peoniflorin and tetramethylpyrazine

Angiogenesis contributes to plaque instability in atherosclerosis and further increases cardio-cerebrovascular risk. Circular RNAs (circRNAs) are promising biomarkers and potential therapeutic targets for atherosclerosis. Previous studies have demonstrated that tetramethylpyrazine (TMP) and paeoniflorin (PF) combination treatment (TMP-PF) inhibited oxidized low-density lipoprotein (ox-LDL)-induced angiogenesis in vitro. However, whether circRNAs regulate angiogenesis in atherosclerosis and whether TMP-PF can regulate angiogenesis-related target circRNAs in atherosclerosis are unknown. In this study, human RNA sequencing (RNA-seq) data were analysed to identify differentially expressed (DE) circRNAs in atherosclerosis and to obtain angiogenesis-associated circRNA-microRNA (miRNA)-messenger RNA (mRNA) networks. Target circRNA-related mechanisms in angiogenesis in atherosclerosis and the regulatory effects of TMP-PF on target circRNA signalling were studied in ox-LDL-induced human umbilical vein endothelial cells (HUVECs) by cell proliferation, migration, tube formation, and luciferase reporter assays, real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting. A novel circRNA (circular stimulator of chondrogenesis 1, circSCRG1) was initially identified associated with angiogenesis in atherosclerosis, and circSCRG1 silencing up-regulated miR-1268b expression, increased nuclear receptor subfamily 4 group A member 1 (NR4A1) expression and then promoted ox-LDL-induced angiogenesis. TMP-PF (1 μmol/L TMP combined with 10 μmol/L PF) up-regulated circSCRG1 expression, mediated miR-1268b to suppress NR4A1 expression and then inhibited ox-LDL-induced angiogenesis. However, circSCRG1 silencing abolished the inhibitory effects of TMP-PF on ox-LDL-induced angiogenesis, which were rescued by the miR-1268b inhibitor. In conclusion, circSCRG1 might serve as a new target regulating angiogenesis in atherosclerosis via the circSCRG1/miR-1268b/NR4A1 axis and TMP-PF could regulate the circSCRG1/miR-1268b/NR4A1 axis to inhibit angiogenesis in atherosclerosis in vitro, indicating a novel angiogenesis signalling circSCRG1/miR-1268b/NR4A1 pathway in atherosclerosis and the regulatory effects of TMP-PF, which might provide a new pharmaceutical strategy to combat atherosclerotic plaque instability.

Topics: Apoptosis; Atherosclerosis; Cell Proliferation; Human Umbilical Vein Endothelial Cells; Humans; Lipoproteins, LDL; MicroRNAs; Nuclear Receptor Subfamily 4, Group A, Member 1; Plaque, Atherosclerotic; RNA, Circular

It is well-known that the public still have been facing on a severe issue about the inconsistency of quality and therapeutic efficacy of traditional medicines. Recently, Professor Chang-Xiao Liu has created a new promising concept for identifying relevant quality-markers (Q-marker) from herbs, their formulas and manufacturing products. Therefore, building up a new approach is necessary for us to bridge over quality to efficacy of pharmaceutical products.. In this paper, five candidate Q-markers, astragaloside IV, paeonflorin, amygdalin, tetramethylpyrazine, ferulic acid in Buyanghuanwu injection (BYHWI) had been designed to carry out in rat by using single and polypharmacokinetic models for total quanta to ascertain adequate Q-marker.. The Q-marker transitivity in vivo was studied with polypharmacokinetic model and its similarity approach, which were modeled with TQSM principle. The Q-marker was ascertained with transitive similarity and bioavailability in polypharmacokinetics. Their concentrations in plasma sample of white rat were determined by RP-HPLC. Data analyses were used by the DAS software for singles and myself-written-program with EXCEL for multiples.. In BYHWI, five candidate Q-marker pharmacokinetic profiles were singly fixed to two compartmental models in rat using classical compartmental analysis, but there were tremendous differences among which the candidate parameters were fluctuated from nearly 3552 folds to equivalency. The theoretical value of TQSM polypharmacokinetic parameters such as AUC. The results represented that the optimum Q-marker in BYHWI is astragaloside Ⅳ, whose transitivity in vivo similarity was close to the behavior of polypharmacokinetics with maximum bioavailability to the total quanta. It is feasible for Q-marker in CMMs to screen on the comparison of single pharmacokinetic behavior and bioavailability to the total quanta.

