Terminalia arjuna,an ayurvedic cardiotonic,increases contractile force of rat isolated atria

The direct effects of aqueous, ethanolic, chloroform and petroleum ether extracts of Terminalia arjuna (family: Combretaceae) bark, an ayurvedic remedy for cardiovascular disorders, were studied on isolated atria of rats. The aqueous extract produced a substantial positive inotropic effect (EC₅₀ = 0.25 mg/mL) but no change in the rate. The ethanol, chloroform and petroleum ether extracts all decreased the rate of contraction. A slight increase in force was seen with ethanol and chloroform extracts. Higher concentrations of the chloroform extract had a negative inotropic effect. The ethanol extract decreased the maximum following frequency of the left atria. It is concluded that Terminalia arjuna has a significant positive inotropic property on rat atria in vitro which could contribute to its efficacy in treating cardiovascular disorders.     

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.     

Effects of an aqueous extract of Terminalia arjuna on isolated rat atria and thoracic aorta

Terminalia arjuna (Combretaceae) is used traditionally in ayurveda, to treat a variety of cardiovascular disorders. The aims of this study were to characterize the positive inotropic effect of the aqueous extract of T. arjuna bark in isolated paced rat left atria and to study its effects on a vascular smooth muscle preparation, the rat thoracic aorta. The crude and semipurified aqueous extracts produced a positive inotropic effect of rat atria and the maximum contraction was comparable to that produced by isoprenaline. The positive inotropic effect of the extract was completely blocked by a β-adrenoceptor blocker, propranolol, and an uptake-1 blocker, cocaine. In precontracted aorta, the aqueous extract produced a contraction followed by relaxation. Propranolol did not block the relaxant effect of the aqueous extract. It is concluded that the positive inotropic effect of the aqueous extract was mediated via an action on β₁-adrenoceptors and was likely to be due to the release of noradrenaline from the sympathetic nerve endings. The vasorelaxant effect of the extract, however, was not mediated via an action on β₂ adrenoceptor.     

The vascular action of aqueous extracts of Foeniculum vulgare leaves

The vascular effects of aqueous extracts of Foeniculum vulgare leaves were tested using pentobarbital-anaesthetised rats. An intravenous administration of the lyophilized boiled water extract of leaves produced a significant dose-related reduction in arterial blood pressure, without affecting the heart rate or respiratory rate. In contrast the non-boiled aqueous extract showed very little hypotensive activity. The hypotensive effect of the boiling water extract appeared not to be mediated via adrenergic, muscarinic, ganglionic or serotonergic receptors; however, histamine antagonists inhibited the hypotensive effect in a dose-related manner.     

Terminalia arjuna extract modulates the contraction of rat aorta induced by KCl and norepinephrine

The bark of Terminalia arjuna is in clinical use for the management of cardiovascular disorders in India. The objective of this study was to investigate the contractile response induced by the extract on rat aorta, a vascular smooth muscle. Terminalia arjuna relaxed the contraction, induced by both KCl (60 mM ) and norepinephrine (NE, 3 μM ). Inhibition was more prominent (80%) in the NE induced contraction than the KCl induced contraction (30%). Under similar conditions diltiazem, a calcium channel blocker (Dz, 1.0 μM ), inhibited 68% of the KCl induced and 30% of NE induced contraction. Thus it appears that the action of Terminalia arjuna extract differs from that of diltiazem in that it is more specific for alpha-adrenergic receptor agonists. It indirectly inhibited the contraction induced by norepinephrine by acting on K (Ca) channel by hyperpolarizing the smooth muscle membrane.     

Terminalia arjuna in coronary artery disease: Ethnopharmacology,pre-clinical,clinical & safety evaluation

Ethnopharmacological relevance

Terminalia arjuna (Roxb.) Wight & Arn. is one of the most popular and beneficial medicinal plants in indigenous system of medicine for the treatment of cardiovascular diseases. This comprehensive review provides latest updates on traditional use, phytochemistry, pharmacological and toxicological data, clinical efficacy and safety of Terminalia arjuna as well as outlined strategies for future research and development to scientifically validate the therapeutic potential of this plant.

