Hypotensive Principle Research Articles

From Plant-derived Hypotensive Principle(s) to Mysteries of the Relationship between Poisons of the Tempyo Era and the "Taketori-Monogatari" Story

Unlike many researchers of natural product chemistry, I was fortunate to have the opportunity to study phytochemical metabolites and isolates of microbial origin. I began my career isolating the active compound(s) from the medicinal plants. After obtaining a Ph.D. degree from Tohoku University, I flew to Chicago, College of Pharmacy, University of Illinois, where I carried out research on the chemistry of acronycine and discovered several interesting chemical reactions regarding this alkaloid. After returning to Japan, I began to work at the Kitasato Institute, to search for novel antitumor antibiotics. During this period, 27 new antibiotics were isolated, and the new chemical structures were elucidated. After rejoining the Pharmaceutical Institute at Tohoku University, I again began to work on the phytochemical substances, mainly alkaloids. These studies continued after I moved to Aomori University and finally to Nihon Pharmaceutical University. I was interested in the biosynthesis of the alkaloids and found that all alkaloids could be classified into 16 classes based on their method of biosynthesis. I wrote a book about this in Japanese, and subsequently the book was translated into English as "ALKALOIDS-A Treasury of Poisons and Medicines." After completing the publication of this book, I had many chances to write books, mainly concerning poisons and medicines. Totally, I have been able to publish 26 books regarding on these fascinating topics until now. I am feeling very satisfied with my natural product chemistry contributions, especially those of alkaloids and poisons.

English

Excoecaria grahamii, African shrub, is used in many West African countries traditional medicine against different diseases as powerful purgative and biopesticide. There is little work about pharmacological effects of this plant because of its high toxicity. The effects of the aqueous extract of the plant was investigated on rabbit blood pressure and toad isolated and perfused heart activity. E. grahamii extracts (EGE) injection exhibited a dose dependent blood pressure decrease like acetylcholine effect. This activity was inhibited by atropine, suggesting muscarinic effect. Same results (inhibition effects) were found on both electrical and mechanical actions of toad isolated and perfused heart. Previous results obtained with aqueous extracts on smooth intestine muscle exhibit a muscarinic effect (hypotensive principle) then alcoholic extracts showed hypertensive and cardiotonic effects on rabbit. Our results confirm existence of muscarinic activity on rabbit blood pressure and toad heart activity. Key words: Excoecaria grahamii, rabbit blood pressure, toad heart, electrocardiogram.

Simple hypotensive and hypertensive principles from some West Indian medicinal plants.

Abstract Examination of those plant extracts which were previously found (Feng and others, 1962) to have transient depressor activity has led to the isolation of γ-aminobutyric acid, from the leaves of Artocarpus incisa L. and of Piper amalago L. and to the demonstration by paper chromatography of its presence in several extracts. Extracts showing pressor activity were also examined and tyramine has been isolated from Phoradendron wattii Kr. and Urb. and dopamine has been shown by paper chromatography to be present in Piper amalago L. and Stachytarpheta jamaicensis Vahl.

Control of sympathetic activity--new insights; new therapeutic targets?

Recently, a large international group of 25 investigators identified a candidate gene for hypertension which codes for phosducin (Pdc) as a novel player in the sympathetic nervous system [1]. In their study, a wide spectrum of findings documented its so-far unrecognized and apparently important role in experimental and human stress-induced hypertension. This conclusion is based on data ranging from detailed analyses of the sympathetic system in genetically manipulated Pdc �/� (knock-out) mice to the demonstration of its relevance in humans: in two separate cohorts, French Canadian and Afro-American individuals, respectively, a correlation was documented between singlenucleotide polymorphisms (SNPs) in the Pdc gene and stress-dependent blood pressure reactions. The target gene identified by the investigators codes for the G-protein regulator phosducin. In mice, targeted Pdc deletion increased blood pressure, increased catecholamine turnover in the peripheral sympathetic system and prolonged action potential firing. This finding suggests that Pdc is a hypotensive principle, explaining why reduced function of Pdc amplifies the hypertensive reaction to stressors. In other words: Pdc puts a brake on sympathetic activity, and conversely Pdc malfunction will lead to hypertension. What is the site of action of Pdc? The Pdc gene and the Pdc protein are expressed in sympathetic ganglia, although to a much lower extent than in the retina and pineal gland, but not in heart, blood vessels and kidney, important players in blood pressure control. To identify the site of action, experimental manipulations sequentially excluded changes in heart function, vascular function or function of the central nervous system as candidates. Early in life, cardiac morphology was not altered in Pdc�/�mice,butleftventricularcontractilitywasincreased despite no change of sensitivity to adrenoceptor agonists (norepinephrine, dobutamine)—consistent with increased sympathetic nerve traffic. In older animals (>4 months), however, significant hypertrophy was seen with expression of fetal genes as evidence of target organ injury.

