1.Effect of rhynchophylline and isorhynchophylline on the proliferation of rat vascular smooth muscle cell induced by angiotensin Ⅱ
Chinese Pharmacological Bulletin 1987;0(01):-
Aim To study the effect of rhynchophylline and isorhynchophylline on the proliferation of rat vascular smooth muscle cell(VSMCs)induced by angiotensin Ⅱ(AngⅡ)and discuss it's mechanism.Methods A cell proliferating model of VSMC induced by AngⅡ was established.The proliferative activity of VSMC with rhynchophylline and isorhynchophylline was analyzed by MTT method.The effect of rhynchophylline and isorhynchophylline on cell cycle of VSMC was observed by flow cytometry.The effect of rhynchophylline and isorhynchophylline on protein of AT1R gene,NF-?B gene,Stat3 gene,c-Myc gene and c-Fos gene in VSMCs was observed by flow cytometry.The effect of rhynchophylline and isorhynchophylline on c-Myc mRNA and c-Fos mRNA in VSMCs was observed by RT-PCR.Results The proliferation of VSMC induced by AngⅡ stimulation was inhibited by rhynchophylline and isorhynchophylline,and the cell numbers of G0/G1 phase were increased and those of S phase were decreased markedly.At the same time,high expression of the protein of c-Myc gene,c-Fos gene,AT1R gene,NF-?B gene and stat3 gene stimulated by AngⅡ could be inhibited by rhynchophylline and isorhynchophylline significantly,and high expression of c-Myc gene mRNA and c-Fos gene mRNA stimulated by AngⅡ could also be inhibited by rhynchophylline and isorhynchophylline significantly.Conclusions The proliferation of VSMCs induced by AngⅡ can be inhibited by rhynchophylline and isorhynchophylline.The mechanisms are related to preventing VSMCs from G0/G1 phase entering S phase,and down regulating the expression of protein of AT1R gene,NF-?B gene,Stat3 gene,c-Myc gene and c-Fos gene.In addition,c-Myc gene mRNA and c-Fos gene mRNA expression are down regulated as well.
2.Effect of Qingre Jiangya Granule on 64 Young Adult Hypertension Patients with Flaming-up of the Liver Fire Syndrome
Journal of Traditional Chinese Medicine 1993;0(04):-
Objective To evaluate the therapeutic effect and safety of Qingre Jiangya Granule(granule for clearing heat and lowering blood pressure)for the treatment of young adult hypertension patients with flaming-up of the liver fire syndrome.Methods The selected 130 patients were randomized into the treatment group which was administered Qingre Jiangya Granule and the control group which was given Niuhuang Jiangya Pills(bezoar pill for relieving hypertension).Both groups were treated for 4 weeks.Changes in blood pressure,symptoms,blood fat and glucose,hemorheology,and adverse reaction were observed.Results The anti-hypertension effect of the treatment group was significantly superior to that of the control group(P
3.Metabolic Network Construction and Feature Analysis of Hypertension with Syndrome of Ascendant Hyperactivity of Liver Yang
World Science and Technology-Modernization of Traditional Chinese Medicine 2013;(5):942-946
This study was aimed to build metabolic network of hypertension with syndrome of ascendant hyper-activity of liver yang by associating metabolic biomarkers in order to reveal the biological nature of hyperten-sion from the whole view . According to the diagnostic criteria of hypertension with syndrome of ascendant hy-peractivity of liver yang, typical cases were selected and healthy volunteers were enrolled as comparison . Metabolic biomarkers were revealed by metabolomics methods. The metabolic pathways of biomarkers were re-vealed with the KEGG database . The metabolic pathways were connected to establish the metabolic network . Key targets were identified using metabolism node analysis . The results showed that compared with healthy vol-unteers , the metabolic network of hypertension with syndrome of ascendant hyperactivity of liver yang had sig-nificant changes . Norepinephrine , hexanose and arachidonic acid are key network nodes . It was concluded that the metabolic network according to metabolic biomarkers has the advantage in the study on changes of the body under complicated conditions . The study provided a scientific basis for the understanding of biological na-ture of hypertension with syndrome of ascendant hyperactivity of liver yang.
