Cardiotonic and sedative effects of Cecropia pachystachya Mart. (ambay) on isolated rat hearts and conscious mice

Cecropia pachystachya Mart. is popularly called "ambay" and extensively used in herbal medicine of South America for cough and asthma. In Argentina it grows in neotropical rainforest (Ntr C.p.) and in a temperate region (Tp C.p.). In a previous work we showed their hypotensive properties with different potency and toxicity, and now we studied the Tp C.p. effects in isolated heart from rats and central effects of both plants on the open-field test for mice. Tp C.p. produced a positive inotropic effect on isolated rat hearts, which was not affected by 1 microM propranolol, suggesting that it is not due to a beta-adrenergic effect. In contrast, it was prevented by pretreatment with high [K](o) media, which stimulates the Na,K-ATPase pump, suggesting an inhibition of the pump by "ambay", as digital do. In the open-field test, both Ntr C.p. and Tp C.p. similarly decreased the spontaneous locomotion and exploratory behavior of mice at doses between 180 and 600 mg/kg. Ntr C.p. potentiated the effect of 3 mg/kg diazepam to one similar to 10 mg/kg diazepam, but was not antagonized by 0.5 mg/kg flumazenil. Amphetamine at 5 mg/kg prevented the sedative effect of Ntr C.p. Chromatographic analysis showed that both plants have a qualitatively similar fingerprint but quantitatively differed in at least three components. Although the purpose was not to identify them, both plants have at least 10 compounds. Two of them were in higher amount in Tp C.p. than in Ntr C.p., and then, they could be responsible for the cardiovascular toxicity of Tp C.p. In conclusion, the results suggest that ambay has cardiotonic and sedative properties. The sedative effect could be useful in cough treatment. The extract resulted additive to benzodiazepines but it did not bind to the same site on GABA-A receptor, and it was interfered by the dopamine release produced with amphetamine.     

Pharmacological basis for the empirical use of Eugenia uniflora L. (Myrtaceae) as antihypertensive.

The rational basis for the use of Eugenia uniflora L. (Myrtaceae) as antihypertensive in Northeastern Argentina was assessed in normotensive rats. Intraperitoneal administration of the aqueous crude extract (ACE) decreased blood pressure (BP) of normotensive rats dose-dependently until 47.1 +/- 8.2% of control. The effective-dose 50 was 3.1 +/- 0.4 mg dried leaves/kg (d.l./kg) (yielding of ACE: 17% w/w). To determine the origin of hypotensive activity. Alpha-adrenergic antagonistic and vasorelaxant ACE activities were tested. The dose-response curve for phenylephrine on BP was inhibited non-competitively until 80% of its maximal effect (at 8 mg d.l. ACE/kg). Perfusion pressure (PP) of rat hindquarters (previously vasoconstricted by high-K+) was decreased by ACE in a concentration-dependent manner until -32.3 +/- 11.5% of tonic contraction at 1.2 g d.l. ACE/100 ml. In addition, A.C.E demonstrated diuretic activity at a dose (120 mg d.l./kg) higher than the hypotensive one. It was almost as potent as amiloride, but while amiloride induced loss of Na+ and saving of K+, ACE induced decrease in Na+ excretion. The results suggest that the empirical use of Eugenia uniflora L. (Myrtaceae) is mostly due to a hypotensive effect mediated by a direct vasodilating activity, and to a weak diuretic effect that could be related to an increase in renal blood flow.     

The aqueous extract of Terminalia superba (Combretaceae) prevents glucose-induced hypertension in rats

Aim of the study

The stem bark of Terminalia superba (Combretaceae) (TS) is used in traditional Cameroonian medicine as antihypertensive remedy. The aim of this study was to investigate the hypotensive and the antihypertensive effects of the aqueous extract of the stem bark of Terminalia superba.

Materials and methods

Hypertension was obtained in rats by oral administration of 10% d-glucose for 3 weeks. The acute effects of Terminalia superba were studied on blood pressure (BP) and heart rate (HR) after intravenous administration in normotensive rats (NTR) and glucose hypertensive rats (GHR). The antihypertensive effects were studied after oral administration of the extract (50 and 100 mg/kg/day) or nifedipine (10 mg/kg/day) for 3 weeks. At the end of the experiment, BP and HR were measured and reduced glutathione (GSH), malondialdehyde (MDA) and superoxide dismutase (SOD) activity levels were measured in heart, aorta, liver and kidney.

