Antihypertensive effect of the stem bark aqueous extract of Garcinia lucida Vesque (Clusiaceae) in L-NAME-treated rats: Contribution of endothelium-dependent and -independent vasorelaxation.

Garcinia lucida is used in Cameroonian folk medicine to handle a variety of ailments, including arterial hypertension. This study aimed at determining the phytochemical profile and the antihypertensive effect of the stem bark aqueous extract of G. lucida (AEGL). AEGL was subjected to LC-MS analysis, and its effect (75, 150, and 300 mg/kg/day; by gavage) was evaluated against Nω-nitro-L-arginine methyl ester (L-NAME; 40 mg/kg)-induced hypertension in adult male Wistar rats for four consecutive weeks. Blood pressure and heart rate were monitored weekly using tail-cuff plethysmography. The vasorelaxant effect of cumulative concentrations (3-10-30-100-300 µg/mL) of AEGL was examined on endothelium-intact and denuded thoracic aorta rings which were precontracted with KCl (90 mM) or norepinephrine (NE; 10-5 M), and in the absence or presence of L-NAME (10-4 M), indomethacin (10-5 M), methylene blue (10-6 M), tetraethylammonium (TEA, 5 × 10-6 M), glibenclamide (10 × 10-6 M) or propranolol (5 × 10-6 M). The influence of AEGL on the response to NE, KCl, and CaCl2 was also investigated. Six compounds, including Garcinia biflavonoids GB1 and GB2, were identified. AEGL prevented the development of hypertension (p < 0.01 and p < 0.001) without affecting the heart rate. AEGL induced a concentration-dependent relaxation of aortic rings precontracted with NE (EC50 = 7.915 µg/mL) that was significantly inhibited by the removal of the endothelium, L-NAME, or methylene blue (p < 0.05-0.001). Indomethacin, propranolol, TEA, and glibenclamide did not affect AEGL-evoked vasorelaxation. Preincubation of aortic rings with AEGL reduced the magnitude of contraction elicited by CaCl2 but did not alter that of KCl or NE. AEGL possesses an antihypertensive effect that is mediated by both endothelium-dependent and endothelium-independent mechanisms. The activation of the NO/sGC/cGMP pathway accounts for the endothelium-dependent vasorelaxation. These pharmacological effects of AEGL could be attributed to the presence of the Garcinia biflavonoids GB1 and GB2.

Vasorelaxant and Antioxidant Effects of Aframomum pruinosum Gagnep. (Zingiberaceae) Seed Extracts May Mediate Their Cardioprotective Activity against Isoproterenol-Induced Myocardial Infarction.

Aframomum pruinosum seeds are traditionally used in Cameroon to treat cardiac palpitations. The present work evaluates the cardioprotective effects of the aqueous (AE) and ethanolic (EE) extracts from A. pruinosum seeds against isoproterenol-induced myocardial infarction. Male Wistar rats were pretreated for 14 days with AE or EE at doses of 75 and 150 mg/kg/day or propranolol (10 mg/kg/day). On days 15 and 16, they were injected subcutaneously with isoproterenol (85 mg/kg/day). Blood pressure and heart rate were weekly recorded by tail-cuff plethysmography during pretreatment and 24 hours after the second dose of isoproterenol. At the end of the treatment period, serum Lactate Dehydrogenase (LDH), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), cardiac nitric oxide (NO), myeloperoxidase (MPO), and oxidative stress parameters (SOD, catalase, MDA, and GSH) were assayed. Sections of left ventricle tissue were subjected to histological analysis. The vasorelaxant effects of cumulative concentrations of AE or EE (3-300 µg/mL) were evaluated on intact or endothelium-denuded isolated aorta rings precontracted with noradrenaline (1 µM). The vasorelaxant effects of the plant extracts were also tested in the presence of N ω -nitro-L-arginine methyl ester (L-NAME; 100 µM). AE and EE significantly prevented blood pressure decrease and heart rate increase elicited by isoproterenol. Both plant extracts inhibited the increase in ALT, AST, NO, and MPO but did not prevent LDH surge. Oxidative stress parameters were improved following A. pruinosum pretreatment. AE and EE highly reduced cardiomyocyte necrosis and fibrosis but did not prevent leukocyte infiltration. Both extracts induced a concentration-dependent vasorelaxation that was significantly inhibited by the destruction of the endothelium and by L-NAME. Extracts of A. pruinosum exhibited cardioprotective effects, and EE was the most active. The cardioprotective effects of A. pruinosum extracts could be ascribed to their antioxidant, antinecrotic, and endothelium-dependent vasorelaxant effects.

