The aerial parts of Guazuma ulmifolia Lam. protect against NSAID-induced gastric lesions

Guazuma ulmifolia Lam., a member of the Sterculiaceae family, is used in folk medicine because of its antioxidant, antimicrobial and antihypertensive properties. Most of the research work carried out on this plant has focused on the bark because of its high concentration of antioxidant proanthocyanidins. The flowers and leaves of Guazuma ulmifolia, though less studied, are also used as a remedy for different conditions, such as kidney and gastrointestinal diseases, fever and diabetes. The aim of this study was to assess the gastroprotective effects of an aqueous suspension of the ethanolic extract from leaves and flowers of Guazuma ulmifolia in a model of acute gastric ulcer induced by diclofenac as ulcerogenic agent, using the proton pump inhibitor omeprazole as a protection reference. Therefore, the extract was administered two times orally to three groups of Wistar rats at doses of 500, 250 and 125mg/kg, with a 24-h interval between doses. Diclofenac (100mg/kg) was given 1h after the last administration of the extract. Pretreatment with Guazuma ulmifolia or omeprazole decreased the ulcerated area in a dose-dependent way. Myeloperoxidase activity as a marker of neutrophil infiltration was slightly reduced in vivo, whereas in vitro, anti-inflammatory activity was clearly inhibited in a dose-dependent way. The lowest doses of the extract significantly decreased the levels of lipoperoxides, and superoxide dismuthase activity increased to a similar extent as with omeprazole (P<0.001). Examination of glutathione metabolism reflected a significant rise in glutathione peroxidase activity at the highest dose of Guazuma ulmifolia. Finally, there was a faint elevation in prostaglandin E(2) levels with all doses, though the depletion induced by diclofenac could not be reverted. We conclude that the aerial parts of Guazuma ulmifolia protect gastric mucosa against the injurious effect of NSAIDs mainly by anti-inflammatory and radical-scavenging mechanisms.     

The anti-diabetic properties of Guazuma ulmifolia Lam are mediated by the stimulation of glucose uptake in normal and diabetic adipocytes without inducing adipogenesis

ETHNOPHARMACOLOGICAL IMPORTANCE: Guazuma ulmifolia Lam (Sterculiaceae) is a plant extensively used in México for the empirical treatment of type 2 diabetes. AIM OF THE STUDY: To investigate the anti-diabetic mechanisms of Guazuma ulmifolia. MATERIALS AND METHODS: Non-toxic concentrations of Guazuma ulmifolia aqueous extracts (GAE) were assayed on adipogenesis and 2-NBDglucose uptake in the murine 3T3-F442A preadipose cell line. RESULTS: GAE added to adipogenic medium (AM) did not affect adipogenesis at any of the tested concentrations (1-70 microg/ml), whereas in AM lacking insulin GAE 70 microg/ml induced triglyceride accumulation by 23%. On the other hand, GAE 70 microg/ml stimulated 2-NBDG uptake by 40% in insulin-sensitive 3T3-F442A adipocytes and by 24% in insulin-resistant adipocytes, with respect to the incorporation showed by insulin-sensitive adipocytes stimulated with the hormone. CONCLUSION: Guazuma ulmifolia exerts its anti-diabetic effects by stimulating glucose uptake in both insulin-sensitive and insulin-resistant adipocytes without inducing adipogenesis.     

