Stereochemical considerations in relation to the pharmacological activity of Pterotaberna alkaloids

Five 2-acylindole alkaloids, isolated from the leaves of Pterotaberna inconspicua, were pharmacologically investigated. The major alkaloids methuenine and 16-epimethuenine showed some interesting pharmacological features, whereas the minor alkaloids including 6-oxomethuenine and methuenine N-oxide were almost devoid of these pharmacological properties. Methuenine, being the most potent, was characterized as a non competitive antagonist against acetylcholine (pD'2=5.10 +/- 0.11) and histamine (pD'2 = 5.13 +/- 0.14) in guinea-pig ileum. Its potency was comparable to that of papaverine. 16-Epimethuenine behaved as a weak antihistaminic (pA2 = 6.55 +/- 0.08). The stereochemistry of both components is discussed in relation to their pharmacological activity.     

Hypoglycaemic effect of spergularia purpurea in normal and streptozotocin-induced diabetic rats

Single and repeated oral administration of the water extracts of Spergularia purpurea (SP) at a dose of 10 mg/kg were tested on hypoglycaemic activity in normal and streptozotocin-induced diabetic rats. In normal rats, the water extract of SP decreased significantly the plasma glucose levels 4 h after single oral administration (P<0.01), and one week after repeated oral administration (P<0.05). A significant decrease of plasma glucose levels was observed 6 h after a single oral administration of the water extract of S. purpurea in severe hyperglycaemic rats (n=6) from 22.78+/-0.60 to 11.21+/-0.49 mmol/l (P<0.001). On other hand, water extract of S. purpurea normalised plasma glucose levels after two weeks of repeated oral administration in diabetic rats; 24.05+/-1.16 versus 7.18+/-0.51 mmol/l (P<0.001) at the start and 2 weeks after water extract administration, respectively. We conclude that the water extract of SP induces hypoglycaemic activity when administered orally in normal and STZ diabetic rats. In order to determine the active principle (s) responsible of the hypoglycaemic effect, preliminary phytochemical analysis of the water extract has been investigated.     

Mechanisms of relaxant action of a crude hexane extract of Gnaphalium liebmannii in guinea pig tracheal smooth muscle

We investigated the mechanisms of action of Gnaphalium liebmannii which is used as a folk medicine in México for treating various respiratory diseases such as gripe, fever, asthma, cough, cold, bronchitis, expectorating, and bronchial affections. The tension changes of guinea pig tracheal segments were isometrically recorder on a polygraph. Hexane extract of Gnaphalium liebmannii was the most active relaxant extract (IC(30)=54.23+/-19.79 microg/mL with 99.5+/-3.2 % of relaxation), followed by dichloromethane extract (IC(30)=120.22+/-5.27 microg/mL) and methanol extract (IC(30)=190.25+/-30.02 microg/mL). Hexane extract produced a parallel rightward shift of the concentration-response curve of carbachol in a competitive manner (pA(2)=-2.4), but did not modify the concentration-response curves for histamine. The relaxant effect of hexane extract of Gnaphalium liebmannii was unaffected by the presence of propranolol (3x10(-6)M) or glibenclamide (10 microM). However hexane extract produced a leftward shifts of the concentration-response curve of forskolin (10(-8) to 10(-3)M), nitroprusside (10(-10) to 10(-6)M), isoproterenol (3x10(-10) to 3x10(-5)M) and aminophylline (10(-11) to 10(-2)M). The above results suggest that Gnaphalium liebmannii induce relaxation of the tracheal muscle, probably via phosphodiesterase inhibition. The bronchodilator effect of Gnaphalium liebmannii might explain in part their traditional use as anti-asthmatic remedy.     

Effects of Syzygium cordatum (Hochst.) [Myrtaceae] leaf extract on plasma glucose and hepatic glycogen in streptozotocin-induced diabetic rats