Topics: Amygdalin; Animals; Biological Availability; Biomarkers; Chromatography, High Pressure Liquid; Coumaric Acids; Drugs, Chinese Herbal; Glucosides; Injections; Monoterpenes; Pyrazines; Rats, Wistar; Saponins; Triterpenes

To investigate the synergistic effects of Chuanxiong-Chishao herb-pair (CCHP) on promoting angiogenesis in silico and in vivo.. The mechanisms of action of an herb-pair, Chuanxiong-Chishao, were investigated using the network pharmacological and pharmacodynamic strategies involving computational drug target prediction and network analysis, and experimental validation. A set of network pharmacology methods were created to study the herbs in the context of targets and diseases networks, including prediction of target profiles and pharmacological actions of main active compounds in Chuanxiong and Chishao. Furthermore, the therapeutic effects and putative molecular mechanisms of Chuanxiong-Chishao actions were experimentally validated in a chemical-induced vascular insuffificiency model of transgenic zebrafifish in vivo. The mRNA expression of the predicted targets were further analyzed by real-time polymerase chain reaction (RT-PCR).. The computational prediction results found that the compounds in Chuanxiong have antithrombotic, antihypertensive, antiarrhythmic, and antiatherosclerotic activities, which were closely related to protecting against hypoxic-ischemic encephalopathy, ischemic stroke, myocardial infarction and heart failure. In addition, compounds in Chishao were found to participate in anti-inflflammatory effect and analgesics. Particularly, estrogen receptor α (ESRα) and hypoxia-inducible factor 1-α (HIF-1α) were the most important potential protein targets in the predicted results. In vivo experimental validation showed that post-treatment of tetramethylpyrazine hydrochloride (TMP•HCl) and paeoniflorin (PF) promoted the regeneration of new blood vessels in zebrafifish involving up-regulating ESRα mRNA expression. Co-treatment of TMP•HCl and PF could enhance the vessel sprouting in chemical-induced vascular insuffificiency zebrafifish at the optimal compatibility proportion of PF 10 μmol/L with TMP•HCl 1 μmol/L.. The network pharmacological strategies combining drug target prediction and network analysis identified some putative targets of CCHP. Moreover, the transgenic zebrafifish experiments demonstrated that the Chuanxiong-Chishao combination synergistically promoted angiogenic activity, probably involving ESRα signaling pathway.

Topics: Animals; Cardiovascular Diseases; Drug Synergism; Drugs, Chinese Herbal; Embryo, Nonmammalian; Estrogen Receptor alpha; Gene Expression Regulation; Glucosides; Ligands; Monoterpenes; Neovascularization, Physiologic; Pyrazines; Reproducibility of Results; Zebrafish