Results

Intravenous administration of the aqueous extract of Terminalia superba induced a significant hypotensive response without any change in HR. The hypotensive effect of the extract was unaffected by atropine or propranolol but decreased by reserpine (5 mg/kg) and yohimbine (0.1 mg/kg). In addition, the oral administration of the extract significantly prevented the rise in BP in glucose-hypertensive rats. Finally, the treatment with plant extract significantly blunted the decrease in GSH and the increase in MDA levels associated with hypertension, and significantly prevents the increase in aortic SOD activity.

Conclusions

The present study demonstrates that the aqueous extract of the stem bark of Terminalia superba exhibits hypotensive and anti-hypertensive properties that are, at least in part, related to a withdrawal of sympathetic tone and to an improvement of the antioxidant status, respectively. Overall data validate the use of Terminalia superba as antihypertensive therapy in traditional medicine.     

Antidotal effect of Stenoloma chusanum(L.) Ching against arsenic and ammonium

The antidotal effect of four extracts from Stenoloma chusanum on acute poisoning of mice caused by arsenic and ammonium chloride was observed. The result shows: extracts B and C can reduce the mortality of mice remarkably, while extract C can raise the tolerance of mice by raising their LD50 from 31.1 +/- 4.3 mg/kg to 38.2 +/- 5.9 mg/kg. In the case of the mice poisoned by ammonium chloride, the four extracts can also reduce the mortality, but make no significant difference as compared with the control group statistically (P greater than 0.05).     

Isolation of hypotensive compounds from Solanum sisymbriifolium Lam

The crude hydroalcoholic root extract (CRE) of Solanum sisymbriifolium Lam. has formerly been shown to have hypotensive activity both in normo-and hypertensive rats. Hypotensive activity-guided fractionation of the CRE was performed in anaesthetized normotensive rats, which led to the isolation of the active principles. The intravenous (i.v.) and intraperitoneal (i.p.) values of the CRE in mice were found to be, respectively, 343 and 451 mg/kg, and no lethal effect was caused by doses up to 5.0 g/kg when administered by oral route. Depression of locomotion, increase of breathing rate and piloerection was observed in a general behavior test with doses up to 200 mg/kg i.p., and 1000 mg/kg p.o., respectively. Increase in the gastrointestinal transit was found using 0.1 g/kg, whereas at doses of 0.5 and 1 g/kg, no significant activity was observed in comparison with the control mice. Hexanic and butanolic fractions induced a remarkable hypotension in anaesthetized normotensive rats in doses of 1, 5, 7.5 and 10 mg/kg i.v. Two compounds isolated from the butanolic fraction induced a significant decrease of the blood pressure, HR, amplitude of the ECG and breathing rate when injected in a dose of 1 mg/kg i.v; and both systofic and diastolic, blood pressures were affected in a proportional mode. The hypotensive effect of the two compounds were not influenced by pretreatment with atropine and propranolol; and the pressor response to noradrenaline was not affected by any of them which suggests that neither a direct muscarinic activity, β-adrenoceptor activation nor decrease of sympathetic vascular tone (sympatholitic activity) are probably involved in the mechanism of hypotension. The present study shows that the CRE of S. sisymbriifolium contains at least two hypotensive compounds whose characterization is under way.     