原花青素舒张家兔主动脉和降低动脉血压的研究

目的：研究葡萄籽提取物原花青素(procyanidins，PC)舒张家兔离体主动脉和降低其动脉血压的作用及机制。方法：采用家兔离体胸主动脉环灌流模型，将标本分6组：去内皮、内皮完整、吲哚美辛(1×10^-1 mol·L^-1)、普萘洛尔(1×10^-5 mol·L^-1)、左旋硝基精氨酸N^ω-nitro-L-arginine(L-NNA 1×10^-4 mol·L^-1)或甲烯蓝(MB 1×10^-5 mol·L^-1)，分别累积加入1.25，2.5，5.0 mg·L^-1 PC观察血管张力变化；并观察40 mg·L^-1 PC对去甲肾上腺素（NA）(1×10^-8～1×10^-5 mol·L^-1)、KCl(6.3～100 mmol·L^-1)和CaCl₂ (1×10^-5～1×10^-2 mol·L^-1)诱导血管环收缩曲线的影响。另用家兔颈总动脉插管法，经静脉累积注射4.0，8.0，16，32，64，84 mg·kg^-1 PC后观察血压变化。结果：PC能舒张主动脉血管，并有量效依赖性(r=0.63，P<0.001)，去内皮、L-NNA或MB可减弱PC的舒张作用。PC能抑制NA，KCl和CaCl₂的量效收缩反应。PC能降低家兔正常动脉血压并有量效依赖性(r=0.92，P<0.001)。结论：PC舒张血管的作用是通过抑制细胞内Ca²⁺释放和电压依赖性Ca²⁺通道而减少Ca²⁺内流；也与内皮释放的NO有关；PC可降低家兔正常的动脉血压。     

Vasorelaxant and antihypertensive effect of Cocos nucifera Linn. endocarp on isolated rat thoracic aorta and DOCA salt-induced hypertensive rats

Ethnopharmacological relevance

The fruits of Cocos nucifera Linn. (Arecaceae) have long been used in traditional medicine for the treatment of cardio-metabolic disorders.

Aim of the study

To evaluate the ethanolic extract of Cocos nucifera Linn. endocarp (CNE) for its vasorelaxant activity on isolated rat aortic rings and antihypertensive effects in deoxycorticosterone acetate (DOCA) salt-induced hypertensive rats.

Materials and methods

Cocos nucifera Linn. endocarp was extracted with ethanol and characterized by HPLC. CNE was examined for its in vitro vascular relaxant effects in isolated norepinephrine, phenylephrine or potassium chloride pre-contracted aortic rings (both intact endothelium and denuded). In vivo anti-hypertensive studies were conducted in DOCA salt-induced uninephrectomized male Wistar rats.

Results

Removal of endothelium or pretreatment of aortic rings (intact endothelium) with l-NNA (10 μM) or ODQ (10 μM) followed by addition of contractile agonists prior to CNE significantly blocked the CNE-induced relaxation. Indomethacin (10 μM) and atropine (1 μM) partially blocked the relaxation, whereas glibenclamide (10 μM) did not alter it. CNE significantly reduced the mean systolic blood pressure in DOCA salt-induced hypertensive rats (from 185.3 ± 4.7 mmHg to 145.6 ± 6.1 mmHg). The activities observed were supported by the polyphenols, viz. chlorogenic acid, vanillic acid and ferulic acid identified in the extract.

Conclusions

These findings reveal that the vasorelaxant and antihypertensive effects of CNE, through nitric oxide production in a concentration and endothelium-dependent manner, is due to direct activation of nitric oxide/guanylate cyclase pathway, stimulation of muscarinic receptors and/or via cyclooxygenase pathway.     

Antihypertensive activities of the aqueous extract of Kalanchoe pinnata (Crassulaceae) in high salt-loaded rats

Ethnopharmacological relevance

The leaves of Kalanchoe pinnata (Crassulaceae) are used in Cameroon folk medicine to manage many diseases such as cardiovascular dysfunctions. In this work, we aimed to evaluate the activities of aqueous leaf extract of Kalanchoe pinnata on the blood pressure of normotensive rat (NTR) and salt hypertensive rats (SHR), as well as its antioxidant properties.

Materials and methods

Hypertension was induced in rats by oral administration of 18% NaCl for 4 weeks. For the preventive study, three groups of rats received 18% NaCl solution and the plant extract at 25 mg/kg/day, 50 mg/kg/day or 100 mg/kg/day by gavage. Two positive control groups received 18% NaCl solution and either spironolactone (0.71 mg/kg/day) or eupressyl (0.86 mg/kg/day) by gavage for 4 weeks. At the end of this experimental period, systolic arterial pressure (SAP), diastolic arterial pressure (DAP) and heart rate (HR) were measured by the invasive method. Some oxidative stress biomarkers (reduced glutathione (GSH), superoxide dismutase (SOD), nitric monoxide (NO) were evaluated in heart, aorta, liver and kidney. NO level was indirectly evaluated by measuring nitrite concentration.