4.Analysis on Medication Principles of Formulas in Treating Insomnia from Spleen and Stomach Based on Literatures
Chinese Journal of Information on Traditional Chinese Medicine 2016;23(7):51-53
Objective To discuss the medication principles of diagnosis and treatment for insomnia from spleen and stomach; To provide references for clinical treatment for insomnia.Methods Relevant articles about diagnosis and treatment forinsomnia from spleen and stomach were searched in CNKI and Wanfang Data through computers, the data were input into Traditional Chinese Medicine Inheritance Supporting System (V2.5) and then association rules, apriori arithmetic, improved mutual information method, and complex system entropy cluster methods were used to analyze the medication principles of diagnosis and treatment for insomnia from spleen and stomach. Results Through screening, totally 87 prescriptions were included, involving 165 herbal medicine. Data mining results showed that there were 30 high-frequency herbal medicine, 19 high-frequency medicinal combinations, and 4 medicinal association rules. Evolution led to 13 medicinal combinations of 2 herbal medicine and 3 new prescriptions. Conclusion The main method of diagnosis and treatment for insomnia from the spleen and stomach is regulating qi activity of spleen and stomach. The features of common medicine are invigorating spleen to reduce phlegm, clearing stomach and calming the adverse-rising energy, and tonifying qi and soothing nerves, which can offer references for clinical treatment for insomnia.
5.Study on Effects of Pingan Prescription on Frontal Cortex of SHR with 1H-NMR-based Metabolic Technology
Jun XIE ; Haiqiang JIANG ; Yunlun LI
World Science and Technology-Modernization of Traditional Chinese Medicine 2013;(5):935-941
This article applied 1H-NMR-based metabolic technology combined with pattern recognition method to study metabolic changes of brain frontal cortex among spontaneously hypertensive rats ( SHR ) and evaluate Pingan prescription treatment effect . It was aimed to explore the valuable information between hypertension and brain damage in order to provide a scientific basis for the mechanism of Pingan prescription . Rats were ran-domly divided into four groups , which were the normal control group , hypertension model group , captopril group and the Pinggan prescription group . Medications were administered continuously for 14 days . Then , the
frontal lobe tissues of rats in each group were removed . The 1H-NMR based metabolic technology combined with pattern recognition method were used in the detection and analysis of frontal lobe tissues of rats from four group in order to find characteristic metabolites . The results of the principal components analysis ( PCA ) and partial least squares discriminant analysis (PLS-DA) showed that captopril group and Pinggan prescription group were significantly different from the hypertension model group . And the classification tendency of rat sam-ples from the Pinggan prescription group and the captopril group were obvious , which suggested that Pinggan prescription can obviously improve the rat's overall metabolism. The four metabolites were identified as glucose, galactose , dopamine and succinic acid . It was concluded that hypertension damaging frontal tissues may mainly express in energy metabolism and nerve damage . And Pinggan prescription can effectively reduce blood pressure and relieve metabolic abnormalities due to disease through the influence on its metabolites .
6.The mechanism of action of valsartan studied by HPLC-TOF/MS.
Wenqing YANG ; Yunlun LI ; Haiqiang JIANG
Acta Pharmaceutica Sinica 2015;50(7):875-81
High performance liquid chromatography-time-off-flight mass spectrometer (HPLC-TOFMS) technology coupled with partial least squares discriminant analysis (PLS-DA) processed by SIMCA-P software was applied to investigate serum endogenous metabolites alternations of valsartan in spontaneous hypertension rats (SHR). And MetPA platform was used to connect identified potential biomarkers in corresponding metabolic pathways to find possible therapeutic mechanism of valsartan. Valsartan significantly declined the blood pressure of SHRs (P < 0.05) at fourth week. The metabolic profiling significantly changed and four metabolites involved in G protein-coupled pathway were identified. Metabolomics is able to detect holistic and microcosmic alternations in organism, so as to elucidate therapeutic mechanism of drugs.