Autonomic nervous system mediates the cardiovascular effects of Rhodiola sacra radix in rats

ETHNOPHARMACOLOGICAL RELEVANCE: Rhodiola sacra (Crassulaceae) exhibits cardiovascular bioactivities and is used in Tibetan medicine for promoting circulation and preventing hypertension. However, the underlying mechanisms of its cardiovascular effects are poorly understood. AIM OF THE STUDY: The aim of this study was therefore to evaluate the cardiovascular activity of water-soluble fraction (WtF) and n-butanol-soluble fraction (BtF) of Rhodiola sacra radix and to explore its mechanism of action in propofol anesthetized Sprague-Dawley rats. MATERIALS AND METHODS: The changes of blood pressure, heart rate and cardiac contractility after systemic administration of the extracts (10-75mg/kg) were examined for at least 40min. Different antagonists were used to evaluate the mechanisms of cardiovascular effects of the extracts. RESULTS: Intravenous injection of the WtF (10, 25, 35, 50 or 75mg/kg) exhibited dose-dependent hypotension and increases in heart rate and cardiac contractility. In contrast, mild alterations in the same cardiovascular parameters were detected only at high dose (75mg/kg) BtF. The WtF-induced hypotensive, positive inotropic and chronotropic effects were significantly abolished by pretreatment with hexamethonium (30mg/kg, i.v.) or reserpine (5mg/kg, i.v.), whereas the hypotensive, but not the positive inotropic or chronotropic effect was potentiated by captopril (2.5mg/kg, i.v.). Pretreatment with methylatropine (1mg/kg, i.v.), on the other hand, reversed the positive inotropic and chronotropic but not the hypotensive effects of WtF. The WtF-induced cardiovascular responses were not affected in rats pretreated with N(G)-nitro-l-arginine methyl ester (20mg/kg, i.v.). CONCLUSIONS: We conclude that systemic administration of the WtF of Rhodiola sacra radix elicited a potent hypotensive effect that was mediated by the withdrawal of sympathetic vasomotor tone and interaction with the circulatory angiotensin system. The positive inotropic and chronotropic effects of WtF may result from a direct vagal inhibition on the heart.     

Effect of a diterpenoid from Salvia cinnabarina on arterial blood pressure in rats

The effect of a diterpenoid isolated from Salvia cinnabarina, 3,4-seicosopimar-4(18),7,15-triene-3-oic acid (SCB), on arterial blood pressure was evaluated in anaesthetized rats. Male Wistar rats, anaesthetized with urethane (sol. 10% p/v; 10 mL/kg), underwent surgery for continuous monitoring of arterial blood pressure. After preliminary experiments to evaluate the dose response (3, 10 and 30 mg/kg i.v.) of SCB, a dose of 3 mg/kg was chosen for all successive experiments. On different groups of rats treated with the ganglion-blocking agent chlorisondamine (2.5 mg/kg i.p.) the effect of SCB (3 mg/kg i.v.) was evaluated before and following an infusion of the nitric oxide synthase inhibitor L-NAME (0.3 mg/kg/min i.v.). Intravenous administration of SCB at doses of 3, 10 and 30 mg/kg led to a fall in mean arterial blood pressure (MABP) of 14.75 +/- 1.44 mmHg, 36.60 +/- 31.40 mmHg and 31.40 +/- 6.28 mmHg, respectively (n = 4-5), that was not modified by treatment of the rat with chlorisondamine nor with L-NAME. The results demonstrate a hypotensive effect of SCB - due to a peripheral mechanism but independent of endothelial nitric oxide release.     

Inhibitory effects of Santolina chamaecyparissus extracts against spasmogen agonists

Several extracts of Santolina chamaecyparissus ssp. squarrosa antagonized in a concentration-dependent way the contractions of rat duodenum, guinea-pig ileum, rat vas deferens and rat uterus as induced by acetylcholine, histamine, noradrenaline, oxytocin and serotonin. Polar extracts were less active than apolar extracts, and it was necessary to assay the former at higher concentrations. Only the lyophilized aqueous extract produced a slight hypotensive effect when given intravenously at 150 mg/kg to urethananesthetized rats.     