Assessment of the In Vitro Cytotoxicity Effects of the Leaf Methanol Extract of Crinum zeylanicum on Mouse Induced Pluripotent Stem Cells and Their Cardiomyocytes Derivatives.

Crinum zeylanicum (C. zeylanicum) is commonly used in African folk medicine to treat cardiovascular ailments. In the present study, we investigated the cytotoxic effect of the leaf methanol extract of C. zeylanicum (CZE) using mouse pluripotent stem cells (mPSCs). mPSCs and their cardiomyocytes (CMs) derivatives were exposed to CZE at different concentrations. Cell proliferation, differentiation capacity, and beating activity were assessed using xCELLigence system and microscopy for embryoid body (EB) morphology. Expression of markers associated with major cardiac cell types was examined by immunofluorescence and quantitative RT-PCR. Intracellular reactive oxygen species (ROS) levels were assessed by dichlorodihydrofluorescein diacetate staining. The results showed that the plant extract significantly reduced cell proliferation and viability in a concentration- and time-dependent manner. This was accompanied by a decrease in EB size and an increase in intracellular ROS. High concentrations of CZE decreased the expression of some important cardiac biomarkers. In addition, CZE treatment was associated with poor sarcomere structural organization of CMs and significantly decreased the amplitude and beating rate of CMs, without affecting CMs viability. These results indicate that CZE might be toxic at high concentrations in the embryonic stages of stem cells and could modulate the contracting activity of CMs.

Vasorelaxant-Mediated Antihypertensive Effect of the Leaf Aqueous Extract from Stephania abyssinica (Dillon & A. Rich) Walp (Menispermaceae) in Rat.

Stephania abyssinica is a medicinal plant used in Cameroon alternative medicine to treat arterial hypertension (AHT). Previous in vitro studies demonstrated the endothelium nitric oxide-independent vasorelaxant property of the aqueous extract from Stephania abyssinica (AESA). But its effect on AHT is unknown. The present study was undertaken to explore other vasorelaxant mechanisms and to determine the antihypertensive effects of AESA in male Wistar rats. Phytochemical analysis of AESA was carried out using the liquid chromatography-mass spectrometry (LC-MS) method. The vasorelaxant effects of AESA (1-1000 µg/mL) were studied on rat isolated thoracic aorta rings, in the absence or presence of indomethacin (10 µM) or methylene blue (10 µM). The inhibitory effect of AESA on phenylephrine (PE, 10 µM) or KCl- (60 mM) induced contraction as well as the intracellular calcium release was also evaluated. The in vivo antihypertensive activity of AESA (43, 86, or 172 mg/kg/day) or captopril (20 mg/kg/day) administered orally was assessed in L-NAME- (40 mg/kg/day) treated rats. Blood pressure and heart rate (HR) were measured at the end of each week while serum or urinary nitric oxide (NO), creatinine, and glomerular filtration rate (GFR) were determined at the end of the 6 weeks of treatment, as well as histological analysis of the heart and the kidney. The LC-MS profiling of AESA identified 9 compounds including 7 alkaloids. AESA produced a concentration-dependent relaxation on contraction induced either by PE and KCl, which was significantly reduced in endothelium-denuded vessels, as well as in vessels pretreated with indomethacin and methylene blue. Moreover, AESA inhibited the intracellular Ca2+ release-induced contraction. In vivo, AESA reduced the AHT, heart rate (HR), and ventricular hypertrophy and increased serum NO, urine creatinine, and GFR. AESA also ameliorated heart and kidney lesions as compared to the L-NAME group. These findings supported the use of AESA as a potential antihypertensive drug.