Results

Kalanchoe pinnata extract prevented significantly the increase of systolic and diastolic arterial pressures in high salt-loaded rats (SHR). In SHR, concomitant administration of Kalanchoe pinnata at 25, 50 and 100 mg/kg/day significantly prevented the increase in blood pressure by 32%, 24% and 47% (for SAP); 35%, 33% and 56% (for DAP), respectively. No significant change was recorded in heart rate of those rats. The plant extract improved antioxidant status in various organs, but more potently in aorta. Thus, antioxidant and modulatory effects of Kalanchoe pinnata at the vasculature might be of preponderant contribution to its overall antihypertensive activity.

Conclusion

The work demonstrated that the concomitant administration of high-salt and the aqueous extract of Kalanchoe pinnata elicits prevention of salt-induced hypertension in rat. This antihypertensive activity is associated with an improvement of antioxidant status. Overall, results justify and support the use of Kalanchoe pinnata as antihypertensive medicine.     

Antihypertensive and vasodilator effects of methanolic and aqueous extracts of Tribulus terrestris in rats

The effects of methanolic and aqueous extracts of Tribulus terrestris on rat blood pressure (BP) and the perfused mesenteric vascular bed were investigated. The extracts dose-dependently reduced BP in spontaneously hypertensive rats (SHRs) with the aqueous fraction being more potent than the methanolic fraction at all doses tested. In vitro, the methanolic but not aqueous extract produced a dose-dependent increase in perfusion pressure of the mesenteric vascular bed. When perfusion pressure was raised with phenylephrine (10(-5) M), the aqueous extract produced a dose-dependent reduction in perfusion pressure at all doses. A low dose of the methanolic extract produced a vasoconstrictor effect while higher doses produced dose-dependent reduction in perfusion pressure. L-NAME (10(-4) M) significantly reduced but did not abolish vasodilation induced by the extracts. Vasodilator responses to aqueous and methanolic fractions were significantly reduced in preparations where perfusion pressure was raised with KCl (60 mM). A combination of KCl and L-NAME abolished the vasodilator responses induced by the extracts. It was concluded that methanolic and aqueous extracts of Tribulus terrestris possess significant antihypertensive activity in spontaneously hypertensive rats. The antihypertensive effects appeared to result from a direct arterial smooth muscle relaxation possibly involving nitric oxide release and membrane hyperpolarization.     

Vasodilator effect of the extracts and some coumarins from the stem bark of Mammea africana (Guttiferae)

CH(2)Cl(2) fraction obtained from the stem bark of Mammea africana inhibited noradrenaline (NA) or KCl-induced contraction in isolated guinea pig and rat aorta. The vasorelaxant potency of the CH(2)Cl(2) fraction of Mammea africana was diminished by a pre-treatment with Nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthase, which was however not affected by indomethacin pre-treatment. These findings indicated that the vasorelaxant effect of Mammea africana may be partially endothelium dependent, mediated by nitric oxide and that vasoactive prostanoids might not be contributing to the vasorelaxation effect. Three bioactive compounds were isolated from this CH(2)Cl(2) fraction and identified as 4-n-propylcoumarins (1) (mammea B/BB), 4-phenylcoumarins (2) (mammea A/AA or mammeisin) and (B/BA) (3) and might involved in the vasorelaxant effect of the extract. The mechanisms of the vasorelaxant effect might therefore be multiple, including endothelium dependence and the mechanisms, which interfere with the liberation of Ca(2+) into the muscle cell.     

Role of nitric oxide in the vasorelaxant and hypotensive effects of extracts and purified tannins from Geum japonicum

