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1.
Acta Pharmaceutica Sinica ; (12): 374-381, 2024.
Article in Chinese | WPRIM | ID: wpr-1016650

ABSTRACT

This study aims to investigate the effect of salvianolic acid B (Sal B), the active ingredient of Salvia miltiorrhiza, on H9C2 cardiomyocytes injured by oxygen and glucose deprivation/reperfusion (OGD/R) through regulating mitochondrial fission and fusion. The process of myocardial ischemia-reperfusion injury was simulated by establishing OGD/R model. The cell proliferation and cytotoxicity detection kit (cell counting kit-8, CCK-8) was used to detect cell viability; the kit method was used to detect intracellular reactive oxygen species (ROS), total glutathione (t-GSH), nitric oxide (NO) content, protein expression levels of mitochondrial fission and fusion, apoptosis-related detection by Western blot. Mitochondrial permeability transition pore (MPTP) detection kit and Hoechst 33342 fluorescence was used to observe the opening level of MPTP, and molecular docking technology was used to determine the molecular target of Sal B. The results showed that relative to control group, OGD/R injury reduced cell viability, increased the content of ROS, decreased the content of t-GSH and NO. Furthermore, OGD/R injury increased the protein expression levels of dynamin-related protein 1 (Drp1), mitofusions 2 (Mfn2), Bcl-2 associated X protein (Bax) and cysteinyl aspartate specific proteinase 3 (caspase 3), and decreased the protein expression levels of Mfn1, increased MPTP opening level. Compared with the OGD/R group, it was observed that Sal B had a protective effect at concentrations ranging from 6.25 to 100 μmol·L-1. Sal B decreased the content of ROS, increased the content of t-GSH and NO, and Western blot showed that Sal B decreased the protein expression levels of Drp1, Mfn2, Bax and caspase 3, increased the protein expression level of Mfn1, and decreased the opening level of MPTP. In summary, Sal B may inhibit the opening of MPTP, reduce cell apoptosis and reduce OGD/R damage in H9C2 cells by regulating the balance of oxidation and anti-oxidation, mitochondrial fission and fusion, thereby providing a scientific basis for the use of Sal B in the treatment of myocardial ischemia reperfusion injury.

2.
Chinese journal of integrative medicine ; (12): 1066-1076, 2023.
Article in English | WPRIM | ID: wpr-1010314

ABSTRACT

OBJECTIVE@#To explore the protective effect of Huoxin Pill (HXP) on acute myocardial ischemia-reperfusion (MIRI) injury in rats.@*METHODS@#Seventy-five adult SD rats were divided into the sham-operated group, model group, positive drug group (diltiazem hydrochloride, DH), high dose group (24 mg/kg, HXP-H) and low dose group (12 mg/kg, HXP-L) of Huoxin Pill (n=15 for every group) according to the complete randomization method. After 1 week of intragastric administration, the left anterior descending coronary artery of the rat's heart was ligated for 45 min and reperfused for 3 h. Serum was separated and the levels of creatine kinase (CK), creatine kinase isoenzyme (CK-MB) and lactate dehydrogenase (LDH), superoxide dismutase (SOD), and malondialdehyde (MDA), hypersensitive C-reactive protein (hs-CRP) and interleukin-1β (IL-1β) were measured. Myocardial ischemia rate, myocardial infarction rate and myocardial no-reflow rate were determined by staining with Evans blue and 2,3,5-triphenyltetrazolium chloride (TTC). Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (BATMAN) databases were used to screen for possible active compounds of HXP and their potential therapeutic targets; the results of anti-inflammatory genes associated with MIRI were obtained from GeneCards, Drugbank, Online Mendelian Inheritance in Man (OMIM), and Therapeutic Target Datebase (TTD) databases was performed; Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were used to analyze the intersected targets; molecular docking was performed using AutoDock Tools. Western blot was used to detect the protein expression of Toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NFκB)/NOD-like receptor protein 3 (NLRP3).@*RESULTS@#Compared with the model group, all doses of HXP significantly reduced the levels of LDH, CK and CK-MB (P<0.05, P<0.01); HXP significantly increased serum activity of SOD (P<0.05, P<0.01); all doses of HXP significantly reduced the levels of hs-CRP and IL-1β (P<0.05, P<0.01) and the myocardial infarction rate and myocardial no-reflow rate (P<0.01). GO enrichment analysis mainly involved positive regulation of gene expression, extracellular space and identical protein binding, KEGG pathway enrichment mainly involved PI3K-Akt signaling pathway and lipid and atherosclerosis. Molecular docking results showed that kaempferol and luteolin had a better affinity with TLR4, NFκB and NLRP3 molecules. The protein expressions of TLR4, NFκB and NLRP3 were reduced in the HXP group (P<0.01).@*CONCLUSIONS@#HXP has a significant protective effect on myocardial ischemia-reperfusion injury in rats, and its effect may be related to the inhibition of redox response and reduction of the inflammatory response by inhibiting the TLR4NFκB/NLRP3 signaling pathway.


Subject(s)
Humans , Rats , Animals , NF-kappa B/metabolism , Myocardial Reperfusion Injury/drug therapy , NLR Family, Pyrin Domain-Containing 3 Protein , Rats, Sprague-Dawley , C-Reactive Protein , Toll-Like Receptor 4 , Phosphatidylinositol 3-Kinases/metabolism , Molecular Docking Simulation , Signal Transduction , Myocardial Infarction/drug therapy , Creatine Kinase , L-Lactate Dehydrogenase/metabolism , Superoxide Dismutase/metabolism
3.
Chinese Pharmacological Bulletin ; (12): 1411-1416, 2023.
Article in Chinese | WPRIM | ID: wpr-1013739

