cardiovascular-agents and tetramethylpyrazine

Some of the active phytochemicals in herbal medicine are finding therapeutic use. For example, patients with heart disease are reported to benefit from treatment with herbal medicine with fewer side effects. Previous studies showed the inhibitory effects of tetramethylpyrazine, an active component of medicinal herb, on phosphodiesterase that is associated with heart disease and the cardio-protective effects of other herbal medicine that was used to protect ischemia-reperfusion injury of rat hearts. Individual herbal medicines show antipyretic, analgesic and anti-inflammatory and anti-cancer effects. In addition to sharing many therapeutic activities, the active components of herbal medicine are also used in nutrient supplement for cardiovascular disease. Numerous in vitro studies of herbal medicine on different cell lines and in vivo study of herbal medicine have been reported. However, the mechanism of actions remains unclear. The present review aims to give an overview of the recent development of herbal medicine in treatment of cardiovascular disease, and covers the possible mechanism of action of some of active principles. The study will provide insights into drug action and demonstrate the therapeutic benefits of herbal medicine for the treatment of cardiovascular disease.

Topics: Alkaloids; Astragalus propinquus; Biphenyl Compounds; Cardiovascular Agents; Drugs, Chinese Herbal; Flavonoids; Glycyrrhizic Acid; Herbal Medicine; Humans; Lignans; Phenanthrenes; Pyrazines

Drugs with the efficacy of modifying rheological properties of blood, blood vessels and their interactions are denoted by "hemorheologicals". Drugs of anti-hyperviscosemia, anti-coagulants, anti-platelet drugs, anti-thrombotics, vasodilators, endothelial cell protectors and anti-arthrosclerosis should be considered as hemorheologicals due to the actions in keeping blood fluidity and in maintaining normal vascular functions. The studies in hemorheology indicate that a tendency of hyperviscosity, hypercoagulation and being prone to thrombosis is prevalent in the elderly. Hemorheologicals are importance for and aging and life-threatening diseases. Blood stasis syndrome is a common pathological syndrome in the elderly. In traditional Chinese medicine, the treatment for the syndrome is by herbs which activates blood circulation to remove blood stasis. The herbs have the efficacy of improving hemorheological events. Therefore, the herbs are the source for developing hemorheologicals. Ligustrazine isolated from Chuangxiong is an example. It showed significant inhibition on shear induced platelet aggregation and on platelet intracellular calcium demonstrated by laser confocal microscope.

Topics: Aged; Animals; Anticoagulants; Blood Viscosity; Cardiovascular Agents; Coronary Disease; Drugs, Chinese Herbal; Fibrinolytic Agents; Hemodynamics; Hemorheology; Humans; Platelet Aggregation; Platelet Aggregation Inhibitors; Pyrazines; Rats; Rats, Wistar; Stroke; Thrombosis

A series of novel Ligustrazinyl amides was designed, synthesized and evaluated for their protective effect on the injured vascular endothelial cells. The preliminary results demonstrated that some compounds possessed more potent activities than that of Ligustrazine in stimulating replication of the injured human umbilical vascular endothelial cells (HUVECs) that is damaged by hydrogen peroxide. Among the active compounds, compounds 8i, 8t and 8u exhibited the highest potency with low EC₅₀ values of 0.037, 0.070 and 0.055 mM, respectively. Structure-activity relationships were briefly discussed.

Topics: Amides; Cardiovascular Agents; Cells, Cultured; Drug Design; Endothelial Cells; Humans; Pyrazines; Structure-Activity Relationship