The present study investigates the hypoglycaemic effect of Syzygium cordatum (Hochst.) [Myrtaceae] leaf extract in non-diabetic and streptozotocin (STZ)-induced diabetic rats. Oral glucose tolerance tests (OGGT) were conducted in non-diabetic and STZ-diabetic rats using orally administered glucose (1.4 g 100 g(-1) body weight) followed by either the leaf extract (6 mg 100 g(-1) body weight) or subcutaneous (sc) injection of metformin (50 mg 100 g(-1)). Weekly plasma glucose and terminal hepatic glycogen concentrations were recorded in control STZ-diabetic rats and diabetic rats orally treated with the leaf extract once every third day for 4 weeks. Administration of the leaf extract decreased plasma glucose from 7.7+/-0.9 mmol l(-1) to 3.7+/-0.6 mmol l(-1) (n = 6), and 21.1+/-2.2 mmol l(-1) to 12.5+/-1.8 mmol l(-1) (n = 7) by 2 1/2 h in non-diabetic and STZ-diabetic rats, respectively. OGTT data in metformin-treated rats were similar at the corresponding time in all groups, except for significant blood glucose reduction by the drug in non-diabetic rats between 1 and 1 1/2 h after treatment. Oral administration of the extract did not affect plasma glucose concentration in STZ-diabetic rats after 4 weeks, although it significantly increased hepatic glycogen content by comparison with untreated STZ-diabetic rats (28+/-5 mg 100 g(-1) body weight, n = 7, versus 16+/-3 mg 100 g(-1) body weight, n = 6). We conclude that Syzygium cordatum leaf extract contains compounds that could be effective in mild diabetes mellitus or in cases of glucose tolerance impairment. The possible mechanism(s) involved in the short-term hypoglycaemic effect of the extract could not be established by the current study.     

Antihistaminic and mast cell stabilizing activity of Striga orobanchioides

The ethanolic and aqueous extracts of the whole plant of S. orobanchioides were evaluated for antihistaminic and mast cell stabilizing activities. Both extracts inhibited histamine-induced contractions of the guinea-pig ileum at the concentration range of 2.5-25 microg/ml in a dose-related manner. At 25 microg/ml, both extracts inhibited the response of histamine (0.5 microg/ml) almost completely. The effect of these two extracts on the degranulation rate of sensitized peritoneal cells of albino rats when challenged with antigen (horse serum) was studied. Triple vaccine was used as adjuvant. Ketotifen and prednisolone were used for comparison. The ethanolic extract at 100 and 200 mg/kg body weight was found to significantly inhibit degranulation of mast cells to an extent of 52.14+/-3.24 and 67.96+/-3.70%, respectively. At the same doses, the aqueous extract showed 42.09+/-2.91 and 60.67+/-3.50% reduction in degranulation of mast cells, respectively. Hence, both extracts markedly protected the rats against antigen-induced challenge of mast cells.     

The Effect of Carum Copticum Extract on Acetylcholine Induced Contraction in Isolated Rat's Ileum

AimsThere are many biological investigations for determining an effective cure for the dysfunction of gastrointestinal tracts, using herbal medicine. It has been reported that Carum Copticum is a bactericidal agent and possesses anticholinergic, antihistaminic and b-adrenergic stimulatory effects in some tissues. However, these effects of Carum Copticum on mechanical activities of isolated intestine are not clearly identified yet. The present study has been designed to find out the specific effects of Carum Copticum on mechanical activity of isolated rat's ileum.Materials and MethodsIn this study rat's ileum contraction was recorded through an isolated tissue chamber in an organ bath by using isotonic transducer and oscillographic device. The effect of Carum Copticum extract on acetylcholine induced contraction in isolated rat's ileum was evaluated.ResultsOur findings showed that 1% aqueous extract of Carum Copticum reduces the basal contractile activity of rat's ileum. The extract also reduced acetylcholine induced contraction to 40% of its maximum response. The inhibitory action of Carum Copticum extract on acetylcholine induced contraction was similar but slower than that of atropine sulfate.ConclusionThe results of this study showed an inhibitory effect of Carum Copticum extract on acetylcholine induced contraction in rat's ileum.     

Effects of an aqueous extract of Ferula ovina on rabbit and guinea pig smooth muscle

The effects of an aqueous extract of Ferula ovina were tested in vitro using isolated segments of rabbit and guinea pig intestine, trachea and aorta. The extract inhibited the spontaneous movements of rabbit jejunum and guinea pig ileum and the contractions induced by acetylcholine. The aqueous extract also inhibited the contractions of rabbit trachealis muscle induced by acetylcholine and the contractions of guinea pig trachealis muscle induced by histamine. These inhibitions were dose-dependent and reversible. However, the aqueous extract did not inhibit the contractions of rabbit and guinea pig aortic rings induced by norepinephrine. These data suggest that this plant has non-specific anticholinergic and antihistaminic antispasmodic effects.     

Cardiovascular effects of an extract from the roots of a shrub Elaeophorbia drupifera.