ABSTRACT

Cardiomyocytes are highly differentiated terminal cells with poor self-renewal ability. Therefore, after myocardial infarction necrotic cardiomyocytes cannot be effectively replenished, and the infarcted area is quickly replaced by fibrous tissue, which seriously affects cardiac function. The reduction of the number of myocardial cells and the destruction of the structural integrity of the heart have caused cardiovascular diseases such as myocardial infarction and heart failure, which continue to endanger human life and health. At present, the treatment of coronary heart disease has made great progress. The commonly used treatment options for myocardial repair after myocardial infarction mainly include stem cell transplantation, exosome mediation and microenvironment construction, but all of them are difficult to solve to varying degrees. Cardiac fibroblasts occupy the majority of cardiac cells, and the distribution characteristics of fibroblasts and their role in the process of myocardial infarction make them important effector cells after myocardial infarction. Therefore, this article reviews the source, distribution, post-infarction status of myocardial fibroblasts and the effect of fibroblasts on cardiomyocytes, in order to provide new treatment ideas and solutions for fibroblasts in the repair and regeneration of myocardial cells after myocardial infarction.

4.
China Journal of Chinese Materia Medica ; (24): 1858-1865, 2023.
Article in Chinese | WPRIM | ID: wpr-981404

ABSTRACT

To optimize the extraction process of Chuanxiong Rhizoma-Gastrodiae Rhizoma herb pair by network pharmacology combined with analytic hierarchy process(AHP)-entropy weight method and multi-index orthogonal test. The potential active components and targets of Chuanxiong Rhizoma-Gastrodiae Rhizoma were screened by network pharmacology and molecular docking, and the process evaluation indexes were determined with reference to the Chinese Pharmacopoeia(2020 edition). The core components of Chuanxiong Rhizoma-Gastrodiae Rhizoma were determined as gastrodin, parishin B, parishin C, parishin E, ferulic acid, and 3-butylphthalide. With the extraction volume of each indicator and yield of dry extract as comprehensive evaluation indicators, the extraction conditions were optimized by the AHP-entropy weight method and orthogonal test as the ethanol volume of 50%, the solid-liquid ratio of 1∶8(g·mL~(-1)), extraction for three times, and 1.5 h each time. Through network pharmacology and molecular docking, the process evaluation index was determined, and the optimized process was stable and reproducible for the extraction of Chuanxiong Rhizoma-Gastrodiae Rhizoma herb pair, which could provide reference for in-depth research.


Subject(s)
Drugs, Chinese Herbal/pharmacology , Network Pharmacology , Molecular Docking Simulation , Rhizome
5.
Acta Pharmaceutica Sinica ; (12): 1188-1195, 2023.
Article in Chinese | WPRIM | ID: wpr-978688

ABSTRACT

The hyperacute stage of myocardial infarction refers to a period of time within 30 minutes after the occurrence of myocardial infarction, when the symptoms are not obvious and the diagnosis is difficult, and the related pathophysiological mechanism has received less attention. In this study, proteomics was used to investigate the pathological changes in the early hyperacute phase of myocardial infarction, aiming to provide experimental evidence for pathological mechanism of myocardial infarction hyperacute stage. Meanwhile, the intervention effect and related mechanism of salvianolate injection were discussed based on heat shock protein B6 (HSPB6), aiming to benefit the clinical rational use of salvianolate injection. The protein expression changes before and after myocardial infarction model establishment were detected by label-free proteomics via mass spectrometry and analyzed by bioinformatics method. Then the binding effect of salvianolate injection on the commonly differential protein HSPB6 was evaluated by molecular docking technology, which was finally verified by animal experiments. All animal experimental protocols were approved by the Ethics Committee of Xiyuan Hosptial (2022XLC041). The results of this study showed that a total of 2 166 proteins were quantified by lable-free proteomics, of which 194 shared differential proteins were involved in myocardial injury and body regulation in the hyperacute phase of myocardial infarction, mainly involving molecular functions such as protein homodimerization activity, oxygen binding and transport, and serine endopeptidase inhibitor activity. Among them, HSPB6 protein is involved in the regulation of myocardial function. Molecular docking results indicated that magnesium salvianolate acetate, which is the main component of salvianolate injection, had the lowest binding energy with HSPB6 protein: -14.53 kcal·mol-1. Animal experiments showed that compared with the Sham group, the model group had significantly lower ejection fraction (EF) and fractional shortening (FS) (P < 0.001), cardiac blood perfusion decreased significantly (P < 0.001). There were obvious pathological changes such as myocardial fiber disorder, cardiomyocyte edema and interstitial small blood vessel congestion; the injury of cardiac function of rats in the administration group was attenuated, and the FS of rats in the low-dose group was significantly improved (P < 0.05), the pathological injury of myocardial tissue was markedly mitigated, and the expression of HSPB6 protein was up-regulated to varying degrees (P < 0.01, P < 0.001). In conclusion, salvianolate injection could be able to improve the cardiac function and pathological morphology of rats in the early hyperacute stage of myocardial infarction, and its mechanism may be related to the promotion of expression of HSPB6.