Hypotensive Activity of Tacca chantrieri. and Its Hypotensive Principles

The rhizomes of Tacca chantrieri. Andre (Taccaceae) have been used in Chinese medicines for the treatment of various diseases including high blood pressure, burns, gastric ulcers, enteritis, and hepatitis. The rhizomes of this plant have been found to contain a wide array of saponins and other compounds. The aims of the current study were to investigate the hypotensive activity of the ethanol extract (TCE) and both the crude (TCS) and purified saponin extract of T. chantrieri., and thus to characterize the hypotensive principles. TCE and TCS at the dose of 5 mg/kg caused hypotension and bradycardia in normotensive rats under pentobarbital anesthesia. Both TCE and TCS caused a decrease in the force and rate of contractions in isolated rat atria. The vasorelaxant activity of TCE and TCS could be demonstrated when tested on the aortic ring with endothelium intact. It is therefore implied that TCE and TCS exert both their hypotensive effect and bradycardia by affecting the heart as well as blood vessels. Separation of the crude saponin extract of T. chantrieri. yielded four fractions with hypotensive activity. Fraction 1 contained diarylheptanoid glucosides, fraction 2 was a mixture of the glucosides and saponins, and fractions 3 and 4 contained spirostanol saponins. It is likely that in addition to the saponins, other constituents (diarylheptanoid glucosides) are involved in the hypotensive activity of T. chantrieri..

Hypotensive Constituents from the Pods ofMoringa oleifera

Hypotensive activity of the ethanolic and aqueous extracts of Moringa oleifera whole pods and their parts, namely, coat, pulp, and seed was investigated. The activity of the ethanolic extract of both the pods and the seeds was equivalent at the dose of 30 mg/kg. The ethyl acetate phase of the ethanolic extract of pods was found to be the most potent fraction at the same dose. Its bioassay-directed fractionation led to the isolation of thiocarbamate and isothiocyanate glycosides which were also the hypotensive principles of the pods as observed in case of Moringa leaves. Two new compounds, O-[2'-hydroxy-3'-(2"-heptenyloxy)]-propyl undecanoate (1) and O-ethyl-4-[(alpha-L-rhamnosyloxy)-benzyl] carbamate (2) along with the known substances methyl p-hydroxybenzoate (3) and beta-sitosterol have also been isolated in the present studies. The latter two compounds and p-hydroxybenzaldehyde showed promising hypotensive activity. Structures of all these compounds have been deduced by spectroscopy and chemical reactions.

Naturally occurring 2'-O-methylpurine nucleosides with hypotensive properties.

2'-O-Methylinosine (1) has been isolated for the first time and shown to be an intrinsic hypotensive principle. Its probable in vivo precursor, 2'-O-methyladenosine (3), showed stronger and even orally potent hypotensive activity. Resistance of the methyladenosine (3) against adenosine deaminase is thought to contribute to its long-lasting activity. The effect of both nucleosides (1 and 3) was not accompanied with any significant change in heart rate, which is often observed with adenosine.

Phytochemical Studies on Adhatoda Vasica Nees

A new triterpenoid, 3α-hydroxy-D-friedoolean-5-ene (1), along with the known compounds, epitaraxerol (2) and peganidine (3), which have been isolated for the first time from the aerial parts of Adhatoda vasica Nees. The structures of these compounds were elucidated by spectral studies. X- Ray diffraction studies on a bronchodilating and hypotensive principle of A. vasica, vasicinone (4), were also carried out.

Hypotensive effect of Laurelia sempervirens (Monimiaceae) on normotensive rats

AbstractThe leaves of Laurelia sempervirens (Monimiaceae), an endemic Chilean tree known as ‘Laurel’, were used by the Mapuche Amerindians for treating headache and as a diuretic. Intravenous administration of a hydroalcoholic L. sempervirens extract to rats, elicited a hypotensive response of −27.0%±2.0% in the mean blood pressure of normotensive animals at a dose of 5 mg crude extract ± kg body weight. Bioassay‐guided isolation of the active ‘Laurel’ metabolites led to the alkaloid laurotetanine as the main hypotensive principle of L. sempervirens leaves. At 1 mg/kg body weight, laurotetanine produced a hypotensive response of −29.0%±2.1% in the mean blood pressure of normotensive rats, with a duration of 2 min, both comparable to those elicited by the crude extract at 5 mg/kg. In the acute oral toxicity study, ‘Laurel’ proved to be a very low toxicity crude drug at doses up to 3 g crude extract/kg body weight. The data obtained support the use of L. sempervirens in Mapuche traditional medicine.