A crude extract was prepared from the roots of E. drupifera. Lethality studies in mice showed a dose-mortality relationship with an LD(50) of 145 mg/kg mice i.p. The extract (2-260 microg/kg. i.v.) was tested in graded doses on the blood pressure and heart rate of urethane anaesthetized rats. The results showed that the extract decreased both the blood pressure and heart rate in a dose-dependent manner. The maximum decrease in blood pressure (control, 78.3 +/- 6. 5 mmHg) and heart rate (control, 120.2 +/- 5.5 beats/min) produced by the extract was about 46.2% and 41.7% (% control), respectively. Blocking the beta adrenoceptors with propranolol (0.5 microg/kg. i.v. ) did not prevent the action of the extract on both the blood pressure and heart rate, suggesting that the extract was acting at a different site. This view was supported by the observation that the extract significantly depressed the increase in blood pressure and heart rate caused by bilateral occlusion of the common carotid artery. Also, the extract was found to prolong ACh-induced hypotension in the rats. In animals pretreated with atropine sulphate (0.2 mg/kg. i.v), the extract was less effective in depressing the blood pressure. However, this atropine antagonism was surmounted by raising the concentration of the extract. Finally, in vitro studies using isolated arterial strips revealed that the extract also had a relaxant effect on vascular smooth muscle. This relaxant effect was dose-dependent and was attenuated and/or abolished by phentolamine (0.5 microg/mL). Also, the extract relaxed aortic strips precontracted with noradrenaline (1 x 10(-7) mol L(-1)) but failed to relax strips precontracted with KCl (50 mmol/L). We conclude that the crude extract from the roots of E. drupifera probably contains acetylcholine-like agent(s) which interferes with the cholinergic mechanism, as well as catecholamine-like agent(s) exhibiting mainly alpha-adrenoceptor activity.     

Tannins and catechin gallate mediate the vasorelaxant effect of Arbutus unedo on the rat isolated aorta

This study examined the vascular effect of Arbutus leaves (aqueous extract) and described the isolation of several fractions responsible for their vasorelaxant activity. The aqueous extract (AE) of leaves was tested on rat aortic rings precontracted with 0.1 microm noradrenaline. At 10(-2) g/L, AE produced an endothelium dependent relaxation of 66% +/- 5%, (n = 8). The leaves of Arbutus were then extracted successively with different solvents and the methanol extract was the most active. When tannins (primarily condensed tannins) were precipitated from the methanol extract, they showed a strong vasorelaxant activity (87% +/- 4%, n = 5), whereas the elimination of tannins in the methanol extract reduced significantly its vasorelaxant activity (42% +/- 8%, n = 8, p < 0.005). The methanol extract was further separated semi-preparatively by reversed-phase HPLC. Four fractions (Fr2, Fr3, Fr4 and Fr6) were the most active and produced 88% +/- 2% (n = 5), 75% +/- 6% (n = 5), 76% +/- 3% (n = 7) and 77% +/- 3% (n = 10) relaxation, respectively. These four fractions mainly correspond to polyphenol compounds. Analysis of Fr6 indicated that this fraction contained catechin gallate. In conclusion, the vasorelaxant activity of Arbutus is likely to be due to polyphenol compounds, primarily condensed tannins and catechin gallate.     

Assessment of the effect of Maytenus ilicifolia (espinheira santa) extract on the labeling of red blood cells and plasma proteins with technetium-99m

We are trying to develop a model to assess properties of products utilized in popular medicine. Maytenus ilicifolia is used in herbal medicine. Red blood cells (RBC) labeled with technetium-99m (99mTc) are employed in nuclear medicine. This labeling procedure depends on a reducing agent and stannous chloride is used. There is evidence that this labeling may be altered by drugs. We have investigated the possibility of M. ilicifolia extract being capable to alter the labeling of blood elements with 99mTc. Blood was incubated with M. ilicifolia extract. Stannous chloride solution and Tc-99m were added. Blood was centrifuged and plasma (P) and blood cells (C) were isolated. Samples of P or C were also precipitated, centrifuged and insoluble (IF) and soluble (SF) were separated. The percentages of radioactivity (%ATI) in C, IF-P and IF-C was calculated. The %ATI decreased on C from 93.6+/-2.3 to 29.0+/-2.7, on IF-P from 77.6+/-1.2 to 7.5+/-1.0 and on IF-C from 80.0+/-3.4 to 12.6+/-4.8. Once in RBC labeling procedure with 99mTc depends on the presence of stannous (+2) ions, the substances of the M. ilicifolia extract could increase the valence these ions to stannic (+4). This fact would decrease the %ATI on blood elements and indicate the presence of oxidant agents in the M. ilicifolia extract.