7.Intervention effect of Captopril on serum of spontaneous hypertension rats based on metabonomic research
Wenqing YANG ; Haiqiang JIANG ; Yunlun LI ; Yanping ZANG ; Yanjun CHU
Chinese Pharmacological Bulletin 2016;32(7):998-1003
Aims To analyze the intervention effect of Captopril on serum endogenous metabolites alternations in spontaneous hypertension rats ( SHR) and to investi-gate possible therapeutic mechanism .Methods The rapid resolution liquid chromatography/quadrupole-time of flight tandem mass spectrometry ( RRLC-Q-TOF-MS) and technology coupled with partial least squares discriminant analysis ( PLS-DA ) processed by SIMCA-P software were used to distinguish significantly different variables and identify potential biomarkers . Results Compared to the normal group , metabolic profiling changed significantly in model group and Cap-toril group .Totally 4 metabolins and their metabolic pathways were detected , which were closely related to the endothelial function .Conclusion Metabolomics reveals possible therapeutic mechanism of Captopril for protecting endothelial function from overall metabolism of the body .It also shows unique potential in terms of interpretation of the complex mechanisms of drugs .
8.Establishment and Metabolomics Analysis of Rat Model of High-normal Blood Pressure with Excessive Phlegm-dampness Syndrome
Qiang JIA ; Qiming YIN ; Yunlun LI ; Dongmei QI
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(24):171-178
ObjectiveTo construct the rat model of high-normal blood pressure with excessive phlegm-dampness syndrome and analyze the serum metabolites and explain the metabolic characteristics of the model rats. MethodThe model rats of high-normal blood pressure with excessive phlegm-dampness syndrome were fed with high-fat diet and intraperitoneal injected with 7.625 mg·kg-1 of Nω-nitro-L-arginine (L-NNA), while rats in the normal group were fed chow diet and injected with the same amount of normal saline. The model was evaluated from the aspects of the general state, body weight, blood pressure and serum biochemical indexes, such as triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), blood glucose, malondialdehyde (MDA) and glutathione peroxidase (GSH-Px). Liquid chromatography-mass spectrometry was used to analyze the changes of metabolites in rats serum. The conditions were as follows:mobile phase of 0.05% formic acid aqueous solution (A)-0.05% formic acid acetonitrile solution (B) for gradient elution (0-3 min, 2%B; 3-9 min, 2%-40%B; 9-18 min, 40%-98%B), electrospray ionization (ESI), positive and negative ion detection modes, acquisition range of m/z 80-1 000. Univariate and multivariate statistical analysis were used to screen the differential metabolites between groups which were used to metabolic pathways enrichment analysis. ResultCompared with the normal group, the rats in the model group had the characteristics of darker fur, lazy movement and loose stools, the body weight, blood glucose and contents of TG, TC, LDL-C, MDA increased significantly (P<0.05, P<0.01) and GSH-Px level decreased significantly (P<0.01), the blood pressure remained stable at about 160/88 mmHg (1 mmHg≈0.133 kPa). A total of 115 differential metabolites were screened in the positive and negative ion modes, of which 45 were up-regulated and 70 were down-regulated [variable importance in the projection (VIP) value>1, P<0.05 and fold change (FC)≥2], including indoleacetaldehyde, 5-hydroxytryptamine, lysophosphatidylcholine, phosphatidylcholine, xanthine and so on, which regulated blood pressure mainly through glycerophospholipid metabolism, linoleic acid metabolism, tryptophan metabolism and arachidonic acid metabolic pathways. ConclusionFeeding with high-fat diet and intraperitoneal injection of L-NNA can successfully construct the rat model of high-normal blood pressure with excessive phlegm-dampness syndrome, and indoleacetaldehyde, 5-hydroxytryptamine, lysophosphatidylcholine, phosphatidylcholine and xanthine can be used as characteristic serum differential metabolites of the rat model.