Materials and methods

Information about Terminalia arjuna was collected via a systematic electronic and library search of various indexed and non-indexed journals, some local books and varied articles published on ethnopharmacology, phytochemistry and traditional uses. Various pre-clinical (2000–2014) and clinical studies (1990–2014) have also been considered regarding efficacy and safety profile of Terminalia arjuna.

Results

Evidence from various in vitro, in vivo and clinical trials reveal the pleiotropic effects of Terminalia arjuna such as anti-atherogenic, hypotensive, inotropic, anti-inflammatory, anti-thrombotic and antioxidant actions for treatment of various cardiovascular disorders. It is clearly documented that this plant has a good safety profile when used in conjunction with other conventional drugs. However, there is a paucity of data regarding the exact molecular mechanism of its action, appropriate form of drug administration, whether whole crude drug or aqueous or alcoholic extract should be used, toxicological studies and its interaction with other drugs.

Conclusions

In conclusion, this review highlights the importance as well as pleiotropic actions and functional aspects of Terminalia arjuna especially in cardiovascular diseases. Though, various pharmacological studies and clinical trials support its benefit in the CVD as per traditional use, new clinical trials using more rigorous state of the art technology and in a larger population setup are warranted to assess the traditional putative efficacy of Terminalia arjuna.     

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%.     

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.     

Blood pressure lowering effect of the aqueous extract of the stem of Ipomoea acanthocarpa (convolvulaceae) in spontaneously and salt-loaded hypertensive rats

Spontaneously hypertensive (SHR) and salt-loaded hypertensive rats (SLHR) were submitted to a daily treatment by gavage of 2 mL/100 g body weight of the aqueous extract of the stem of Ipomoea acanthocarpa (30 mg/mL stock solution). A fall in blood pressure of nearly 13% was observed after two successive administrations of the aqueous extract. After 14 days of treatment, the blood pressure fell by more than 30±8%. The hypotensive effect might be due to a direct vascular smooth muscle effect or to its already observed high diuretic effects or might be acting by some other mechanism.     

Possible mechanisms of action of the neutral extract from Bidens pilosa L. leaves on the cardiovascular system of anaesthetized rats

The aim of this study was to investigate the hypotensive and cardiac effects of the neutral extract from Bidens pilosa leaves. Intravenous administration of the extract resulted in a biphasic dose-related hypotensive activity. In normotensive rats (NTR), B. pilosa decreased systolic blood pressure by 18.26%, 42.5% and 30% at doses of 10, 20 and 30 mg/kg, respectively. In spontaneously hypertensive rats (SHR), the decrease in systolic blood pressure was 25.77%, 38.96% and 28.64% at the above doses, respectively. These doses induced hypotension by 27%, 34.13% and 18.73% respectively in salt-loaded hypertensive rats. In NTR, B. pilosa reduced heart rate by 23.68% and 61.18% at doses of 20 and 30 mg/kg, respectively. The force of contraction of the heart was only affected at 30 mg/kg. The initial phase of hypotensive response was partially inhibited by atropine while propranolol increased this effect. These results suggest that B. pilosa exhibited its fi rst hypotensive effects by acting on the cardiac pump efficiency and secondly through vasodilation.     

Hypotensive and cardio-chronotropic constituents of Tinospora crispa and mechanisms of action on the cardiovascular system in anesthetized rats

Ethnopharmacological relevance

Tinospora crispa has been used in folkloric medicine for the control of blood pressure. We previously found that an extract of Tinospora crispa stems decreased the mean arterial blood pressure (MAP) with a transient decrease, followed by an increase in the heart rate (HR) in rats.

Aim of the study

To identify the active components of the Tinospora crispa extract and investigate the mechanisms of action on blood pressure and heart rate in anesthetized rats.

Materials and methods

The active components of Tinospora crispa extract were separated by column chromatography and a preparative HPLC. The effects and mechanisms of the active compounds on blood pressure and heart rate were studied in anesthetized, normal and reserpinized rats in vivo.