6.
Acta Pharmaceutica Sinica ; (12): 1149-1155, 2023.
Article in Chinese | WPRIM | ID: wpr-978683

ABSTRACT

In order to investigate the effects of asiaticoside (Ass) on H9C2 cardiomyocytes, the present study examined the potential intervention of Ass on the proliferation and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/Bcl-2 homology domain protein (Beclin-1) signaling pathway in H9C2 cardiomyocytes following oxygen and glucose deprivation/reperfusion (OGD/R) injury. H9C2 cardiomyocytes were selected as the research objects, and the activity of H9C2 was detected by cell counting kit-8 (CCK-8). H9C2 cells were divided into control group, OGD/R group, Ass low concentration group (10 μmol·L-1), Ass high concentration group (80 μmol·L-1) and Ass high concentration + chloroquine group (80 μmol·L-1 + 50 μmol·L-1). The control group was cultured under normal conditions, and the other groups were treated with oxygen and glucose deprivation for 4 h and reperfusion for 2 h. The activity and content of aspartic aminotransferase (AST), lactate dehydrogenase (LDH) and creatine kinase (CK) in the supernatant of H9C2 cardiomyocytes were detected by enzyme-linked immunosorbent assay. Autophagy staining assay kit with monodansylcadaverine (MDC) method to observe cellular autophagy; molecular docking technique to identify the molecular targets of Ass. Immunofluorescence was used to observe the effect of the drug on cell number. The expression levels of PI3K, Akt, selective autophagy adaptor protein (P62) and Beclin-1 were detected by Western blot. Compared with OGD/R group, Ass group had a protective effect from 10-80 μmol·L-1, and the activities and contents of AST, LDH and CK were decreased. The protein expression levels of PI3K, Akt, P62 and Beclin-1 were decreased. Compared with the administration group, the activities and contents of AST, LDH and CK in Ass high-concentration + chloroquine group were significantly decreased, and the protein expression levels of PI3K, Akt, Beclin-1 and P62 were significantly decreased. Immunofluorescence showed that the inhibitor group and each administration group had different degrees of protective effect compared with the model group. Asiaticoside can reduce the injury of H9C2 cardiomyocyte induced by OGD/R, reduce the content of AST, LDH and CK, reduce the expression level of P62 protein, and reduce autophagy, which may be closely related to the inhibition of PI3K/Akt/Beclin-1 signaling pathway activation.

7.
Acta Pharmaceutica Sinica ; (12): 1904-1912, 2023.
Article in Chinese | WPRIM | ID: wpr-978664

ABSTRACT

Based on the technology of platelet proteomics, the key regulatory proteins and pathogenesis of coronary heart disease with phlegm and blood stasis syndrome were explored and analyzed. Based on the previous laboratory research, the model of coronary heart disease in mini-swine with phlegm-stasis cementation syndrome was duplicated. The model was judged by the changes in blood lipid and myocardial tissue characteristics. Furthermore, the platelet proteins were studied by quantitative proteomics, and the differentially expressed proteins were screened. The critical regulatory proteins and biological pathways of coronary heart disease with phlegm-stasis cementation syndrome were analyzed by bioinformatics. After ten weeks of modeling, the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), very low density lipoprotein (VLDL-C), triglyceride (TG), creatine kinase (CK) and creatine kinase-MB (CK-MB) in the model group were significantly increased, reflecting the pathological changes such as increased blood lipid, abnormal coagulation function and myocardial ischemia in the model group. In addition, compared with the sham group, there were 26 up-regulated proteins and 8 down-regulated proteins in the platelets of the model group. Combined with bioinformatics analysis, it was found that differential proteins mainly involved in glycolysis/gluconeogenesis, pyruvate metabolism, lipid and atherosclerosis, Ras protein signal transduction. Among them, lactate dehydrogenase B (LDHB), alcohol dehydrogenase 5 (ADH5), neuroblastoma ratsarcoma viral oncogene homolog (NRAS) and Kirsten ratsarcoma viral oncogene homolog (KRAS) play a central role when interacting with other proteins and simultaneously participate in multiple action pathways. The results showed that LDHB, ADH5, NRAS, and KRAS may be the marker proteins in CHD with phlegm-stasis cementation syndrome by regulating glycolysis/gluconeogenesis, pyruvate metabolism, lipid and atherosclerosis, Ras protein signal transduction and other biological processes.

8.
China Journal of Chinese Materia Medica ; (24): 5863-5870, 2023.
Article in Chinese | WPRIM | ID: wpr-1008784

ABSTRACT

This study aims to investigate the effects of baicalein(BAI) on lipopolysaccharide(LPS)-induced human microglial clone 3(HMC3) cells, with a focus on suppressing inflammatory responses and elucidating the potential mechanism underlying the therapeutic effects of BAI on ischemic stroke via modulating the cAMP-PKA-NF-κB/CREB pathway. The findings have significant implications for the application of traditional Chinese medicine in treating cerebral ischemic diseases. First, the safe dosage of BAI was screened, and then an inflammation model was established with HMC3 cells by induction with LPS for 24 h. The cells were assigned into a control group, a model group, and high-, medium-, and low-dose(5, 2.5, and 1.25 μmol·L~(-1), respectively) BAI groups. The levels of superoxide dismutase(SOD) and malondialdehyde(MDA) in cell extracts, as well as the levels of interleukin-1β(IL-1β), IL-6, tumor necrosis factor-α(TNF-α), and cyclic adenosine monophosphate(cAMP) in the cell supernatant, were measured. Western blot was performed to determine the expression of protein kinase A(PKA), phosphorylated cAMP-response element binding protein(p-CREB), and nuclear factor-kappa B p65(NF-κB p65). Hoechst 33342/PI staining was employed to assess cell apoptosis. High and low doses of BAI were used for treatment in the research on the mechanism. The results revealed that BAI at the concentrations of 10 μmol·L~(-1) and below had no impact on normally cultured HMC3 cells. LPS induction at 200 ng·mL~(-1) for 24 h reduced the SOD activity and increased the MDA content in HMC3 cells. However, 5, 2.5, and 1.25 μmol·L~(-1) BAI significantly increased the SOD activity and 5 μmol·L~(-1) BAI significantly decreased the MDA content. In addition, BAI ameliorated the M1 polarization of HMC3 cells induced by LPS, as indicated by cellular morphology. The results of ELISA demonstrated that BAI significantly lowered the levels of TNF-α, IL-1β, IL-6, and cAMP in the cell supernatant. Western blot revealed that BAI up-regulated the protein levels of PKA and p-CREB while down-regulating the expression of NF-κB p65. Hoechst 33342/PI staining results indicated that BAI mitigated the apoptosis of HMC3 cells. Overall, the results indicated that BAI had protective effects on the HMC3 cells induced by LPS, and could inhi-bit inflammatory response and improve cell apoptosis, which might be related to the regulation of the cAMP-PKA-NF-κB/CREB pathway.


