Animals ; Antihypertensive Agents ; pharmacology ; Heme Oxygenase (Decyclizing) ; drug effects ; metabolism ; Losartan ; pharmacology ; Rats ; Water-Electrolyte Balance

This paper reviewed the advances on effective constituents and biological activities of coumarins in recent ten years. Coumarins are a group of important natural compounds, and have been found to have multi-biological activities such as anti-HIV, anti-tumor, anti-hypertension, anti-arrhythmia, anti-osteoporosis, assuaging pain, preventing asthma and antisepsis. Therefore, further investigation should emphasize on improving techniques for extraction and separation, searching the effective precursory compound, and synthesizing and screening out courmarin derivatives with high activity and low toxicity.
Animals ; Anti-Arrhythmia Agents ; pharmacology ; Anti-HIV Agents ; pharmacology ; Antihypertensive Agents ; pharmacology ; Antineoplastic Agents, Phytogenic ; pharmacology ; Coumarins ; isolation & purification ; pharmacology ; Humans ; Plants, Medicinal ; chemistry

As a traditional Chinese medicine, Valeriana jatamansi has a long history of application in China. It is widely distributed and commonly adopted by many ethnic groups. In particular, its roots have a wide range of medicinal value. With the increasingly more attention on it from domestic and foreign researchers, there have been more and more studies on its pharmacological activity and mechanism. This essay summarizes domestic and foreign reports on its pharmacological activity and mechanism.
Animals ; Anti-Infective Agents ; pharmacology ; Antihypertensive Agents ; pharmacology ; Antineoplastic Agents, Phytogenic ; pharmacology ; Central Nervous System Depressants ; pharmacology ; Gastrointestinal Tract ; drug effects ; Humans ; Plant Extracts ; adverse effects ; pharmacology ; Valerian

Berbamine (molecular formular C37H40N2O6) is a bi-benzle-isoquinolyl alkaloid extracted from Berberis poiretil Schneid (genus of Berberis, family of Beridaceae), a kind of Chinese plants. In aspect of cardiovascular pharmacology, berbamine shows actions of anti-arrhythmia, anti-myocardial ischemia, vasodilatating to lower blood pressure, and antithrombosis, it could lower heart function and heart rate. Study on its anti-arrhythmia was the deepest one. The significant anti-arrhythmia action can be achieved by inhibiting ionic channels of sodium, potassium, calcium, etc., negative frequency and negative transduction, improving the diastolic excitation threshold of myocardium, prolonging effective refractory period of myocardium. As a direction of researches on new type of antiarrhythmic herbs and herbal drugs, the study on berbamine is worthy of further research and development.
Alkaloids ; pharmacology ; Anti-Arrhythmia Agents ; pharmacology ; Antihypertensive Agents ; pharmacology ; Benzylisoquinolines ; pharmacology ; Heart Rate ; drug effects ; Ion Channel Gating ; drug effects ; Platelet Aggregation ; Platelet Aggregation Inhibitors ; pharmacology

Angiotensin converting enzyme (ACE, EC 3.4.15.1) is a membrane-bound, zinc dependent dipeptidase that catalyzes the conversion of the decapeptide angiotensin I to the potent vasopressor ocatapeptide angiotensin II, by removing two C-terminal amino acids. ACE is well known as a key part of the renin angiotenisn system that regulates blood pressure, and its inhibitors have potential for the treatment of hypertension. This paper reviewed the characteristics of ACE in aspects of its structure-function relationship, gene polymorphism and inhibitor development. In particular, the catalytic mechanisms of the two active sites of somatic ACE in the cleavage of angiotensin I and bradykin are different. Therefore, it would likely provide a new way for exploiting novel ACE inhibitors with fewer side-effects by specifically-targeting the individual active sites of somatic ACE.
Angiotensin-Converting Enzyme Inhibitors ; pharmacology ; Antihypertensive Agents ; pharmacology ; Humans ; Peptidyl-Dipeptidase A ; chemistry ; genetics ; metabolism ; Polymorphism, Genetic ; Structure-Activity Relationship