Results

5 active compounds: adenosine, uridine, salsolinol, higenamine and tyramine were isolated. Adenosine decreased MAP and HR and this effect was inhibited by DMPX (A_2A adenosine receptor antagonist). Uridine increased MAP and decreased HR and this was inhibited by suramin but not by DMPX. Salsolinol decreased the MAP and HR and this was inhibited by phentolamine but not by ICI-118,551 (β₂-adrenoceptor antagonist) or atropine. In reserpinized rats, salsolinol had a hypertensive effect that was inhibited by prazosin and phentolamine, but not by atenolol, and caused an increase in HR that was inhibited by atenolol, but not by prazosin or phentolamine. Higenamine decreased the MAP with an increase in HR. The hypotensive effect was inhibited by ICI-118,551 or atenolol, whereas the increase in HR was not inhibited by ICI-118,551. Atenolol inhibited the increase in HR at a small dosage of higenamine but potentiated it at a higher dosage. In reserpinized rats, a small dosage of higenamine tended to potentiate the effect but at a higher dosage it caused inhibition. ICI-118,551 significantly inhibited this hypotensive effect. Tyramine caused an increase in MAP and HR and these effects almost disappeared in reserpinized rats.

Conclusions

The results demonstrate that these 5 compounds from Tinospora crispa acted in concert on the cardiovascular system of anesthetized rats. Salsolinol, tyramine and higenamine acted via the adrenoreceptors, whereas uridine and adenosine acted via the purinergic adenosine A₂ and P₂ receptors to decrease blood pressure with a transient decrease of HR followed by an increase.     

沙苑子总黄酮对 SHR 的降压及血流动力学影响

目的 :观察沙苑子总黄酮对自发性高血压大鼠 (SHR)的降压作用及在麻醉状态下对其血流动力学的影响。方法 :采用尾动脉测压法及多导生理记录仪分别记录沙苑子总黄酮灌胃后血压及血流动力学的变化。结果 :沙苑子总黄酮灌胃 (100 ,200mg·kg^-1)使清醒SHR血压明显下降 (分别下降 7.1% ,P<0.05及9.3% ,P<0.01) ,动物心率无明显变化。沙苑子总黄酮 (200mg·kg-1)对麻醉SHR心输出量和心率影响不大 ,但可显著降低SHR的总外周阻力 (下降20% ,P<0.05) ,从而引起SHR收缩压、舒张压的显著下降 ,其中舒张压的下降更为明显。结论 :沙苑子总黄酮有明显的降压作用 ,主要是通过降低外周阻力引起的。     

Terminalia arjuna: an Ayurvedic Cardiotonic,Regulates Lipid Metabolism in Hyperlipaemic Rats

The lipid lowering action of the bark powder of Terminalia arjuna (T. arjuna ) has been studied in triton and cholesterol fed rats. Serum lipids were found to be lowered by T. arjuna (100 mg/kg, b.w.) in triton induced hyperlipaemia. Chronic feeding of this powder (100 mg/kg, b.w., p.o.) in animals simultaneously fed with cholesterol (25 mg/kg, b.w.) for 30 days, caused lowering in lipids and protein levels of β-lipoproteins followed by an increase in high density lipoprotein-cholesterol compared with the cholesterol fed groups. T. arjuna alters lipolytic activities in plasma, liver, heart and adipose tissues of hyperlipaemic rats. The lipid lowering action of this natural product is mediated through inhibition of hepatic cholesterol biosynthesis, increased faecal bile acid excretion and enhanced plasma lecithin:cholesterol acyltransferase activity and stimulation of receptor mediated catabolism of low density lipoprotein.     

Effect of Terminalia arjuna extract on KCl induced contractions in the rat vas deferens

Experiments were carried out to elucidate the effects of extracts from Terminalia arjuna on potassium chloride (160 mM) induced contraction in smooth muscle. The petroleum ether extract did not exhibit a response, whereas the preincubation of tissue with the alcoholic extract inhibited contraction. Experimental approaches, described here, lead to the speculation that T. arjuna may impart its action through the modulation of Ca²⁺ ions across the cellular membrane.     