Subject(s)
Humans , NF-kappa B/metabolism , Microglia , Tumor Necrosis Factor-alpha/metabolism , Interleukin-6/metabolism , Lipopolysaccharides/pharmacology , Cyclic AMP-Dependent Protein Kinases/metabolism , Superoxide Dismutase/metabolism
9.
China Journal of Chinese Materia Medica ; (24): 4156-4163, 2023.
Article in Chinese | WPRIM | ID: wpr-1008612

ABSTRACT

This study explored the effects of Buyang Huanwu Decoction(BYHWD) on platelet activation and differential gene expression after acute myocardial infarction(AMI). SD rats were randomly divided into a sham-operated group, a model group, a positive drug(aspirin) group, and a BYHWD group. Pre-treatment was conducted for 14 days with a daily oral dose of 1.6 g·kg~(-1) BYHWD and 0.1 g·kg~(-1) aspirin. The AMI model was established using the high ligation of the left anterior descending coronary artery method. The detection indicators included myocardial infarct size, heart function, myocardial tissue pathology, peripheral blood flow perfusion, platelet aggregation rate, platelet membrane glycoprotein CD62p expression, platelet transcriptomics, and differential gene expression. The results showed that compared with the sham-operated group, the model group showed reduced ejection fraction and cardiac output, decreased peripheral blood flow, and increased platelet aggregation rate and CD62p expression, and activated platelets. At the same time, TXB_2 content increased and 6-keto-PGF1α content decreased in serum. Compared with the model group, BYHWD increased ejection fraction and cardiac output, improved blood circulation in the foot and tail regions and cardiomyocytes arrangement, reduced myocardial infarct size and inflammatory infiltration, down-regulated platelet aggregation rate and CD62p expression, reduced serum TXB_2 content, and increased 6-keto-PGF1α content. Platelet transcriptome sequencing results revealed that BYHWD regulated mTOR-autophagy pathway-related genes in platelets. The differential gene expression levels were detected using real-time quantitative PCR. BYHWD up-regulated mTOR, down-regulated autophagy-related FUNDC1 and PINK genes, and up-regulated p62 gene expression. The results demonstrated that BYHWD could regulate platelet activation, improve blood circulation, and protect ischemic myocardium in AMI rats, and its mechanism is related to the regulation of the mTOR-autophagy pathway in platelets.


Subject(s)
Rats , Animals , Rats, Sprague-Dawley , Drugs, Chinese Herbal/therapeutic use , Myocardial Infarction/genetics , Myocardium/metabolism , Aspirin/therapeutic use , TOR Serine-Threonine Kinases/metabolism , Membrane Proteins/metabolism , Mitochondrial Proteins
10.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 109-120, 2022.
Article in Chinese | WPRIM | ID: wpr-940295

ABSTRACT

ObjectiveTo explore the regulatory effect of Quyu Huatan Tongmai prescription on intestinal mircoflora of hyperlipidemia golden hamster and scientific evidence for the compatibility. MethodSyrian golden hamsters were randomized into normal, model, prescription, stasis-dispelling (Quyu), phlegm-dissolving (Huatan), and detoxification (Jiedu) groups, with 8 in each group. Hyperlipidemia in golden hamsters was induced by high-fat diet (4 weeks). Then hamsters in the Quyu group (1.11 g·kg-1), Huatan group (0.39 g·kg-1), Jiedu group (0.07 g·kg-1), and prescription group (1.42 g·kg-1) were given (ig) corresponding drugs and those in the normal group and the model group received (ig) distilled water of equivalent volume, once a day for 6 weeks. Serum lipids were determined, and hematoxylin-eosin (HE) staining was used to observe the pathological morphology of the liver. Feces were collected for 16S rRNA gene high-throughput sequencing of intestinal flora. ResultCompared with normal group, the model group demonstrated increase in body weight (P<0.05, P<0.01) and blood lipids (P<0.01), decrease in intestinal flora diversity (P<0.05, P<0.01), and variation of the relative abundance of intestinal flora at phylum, family, and genus levels (P<0.05, P<0.01). Compared with the model group, Quyu Huatan Tongmai prescription controlled the body weight change, reduced the serum triglyceride (TG), total cholesterol (TC), and low density lipoprotein cholesterol/high density lipoprotein cholesterol ratio (LDL-C/HDL-C) (P<0.05, P<0.01), improved the structure of intestinal flora, decreased the ratio of Firmicutes to Bacteroides (P<0.01), raised the abundance of Bacteroidaceae, Porphyromonadaceae, Rikenellaceae, and Pasteurella (P<0.05, P<0.01), and lowered the relative abundance of Coriobacterium (P<0.05) in hyperlipidemia golden hamsters. All the split prescriptions improved blood lipids and intestinal flora of the hamsters and particularly, the lipids-lowering effect of the Jiedu group and the regulation of flora in the Huatan group were closer to those of the prescription group. ConclusionQuyu Huatan Tongmai prescription and the split prescriptions all alleviated the hyperlipidemia of golden hamsters to different degrees possibly by regulating intestinal flora structure and improving intestinal microecology. The effect of the prescription group was most significant, and coming in second was the Huatan group. This study also provides scientific evidence for the effect of Quyu Huatan Tongmai prescription.