Astragaloside IV and tetramethylpyrazine have been extensively used in the cardio-cerbrovascular diseases of medicine as a chief ingredient of glycoside or alkaloid formulations for the treatment of stroke and myocardial ischemia diseases.. To investigate the effects of astragaloside IV (ASG IV) and tetramethylpyrazine (TMPZ) on cerebral ischemia-reperfusion (IR) injury model in rat model.. Rats were randomly divided into the following five groups: sham group, IR group and treatment group including ASG IV, ASG IV-TMPZ and nimodipine treatment. The therapeutic effect was evaluated by micro-positron emission tomography (Micro-PET) using (18)F-fluoro-2-deoxy-d-glucose. The neurological examination, infarct volume and the levels of oxidative stress- and cell apoptosis-related molecules were assessed.. Micro-PET imaging showed that glucose metabolism in the right hippocampus was significantly decreased in the IR group compared to the sham group (P<0.01). ASG IV and ASG IV-TMPZ treatments reversed the decreased glucose metabolism in the model group (P<0.05 and P<0.01, respectively). IR induced the increase of Caspase-3 mRNA levels, MDA content and iNOS activity, but it caused the decrease of SOD activity and Bcl-2 expression compared the sham group (P<0.01). ASG IV-TMPZ and ASG IV reversed the IR-induced changes of these parameters, i.e. the down regulation of Caspase-3 mRNA, MDA content and iNOS activity, and the up regulation of SOD activity and Bcl-2 expression (P<0.05).. This study showed that ASG IV-TMPZ played a pivotal synergistic protective role against focal cerebral ischemic reperfusion damage in a rat experimental model.

Topics: Animals; Astragalus Plant; Cardiovascular Agents; Caspase 3; Disease Models, Animal; Drug Synergism; Glucose; Hippocampus; Ischemic Attack, Transient; Male; Malondialdehyde; Neuroprotective Agents; Nimodipine; Nitric Oxide Synthase Type II; Phytotherapy; Plant Extracts; Positron-Emission Tomography; Proto-Oncogene Proteins c-bcl-2; Pyrazines; Random Allocation; Rats; Rats, Sprague-Dawley; Reperfusion Injury; RNA, Messenger; Saponins; Superoxide Dismutase; Triterpenes

A series of novel stilbene derivatives containing ligustrazinyl moiety was designed, synthesized, and assayed for their protective effects on damaged endothelial cells. The results showed that most ligustrazinyl stilbene derivatives exhibited high protective effects on the human umbilical vascular endothelial cells (HUVECs) damaged by hydrogen peroxide in comparison with Ligustrazine. The stilbene derivatives A6, A9, A11, A21, A24, A25, and A27 exhibited high potency with low EC(50) values ranged from 0.0249 μm to 0.0898 mm. Compound A27 displayed EC(50) 0.0249 μm, which is 30,000 times higher than that of Ligustrazine, presenting a most promising lead for further investigation. Structure-activity relationships were briefly discussed.

Topics: Cardiovascular Agents; Drug Design; Human Umbilical Vein Endothelial Cells; Humans; Hydrogen Peroxide; Oxidative Stress; Pyrazines; Stilbenes; Structure-Activity Relationship

A series of novel Ligustrazinyl acylguanidines was designed, synthesized and evaluated for their protective effect on injured vascular endothelial cell (ECV-304). The preliminary results demonstrated that some compounds possessed more potent activities than that of Ligustrazine in stimulating replication of the injured endothelial cell. Among the active compounds, compounds 8b, 8f and 8l displayed remarkable antioxidative activity with low EC(50) values of 0.097, 0.059 and 0.094 mM, respectively. Structure-activity relationships were briefly discussed.

Topics: Antioxidants; Cardiovascular Agents; Cell Line; Cell Proliferation; Cell Survival; Drug Design; Endothelial Cells; Guanidines; Humans; Inhibitory Concentration 50; Pyrazines; Structure-Activity Relationship

A series of novel ligustrazinyloxy-cinnamic acid derivatives were designed, synthesized and evaluated for their inhibitory effect on adenosine diphosphate (ADP)-induced platelet aggregation in vitro, and also assayed for their protective effect against hydrogen peroxide (H(2)O(2))-induced oxidative damage on ECV-304 cells. Some compounds exhibited high activity in one or both of the assays, of which, compound 2e displayed the highest protective effect on the proliferation of the damaged ECV-304 cells (EC(50) = 0.020 mM), and compound 2f was the most active anti-platelet aggregation agent (EC(50) = 0.054 mM). Structure-activity relationships were briefly discussed.