Hypotensive effect of aqueous saffron extract (Crocus sativus L.) and its constituents,safranal and crocin,in normotensive and hypertensive rats

In this study, the effects of saffron (Crocus sativus) stigma aqueous extract and two active constituents, crocin and safranal, were investigated on blood pressure of normotensive and desoxycorticosterone acetate‐induced hypertensive rats. Three doses of crocin (50, 100 and 200 mg/kg), safranal (0.25, 0.5 and 1 mg/kg) and the aqueous extract (2.5, 5 and 10 mg/kg) were administered intravenously in different groups of normotensive and hypertensive animals and their effects on mean arterial blood pressure (MABP) and heart rate (HR) were evaluated. The aqueous extract of saffron stigma, safranal and crocin reduced the MABP in normotensive and hypertensive anaesthetized rats in a dose‐dependent manner. For example, administrations of 10 mg/kg of aqueous extract, 1 mg/kg of safranal and 200 mg/kg of crocin caused 60 ± 8.7, 50 ± 5.2 and 51 ± 3.8 mmHg reductions in MABP, respectively. It can be concluded that the aqueous extract of saffron stigma has hypotensive properties which appear to be attributable, in part, to the actions of two major constitutes of this plant, crocin and safranal. It seems that safranal is more important than crocin for lowering down blood pressure of rats. Copyright © 2009 John Wiley & Sons, Ltd.     

Fraxinus excelsior L. evokes a hypotensive action in normal and spontaneously hypertensive rats

The hypotensive effect of an aqueous extract of Fraxinus excelsior L. was investigated in both normotensive (WKY) and spontaneously hypertensive rats (SHR). Daily oral administration of Fraxinus excelsior (20 mg/kg) aqueous extract for 3 weeks produced a significant decrease in systolic blood pressure (SBP) with variation coefficient (Delta%) of 13.5% in SHR (p<0.01) and 9% in WKY rats (p<0.05). The aqueous extract of Fraxinus excelsior significantly enhanced the urination in both SHR (p<0.05 compared to control) and WKY (p<0.05 compared to control). Irbesartan (Avapro), an angiotensin II antagonist, was used as reference drug. Furthermore, oral administration of aqueous Fraxinus excelsior extract at a dose of 20 mg/kg produced a significant increase in urinary excretion of sodium (p<0.01 compared to control), potassium (p<0.001 compared to control) and chlorides (p<0.01) in SHR rats. In normal rats, the aqueous Fraxinus excelsior extract administration induced a significant increase of the urinary elimination of sodium (p<0.05 compared to control), chlorides (p<0.01 compared to control) and potassium (p<0.01 versus control). While there were no significant changes in heart rate (HR) after Fraxinus excelsior treatment in both SHR and WKY rats, glomerular filtration rate (GFR) showed a significant increase in SH rats (p<0.001) after Fraxinus excelsior treatment. These results suggest that oral administration of aqueous extract of Fraxinus excelsior exhibited hypotensive and diuretic actions.     

The hypotensive mechanisms for the aqueous stem bark extract of Musanga cecropioides in Sprague-Dawley rats

The present study was designed to evaluate the hypotensive properties and the mechanisms of action of the stem bark aqueous extract of Musanga cecropioides R.Br. Apud Tedlie (MCW) in anesthetized rats of Sprague-Dawley strain, through an invasive direct blood pressure measuring procedure. Thirty adult rats, weighing 150-230 g, were grouped into five groups of six rats each. The effects of the intravenous graded doses (0.0005-0.05 mg/kg) of the extract on the blood pressure indices were investigated. Its underlying mechanisms were also studied using additional five groups of rats. The results showed that the extract caused a dose dependent fall in the systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure and heart rate of the rats. Bilateral carotid artery occlusion (BCO) caused a reflex increase in mean arterial pressure and heart rate which were significantly attenuated by the extract injection. Angiotensin Converting Enzyme (ACE) blockade with 5 mg/kg of Captopril and cholinergic blockade with 0.2 mg/kg of atropine significantly attenuated the hypotensive response to MCW. However, the pattern of MAP fall in rats pretreated with a combination of Promethazine (1 mg/kg) and Cimetidine (15 mg/kg) was not significant. The results of the study was able to demonstrate dose dependent hypotensive effect of MCW and that its vasorelaxant effects may be through inhibition of sympathetic, cholinergic control of the arterial pressure and most significantly through ACE blockade. However, the phytochemical, elemental and toxicological studies of this potential antihypertensive still needed to be investigated.     