9.A Randomized,Double-blind,Multi-center Clinical Trial of Tengfu Jiangya Tablets Combined with Valsartan/Amlodipine in Treatment of Grade 2 Hypertension with Hyperactivity of Liver Yang
Yuchen QI ; Yunlun LI ; Yujie WU ; Haiquan WANG ; Yu WANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(9):83-92
ObjectiveTo observe the clinical efficacy and safety of Tengfu Jiangya tablets combined with valsartan/amlodipine in the treatment of grade 2 hypertension with liver Yang hyperactivity syndrome. MethodAccording to a randomized,double-blind,and placebo parallel control method,288 patients with grade 2 hypertension with liver Yang hyperactivity from 7 subcenters were included. They were randomly divided into an observation group (144 cases) and a control group (144 cases),and then treated with Tengfu Jiangya tablets combined with valsartan/amlodipine and placebo combined with valsartan/amlodipine,respectively. The efficacy was evaluated after four weeks of intervention. During the experiment,the safety indicators and adverse reaction events of the subjects were recorded for safety evaluation,and the efficacy indicators and TCM syndrome scores were recorded for effectiveness evaluation. Sensitivity analysis was also conducted on the statistical results of the main efficacy indicators such as blood pressure (BP) compliance rate to ensure the accuracy of the analysis results. 88 groups of blood samples from each of the treatment and control groups were included as test subjects. Fasting blood samples were collected from the patients in the clinical trial on the day before and after medication,and enzyme linked immunosorbent assay (ELISA) was performed on the treated serum. The levels of arachidonic acid (AA),thromboxane B2 (TXB2),and prostaglandin E2 (PGE2) in the serum of the patients before and after treatment were measured to explore the regulation of inflammatory factors in the body by Tengfu Jiangya tablets. ResultA total of 271 patients (133 in the observation group and 138 in the control group) completed the trial. There was no statistically significant difference before and after treatment in such safety indicators as the blood routine (white blood cells,red blood cells,and platelets),urine routine (urinary protein and urinary red blood cells),alanine aminotransferase,aspartate aminotransferase,creatinine,urea,and abnormal electrocardiogram,and no serious adverse reactions were observed. After four weeks,the systolic blood pressure (SBP) difference and diastolic blood pressure (DBP) difference of patients in the observation group were greater than those in the control group(P<0.01). According to the criteria for determining the antihypertensive effect,the overall response rate in the observation group[89.47%(119/133)] was higher than that in the control group[57.97%(80/138)] (Z=2.593,P<0.01). The SBP compliance rate was 61.65%(82/133) and 37.68%(52/138) in the observation group and control group, respectively. The DBP compliance rate in the observation group was 78.20%(104/133),while in the control group it was 55.07%(76/138). The overall BP compliance rate in the observation group was 48.12%(64/133),while in the control group it was 23.19%(32/138). The BP compliance rates in the observation group were all significantly higher than those in the control group(χ2=15.571,16.236,18.404,P<0.01). According to the criteria for evaluating the therapeutic effect of TCM syndrome integration,the overall response rate of the observation group[57.89%(77/133)] was higher than that of the control group[38.41%(53/133)] (Z=-3.172,P<0.01).Compared with those before treatment, the levels of serum AA and TXB2 in the two groups were significantly decreased after treatment (P<0.01), and the level of PGE2 in the observation group was significantly increased (P<0.01). Compared with those of the control group after treatment, the levels of AA and TXB2 in the observation group were significantly decreased, while the level of PGE2 was significantly increased (P<0.01). The results suggest that Tengfu Jiangya tablets can effectively reduce inflammatory factors,reduce the production of inflammatory mediators,and thus prevent the occurrence of inflammatory reactions in the treatment of patients with grade 2 hypertension. ConclusionTengfu Jiangya tablets can more effectively reduce patients' SBP and DBP,improve their BP compliance rates,and improve their TCM syndromes in the treatment of grade 2 hypertension with liver Yang hyperactivity. Its clinical application is safe. Tengfu Jiangya tablets has outstanding clinical efficacy and can be used as an effective intervention method for the treatment of grade 2 hypertension with liver Yang hyperactivity syndrome.