C-fiber-evoked autonomic cardiovascular effects after injection of Piper betle inflorescence extracts

Piper betle inflorescence extracts contain eugenol (6.2%) and safrole (78.9%). Intravenous injections of water extracts of P. betle inflorescence (PBE), eugenol, and safrole in rats induced hypotensive and bradycardiac effects, whereas both intraarterial and intrathecal injections of PBE, eugenol and safrole resulted in hypotensive and tachycardiac effects. Moreover, the effects of intravenous injections of PBE were reversed or inhibited by the pretreatment with bilateral vagotomy, atropine (1 mg/kg, i.p.) and capsaicin (100 mg/kg, s.c.). Effects of intraarterial injections of PBE on blood pressure were inhibited by the pretreatment with substance P (SP) antagonist (1 nmol, i.t.) and clonidine (2.5 μg, i.t.), while heart rate was only inhibited by the pretreatment with SP antagonist (1 nmol, i.t.). In addition, the tachycardia resulting from intrathecal injections of PBE was inhibited by pretreatment with propranolol (0.3 mg/kg, i.v.). Eugenol and safrole induced the same pattern on blood pressure and heart rate changes as PBE in rats after various treatments. This report suggests that acute administration of betel inflorescence extracts by different routes may activate C-fiber-evoked parasympathetic and sympathetic cardiovascular reflexes in rats.     

Activation of nitric oxide signaling pathway mediates hypotensive effect of Muntingia calabura L. (Tiliaceae) leaf extract

The cardiovascular effect of the crude methanol extract from the leaf of Muntingia calabura L. (Tiliaceae) was investigated in the anesthetized rats. The crude methanol extract was sequentially fractionated to obtain the water-soluble extract (WSE). Intravenous administration of the WSE (10, 25, 50, 75 or 100 mg/kg) produced an initial followed by a delayed decrease in systemic arterial pressure (SAP) in a dose-dependent manner. The M. calabura-induced initial hypotension lasted for 10 min and the delayed depressor effect commenced after 90 min and lasted for at least 180 min post-injection. The same treatment, on the other hand, had no appreciable effect on heart rate (HR) or the blood gas/electrolytes concentrations. Both the initial and delayed hypotensive effects of WSE (50 mg/kg, i.v.) were significantly blocked by pre-treatment with a nonselective nitric oxide (NO) synthase (NOS) inhibitor, N(G)-nitro-L-arginine methyl ester ((L)-NAME, 0.325 mg/kg/min for 5 min) or a soluble guanylate cyclase (sGC) inhibitor, 1H-[1,2,4]oxadiazole[4,3-alpha]quinoxalin-1-one (ODQ, 0.2 mg/kg/min for 5 min). Moreover, whereas the initial depressor effect of WSE was inhibited by pre-treatment with a selective endothelial NOS (eNOS) inhibitor, N5-(1-Iminoethyl)-L-ornithine ((L)-NIO, 1 mg/kg/min for 5 min), the delayed hypotension was attenuated by a selective inducible NOS (iNOS) inhibitor, S-methylisothiourea (SMT, 0.5 mg/kg/min for 5 min). Administration of WSE also produced an elevation in plasma nitrate/nitrite concentration, as well as an increase in the expression of iNOS protein in the heart and thoracic aorta. These results indicate that WSE from the leaf of M. calabura elicited both a transient and delayed hypotensive effect via the production of NO. Furthermore, activation of NO/sGC/cGMP signaling pathway may mediate the M. calabura-induced hypotension.     

Saponins from the leaves of Musanga cecropioïdes (cecropiaceae) constitute a possible source of potent hypotensive principles

The aqueous leaf extract and saponins extracted from the aqueous leaf extract of Musanga cecropioïdes exhibited potent hypotensive effects in both normotensive and hypertensive rats. The intravenous administration (direct invasive blood pressure study technique) of 15–30 mg/kg body weight of the aqueous leaf extract produced a fall in blood pressure (BP) of 35%–57% in hypertensive rats and 27% in normotensive individuals. This BP fall was followed by a transient rise, while saponins extracted from the aqueous extract of the leaves of MC produced a fall in BP of 55% in hypertensive and 30% in normotensive rats. In the indirect (tail cuff) blood pressure study, the effect was also dose-dependent. The oral administration of 300 mg/kg body weight of the aqueous leaf extract produced a BP fall of over 30% by 12 h following extract administration while the saponins (0.02–0.8 mg/kg body weight) produced a fall of 10% to 53%.     