To verify established the total quantum statistic moments model with astragaloside IV, paeoniflorin, tetramethylpyrazine in Buyanghuanwu injection, in order to establish a pharmacokinetic experimental method with multi-component traditional Chinese medicine (TCM) compound system.. The RP-HPLC was adopted, with the chromatographic column of C18, 4.6 mm x 250 mm, 5 microm. As for astragaloside IV, the ELSD detector was adopted with acetonitrile-water (35: 65) as the mobile phase at 1 mL x min(-1); the pressure of column was (15.0 +/- 0.408) MPa, the column temperature was 30 degrees C. Regarding paeoniflorin and tetramethylpyrazine, the detection of wavelengths was 254 nm, with acetonitrile-water (35:65) as the mobile phase at 1 mL x min(-1), the column pressure of (15.17 +/- 0.41) MPa. The pharmacokinetic parameters for single component were dealt with DAS and the total quantum statistical moment (TQSM) parameters were calculated using formulations.. All of the three components followed the two compartmental pharkacokinetic model (P < 0.01) in rats. Compared with the superimposed total concentration, each single component showed difference in parameters up to 10 000 times at most, whereas the RSD of TQSM parameters was 3.510%. The TQSM pharmacokinetic parameters of the three components in Buyanghuanwu injection showed that AUC(t), MRT(t), VRT(t), CL(t), V(t), were (119.8 +/- 27.20) g x min x L(-1), (210.0 +/- 54.49) min, (5.608 +/- 2.723) x 10(4) min2, (0.319 6 +/- 0.068 8) mL x min(-1) x kg(-1) and (64.12 +/- 8.243) mL x kg(-1), respectively, suggesting that the half-life time for the three components were (145.5 +/- 37.76) min and 95% of them were metabolized within 0-674. 2 min.. The TQSM can be used to study pharmacokinetic parameters of multi-component TCM compound, because the method can characterize the pharmacokinetic regularity of quantum-time change in a multi-component system.

Topics: Animals; Benzoates; Bridged-Ring Compounds; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Glucosides; Male; Medicine, Chinese Traditional; Models, Statistical; Monoterpenes; Pyrazines; Rats; Saponins; Triterpenes

Effects of four Si-Wu-Tang (SWT)'s constituents, fructose (Fru), paeoniflorin (Pae), ferulic acid (FA), tetramethyl pyrazine (TP), and their combination on irradiated mice as model of anaemia were investigated, with the purpose of further understanding the relationship between SWT's constituents and activities. Similarly to SWT, oral administration of Fru, Pae, FA, TP and their combination, to some extent, all showed effects of increasing the number of peripheral leukocyte and increasing four types of progenitor cells in bone marrow, including colony-forming unit-granulocyte-macrophage (CFU-GM), colony-forming unit-mature erythroid (CFU-E), colony-forming unit-immature erythroid (BFU-E) and colony-forming unit-multipotential (CFU-mix). Pae and FA showed significant body weight reducing effect, which were largely abolished when they were combined with Fru and TP. The SWT, Fru and combination significantly increased the thymus index while Pae significantly decreased it. Both SWT and TP significantly increased the spleen index but the combination did not. The results suggested that multiple constituents contribute to the promoting effect of SWT on hematopoiesis. Although being a very common compound in plants, the Fru has a special contribution to SWT's effect, which cannot be neglected. It may be an important active constituent that is responsible for SWT's promoting effect on hematopoiesis and immunity. Another suggestion is that when being combined, some effect of one constituent, sometimes is unexpected side effect, may be abolished by other. This may reflect the advantage of multiple constituent characteristics possessed by most TCMs.

Topics: Animals; Benzoates; Body Weight; Bone Marrow Cells; Bridged-Ring Compounds; Colony-Forming Units Assay; Coumaric Acids; Disease Models, Animal; Dose-Response Relationship, Radiation; Drugs, Chinese Herbal; Female; Fructose; Gamma Rays; Glucosides; Hematopoietic Stem Cells; Mice; Mice, Inbred C57BL; Monoterpenes; Pyrazines; Radiation-Protective Agents; Stem Cells; Thymus Gland

A traditional Chinese medicine, Shimotsu-to, consisting of four herbs: Japanese angelica root, cnidium rhizome, peony root and rehmannia root, has been reported to improve spatial working memory in rats. The present results indicate that Paeoniflorin and tetramethylpyrazine (TMP) extracted from peony root and cnidium rhizome, respectively, are candidates for cognitive enhancer.

Topics: Aging; Animals; Basal Ganglia; Benzoates; Bridged-Ring Compounds; Cognition; Discrimination Learning; Free Radical Scavengers; Glucosides; Male; Maze Learning; Memory, Short-Term; Monoterpenes; Nootropic Agents; Plants, Medicinal; Pyrazines; Rats; Rats, Inbred F344; Rats, Wistar