Crude extracts and three purified tannins from Geum japonicum Thunberg (Rosaceae) were examined for relaxant effects in isolated rat thoracic aorta and for hypotensive effects in anesthetized normotensive and hypertensive rats. The acetone extract and the butyl alcohol extract of Geum japonicum at a cumulative concentration of 30mug/ml potently relaxed phenylephrine-precontracted aortic rings by 73+/-5% and 80+/-7%, respectively, without affecting the resting tension of these vessels. Removal of the vascular endothelium, inhibition of nitric oxide (NO) synthase with N(omega)-nitro-l-arginine (l-NA) or inhibition of cGMP biosynthesis with methylene blue all abolished the vasorelaxant effects of the Geum japonicum extracts. Addition of l-arginine, the substrate for NO biosynthesis, reversed the inhibitory effects of l-NA. Similar vasorelaxant effects of 82+/-10%, 61+/-8% and 82+/-14%, were observed with the purified tannins, penta-O-galloyl-beta-glucoside, casuariin and 5-desgalloylstachyurin, respectively, at a cumulative concentration of 10muM. Intravenous injection of the butyl alcohol extract of Geum japonicum at a cumulative dose of 2.5mg/kg into both hypertensive and normotensive rats resulted in a marked reduction in the mean arterial blood pressure by 46+/-6% and 34+/-7%, respectively, which was abolished by prior injection of l-NA. Therefore, these results suggest that tannins may be responsible for the vasorelaxant and hypotensive effects of Geum japonicum, mediated via endogenous NO and subsequent cGMP formation. The data suggest that extracts of Geum japonicum may have potential use as new anti-hypertensive agents for lowering arterial blood pressure in hypertensive patients.     

Antihypertensive, vasorelaxant and inotropic effects of an ethanolic extract of the roots of Saururus chinensis

AIM OF THE STUDY: The present study was performed to evaluate the cardiovascular effects of ethanolic extract of the roots of Saururus chinensis (EERSC) in rats. MATERIALS AND METHODS: The effects of EERSC on the vascular responses of isolated rat aorta, the cardiac functions in isolated rat heart, and the antihypertensive effects in spontaneously hypertensive rats (SHRs) were evaluated. RESULTS: In isolated rat aortic preparations, EERSC exhibited a potent vasorelaxant effect with EC(50) value of 9.1 microg/ml. This relaxation was significantly inhibited by denudation of endothelial layer or by pretreatment with N(G)-nitro-l-arginine methyl ester. In addition, the raising extracellular K(+) (45 mM), or pretreatment with tetraethylammonium (10 mM) significantly inhibited EERSC-induced vasorelaxation in endothelium-denuded aortic rings. In isolated rat hearts, EERSC significantly reduced cardiac functions such as left ventricle pressure and heart rate. In an antihypertensive study with SHRs, long-term oral administrations of EERSC decreased blood pressure of SHRs (approximately 20 mmHg). CONCLUSIONS: These results suggest that chronic treatment with EERSC exerts an antihypertensive effect in SHRs, and its direct vasorelaxant properties and negative inotropic actions may contribute to reduce the elevated blood pressure.     

Vascular effects and antioxidant activity of two Combretum species from Democratic Republic of Congo

Ethnopharmacological relevance

Combretum racemosum P. Beauv (Combretaceae) leaves (CrLv) and root bark (CrRB) and Combretum celastroides subsp. laxiflorum Welw (Combretaceae) leaves (ClLv) are used in Congolese traditional medicine for several therapeutic purposes, notably for the treatment of conditions consistent with hypertension. The present study aims to investigate the vasorelaxant and in vitro antioxidant activities of these plants polar extracts and to examine the in vivo antihypertensive effect of the extract which displays the most potent vasorelaxant effect.

Material and methods

The vasorelaxant effect of CrLv, CrRB and ClLv methanolic extracts was studied on rat aorta rings pre-contracted with phenylephrine (PE, 1 μM) in the presence or absence of the endothelium. In some experiments, prior to the addition of the extract, rings were incubated for 30 min with either L-N^G-nitroarginine methyl ester (L-NAME; 100 μM), a nitric oxide synthase (NOS) inhibitor, indomethacin (10 μM), a cyclooxygenase inhibitor, or 1 H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10 μM), a guanylate cyclase inhibitor. The antioxidant activity was determined by the measurement of the scavenging ability of extracts towards the stable free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH). Blood pressure was measured on normotensive Wistar rats and spontaneously hypertensive rats (SHR) treated orally with a daily dose (40 mg/kg) of the CILv extract for 5 weeks. Tested extracts have been characterised by TLC profiles targeted at flavonoids.