Pharmacological studies on hypotensive, diuretic and vasodilator activities of chrysin glucoside from Calycotome villosa in rats

The present study was undertaken in normotensive anaesthetized male rats that received a continuous perfusion of a chrysin glucoside isolated from the flowers and leaves of Calycotome villosa subsp intermedia at a dose of 2.5 mg/kg, or furosemide (control diuretic) at a dose of 0.5 mg/kg. Compared with the control rats receiving NaCl (0.9%), the urine flow, glomerular filtration and electrolyte excretion (Na+, K+) increased significantly in rats treated with chrysin glucoside (p < 0.001). A similar effect was observed in the rats perfused with furosemide. Intravenous injections of bolus doses (1-3 mg/kg) of the chrysin glucoside to anaesthetized rats elicited an immediate and dose-dependent decrease in mean arterial blood pressure (MABP). Pretreatment of the rats with the nitric oxide synthase inhibitor, l-NOArg (10 mg/kg), reduced partially, but significantly (p < 0.01), the maximal decrease in MABP elicited by chrysin glucoside. In the rat isolated aorta preparation, chrysin glucoside (10-100 microm) inhibited in a concentration-dependent manner the noradrenaline (1 microm) induced contractions (IC(50) = 52 microm). This relaxant activity of chrysin glucoside was significantly reduced by incubation of the endothelium-intact rings with l-NOArg (100 microm), (80 +/- 4.7% vs 48 +/- 5.06% in the absence of L-NOArg). In conclusion, these results demonstrate a diuretic and hypotensive action of a chrysin glucoside from Calycotome villosa in anaesthetized rats and indicating an action on renal function, and an active vascular relaxation mediated partially through nitric oxide release.     

Effect of Tulbaghia violacea on the blood pressure and heart rate in male spontaneously hypertensive Wistar rats

Ethnopharmacological relevance

Tulbaghia violacea Harv. (Alliaceae) is a small bulbous herb which belongs to the family Alliaceae, most commonly associated with onions and garlic. In South Africa, this herb has been traditionally used in the treatment of various ailments, including fever, colds, asthma, paralysis, hypertension and stomach problems. The aim of this study was to evaluate the effect of methanol leaf extracts (MLE) of Tulbaghia violacea on the blood pressure (BP) and heart rate (HR) in anaesthetized male spontaneously hypertensive rats; and to find out the mechanism(s) by which it acts.

Materials and methods

The MLE of Tulbaghia violacea (5–150 mg/kg), angiotensin I human acetate salt hydrate (ang I, 3.1–100 μg/kg), angiotensin II human (ang II, 3.1–50 μg/kg), phenylephrine hydrochloride (phenylephrine, 0.01–0.16 mg/kg) and dobutamine hydrochloride (dobutamine, 0.2–10.0 μg/kg) were infused intravenously, while the BP and HR were measured via a pressure transducer connecting the femoral artery and the Powerlab.

Results

Tulbaghia violacea significantly (p < 0.01) reduced the systolic, diastolic, and mean arterial BP; and HR dose-dependently. Ang I, ang II, phenylephrine and dobutamine all increased the BP dose-dependently. The hypertensive effect of ang I and the HR-increasing effect of dobutamine were significantly (p < 0.01) decreased by their co-infusion with Tulbaghia violacea (60 mg/kg). However, the co-infusion of ang II or phenylephrine with Tulbaghia violacea (60 mg/kg) did not produce any significant change in BP or HR when compared to the infusion of either agent alone in the same animal.

Conclusions

Tulbaghia violacea reduced BP and HR in the SHR. The reduction in BP may be due to actions of the MLE on the ang I converting enzyme (ACE) and β₁ adrenoceptors.     

泽泻汤对小鼠血压作用的实验研究

目的 研究泽泻汤对正常小鼠血压的影响及其特点.方法 采用清醒状态下小鼠尾动脉间接测压法,分别测定泽泻汤Ⅰ、Ⅱ、Ⅲ、Ⅳ 4个剂量组腹腔注射给药前后不同时间点的血压和心率.结果 泽泻汤Ⅱ、Ⅲ、Ⅳ 3个剂量组(给药量依次为90,180,360 mg/kg)对正常血压小鼠具有显著降压作用(P< 0. 05).泽泻汤的降压效果与剂量之间在给药10 min和30 min时呈现出较好的量效相关性.同时还观察到泽泻汤Ⅳ剂量组(给药量为360 mg /kg)具有一定的减慢心率作用.结论 泽泻汤对正常血压小鼠有降压作用,并有一定的药物量效关系,同时具有一定的减缓心率作用.该结果为今后深入的研究泽泻汤降压药效评价和作用机制奠定了基础.     