The primary object of this fundamental research was to survey the synergistic cardiovascular effects of iptakalim, a novel ATP-sensitive potassium channel (K(ATP)) opener, and clinical first-line antihypertensive drugs, such as calcium antagonists, thiazide diuretics and β receptor blockers by a 2 x 2 factorial-design experiment. It would provide a theoretical basis for the development of new combined antihypertensive therapy program after iptakalim is applied to the clinic. Amlodipine besylate, hydrochlorothiazide and propranolol were chosen as clinical first-line antihypertensive drugs. Blood pressure, heart rate (HR) and cardiac functions were observed in anesthetized normal rats by an eight-channel physiological recorder. The results showed that iptakalim monotherapy in a low dose could produce significant antihypertensive effect. There was no interaction between iptakalim and amlodipine on the maximal changes of systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MABP), the left ventricular systolic pressure (LVSP), and the left ventricular end-diastolic pressure (LVEDP) (P > 0.05). However, the effects of combination iptakalim/amlodipine on the maximal changes of SBP, DBP, MABP, LVSP and LVEDP were more obvious than those of iptakalim or amlodipine monotherapy. And there was strong positive interaction between iptakalim and amlodipine on the maximal changes of HR (P>0.05). According to the maximal changes of DBP, MABP, LVSP and LVEDP (P < 0.05) of combination iptakalim with hydrochlorothiazide, there was strong positive interaction between them. But there was no interaction between iptakalim and hydrochlorothiazide on the maximal drop of SBP and HR (P > 0.05). According to the maximal drops of DBP, MABP of combination iptakalim with propranolol, there was strong positive interaction between them (P < 0.05). But there was no interaction between iptakalim and propranolol on the maximal changes of SBP, LVSP, LVEDP and HR (P > 0.05). In conclusion, it was the first time to study the effects of amlodipine, hydrochlorothiazide or propranolol, which had different mechanisms of action from iptakalim, on cardiovascular effects of iptakalim in anesthetized normal rats. This study proved that the combination of iptakalim with hydrochlorothiazide or propranolol respectively had significant synergism on lowering blood pressure, while the combination of iptakalim/amlodipine had additive action on lowering blood pressure. Meanwhile the antihypertensive effect was explicit, stable and long-lasting. Iptakalim thus appears suitable for the clinical treatment of hypertensive people who need two or more kinds of antihypertensive agents.
Amlodipine ; pharmacology ; Animals ; Antihypertensive Agents ; pharmacology ; Blood Pressure ; drug effects ; Drug Synergism ; Heart Rate ; Hydrochlorothiazide ; pharmacology ; Hypertension ; Propranolol ; pharmacology ; Propylamines ; pharmacology ; Rats

Coumarins are a group of important natural compounds, and have been found to have multi-biological activities such as anti-HIV, anti-tumor, anti-hypertension, anti-arrhythmia, anti-osteoporosis, assuaging pain, preventing asthma and antisepsis. One of which is its anti-tumor effect and that is a research focus on. Therefore, we believe that it is necessaryto carry out further studies on the effect of coumarins compounds in anti-tumor. Investigation should emphasize on improving techniques for extraction and separation, searching the effective precursory compound, and synthesizing and screening out courmarin derivatives with high activity and low toxicity. Here the recent research progress in anti-tumor effect of coumarins compounds is reviewed.
Anti-Arrhythmia Agents ; pharmacology ; therapeutic use ; Anti-HIV Agents ; pharmacology ; therapeutic use ; Antihypertensive Agents ; pharmacology ; therapeutic use ; Antineoplastic Agents, Phytogenic ; pharmacology ; therapeutic use ; Coumarins ; pharmacology ; therapeutic use ; Humans ; Neoplasms ; drug therapy

OBJECTIVETo isolate the active component from Dioscorea cirrhosa Lour and test its activity in lowering blood pressure.