11.
Chinese journal of integrative medicine ; (12): 99-105, 2022.
Article in English | WPRIM | ID: wpr-922581

ABSTRACT

The abnormality of platelet function plays an important role in the pathogenesis and evolution of blood stasis syndrome (BSS). The explanation of its mechanism is a key scientific issue in the study of cardiovascular and cerebrovascular diseases and treatment. System biology technology provides a good technical platform for further development of platelet multi-omics, which is conducive to the scientific interpretation of the biological mechanism of BSS. The article summarized the pathogenesis of platelets in BSS, the mechanism of action of blood activating and stasis resolving drugs, and the application of genomics, proteomics, and metabonomics in platelet research, and put forward the concept of "plateletomics in BSS". Through the combination and cross-validation of multi-omics technology, it mainly focuses on the clinical and basic research of cardiovascular and cerebrovascular diseases; through the interactive verification of multi-omics technology and system biology, it mainly focuses on the platelet function and secretion system. The article systematically explains the molecular biological mechanism of platelet activation, aggregation, release, and other stages in the formation and development of BSS, and provides a new research idea and method for clarifying the pathogenesis of BSS and the mechanism of action of blood activating and stasis resolving drugs.


Subject(s)
Blood Platelets , Hemostasis , Platelet Activation , Proteomics , Technology
12.
Chinese journal of integrative medicine ; (12): 281-288, 2022.
Article in English | WPRIM | ID: wpr-928922

ABSTRACT

DNA hypermethylation is an epigenetic modification that plays a critical role in the oncogenesis of myelodysplastic syndromes (MDS). Aberrant DNA methylation represses the transcription of promotors of tumor suppressor genes, inducing gene silencing. Realgar (α-As4S4) is a traditional medicine used for the treatment of various diseases in the ancient time. Realgar was reported to have efficacy for acute promyelocytic leukemia (APL). It has been demonstrated that realgar could efficiently reduce DNA hypermethylation of MDS. This review discusses the mechanisms of realgar on inhibiting DNA hypermethylation of MDS, as well as the species and metabolisms of arsenic in vivo.


Subject(s)
Humans , Arsenicals/therapeutic use , DNA , DNA Methylation/genetics , Myelodysplastic Syndromes/genetics , Sulfides
13.
China Journal of Chinese Materia Medica ; (24): 1327-1335, 2022.
Article in Chinese | WPRIM | ID: wpr-928059

ABSTRACT

Protective effect of Qilong Capsules(QL) on the myocardial fibrosis and blood circulation of rats with coronary heart disease of Qi deficiency and blood stasis type was investigated. Sleep deprivation and coronary artery ligation were used to construct a disease-symptom combination model, and 60 SD rats were divided into sham operation(sham) group, syndrome(S) group, disease and syndrome(M) group and QL group randomly. The treatment group received administration of QL 0.4 g·kg~(-1)·d~(-1). Other groups were given the same amount of normal saline. The disease indexes of each group [left ventricular end diastolic diameter(LVESD), left ventricular end systolic diameter(LVEDD), left ventricular ejection fraction(LVEF), left ventricular axis shortening rate(LVFS), myocardial histopathology, platelet morphology, peripheral blood flow] and syndrome indexes(tongue color, pulse, grip power) were detected. In sham group, cardiomyocytes and myocardial fibers were arranged neatly and densely with clear structures. The tongues' color in sham were light red, and the pulse shape were regular. RGB is a parameter reflected the brightness of the image of the tongue. In the S group, the amplitude and frequency of the animal's pulse increased accompanied by decreasing R,G,B, however, the decreased R,G,B was accompanied by reduced pulse amplitude in M group. And in M group, we observed fuzzy cell morphology, hypertrophied myocytes, disordered arrangement of cardiomyocytes and myocardial fibers, reduced peripheral blood flow and increased collagen volume fraction(CVF). Increased LVESD and LVEDD, and decreased LVEF and LVFS represented cardiac function in S group was significantly lower than that in sham. In QL group, the tongue's color was red and the pulse was smooth. The myocardial fibers of the QL group were arranged neatly and secreted less collagen. It improved the blood circulation in the sole and tail, and reversed the increasing of LVEDD, LVESD and the decreasing of LVEF and LVFS of M group. Platelets in M and S group showed high reactivity, and QL could decrease aggregation risk. In conclusion, Qilong Capsules has an obvious myocardial protective effect on ischemic cardiomyopathy, which may inhibit the degree of myocardial fibrosis and reduce platelet reactivity.


Subject(s)
Animals , Rats , Capsules , Cardiomyopathies/drug therapy , Fibrosis , Myocytes, Cardiac , Qi , Rats, Sprague-Dawley , Stroke Volume , Ventricular Function, Left
14.
China Journal of Chinese Materia Medica ; (24): 1031-1038, 2022.
Article in Chinese | WPRIM | ID: wpr-928023

ABSTRACT

This study aims to explore the pharmacodynamic effect of baicalin on rat brain edema induced by cerebral ischemia reperfusion injury and discuss the mechanism from the perspective of inhibiting astrocyte swelling, which is expected to serve as a refe-rence for the treatment of cerebral ischemia with Chinese medicine. To be specific, middle cerebral artery occlusion(suture method) was used to induce cerebral ischemia in rats. Rats were randomized into normal group, model group, high-dose baicalin(20 mg·kg~(-1)) group, and low-dose baicalin(10 mg·kg~(-1)) group. The neurobehavior, brain index, brain water content, and cerebral infarction area of rats were measured 6 h and 24 h after cerebral ischemia. Brain slices were stained with hematoxylin and eosin(HE) for the observation of pathological morphology of cerebral cortex after baicalin treatment. Enzyme-linked immunosorbent assay(ELISA) was employed to determine the content of total L-glutathione(GSH) and glutamic acid(Glu) in brain tissue, Western blot to measure the content of glial fibrillary acidic protein(GFAP), aquaporin-4(AQP4), and transient receptor potential vanilloid type 4(TRPV4), and immunohistochemical staining to observe the expression of GFAP. The low-dose baicalin was used for exploring the mechanism. The experimental results showed that the neurobehavioral scores(6 h and 24 h of cerebral ischemia), brain water content, and cerebral infarction area of the model group were increased, and both high-dose and low-dose baicalin can lower the above three indexes. The content of GSH dropped but the content of Glu raised in brain tissue of rats in the model group. Low-dose baicalin can elevate the content of GSH and lower the content of Glu. According to the immunohistochemical staining result, the model group demonstrated the increase in GFAP expression, and swelling and proliferation of astrocytes, and the low-dose baicalin can significantly improve this situation. The results of Western blot showed that the expression of GFAP, TRPV4, and AQP4 in the cerebral cortex of the model group increased, and the low-dose baicalin reduce their expression. The cerebral cortex of rats in the model group was severely damaged, and the low-dose baicalin can significantly alleviate the damage. The above results indicate that baicalin can effectively relieve the brain edema caused by cerebral ischemia reperfusion injury in rats, possibly by suppressing astrocyte swelling and TRPV4 and AQP4.


