactive Protein , Metabolism , Disease Models, Animal , Drugs, Chinese Herbal , Mice, Inbred C57BL , Mice, Knockout , Random AllocationABSTRACT
Vulnerable plaque rupture is the main cause of acute coronary syndrome (ACS), a representative cardiovascular thrombotic disease. Considering that the Western medical pathogenetic recognition on vulnerable plaque inflammatory reaction and thrombus formation is similar to the etiopathogenesis and clinical characteristics of toxin and stasis as well as the clinical manifestation of toxic-stasis in TCM, the authors believe that it is necessary to expand the previous TCM thinking on taking blood stasis as the main etiopathogenesis for ACS to that ACS is caused by the toxic-stasis induced vulnerable plaque rupture. Therefore to make sense, depending evidence-based medical principle, the relationship between toxic-stasis and vulnerable plaque forming and rupturing, and to form the clinical norm for diagnosis and treatment of toxic-stasis should be helpful for the prevention and control of ACS.
Subject(s)
Humans , Acute Coronary Syndrome , Diagnosis , Pathology , Therapeutics , Coronary Thrombosis , Diagnosis , Pathology , TherapeuticsABSTRACT
<p><b>OBJECTIVE</b>To evaluate the characteristics of autophagy in fibrotic and postoperative remnant liver.</p><p><b>METHODS</b>Male Wistar rats were randomly divided into three groups: control group; fibrosis group, which received the solution of CCl4 in oil twice a week for 5 weeks; and hepatectomy group, which underwent 70% hepatectomy. Liver tissues and plasma were harvested 18 hours after the surgery. The rats' general conditions and plasma liver function were observed. Histopathological characteristics and regeneration were observed with microscope and transmission electron microscope. Qualitative analysis of autophagosome was made base on the data from transmission electron microscope.</p><p><b>RESULTS</b>Compared with the control group, plasma total protein and albumin level significantly decreased in the fibrosis group (P < 0.01). Proliferating cell nuclear antigen (PCNA) index was 85%-95% in the fibrosis group. Plasma alanine aminotransferase and aspartate aminotransferase levels significantly increased in the hepatectomy group compared with the control group (P < 0.01), while the autophagical index significantly decreased in both the fibrosis group and hepatectomy group compared with the control group (-95%, P < 0.01; -19%, P < 0.05, respectively). PCNA index was 20%-30% in the hepatectomy group.</p><p><b>CONCLUSIONS</b>Autophagy is weakened after fibrosis and hepatectomy, although it differs between these two processes. Proper regulation of autophagy may help facilitate the recovery of the residual liver function after hepatectomy.</p>
Subject(s)
Animals , Humans , Male , Rats , Alanine Transaminase , Blood , Aspartate Aminotransferases , Blood , Autophagy , Disease Models, Animal , Hepatectomy , Liver , Metabolism , Pathology , General Surgery , Liver Cirrhosis , Metabolism , Pathology , General Surgery , Proliferating Cell Nuclear Antigen , Metabolism , Random Allocation , Rats, WistarABSTRACT
<p><b>OBJECTIVE</b>To observe the regulatory effect of Chinese herbal compound for detoxifying and activating blood circulation on expression of nuclear factor-kappaB (NF-kappaB) and matrix metalloproteinase-9 (MMP-9) in aorta of apolipoprotein E gene knocked-out (ApoE (-/-)) mice.</p><p><b>METHODS</b>ApoE (-/-) mice of 13-week old were divided into two groups and fed with normal diet (Group A) and hyperlipidemic diet (Group B) respectively, the latter was subdivided into 7 groups as Group B1 - 7. Besides, a normal control group was set up with C57BL/6J mice. The drugs used for intervention were polydatin (PD, with 26.6 mg/kg as one dose) for detoxifying and Xiongshao Capsule (XC, with 110 mg/kg as one dose) for activating blood circulation respectively. The intervention was started 19 weeks later by treated Group B1 with PD one dose daily, Group B2 with XC one dose daily, Group B3 with PD and XC each 2 doses daily, Group B4 with PD and XC each one dose daily, Group B5 with PD and XC each half dose daily, Group B6 with lovastatin. To the Group B 7 (as a hyperlipidemia model group) as well as Group A and the normal control group, normal saline was given. After 17 weeks of intervention, the expressions of NF-kappaB and MMP-9 in aorta of mice were determined with immunohistochemical assay.</p><p><b>RESULTS</b>Expressions of NF-kappaB and MMP-9 in aorta and sclerotic plaque were higher in group B7 than those in the normal control group, which were lowered in group B1 - 6 (P < 0.01), and the optimal effect was shown in group B3 (P <0.01).</p><p><b>CONCLUSION</b>Combined use of Chinese herbal medicine for detoxifying and activating blood circulation could reduce expression of NF-kappaB and MMP-9 in aorta of ApoE (-/-) mice, and the effect of the combination of the two was superior to that of use either of them.</p>
Subject(s)
Animals , Female , Male , Mice , Anticholesteremic Agents , Pharmacology , Aorta , Metabolism , Physiology , Apolipoproteins E , Genetics , Blood Flow Velocity , Capsules , Drugs, Chinese Herbal , Pharmacology , Immunohistochemistry , Lovastatin , Pharmacology , Matrix Metalloproteinase 9 , Mice, Inbred C57BL , Mice, Knockout , Muscle, Smooth, Vascular , Metabolism , NF-kappa BABSTRACT
The changing of atherosclerosis (AS) plaque from stable to unstable is closely related to the incidence of cardio-cerebrovascular events. So, to stabilize AS plaque become the hot point of the modern study on prevention and treatment of cardio-cerebrovascular diseases. The formation of AS plaque is a very long and complicated process with the participation of many factors. However, inflammation reaction plays an important role in the formation and rupture of unstable plaque. Traditional Chinese medicine (TCM) shows latent therapeutic advantages in stabilizing AS plaque with its characteristics of multi-way, multi-link, and multi-target point and all-sided treatment as well as its rather milder adverse reactions. The paper gives a comparatively systematic retrospection of study on unstable plaque treated by integrated Chinese and Western medicine conducted in recent years. Combined with the related topics conducted by the authors, they raise the theory of "unstable plaque is induced by toxinduced by toxin and stagnation", and introduce the study on the intervention of unstable plaque by removing toxic substances and activating blood flow. They believe that the explorative study can provide objective experimental and clinical basis for TCM therapeutic method in stabilizing AS plaque.