METHODSThe serial components were obtained from the total extract, ligroin extract, ethyl acetate, n-butyl alcohol extract and water extract. The isolated active components were administered in rats via the common carotid artery canulation and tail vein injection to test their effects on blood pressure.

RESULTSThe component A isolated and purified from normal butanol showed obvious effect in lowering the blood pressure of rats.

CONCLUSIONThe isolated active component from Dioscorea cirrhosa Lour possesses obvious blood pressure-lowering activity.

Animals ; Antihypertensive Agents ; isolation & purification ; pharmacology ; Blood Pressure ; drug effects ; Dioscorea ; chemistry ; Drugs, Chinese Herbal ; pharmacology ; Male ; Plant Extracts ; pharmacology ; Rats ; Rats, Sprague-Dawley

The paper is aimed to investigate the pharmacokinetic (PK) and the pharmacodynamic (PD) properties of carvedilol using indirect response and effect-compartment link models, and compare the fitness of PK-PD models. Twenty male healthy Chinese volunteers received a single oral dose of 20 mg of carvedilol. The plasma concentrations of carvedilol were determined by reversed-phase HPLC method with fluorescence detection, and the pharmacokinetic parameters were calculated by DAS2.0. The mean arterial blood pressure was measured and the pharmacodynamics of carvedilol was characterized by tail-cuff manometry. The main pharmacokinetic parameters of carvedilol were as follows, t1/2 (4.56 +/- 2.56) h, Cmax (46.29 +/- 21.07) ng x mL(-1), AUC(0-infinity) (173.76 +/- 87.36) ng x mL(-1) x h. The estimated Kin was (0.41 +/- 0.31)% h(-1), Kout was (0.40 +/- 0.26) h(-1), the IC50 value was (24.40 +/- 21.10) ng x mL(-1) and the area under the effect curve (AUE) was (3.82 +/- 1.46)% h for the indirect response PD model. The Ke0 was (0.35 +/- 0.27) h(-1), the EC50 was (24.30 +/- 24.30) ng x mL(-1), and the AUE was (5.65 +/- 2.54)% h for the effect-compartment model. The HPLC method can be used for the pharmacokinetic study of carvedilol. The proposed effect-compartment link model provided more appropriate and better-fitting PK/PD characteristics than the indirect response model in Chinese healthy volunteers according to Akaike's information criterion values.
Antihypertensive Agents ; pharmacokinetics ; pharmacology ; Area Under Curve ; Blood Pressure ; drug effects ; Carbazoles ; blood ; pharmacokinetics ; pharmacology ; Humans ; Male ; Models, Cardiovascular ; Propanolamines ; blood ; pharmacokinetics ; pharmacology

By using the pharmacophore model of mineralocorticoid receptor antagonists as a starting point, the experiment stud- ies the method of traditional Chinese medicine formula design for anti-hypertensive. Pharmacophore models were generated by 3D-QSAR pharmacophore (Hypogen) program of the DS3.5, based on the training set composed of 33 mineralocorticoid receptor antagonists. The best pharmacophore model consisted of two Hydrogen-bond acceptors, three Hydrophobic and four excluded volumes. Its correlation coefficient of training set and test set, N, and CAI value were 0.9534, 0.6748, 2.878, and 1.119. According to the database screening, 1700 active compounds from 86 source plant were obtained. Because of lacking of available anti-hypertensive medi cation strategy in traditional theory, this article takes advantage of patent retrieval in world traditional medicine patent database, in order to design drug formula. Finally, two formulae was obtained for antihypertensive.
Antihypertensive Agents ; chemistry ; pharmacology ; Databases, Factual ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Medicine, Chinese Traditional ; methods ; Mineralocorticoid Receptor Antagonists ; chemistry ; pharmacology ; Models, Molecular