Results

All tested extracts showed an important DPPH scavenging activity, ranging from 0.6 to 1.1 quercetin-equivalents. They caused a concentration-dependent vasorelaxation on intact aortic rings pre-contracted with PE (1 μM). The responses to CrRB and CrLv methanolic extracts reached 74.0±5.1% and 62.2±8.6% at a cumulative concentration of 50 μg/ml, respectively. The ClLv (10 μg/ml) extract was more active and, in the same conditions, relaxed aortic rings by 90.3±5.8%. The vasorelaxant activity of all extracts disappeared or was significantly attenuated by removal of the endothelium or after pretreatment with L-NAME or ODQ. Indomethacin only inhibited the activity of CrLv and CrRB extracts. The ClLv extract was able to lower the systolic blood pressure in SHR rats by 7% after a 5-week treatment.

Conclusions

The present study shows that methanolic extracts from ClLv, CrRB and CrLv have an antioxidant activity and an endothelium-dependent vasorelaxant effect. ClLv induces the vasorelaxant effect through the NO-cGMP pathway while CrLv and CrRB extracts also act via a prostanoid pathway. ClLv extract demonstrated a modest but significant antihypertensive activity in SHR rats.     

Arbutus unedo induces endothelium-dependent relaxation of the isolated rat aorta

Arbutus unedo L. (Ericaceae) is used in oriental Morocco to treat arterial hypertension. We studied its vasodilator effect and mechanisms of action in vitro. The root aqueous extract of Arbutus (0.25 mg/mL) produced a relaxation of noradrenaline-precontracted ring preparations of rat aorta with intact endothelium. Relaxation by Arbutus did not occur in specimens without endothelium and was inhibited by pretreatment with 100 microM N(G)-methyl-L-arginine (L-NMA), 10 microM methylene blue or 50 microM 1H-[1,2,4] oxadiazolo [4,3-a] quinoxaline-1-one (ODQ) but not by 10 microM atropine. These results suggest that Arbutus produces an endothelium-dependent relaxation of the isolated rat aorta which may be mediated mainly by a stimulation of the endothelial nitric oxide synthase by mechanisms other than activation of muscarinic receptors.     

The antihypertensive and vasodilator effects of aqueous extract from Berberis vulgaris fruit on hypertensive rats

The aqueous extract from Berberis vulgaris fruit (B.V.) was tested to evaluate its antihypertensive effects on DOCA-induced hypertension in the rats. Hypertension was induced in male Sprague-Dawley rats (200-250 g) by DOCA-salt injection (20 mg/kg, twice weekly, for 5 weeks, s.c.) plus NaCl (1%) which was added to the animals' drinking water. Then 5 weeks later, the rats were anaesthetized with thiopental (30 mg/kg, i.p.) and the arterial blood pressure was measured. The mean arterial blood pressure and heart rate were 231 +/- 6.4 (mmHg) and 506 +/- 12 (beats/min), respectively. Administration of B.V. extracts significantly reduced the rat arterial blood pressure. In in vitro studies, rings of descending aorta were cut and mounted for isometric tension recording in an organ chamber containing Krebs solution. Mesenteric beds were also removed and perfused with Krebs solution. After 1 h of stabilization, preparations (aortic rings or mesenteric beds) were precontracted with phenylephrine (10(-5) M), then different concentrations of B.V. (0.4, 2 and 4 mg/mL) were added which caused a relaxation in these vessels. To investigate the mechanism of action of the extract, the tissues were incubated with either L-NAME (10(-5) M) or indomethacin (10(-5) M) for 20 min. In the aortic rings L-NAME pretreatment could only reduce the vasodilatory effects of a low concentration of B.V. (0.4 mg/mL), but indomethacin was without effect. In isolated perfused mesenteric beds preincubation with either L-NAME or indomethacin did not modify the vasodilator effects of the aqueous extract from B.V. fruit. The present results suggest that the antihypertensive and vasodilatory effects of B.V. fruit extract are mainly endothelial-independent and it may be used to treat hypertension, a status with endothelial dysfunction.     

Cochlospermum vitifolium induces vasorelaxant and antihypertensive effects mainly by activation of NO/cGMP signaling pathway

Aim of the study

Cochlospermum vitifolium is a medicinal plant used for the treatment of diabetes, hepatobilary and cardiovascular illnesses. The aim of current study was to determine the in vivo antihypertensive and in vitro functional vasorelaxant mechanism of methanol extract of Cochlospermum vitifolium (MECv) and naringenin (NG).