ChemInform Abstract: Synthesis of Amidoureas and the Nature of Caracasanamide, the Hypotensive Principle of Verbesina caracasana.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Cardiovascular responses in the normotensive rat produced by intravenous injection of gambirine isolated from Uncaria callophylla Bl. ex Korth

Among several alkaloids, including dimeric indoles, isolated from Uncaria callophylla, gambirine which is an alkaloid unique to this plant, has been found to be another hypotensive principle from the plant. Intravenous injections of gambirine in the dose range of 0.2 to 10.0 mg/kg caused a dose-related fall in both systolic and diastolic blood pressures as well as heart rate. At all doses gambirine showed a prompt onset of action and at the higher doses (5.0–10 mg/kg), marked persistence of hypotension accompanied by severe bradycardia were observed. In addition, higher doses of gambirine produced a more marked decrease in diastolic than systolic pressure while at lower doses both decreased equally. It is suggested that the hypotensive effect of gambirine may be peripheral in origin and is associated, at least in part, with a cardiac action.

Isolation and structure elucidation of novel hypotensive agents, niazinin A, niazinin B, niazimicin and niaziminin A + B from Moringa oleifera: the first naturally occurring thiocarbamates

Novel hypotensive principles, niazinin A 1, niazinin B 2, niazimicin 4 and niaziminin A and B 6+7, have been obtained from the ethanolic extract of the fresh leaves of Moringa oleifera, employing a bioassay-guided isolation procedure. Their structures have been elucidated through spectroscopic (including 2D NMR techniques) and chemical methods. These compounds are mustard oil glycosides which are very rare in Nature and are also the first examples of naturally occurring thiocarbamates.

Synthesis of amido-ureas and the nature of caracasanamide, the hypotensive principle of Verbesina caracasana

Syntheses of the (E)-1 and (Z)-2 forms of 1-(3-methylbut-2-enyl)-3-{4-[3-(3,4-dimethoxyphenyl)-prop-2-enamido]butyl}urea, proposed structures for the natural hypotensive caracasanamide, have been carried out. The compounds were found not to be identical with the natural products, the structures of which have now been revised from containing a urea to containing a corresponding guan-idine segment. Using aminoiminomethanesulfonic acid or 3-methylbut-2-enylcyanamide as reagents, the synthesis can be diverted to caracasanamide 15(R = H) through an amine intermediate.

Hypotensive compounds isolated from alcohol extract of the unossified horn of Cervus elaphus L. var. xanthopygus Milne-Edwarg (Rokujo). I. Isolation of lysophosphatidyl choline as a hypotensive principle and structure-activity study of related compounds.

By the use of spontaneously hypertensive rats (SH rats) as a screening system, two hypotensive compounds were isolated from alcohol extract of the unossified horn of Cervus elaphus L. var. xanthopygus (Rokujo). One of the two compounds was identified as lysophosphatidyl choline (LPC). It was shown by gas chromatography that palmitic acid (C16 : 0) accounted for about half of the fatty acid content. Next, the effects of various LPCs on SH rats were examined. Eleven LPCs with C10 : 0 to C20 : 0 fatty acids were examined, and all except for those with C10 : 0 and C20 : 0 fatty acids showed the hypotensive effect (3 mg/kg, i.v.). In particular, C14 : 0 and C16 : 0-LPC showed rather potent activity. On the other hand, of the six LPCs with unsaturated fatty acids, only C16 : 1-LPC showed the hypotensive effect (3 mg/kg). It was concluded that at least a part of the hypotensive action of alcohol extract of Rokujo is due to LPC.

Isolation and identification of hypotensive principles in red-mold rice.