Subject(s)
Animals , Rats , Aquaporin 4/genetics , Astrocytes , Brain Edema/drug therapy , Brain Ischemia/metabolism , Flavonoids , Infarction, Middle Cerebral Artery/drug therapy , Rats, Sprague-Dawley , Reperfusion , TRPV Cation Channels/therapeutic use
15.
Chinese Journal of Pharmacology and Toxicology ; (6): 734-734, 2021.
Article in Chinese | WPRIM | ID: wpr-909578

ABSTRACT

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 dis?ease 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, biologi?cal pathway and protein interaction of the different proteins were analyzed by bioinformatics, so as to identify the molecu?lar 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 syn?drome 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.

16.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 33-39, 2021.
Article in Chinese | WPRIM | ID: wpr-906390

ABSTRACT

Objective:To explore the antidepressant mechanism of Yinxing Mihuan oral solution (YMO) by investigating its effect on depression model rats. Method:The depression rats were induced by isolation combined with chronic unpredictable mild stress (CUMS) and then randomly divided into model group, fluoxetine group (10 mg·kg<sup>-1</sup>) and high-dose (618 mg·kg<sup>-1</sup>) and low-dose (309 mg·kg<sup>-1</sup>) YMO groups. A blank control group was also set up and ten rats were included in each group. Modeling lasted for 21 consecutive days, and rats were administered the 8th day after stimulation at a dose of 10 mL·kg<sup>-1</sup> for 14 days, except those in the blank control and model groups which were given distilled water. Afterward, the sucrose preference test, open field test, tail suspension test were carried out. The pathological changes of hippocampus in depression rats were observed after hematoxylin-eosin (HE) staining. The content of interleukin-1<italic>β </italic>(IL-1<italic>β</italic>), interleukin-6 (IL-6) and tumor necrosis factor-<italic>α </italic>(TNF-<italic>α</italic>) in the hippocampus of rats in each group and the expression of NOD-like receptor 3 (NLRP3) and other proteins in its related activation signaling pathways were detected with multi-factor detection (Luminex) and Western blot. Result:After 14 days of continuous administration, compared with the blank control group, the model group witnessed significantly reduced sugar water consumption rate and the times of rearing and significantly prolonged cumulative time of immobility during tail suspension (<italic>P</italic><0.05, <italic>P</italic><0.01). Compared with the model group, the fluoxetine group and the high-dose YMO group saw increases in the times of rearing, times of crossing and sugar water consumption rate and a significant decrease in the cumulative time of immobility during tail suspension (<italic>P</italic><0.05, <italic>P</italic><0.01). The results of HE staining showed that the neurons in the hippocampus of rats in the high-dose YMO group were arranged in order and slightly loosened, without obvious microglia infiltration observed. The levels of IL-1<italic>β</italic>, IL-6 and TNF-<italic>α</italic> in the hippocampus of the model group increased significantly as compared with the blank control group (<italic>P</italic><0.05, <italic>P</italic><0.01), and their content in the high-dose YMO group was significantly lowered in the comparison with the model group (<italic>P</italic><0.05, <italic>P</italic><0.01). Molecular biology experiments demonstrated that compared with the results of blank group, the expression of purinergic receptor P2X7 (P2RX7), NLRP3, apoptosis-associated speck-like protein (ASC), Caspase-1 and IL-1<italic>β</italic> remarkably increased in the model group (<italic>P</italic><0.05, <italic>P</italic><0.01). Additionally, the expression of P2RX7, NLRP3, ASC, Caspase-1 and IL-1<italic>β </italic>was significantly inhibited in the fluoxetine group and the high-dose YMO group compared with the model group (<italic>P</italic><0.05, <italic>P</italic><0.01). Conclusion:YMO can improve the depression-like behaviors of rats induced by isolation combined with CUMS, and its mechanism of action is related to the regulation of the P2RX7/NLRP3 signaling pathway.

17.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 111-118, 2021.
Article in Chinese | WPRIM | ID: wpr-906338

ABSTRACT

Objective:To study the extraction method and characteristics of vesicle-like nanoparticles (VLNs) in Astragali Radix decoction, and to explore the mechanism of the VLNs in reducing blood glucose by regulating the gut microbiota of db/db diabetic mice. Method:Ultracentrifugation and size exclusion chromatography were used to enrich VLNs from Astragali Radix decoction, and the morphology, particle size and concentration of the VLNs were analyzed by transmission electron microscope and nanoparticle tracking analyzer. The db/db diabetic mice were randomly divided into model group, Astragali Radix VLNs high-, medium- and low-dose (21.1, 10.6, 5.3 g·kg<sup>-1</sup>) groups and metformin group (0.25 g·kg<sup>-1</sup>) according to their blood glucose levels. There were 7 mice in each group, and another 7 C57BL/6 mice were set as the normal group. The mice were given intragastrically for 3 weeks (once a day), and the changes of fasting blood glucose were observed every week. Hematoxylin-eosin (HE) staining was used to observe the pathological morphology of liver and pancreas of diabetic mice. The feces of mice were collected for 16S rRNA diversity detection of intestinal microbes. Result:The size of the nanoparticles obtained by the two methods was about 200 nm. Astragali Radix VLNs extracted by ultracentrifugation had a typical saucer-like shape with the concentration of 3.0×10<sup>11</sup> particles·mL<sup>-1</sup>. The morphology of Astragali Radix VLNs obtained by size exclusion chromatography was relatively poor with the concentration of 2.2×10<sup>11</sup> particles·mL<sup>-1</sup>. After 3 weeks of administration, compared with the model group, Astragali Radix VLNs high-, medium- and low-dose groups could significantly reduce the fasting blood glucose of diabetic mice (<italic>P</italic><0.05, <italic>P</italic><0.01). The VLNs could improve the gut microbiota dysbiosis, significantly decrease the ratio of Firmicutes/Bacteroidota, and increase the relative abundance of beneficial bacteria and reduce the relative abundance of harmful bacteria. Conclusion:Astragali Radix VLNs may reduce the blood glucose of db/db diabetic mice by adjusting the ratio of Firmicutes/Bacteroidota in the intestinal flora.