Antihypertensive Effects of the Methanol Extract and the Ethyl Acetate Fraction from Crinum zeylanicum (Amaryllidaceae) Leaves in L-NAME-Treated Rat.

Arterial hypertension (AHT) is a leading cardiovascular disease, with a high negative impact on the quality of life. Crinum zeylanicum (C. zeylanicum) leaves extract is used in the West region of Cameroon to treat AHT and heart problems. This study aimed to investigate the antihypertensive effect of C. zeylanicum extract in N ω -nitro-L-arginine methyl ester- (L-NAME-) induced hypertensive rats. The aqueous extract of C. zeylanicum (LAE) was obtained by lyophilizing the juice of triturated fresh leaves. The methanol extract (LME) prepared by maceration of the dried leaves was further partitioned to chloroform (LCF), ethyl acetate (LEAF), and residual (LRF) fractions. The total polyphenol, flavonoid content, and antiradical potentials of these extracts were determined. The curative antihypertensive and renal function protective effects of LME and LEAF were evaluated in vivo on L-NAME-induced hypertensive rats. Hypertension was induced in rats by oral administration of L-NAME (30 mg/kg/day) for 3 consecutive weeks. Thereafter, plant extracts were administered orally at the doses of 30, 60, and 120 mg/kg/day, concomitantly with L-NAME for three other weeks. Body weight, heart rate, and arterial blood pressure were measured at the end of each week throughout the experimental period. At the end of the treatment, 24-hour urine and plasma were collected to assay nitric oxide (NO), creatinine, and protein. The results revealed that LEAF has the higher content of total polyphenol and flavonoid and exhibited the best antiradical potential. Moreover, treatment of hypertensive rats with LME and LEAF significantly (p < 0.001) reduced AHT and heart rate. LME and LEAF significantly increased rat's body mass, plasmatic NO, and urinary creatinine and reduced urine NO and protein contents as compared to the L-NAME group. LME and its LEAF possess potent antihypertensive effects and further protect the renal function in L-NAME-induced hypertensive rats, thus supporting the use of C. zeylanicum in the management of AHT.

The Aqueous Extract from the Stem Bark of Garcinia lucida Vesque (Clusiaceae) Exhibits Cardioprotective and Nephroprotective Effects in Adenine-Induced Chronic Kidney Disease in Rats.

Chronic kidney disease (CKD) is a serious health problem with high morbidity and mortality, mainly attributable to cardiovascular risk. Garcinia lucida is traditionally used in Cameroon for the management of cardiovascular diseases. The aim of this study was to evaluate the cardioprotective and nephroprotective effects of the aqueous extract from the stem bark of G. lucida (AEGL). The in vitro antioxidant effect of AEGL was assessed at concentrations ranging 1-300 µg/mL against DPPH, lipid peroxidation, and AAPH-induced hemolysis. The reducing power and phenolic and flavonoids contents were also determined. CKD was induced by intraperitoneal bolus injection of adenine (50 mg/kg/day) for 4 consecutive weeks to male Wistar rats. AEGL (150 and 300 mg/kg/day) or captopril (20 mg/kg/day) was concomitantly administered with adenine per os. Bodyweight and blood pressure were monitored at baseline and weekly during the test. At the end of the experiment, plasma creatinine, urea, AST, and ALT were quantified. Proteinuria, creatinine excretion, and creatinine clearance were also assessed. The effect on GSH, CAT, and SOD activity was evaluated in cardiac and renal homogenates. Sections of the heart and kidney were stained with hematoxylin and eosin. AEGL exhibited a potent in vitro antioxidant activity and was shown to possess a large amount of phenolic compounds. Adenine alone increased blood pressure, cardiac and kidney mass, proteinuria, protein to creatinine ratio, plasma creatinine, AST, and urea levels (p < 0.05, 0.01, and 0.001). Besides, the bodyweight and creatinine clearance were significantly reduced (p < 0.05 and p < 0.01). All these alterations were blunted by the plant extract, except the bodyweight loss. In addition, AEGL improved GSH levels and CAT and SOD activities. AEGL attenuated adenine-induced glomerular necrosis, tubular dilatation, and cardiac inflammation. AEGL exhibits cardioprotective and nephroprotective effects that may be ascribed to its antihypertensive and antioxidant activities.