Topics: Animals; Cardiovascular Agents; Cell Line; Chemistry Techniques, Synthetic; Cinnamates; Cytoprotection; Drug Design; Endothelial Cells; Platelet Aggregation; Pyrazines; Rabbits; Structure-Activity Relationship

The main purpose of this study was to illustrate the effect of synthetical borneol (SB) on the plasma and brain concentration profile of tetramethylpyrazine phosphate (TMPP) in mice after oral administration of TMPP without or with different amounts of SB. The concentrations of TMPP on the plasma and brain in mice were determined by GC-FID. The pharmacokinetic parameters were computed by software program 3p97. Our data showed that after oral administration of 15, 30, 90 mg kg(-1) of SB, oral bioavailability of TMPP in plasma was 1.52, 2.21, 2.95 times increase, respectively, than that without SB, and 1.12, 1.62, 1.93 times increase, respectively, in brain tissue. The pharmacokinetic data were simulated by non-linear least squares. The results showed that both open two-compartment model and one-order absorption were fitted to TMPP plasma and brain concentration-time course in vivo in mice. The MRT of TMPP showed same results under the conditions without or with SB. SB did enhance the oral absorption of TMPP and the concentration of TMPP in brain tissue, especially in the early period. But the use of SB did not change the behavior in vivo of TMPP.

Topics: Administration, Oral; Animals; Biological Availability; Brain; Camphanes; Cardiovascular Agents; Computer Simulation; Dose-Response Relationship, Drug; Drug Combinations; Intestinal Absorption; Least-Squares Analysis; Male; Mice; Models, Biological; Nonlinear Dynamics; Phosphates; Pyrazines; Reproducibility of Results

The objective of this work is to investigate the percutaneous permeability of 2,3,5,6-tetramethylpyrazine (TMP), an active ingredient originally isolated from Ligusticum wallichii Franch. Certain physicochemical properties of TMP, including its partition coefficient and pH-solubility profile, were studied. The influence of pH on the percutaneous permeation of TMP was studied in vitro using hairless mouse skin. Comparative in vitro permeability of TMP through hairless mouse, rat, rabbit, and human cadaver skin was also investigated. The results indicate that hairless mouse skin and rat skin were about three to four times more permeable to TMP than human cadaver skin. The permeability of TMP through rabbit skin was not significantly different from that of human cadaver skin. The observed lag times for all skin membranes were about 1-2h. Although pharmacokinetic data are not currently available to permit precise calculation of a clinically effective patch size, the data from this study indicate that the transdermal delivery of TMP should nevertheless be possible.

Topics: Administration, Cutaneous; Animals; Cardiovascular Agents; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Humans; Hydrogen-Ion Concentration; In Vitro Techniques; Ligusticum; Mice; Mice, Hairless; Pyrazines; Rabbits; Rats; Rats, Sprague-Dawley; Skin; Skin Absorption; Solubility

Effects of tetramethylpyrazine (TMP) and that of extracts of Charthamus tinctorius L. (CTL) on the macro- and microcirculation in rabbit mesentery were studied. The intestinal arterial blood flow (Qa) was measured using an electromagnetic flowmeter, together with the arterial blood pressure (Pa). The inner diameter and red cell velocity in single arteriole in the mesentery were measured by a video-image technique and a dual-slit photometric method, respectively. Using the measured diameter and red cell velocity, the arteriolar blood flow (Qm) was calculated. Both the Qa and Qm decreased when Pa was decreased after the intravenous administration of TMP, CTL, Nicardipine, Phentolamine and acetylcholine (Ach). Changes in Qa and Qm with changes in Pa were analyzed, and it was found that (i) both the Pa-Qa and Pa-Qm curves, during the administration of TMP or CTL, show different patterns from those during the administration of Nicardipine or Phentolamine; (ii) the Pa-Qa and Pa-Qm curves after the administration of TMP or CTL show similar patterns with those after the administration of Ach.

Topics: Acetylcholine; Adrenergic alpha-Antagonists; Animals; Arterioles; Blood Flow Velocity; Blood Pressure; Calcium Channel Blockers; Cardiovascular Agents; Carthamus tinctorius; Drugs, Chinese Herbal; Microcirculation; Microscopy, Video; Neurotransmitter Agents; Nicardipine; Phentolamine; Pyrazines; Rabbits; Splanchnic Circulation

Topics: Animals; Cardiovascular Agents; Dogs; Hemodynamics; Oxygen Consumption; Propranolol; Pyrazines; Reserpine