Materials and methods

Test material was assayed on rat isolated aorta rings test with- and without-endothelium to determine their vasorelaxant mechanism. Also, the in vivo antihypertensive effect was evaluated on spontaneously hypertensive rat (SHR) model. In addition, presence of NG into the extract was confirmed by reverse phase high performance liquid chromatography (RP-HPLC) analysis.

Results

MECv (120 mg/kg) and NG (50 and 160 mg/kg) showed acute antihypertensive effects on SHR when systolic and diastolic pressure were decreased at 1 h and 24 h after administration, respectively. Vasorelaxant effect of MECv and NG was shifted to the right when endothelium-intact aortic rings were pre-incubated with L-NAME (10 μM) and ODQ (1 μM). Also, NG relaxant curves were displaced to the right in the presence of tetraethylammonium (TEA, 1 mM) and 2-aminopyridine (2-AP, 100 μM) on endothelium-denuded aortic rings.

Conclusion

Experiments described above showed that MECv play an important role in hypertension regulation through NO synthesis and may be PGI₂ production and potassium channel activation on excessive endothelial dysfunction conditions. Unfortunately, presence of NG into the extract is not significant on bioactivity of the extract; however, this compound could be tested and evaluated as structural scaffold for future drug design for development of antihypertensive agents.     

Mechanisms of the anti-hypertensive effect of Hibiscus sabdariffa L. calyces

Previous studies have demonstrated the anti-hypertensive effects of Hibiscus sabdariffa L. (HS) in both humans and experimental animals. To explore the mechanisms of the anti-hypertensive effect of the HS, we examined the effects of a crude methanolic extract of the calyces of HS (HSE) on vascular reactivity in isolated aortas from spontaneously hypertensive rats. HSE relaxed, concentration-dependently, KCl (high K(+), 80 mM)- and phenylephrine (PE, 1 microM)-pre-contracted aortic rings, with a greater potency against the alpha(1)-adrenergic receptor agonist. The relaxant effect of HSE was partly dependent on the presence of a functional endothelium as the action was significantly reduced in endothelium-denuded aortic rings. Pretreatment with atropine (1 microM), L-NAME (10 microM) or methylene blue (10 microM), but not indomethacin (10 microM), significantly blocked the relaxant effects of HSE. Endothelium-dependent and -independent relaxations induced by acetylcholine and sodium nitroprusside, respectively, were significantly enhanced in aortic rings pretreated with HSE when compared to those observed in control aortic rings. The present results demonstrated that HSE has a vasodilator effect in the isolated aortic rings of hypertensive rats. These effects are probably mediated through the endothelium-derived nitric oxide-cGMP-relaxant pathway and inhibition of calcium (Ca(2+))-influx into vascular smooth muscle cells. The present data further supports previous in vivo findings and the traditional use of HS as an anti-hypertensive agent.     

Inhibition of the gastric H+,K+ -ATPase by plectrinone A, a diterpenoid isolated from Plectranthus barbatus Andrews

This work assessed the mechanism underlying the antisecretory gastric acid effect of Plectranthus barbatus Andrews (Lamiaceae) and active constituents. Popularly known as "false-boldo", this plant is used in Brazilian folk medicine to treat gastrointestinal and hepatic ailments. The plant aqueous extract (AE) and isolated compounds were assayed in vivo in pylorus-ligated mice, and in vitro on acid secretion measured as [(14)C]-aminopyrine ([(14)C]-AP) accumulation in rabbit gastric glands and gastric H(+),K(+)-ATPase preparations. Injected into the duodenal lumen, the AE of the plant leaves (0.5 and 1.0 g/kg) decreased the volume (62 and 76%) and total acidity (23 and 50%) of gastric acid secretion in pylorus-ligated mice. Bioguided purification of the AE yielded an active fraction (IC(50)=24 microg/ml) that inhibited acid secretion in rabbit gastric glands with a potency 10 to 18 times greater than that of the originating extract, on both the basal and stimulated acid secretion by histamine (His) (1 microM) or bethanechol (100 microM). At the same concentrations the gastric H(+),K(+)-ATPase activity was also inhibited. The active constituent was chemically identified as the abietanoid dienedione plectrinone A which reduced the H(+),K(+)-ATPase activity with IC(50)=171 microM. The results indicate that inhibition of the gastric proton pump by this diterpenoid may account for the antisecretory acid effect and reputed anti ulcer activity of Plectranthus barbatus.     