During an initial search for pharmacologically active principles in red-mold rice, two hypotensive compounds were isolated and identified. The active principles, A-3 and B-1, were fractionated and purified from the EtOH extract of red-mold rice prepared with Monascus pilosus through extraction with H2O, Amberlite CG-120 column chromatographies and high-performance liquid chromatography on an ODS column. A-3 was identified as acetylcholine chloride by comparison with an authentic sample, and B-1, colorless needles of mp 203-205 °C, was proved to be identical with authentic γ-aminobutyric acid. Intravenously administered A-3 (0.5 μg/kg) and B-1 (250μg/kg) produced potent depression of the carotid arterial blood pressure in spontaneously hypotensive rats, as did the corresponding authentic samples.

Hypotensive compounds isolated from the dried body of Naja naja Kaouthia Lesson. I. Isolation of inosine as a hypotensive principle and structure-activity study of related compounds.

From the dried body of Naja naja Kaouthia from which the internal organs had been removed, three hypotensive compounds were isolated and one of them was identified as inosine.Inosine produced a transient increase in blood pressure followed by a prolonged fall lasting for 30 min in spontaneously hypertensive rats. Next, the relationship between the chemical structure and the hypotensive effect was examined by studying ribose-modified derivatives of inosine. 2'-Deoxyinosine and 3'-deoxyinosine completely lacked hypotensive effect. Phosphorylation at the 3' or 5'-position except for inosine 5'-diphosphoribose and 5'-chloro-5'-deoxyinosine slightly decreased the hypotensive effect. The results indicate that the ribose configuration is important in relation to the hypotensive effect of inosine.

高脂血症および高血圧症の改善効果における栄養の意義と運動の影響

This study was designed to clarify the role of nutrition and physical exercise for preventing hyperlipidemia and hypertension.Sprague-Dawley strain rats were fed on a hypercholesterolemic diet containing 0.5% cholesterol and 0.25% Na cholate. Safflower oil suppressed hypercholesterolemia induced by dietary cholesterol when it was administered as the dietary source of fat. In contrast, administration of lard did not affect such hyperlipidemic state. Serum HDL cholesterol level had a tendency to increase in safflower oil group.Voluntary or forced exercise was loaded on the hypercholesterolemic rats. Both exercises significantly decreased serum triglyceride. Serum total cholesterol level was lowered by voluntary exercise rather than forced one. A reverse correlation was observed between serum total cholesterol and the running distance in voluntary exercise group when the animals were fed sucrose as carbohydrate source. The correlation was lower when starch or fructose was used in place of sucrose.Experiments were conducted to investigate the hypotensive principle (s) in Shii-ta-ke (Lentinus edodes) fruit bodies as well as in their mycelium on the blood pressure of spontaneously hypertensive rats (SHR). The extract of both fruit bodies and mycelia decreased the blood pressure of SHR. Safflower oil, Soya lecithin and highly purified eicosapentaenoic acid were tested in the same manner, and were found to exhibit obvious hypotensive activity.Healthy adult volunteers were supplied for 7 days several kinds of lipid-containing food. Combined administration of butter and eggs remarkably increased serum total cholesterol after 7 days, but single administration of each one did not. Blending oil of rice bran and safflower oil, in contrast, significantly decreased serum total cholesterol and increased HDL cholesterol.These results suggested a close relation between nutrition and exercise in the prevention of hyperlipidemia and hypertension.

Preliminary phytochemical studies of Combretodendron macrocarpum (P. beauv) keay with reference to its hypotensive principles

L'extrait aqueux de l'ecorce de Combretodendron macrocarpum est traditionnellement utilise pour le traitement de la constipation, des hemorroides et des maladies veneriennes et possede des proprietes abortives. Dans cette etude phytochimique les auteurs ont isole et identifie du β-sitesterol, du stigmasterol, de l'octacosan 1-ol et un acide gras dicarboxylique non sature (C16H2604)

Hypotensive principles of Uncaria hooks.

A methanol extract of the Oriental crude drug “chōtōkō”, Uncaria hooks, elicited a strong and long-lasting hypotension on injection into rats. The activity differed considerably from the effects expected for the known constituents, rhynchophylline and its analogues, which elicit only weak transient hypotensive effects. Fractionation of the extract, along with the pharmacological assays, resulted in isolation of three indole alkaloid glucosides, cadambine (1), 3α-dihydrocadambine (2) and 3β-isodihydrocadambine (3). The former (1) was found inactive but the latter two (2 and 3) exhibited strong and long-lasting hypotensive actions similar to the extract. 3β-Dihydrocadambine (4), which was not detected in the extract, also showed a strong hypotensive activity.

Structure of Mahuannin C, a Hypotensive Principle of Ephedra Roots

Structure of Mahuannin C, a Hypotensive Principle of Ephedra Roots