Hypotensive effect of crude root extract of Solanum sisymbriifolium (Solanaceae) in normo- and hypertensive rats

The hypotensive effect of the crude hydroalcoholic extract from root of Solanum sisymbriifolium Lam. (Solanaceae) was investigated both in normotensive and hypertensive rats. The intravenous administration of the extract (50 and 100 mg/kg) produced a significant decrease in blood pressure in anaesthetized hypertensive (adrenal regeneration hypertension + deoxycorticosterone acetate (ARH + DOCA)) rats. Oral administration of the extract (10, 50, 100 and 250 mg/kg) also produced a dose-dependent hypotensive effect in conscious hypertensive animals. In anaesthetized normotensive rats, the extract (50 and 100 mg/kg, i.v.) also induced hypotension in a dose-dependent manner. Lastly, no significant effect on blood pressure was produced by the extract when administered orally (10, 50, 100, 250, 500 and 1000 mg/kg) to conscious normotensive rats.     

Hypotensive Activity of Lannea coromandelica Bark Extract

An ethanol extract of Lannea coromandelica bark (ELC) showed hypotensive activity in anaesthetized dogs and rats. On intravenous administration (i.v.) at a dose range of 5–100 mg/kg in dogs and 1–25 mg/kg in rats it produced a mild to marked decrease in the arterial blood pressure in a dose dependent manner. The effect did not alter after cholingergic, histaminergic, adrenergic and ganglion receptor blockade. The hypotension was also unchanged in vagotomized and eviscerated dogs, whereas there was a slight increase in hypotension in the spinal preparation. It produced dose related decreases in heart rate, without any effect on respiratory rate.     

钩藤属部分不同种植物药材对正常大鼠血压的影响

目的:观察钩藤属6个不同种药材乙醇提取物对正常大鼠血压的影响。方法:急性降压试验:将大鼠分为正常对照、硝苯地平0.002 g.kg-1以及钩藤、大叶钩藤、侯钩藤、攀茎钩藤、倒挂金钩、北越钩藤乙醇提取物含生药68.4,34.2 g.kg-114组,大鼠十二指肠给药1次,记录给药前及给药后0.5,1.0,1.5,2.0,2.5,3.0 h大鼠颈总动脉血压;慢性降压试验:将大鼠分为正常对照、硝苯地平0.002 g.kg-1以及前述6种药材乙醇提取物34.2,17.1 g.kg-1组,灌胃,每天1次,连续11 d,给药前和给药后第7天和第11天测定大鼠尾动脉血压。以给药后自身血压下降达2.666 kPa以上,同时与对照组比较有显著性差异者为药物降血压有效。结果:钩藤68.4,34.2 g.kg-1给药后0.5 h颈总动脉血压下降达2.666 kPa以上,且与对照组比较有显著性差异(均P<0.01),并维持3 h以上。钩藤34.2 g.kg-1给药后第7,11天,17.1 g.kg-1给药后第11天;大叶钩藤、侯钩藤34.2 g.kg-1给药后第11天,大鼠尾动脉血压下降值达2.666 kPa以上,且与对照组比较有显著性差异(均P<0.01);而攀茎钩藤、倒挂金钩、北越钩藤给药后大鼠颈总动脉、尾动脉血压下降值均未达到2.666 kPa。结论:钩藤、大叶钩藤、侯钩藤能够显著降低正常大鼠血压,攀茎钩藤、倒挂金钩、北越钩藤对正常大鼠血压没有显著影响。