Pharmacological activity of a procyanidin isolated from Sclerocarya birrea bark: Antidiarrhoeal activity and effects on isolated guinea-pig ileum

The antidiarrhoeal activity of a procyanidin isolated from the bark of Sclerocarya birrea was studied, using four models of experimentally induced diarrhoea in rats. The cathartic agents used were: magnesium sulphate, castor oil, arachidonic acid and prostaglandin E₂. At doses of 150 mg/kg, the procyanidin showed antidiarrhoeal activity in all the models of experimentally induced diarrhoea. The procyanidin (2.5 μg/mL-0.64 mg/mL) dose-dependently inhibited the phasic contractions of the isolated guinea-pig ileum spontaneous activity; this inhibition was significantly reduced by hexamethonium (10^?4 M ). It also modified the dose-response curves to acetylcholine in a non-competitive way, and relaxed, in a dose-dependent manner, the contractions induced by acetylcholine (10^?7 M ) and KCI (50 mM ), being five times more potent against acetylcholine. The procyanidin modified the biphasic mechanical response evoked by acetylcholine (10^?7 M ) in isolated guinea-pig ileum, inhibiting the phasic response more profoundly than the tonic one. It is concluded that the antidiarrhoeal activity of the procyanidin isolated from S. birrea bark is related to an inhibition in intestinal motility. The way in which it produces this inhibition can be related to an interference with the subsequent events evoked after muscarinic stimulation.     

Crataegus tanacetifolia leaf extract prevents L-NAME-induced hypertension in rats: a morphological study

Crataegus (hawthorn) has long been used as a folk medicine all around the world. Most of the studies with Crataegus species focus on effects on heart failure and cardiovascular disease. The pharmacological effects of Crataegus have been attributed mainly to the content of flavonoids, procyanidin, aromatic acid and cardiotonic amines.The present study investigated the blood pressure and the structure of the coronary arterial wall of L-NAME-induced hypertensive rats given an aqueous leaf extract of C. tanacetifolia (100 mg/kg), for 4 weeks via gavage.It was observed that C. tanacetifolia, especially the hyperoside fraction, prevented L-NAME-induced hypertension in rats and had beneficial effects on the cardiovascular system.     

Vasorelaxant and antihypertensive effects of methanolic extracts from Hymenocardia acida Tul

Ethnopharmacological relevance

In Congolese traditional medicine, decoctions of Hymenocardia acida root bark (HaRB) and trunk bark (HaTrB) are used for the treatment of conditions assumed to be hypertension. In this work, we propose to study the vasorelaxant effect of HaRB and HaTrB methanolic extracts on isolated rat thoracic aorta, to characterize the group of molecules responsible for the observed vasorelaxant activity, to evaluate the in vitro antioxidant activity of these extracts and to determine the antihypertensive activity of the HaRB extract on spontaneously hypertensive rats (SHR).

Materials and methods

The vasorelaxant effect of the HaRB and HaTrB methanolic extracts was studied on endothelium-intact aortic rings pre-contracted with phenylephrine (PE, 1 μM). The mechanism of this vasorelaxant effect was investigated on endothelium-denuded vessels and on endothelium-intact aortic rings in the presence of three inhibitors: l-N^G-nitroarginine methyl ester (100 μM), indomethacin (10 μM) and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10 μM). To determine the nature of the compounds responsible for the vasorelaxant activity, we carried out a fractionation of the extracts and a thiolysis of the most active fraction followed by a liquid chromatography/electrospray ionization mass spectrometry (LC/ESI-MS) analysis. The extracts antioxidant activity was determined by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) colorimetric assay. In vivo anti-hypertensive activity of the HaRB extract was conducted on SHR.