Multimodal α-Glucosidase and α-Amylase Inhibition and Antioxidant Effect of the Aqueous and Methanol Extracts from the Trunk Bark of Ceiba pentandra.

Postprandial hyperglycemia and oxidative stress are important factors that worsen the health condition of patients with type 2 diabetes. We recently showed that extracts from Ceiba pentandra mitigate hyperglycemia in dexamethasone- and high diet/streptozotocin-induced diabetes. Herein, we evaluated the postprandial regulatory properties and the antioxidant effects of the aqueous (AE) and methanol (ME) extracts from the stem bark of Ceiba pentandra. The phytochemical analysis of AE and ME was performed using the LC-MS technique and the total phenolic and flavonoid assays. Both extracts were tested for their ability to inhibit superoxide anion (O2 •ـ), hydrogen peroxide (H2O2), protein oxidation, alpha-amylase, and alpha-glucosidase activities. The mode of enzyme inhibition was also determined in a kinetic study. AE and ME were both rich in phenolic and flavonoid compounds. ME was 2.13 and 1.91 times more concentrated than AE in phenolic and flavonoid compounds, respectively. LC-MS allowed the identification of 5 compounds in both extracts. ME and AE inhibited O2 •ـ with IC50 of 51.81 and 34.26 µg/ml, respectively. On H2O2, they exhibited IC50 of 44.84 and 1.78 µg/ml, respectively. Finally, they exhibited IC50 of 120.60 and 140.40 µg/ml, respectively, in the inhibition of protein oxidation induced by H2O2, while showing IC50 of 39.26 and 97.95 µg/ml on the protein oxidation induced by AAPH. ME and AE inhibited alpha-amylase with IC50 of 6.15 and 54.52 µg/ml, respectively. These extracts also inhibited alpha-glucosidase, demonstrating IC50 of 76.61 and 86.49 µg/ml. AE exhibited a mixed noncompetitive inhibition on both enzymes, whereas ME exhibited a competitive inhibition on α-amylase and a pure noncompetitive inhibition on α-glucosidase. These results demonstrate that ME and AE scavenge reactive oxygen species and prevent their effects on biomolecules. Besides, ME and AE inhibit carbohydrate digestive enzymes. These properties may contribute to reduce postprandial hyperglycemia and regulate glycemia in diabetic patients.

Antidiabetic properties of aqueous and methanol extracts from the trunk bark of Ceiba pentandra in type 2 diabetic rat.