18.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 147-157, 2021.
Article in Chinese | WPRIM | ID: wpr-906282

ABSTRACT

Objective:To explore the molecular mechanism of Jiangtang Xiaozhi tablets (JTXZT) in the treatment of non-alcoholic fatty liver disease (NAFLD) by means of network pharmacology and molecular docking. Method:With the help of traditional Chinese medicine (TCM) Systems Pharmacology Database and Analysis Platform (TCMSP), TCMs Integrated Database (TCMID), Encyclopedia of TCM (ETCM) and Bioinformatics Analysis Tool for Molecular Mechanism of TCM (BATMAN-TCM), the chemical compositions of medicinal materials in JTXZT were obtained, the compound targets were predicted in SwissTargetPrediction database and STITCH database. The targets of NAFLD were searched by The Human Gene Database (GeneCards), Online Mendelian Inheritance in Man (OMIM), Therapeutic Target Database (TTD) and DisGeNET, and intersection analysis was performed with the targets of the active ingredients to obtain the targets of JTXZT for treatment of NAFLD. Based on STRING 11.0 database, the protein-protein interaction (PPI) network of therapeutic targets was constructed, and the enrichment analysis of therapeutic targets was carried out by DAVID 6.8. Finally, the interaction characteristics of key components and core therapeutic targets of JTXZT for treatment of NAFLD were verified based on molecular docking. Result:The key components of JTXZT for treatment of NAFLD were quercetin, luteolin, kaempferol, berberine, isorhamnetin, betulinic acid, oleanolic acid, ursolic acid. formononetin and hexitol, and the core targets of JTXZT for treatment of NAFLD were mitogen-activated protein kinase 1 (MAPK1), Jun proto-oncogene, activator protein-1 (AP-1) transcription factor subunit (JUN), MAPK3, protein kinase B1 (AKT1 or Akt1), tumor protein p53 (TP53), E1A binding protein p300 (EP300), Fos proto-oncogene, AP-1 transcription factor subunit (FOS), tumor necrosis factor (TNF),amyloid beta precursor protein (APP) and cytochrome P450 family 2 subfamily E member 1 (CYP2E1). Biological function and pathway enrichment analysis showed that JTXZT mainly through xenobiotic metabolic process, oxidation-reduction process, cholesterol metabolic process and other biological processes, regulating phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway, MAPK signaling pathway, NAFLD and insulin signaling pathway to play a role in the treatment of NAFLD. The results of molecular docking showed that the active components of JTXZT had a good affinity with the core targets of JTXZT for the treatment of NAFLD. Conclusion:JTXZT treats NAFLD through multiple active components, multiple key targets and multiple action pathways.

19.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 160-167, 2021.
Article in Chinese | WPRIM | ID: wpr-906002

ABSTRACT

Objective:To analyze the functions and indications, formulation, dosage form and medication characteristics of Chinese patent medicines in the 2020 edition of<italic> Chinese Pharmacopoeia</italic> (part Ⅰ) for treating cough of children, and to provide ideas for the clinical rational application and provide reference for the research and development of new cough medicines for children. Method:The name, dosage form, formulation, functions and indications, usage and dosage, and other information of Chinese patent medicines for cough were collected from the 2020 edition of <italic>Chinese Pharmacopoeia </italic>(part Ⅰ), then relevant information was input into Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine v2.0, and data analysis and mining were carried out through the analysis module of prescription medication rule, VOSviewer 1.6.14 was used to make drug clustering network view of Chinese patent medicines for the treatment of exogenous wind cold, exogenous wind heat and phlegm heat cough. Result:In the 2020 edition of <italic>Chinese Pharmacopoeia </italic>(part Ⅰ), a total of 75 kinds of Chinese patent medicines for treating cough of children were collected, including 34 kinds of Chinese patent medicines for adults and children, 41 kinds of Chinese patent medicines for children only. There were 7 types of traditional Chinese medicine syndromes, such as wind-cold attacking the lung, wind-heat invading the lung and phlegm-heat obstructing the lung. There were 45 Chinese patent medicines for treating exogenous cough, accounting for 60%, among which 35 kinds were used for exogenous wind-heat cough and 10 kinds were used for wind-cold cough. There were 30 kinds of Chinese patent medicines for treating internal injury cough, including 19 kinds of medicines for phlegm heat obstructing the lung, 4 kinds of medicines for phlegm dampness containing the lung and phlegm food stagnation, 2 kinds of medicines for Yin-deficiency lung heat, 1 kind of medicine for the lung and spleen Qi-deficiency. The formulation analysis showed that Glycyrrhizae Radix et Rhizoma, Platycodonis Radix, Scutellariae Radix, Armeniacae Semen Amarum and Citri Reticulatae Pericarpium appeared frequently, which were mainly cold, bitter and sweet herbs, mainly belonged to the lung and stomach meridians. According to the analysis of administration and dosage forms, 71 kinds of Chinese patent medicines were administered through gastrointestinal tract, including 20 kinds of granules, 15 kinds of oral liquids, others included syrups, pills, capsules, tablets, powers, etc. Only 2 suppositories and 2 injections were administered by nongastrointestinal tract. The usage and dosage of most Chinese patent medicines were not clear. Conclusion:In the 2020 edition of <italic>Chinese Pharmacopoeia </italic>(part Ⅰ), the main syndromes of Chinese patent medicines for cough of children are exogenous wind-heat and phlegm-heat obstruction in the lung. Most of the Chinese medicines are cold, bitter and sweet, and their meridians are mainly lung and stomach meridians. Scutellariae Radix, Lonicerae Japonicae Flos and Forsythiae Fructus are the most common medicines of exogenous wind heat syndrome. Perillae Folium, Citri Reticulatae Pericarpium and Ephedrae Herba are the most common medicines of exogenous wind cold syndrome. Meanwhile, Scutellariae Radix, Platycodonis Radix and Armeniacae Semen Amarum are the most common medicines of phlegm heat obstructing the lung syndrome. At present, the dosage forms of Chinese patent medicines used for treating cough of children are too few and the dosage labeling is not comprehensive, so it is necessary to further strengthen the research and development of new Chinese medicines suitable for characteristics of children.