Results

HaRB and HaTrB methanolic extracts produced a concentration-dependent vasorelaxation on intact aortic rings pre-contracted with PE (1 μM). The vasorelaxant responses obtained were 95.3±1.5% (5 μg/ml) and 100.6±3.0% (1 μg/ml), respectively. The effect was markedly attenuated by removal of endothelium or pretreatment of aortic rings with all inhibitors except indomethacin. The LC/ESI-MS analysis of the thiolysis products indicated that the fraction which caused the most important vasorelaxation (97.9±2.5% at 3 μg/ml) was a mixture of procyanidins and prodelphinidins, with a predominance of procyanidins. Both extracts and all fractions from HaRB extract showed a DPPH scavenging activity, ranging from 0.4 to 0.8 quercetin-equivalents. The HaRB methanolic extract reduced the systolic blood pressure in SHR (from 214±3 mmHg to 194±4 mmHg) after a 5-week treatment.

Conclusions

The methanolic extracts of Hymenocardia acida root and trunk bark have vasorelaxant activity. The vasorelaxant effect observed is endothelium-dependent and seems mainly mediated through the NO-cGMP pathway. The COX pathway is not involved. The vasorelaxant activity appears to be due to polymeric procyanidins and prodelphinidins. These extracts also have an antioxidant effect. The extract of Hymenocardia acida root bark shows a significant but weak antihypertensive activity in SHR.     

Dihydrotanshinone, a lipophilic component of Salvia miltiorrhiza (danshen), relaxes rat coronary artery by inhibition of calcium channels

AIM OF THE STUDY: Dihydrotanshinone is a lipophilic component of the medicinal herb Salvia miltiorrhiza (danshen) belonging to the family of Labiatae. In this study, we have investigated the mechanisms of its relaxant effect on rat-isolated coronary artery. MATERIALS AND METHODS: Rat coronary artery rings were precontracted with 1muM 5-hydroxytryptamine (5-HT). Involvement of endothelium-dependant mechanisms were investigated by pretreatment of the artery rings with a cyclooxygenase inhibitor flurbiprofen (10muM), a nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, 100muM), a muscarinic receptor antagonist atropine (100nM), and by mechanical removal of the endothelium. Involvement of endothelium-independent mechanisms was investigated in endothelium-denuded artery rings pretreated with a beta-adrenoceptor antagonist propranolol (100nM), an adenylyl cyclase inhibitor 9-(tetrahydro-2-furanyl)-9H-purine-6-amine (SQ22536, 100muM), a guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ,10muM), and a potassium channel inhibitor tetraethylammonium (TEA, 10mM). Involvement of Ca(2+) channels was investigated in artery rings incubated with Ca(2+)-free buffer and primed with 1muM 5-HT for 5min prior to adding CaCl(2) to elicit contraction. RESULTS: Dihydrotanshinone relaxed the 5-HT-precontracted coronary artery rings with an IC50 value of 10.39+/-1.69muM. None of the above inhibitors or antagonists tested produced a significant change on the vasorelaxant effect of dihydrotanshinone, except ODQ caused a 50% reduction. Pre-incubation of the artery rings for 10min with dihydrotanshinone (100muM) abolished the CaCl(2)-induced vasoconstriction. CONCLUSIONS: These findings suggest that inhibition of Ca(2+) influx in the vascular smooth muscle cells is important for the vasorelaxant effect of dihydrotanshinone, and it is independent of pathways involving the endothelium, muscarinic receptors, beta-adrenoceptors, adenylyl cyclase, and guanylyl cyclase.     

Antiprotozoal activity of Senna racemosa

Methanol extracts of leaves, roots and bark of Senna racemosa (Mill.) H.S. Irwin & Barneby (syn. Cassia racemosa Mill.) were tested for antiprotozooal activity against Giardia intestinalis and Entamoeba histolytica. All of the tested extracts showed good activity against both protozoa species. Extracts from stem bark and leaves were most active, with an IC(50) of 2.10 microg/mL for Giardia intestinalis and 3.87 microg/mL for Entamoeba histolytica. Of the previously isolated compounds from Senna racemosa, the piperidine alkaloid cassine had greater activity against Giardia intestinalis with an IC(50) of 3.28 microg/mL and chrysophanol, a 1,8-dihydroxy-anthraquinone, was the most active agent against Entamoeba histolytica, with an IC(50) of 6.21 microg/mL.