Hypoglycemic effect and chlorogenic acid content in two Cecropia species

The hypoglycemic effect of methanol leaf extracts from Cecropia obtusifolia and C. peltata was evaluated in healthy mice. A significant decrease (p < 0.05) in plasma glucose levels was recorded 2 and 4 h after a single oral administration of methanol extracts (1 g/kg). This effect was correlated with the chlorogenic acid contents in both species; C. peltata, containing 19.84 +/- 1.64 mg of chlorogenic acid/g of dried leaves produced the highest decrease (D(alpha 2,60) = 20.18, p < 0.05) of plasma glucose levels (52.8%). The extracts of C. obtusifolia from Tabasco and Veracruz, showed similar hypoglycemic effects (33.3% and 35.7%, respectively) and chlorogenic acid contents (Tukey(0.05) = 1.8859) (13.3 +/- 3.2 mg/g and 13.1 +/- 1.6 mg/g, respectively). The hypoglycemic effect produced by different doses (0.1, 0.25, 0.50, 0.75 and 1 g/kg body wt, p.o.) of C. peltata showed a lineal relationship with chlorogenic acid content, reaching an ED(50) = 0.540 g/kg body wt for extract, and an ED(50) = 10.8 mg/kg body wt for chlorogenic acid. These results suggest that C. peltata is a better hypoglycemic agent than C. obtusifolia, and it could be considered for developing a phytomedicinal product to carry out clinical trials.     

Behavioural effects of Visnea mocanera extract: Psychostimulant and anxiogenic properties

Neuropharmacological studies were conducted in mice with different extracts from the leaves and fruits of Visnea mocanera L. f. (Theaceae). The combined data obtained from all biological models suggest that the methanol extract from the leaves and the syrup from the fruits appear to have a psychostimulant action, since these extracts increased locomotor activity (the methanol extract at 250 mg/kg p.o.), reduced pentobarbital-induced sleeping time (the methanol extract and syrup at 250 mg/kg p.o.) and produced hyperthermia (the syrup at 250 and 500 mg/kg p.o.). The aqueous fraction (250 and 500 mg/kg p.o.) and syrup (500 mg/kg p.o.) from fruits showed an anxiogenic-like profile in mice when evaluated acutely in the elevated plus-maze test.     

Pharmacological effects of Eugenia uniflora (Myrtaceae) aqueous crude extract on rat's heart

The effect of aqueous crude extract (ACE) of Eugenia uniflora L. (Myrtaceae) was studied on rat's perfused ventricles. This plant is used in South American traditional medicine as an antihypertensive and we already demonstrated previously its hypotensive properties. In this paper, maximal left intraventriclular pressure (P) of rat's hearts beating at 0.2 Hz firstly increased to 162.1+/-11.1% of basal value during 1-3 min of perfusing ACE 0.6%. Maximum rate of contraction (+P) also increased to duplicating +P/P ratio. Both types of effect were significantly decreased by either propranolol 0.35 microM, and pre-treatment with reserpine (5 mg/kg), suggesting that they were caused by a compound that releases cathecolamines with beta-adrenergic action. Nevertheless, after 20 min of perfusing ACE, ventricles decreased P to about 50% of their basal value, suggesting a negative-inotropic compound present in the extract. The perfusion of 1.2% ACE decreased P in a pressure-[Ca](o) curve (0.5-2 mM) in a non-competitive manner, suggesting that an irreversible Ca-blocking compound is also present in the extract. In summary, E. uniflora ACE has a dual effect on the heart related to its hypotensive action and is probably responsible for the therapeutic or adverse effects in patients under cardiac risk.     