The type 2 diabetes is one of the major global health issues that affects millions of people. This study evaluated the antidiabetic activity of aqueous extracts (AECP) and methanol extracts (MECP) from Ceiba pentandra trunk bark on an experimental model of type 2 diabetes (T2D). This model was induced in rats by the combination of a high-fat diet (HFD) and a single dose of streptozotocin (40 mg/kg, intraperitoneal) at the seventh day of experimentation. Diabetes was confirmed on day 10 by fasting blood glucose more than or equal to 200 mg/dL. Diabetic animals still under HFD were treated orally and twice daily, with MECP and AECP (75 and 150 mg/kg) or metformin (40 mg/kg) for 14 days. During the experiment, blood glucose and animal weights were determined. Oral glucose tolerance test was performed on day 15, followed by animals sacrifice for blood, liver, and pancreas collection. Total cholesterol and triglyceride levels were evaluated in plasma, whereas malondialdehyde (MDA), glutathione (GSH), superoxide dismutase, and catalase were quantified in tissue homogenates. AECP and MECP significantly reduced the hyperglycemia by up to 62% and significantly improved the oral glucose tolerance test. The impaired levels of cholesterol and triglycerides registered in diabetic control were significantly reversed by both extracts at all the doses used. Alterations in diabetic pancreas weight, GSH, and MDA were also significantly reversed by plant extracts. AECP and MECP possess type 2 antidiabetic effects that could result from their ability to improve the peripheral use of glucose, lipid metabolism or from their capacity to reduce oxidative stress. These finding provide a new avenue for better control and management of early or advanced T2D.

Hypoglycemic Properties of the Aqueous Extract from the Stem Bark of Ceiba pentandra in Dexamethasone-Induced Insulin Resistant Rats.

Parts of Ceiba pentandra are wildly used in Africa to treat diabetes and previous works have demonstrated their in vivo antidiabetic effects on type 1 diabetes models. In addition, it has been recently shown that the decoction and the methanol extract from the stem bark of C. pentandra potentiate in vitro, the peripheral glucose consumption by the liver and skeletal muscle slices. But nothing is known about its effect on type II diabetes, especially on insulin resistance condition. We investigated herein the antihyperglycemic, insulin-sensitizing potential, and cardioprotective effects of the dried decoction from the stem bark of Ceiba pentandra (DCP) in dexamethasone-induced insulin resistant rats. DCP phytochemical analysis using LC-MS showed the presence of many compounds, including 8-formyl-7-hydroxy-5-isopropyl-2-methoxy-3-methyl-1,4-naphthaquinone, 2,4,6-trimethoxyphenol, and vavain. Wistar rats were given intramuscularly (i.m.) dexamethasone (1 mg/kg/day) alone or concomitantly with oral doses of DCP (75 or 150 mg/kg/day) or metformin (40 mg/kg/day) for 9 days. Parameters such as body weight, glycemia, oral glucose tolerance, plasma triglycerides and cholesterol, blood pressure, and heart rate were evaluated. Moreover, cardiac, hepatic and aortic antioxidants (reduced glutathione, catalase, and superoxide dismutase), malondialdehyde level, and nitric oxide content were determined. DCP decreased glycemia by up to 34% and corrected the impairment of glucose tolerance induced by dexamethasone but has no significant effect on blood pressure and heart rate. DCP reduced the total plasma cholesterol and triglycerides as compared to animals treated only with dexamethasone. DCP also increased catalase, glutathione, and NO levels impaired by dexamethasone, without any effect on SOD and malondialdehyde. In conclusion, the decoction of the stem bark of Ceiba pentandra has insulin sensitive effects as demonstrated by the improvement of glucose tolerance, oxidative status, and plasma lipid profile. This extract may therefore be a good candidate for the treatment of type II diabetes.

Endothelium nitric oxide-independent vasorelaxant effects of the aqueous extract from Stephania abyssinica on the isolated rat thoracic aorta.