20.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 41-50, 2021.
Article in Chinese | WPRIM | ID: wpr-905925

ABSTRACT

Objective:To investigate the effect of Shuangshen Ningxin capsules (SSNX) on cardiac hemodynamics and cardiac function in rats with coronary microvascular dysfunction. Method:Rats were randomly divided into a sham operation group, a model group, a nicorandil group (5 mg·kg<sup>-1</sup>), and high- (180 mg·kg<sup>-1</sup>), medium- (90 mg·kg<sup>-1</sup>), and low-dose (45 mg·kg<sup>-1</sup>) SSNX groups. Rats received corresponding drugs for 7 days. Two hours after the last administration, the model of coronary microvascular dysfunction was induced by left ventricular injection of embolic microspheres (40-120 μm, about 1 000 microspheres). Twenty-four hours after modeling, left ventricular internal dimension in diastole (LVIDd), left ventricular internal dimension in systole (LVIDs) left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), stroke volume (SV), cardiac output (CO), left ventricular ejection fraction (EF), and left ventricular shortening rate (FS) were detected by echocardiography. Cardiac catheterization was used to observe the arterial systolic blood pressure (SBP), diastolic blood pressure (DBP), left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), maximum rate of increase in left ventricular pressure (LV+dp/dt<sub>max</sub>), and maximum rate of decrease in left ventricular pressure (LV-dp/dt<sub>max</sub>), and the mean arterial pressure (MAP) was calculated. Heart rate (HR) was calculated according to Ⅱ lead ECG. Biochemical analysis was carried out to detect the activities of creatine kinase (CK), creatine kinase-MB (CK-MB), and lactate dehydrogenase (LDH). Enzyme-linked immunosorbent assay (ELISA) was used to detect serum cardiac troponin T (cTnT). Western blot was used to detect the protein expression of Caspase-3, Bcl-2, and Bax, and 2,3,5-triphenyltetrazolium chloride (TTC) staining to observe the area of myocardial infarction. Hematoxylin-eosin (HE) staining was used to observe the morphological changes of the myocardium. Result:As revealed by echocardiography, compared with the sham operation group, the model group showed reduced SV, CO, EF, and FS (<italic>P</italic><0.01), and increased LVIDs and LVEDV (<italic>P</italic><0.01). Compared with the model group, the SSNX groups showed increased EF (<italic>P</italic><0.05, <italic>P</italic><0.01) and FS (<italic>P</italic><0.01), and the high- and medium-dose SSNX groups displayed reduced LVIDs and LVESV, and increased LVEDV, SV, and CO (<italic>P</italic><0.05, <italic>P</italic><0.01). SBP, DBP, MAP, LVSP, LV+dp/dt<sub>max</sub>, and LV-dp/dt<sub>max</sub> in the model group were lower than those in the sham operation group (<italic>P</italic><0.01), while there was no significant difference in HR. SSNX improved hemodynamics of rats, and increased SBP, DBP, MAP, LVSP, LV+dp/dt<sub>max</sub>, LV-dp/dt<sub>max</sub>, and HR as compared with the model group (<italic>P</italic><0.05, <italic>P</italic><0.01). The serum CK, LDH, CK-MB, and cTnT levels in the model group were higher than those in the sham operation group (<italic>P</italic><0.01). Compared with the model group, SSNX groups reduced serum CK, LDH, CK-MB, and cTnT (<italic>P</italic><0.05,<italic> P</italic><0.01). Compared with the sham operation group, the model group displayed increased expression of Caspase-3 protein in the myocardium (<italic>P</italic><0.01) and reduced expression of Bcl-2 protein (<italic>P</italic><0.05). The expression of Caspase-3 protein in the myocardium of SSNX groups was lower than that in the model group, and statistical difference was observed between the low-dose SSNX group and the model group (<italic>P</italic><0.05). Compared with the model group, the SSNX groups exhibited increased expression of Bcl-2 in the rat myocardium, and the statistical difference was observed in the high-dose SSNX group <italic>(P</italic><0.01). As demonstrated by the TTC staining, compared with the model group, SSNX groups showed reduced areas of myocardial infarction (<italic>P</italic><0.01). The HE staining indicated that the pathological injury in myocardial tissues of the SSNX groups was relieved as compared with that in the model group. Conclusion:SSNX can significantly enhance the cardiac function after coronary microvascular dysfunction caused by embolic microspheres, improve cardiac hemodynamics, reduce the area of myocardial infarction, and decrease CK, LDH, CK-MB, and cTnT levels. The mechanism may be related to the inhibition of cardiomyocyte apoptosis to protect the myocardium.

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