Marjoram increases basal gastric acid and pepsin secretions in rat

Considering the high consumption rate of marjoram in the Iranian population, this study was designed to investigate the effects of marjoram extract on gastric acid and pepsin secretion. In this study, Wistar rats (n=12) were divided into two equal case and control groups. Under general anaesthesia with 50 mg/kg i.p. sodium thiopental, laparatomy was done and a cannula inserted in the duodenum. In the case animals marjoram (12.5 mg/kg) was injected into the stomach through the mentioned cannula. The gastric contents were collected by the wash-out technique. Acid and pepsin secretions were then measured by titration and the Anson method, respectively. In the marjoram group, basal acid and pepsin secretions were significantly increased compared with the control group (acid: 20+/-3.36 vs 4.1+/-0.36 micromol/15 min; pepsin: 9.04+/-0.01 vs 5.62+/-0.12 microg/15 min; p<0.001). In the control group, pentagastrin stimulation increased acid secretion in comparison with the basal level (10.14+/-1.34 vs 4.1+/-0.36 micromol/15 min, p<0.001), while in the marjoram group, there was a significant decline (16.46+/-3.23 vs 20+/-3.36 micromol/15 min, p<0.001). In the marjoram group pentagastrin increased pepsin secretion in comparison with the basal state (12+/-0.11 vs 9.04+/-0.1 microg/15 min, p<0.001). It seems that marjoram contains some components that activate chief and parietal cells and increase basal acid and pepsin secretion.     

Synergistic effect of methanol extract of Abies webbiana leaves on sleeping time induced by standard sedatives in mice and anti-inflammatory activity of extracts in rats

During the determination of LD50 values of extracts of Abies webbiana, it was observed that the methanol extract (MEAW) produces sedation of animals. This led to investigation of the effect of MEAW on sleeping time in mice. When various doses of the methanol extract (100, 150, and 200 mg/kg body weight) were administered alone, no hypnotic activity was observed. However, these exhibited significant synergistic effects (P < 0.001) at those dose levels in mice when administered prior to the administration of standard sedatives (pentobarbitone sodium: 50 mg/kg and diazepam: 6 mg/kg, respectively). In addition anti-inflammatory effects of methanol, chloroform, and petroleum ether extracts of Abies webbiana leaves in rats were performed to assess scientific validity of the medicinal claim of Indian folk medicine. The effects of leaf extracts (methanol, chloroform, and petroleum ether) against inflammation were studied by carrageenan-induced paw edema model in rats. The methanol extract (400 mg/kg p.o.) of leaves of Abies webbiana showed the best significant anti-inflammatory activity as compared to that of diclofenac sodium (150 mg/kg p.o.). The LD50 values of methanol, chloroform, and petroleum ether extracts were found to be 986, 1387, and > 3200 mg/kg, respectively. Thus, the therapeutic index of methanol extract may be favorable to open a new vista on combination therapy of hypnotics and may also against inflammation.     

Anti-tumor effects of water-soluble propolis on a mouse sarcoma cell line in vivo and in vitro

The honeybee product propolis and its extracts are known to have biological effects such as antibiotic, anti-viral, anti-inflammatory and anti-tumor activities. This study was designed to investigate whether water-soluble propolis (WSP) inhibits tumor growth. The tumor cell line used was mouse sarcoma 180 (S-180), and its growth was determined in vitro and in vivo with exposure to different concentrations of WSP. The effects of WSP on tumor cells in vitro were evaluated by measuring the intracellular uptake of 3H-thymidine. 3H-thymidine uptake was inhibited in accordance with the concentration of WSP. The minimum concentration of WSP necessary for 3H-thymidine uptake inhibition was 1.0 microg/ml and uptake was suppressed to 88% of the level in non-treated cells at this concentration. In an experiment using tumor-bearing mice, oral administration of WSP was begun 24 hours after transplantation of S-180 cells. WSP was administered to the mice 5 times, every other day for 10 days. The doses were 320 mg/kg (10 mg/mouse) or 960 mg/kg (30 mg/mouse) of body weight. All mice were sacrificed 10 days after transplantation, and tumor growth was evaluated. The orally administered WSP significantly inhibited the growth of transplanted tumors (p < 0.05). Furthermore, histological findings revealed a significant reduction in mitotic cells and tumor invasion of the muscular tissue at both dose-levels of WSP.