BACKGROUND: Stephania abyssinica (Dillon & A. Rich) Walp (Menispermaceae) is a medicinal plant used in the west region of Cameroon to treat arterial hypertension. The present study evaluated the vasorelaxant effects of the aqueous (AESA) and methanol (MESA) extracts from the fresh leaves of S. abyssinica on aorta rings isolated from Wistar rats. METHODS: Aorta rings with intact endothelium were contracted with KCl (60 mM) or phenylephrine (10-5 M) and exposed to cumulative concentrations of each extract, ranging from 10 to 1,000 µg/mL. The vasorelaxant effects of AESA were further evaluated in presence of Nω-nitro-L-arginine methyl ester (L-NAME, 10-4 M), tetraethylammonium (TEA, 5 µM), glibenclamide (5 µM), propranolol (5 µM), and the association glibenclamide-propranolol (AGP). In another set of experiments, the effect of AESA was evaluated on calcium-induced contraction in a hyperpotassic milieu. RESULTS: AESA and MESA exhibited a concentration-dependent vasorelaxation on KCl-contracted aortic rings with respective EC50 of 160.10 and 346.50 µg/mL. AESA similarly relaxed aortic rings contracted with phenylephrine (EC50, 176.80 µg/mL). The vasorelaxant activity of AESA was not significantly affected by L-NAME but was markedly reduced by TEA, glibenclamide, propranolol, and AGP. AESA strongly inhibited the Ca2+-induced contraction by 95%. CONCLUSIONS: These results support the use of S. abyssinica against arterial hypertension and suggest that the vasorelaxant effect of AESA is not mediated via the endothelium/nitric oxide pathway. AESA relaxant properties might be due to an inhibition of Ca2+ influx and/or the activation of ATP-sensitive K+ channels probably via the stimulation of ß-adrenergic receptors.

In vitro anti-hyperglycemic and antioxidant properties of extracts from the stem bark of Ceiba pentandra.

BACKGROUND: The goal of the study was to determine the antidiabetic mechanisms and the antioxidant effects of aqueous (decoction and maceration) and methanol extracts from the stem bark of Ceiba pentandra. METHODS: These extracts were tested in vitro on glucose uptake by skeletal muscles and liver slices and on glucose release by liver slices. The antioxidant activities of C. pentandra extracts were investigated at concentrations ranging from 1 to 300 µg/mL on 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydrogen peroxide (H2O2)-induced hemolysis, H2O2-induced brain lipid peroxidation, hydroxyl (˙OH) radical as well as their reducing power. RESULTS: The decoction similarly to insulin exhibited a significant glucose lowering activity. In a hyperglycemic milieu, it significantly increased glucose uptake by the liver by 56.57% and in the skeletal muscle by 94.19%. In a hypoglycemic milieu, it significantly reduced glucose release by the liver by 33.94%. The decoction, maceration and methanol extracts exhibited a significant radical scavenging activity on DPPH with respective EC50 of 87.84, 54.77 and 6.15 µg/mL versus 2.24 µg/mL observed with ascorbic acid. All the extracts showed a significant antioxidant effect on hydroxyl radical, against lipid peroxidation and H2O2-induced hemolysis. The decoction showed the greatest antihemolytic effect with a maximum inhibition of 77.57% at the concentration of 100 µg/mL. C. pentandra extracts also showed a concentration-dependent reducing power. CONCLUSIONS: These results suggest that the antidiabetic effect of C. pentandra is due to its ability to increase glucose uptake and to reduce glucose release by target organs. The antioxidant properties of C. pentandra extracts are additional benefit for their antidiabetic effects.

Acute and chronic antihypertensive effects of Cinnamomum zeylanicum stem bark methanol extract in L-NAME-induced hypertensive rats.

BACKGROUND: Previous study showed that the aqueous extract of the stem bark of Cinnamomum zeylanicum possesses antihypertensive and vasodilatory properties. The present work investigates the acute and chronic antihypertensive effects of the methanol extract of Cinnamomum zeylanicum stem bark (MECZ) in L-NAME-induced hypertensive rats. METHODS: The acute antihypertensive effects of MECZ (5, 10 and 20 mg/kg) administered intravenously were evaluated in rats in which acute arterial hypertension has been induced by intravenous administration of L-NAME (20 mg/kg). For chronic antihypertensive effects, animals were treated with L-NAME (40 mg/kg/day) plus the vehicle or L-NAME (40 mg/kg/day) in combination with captopril (20 mg/kg/day) or MECZ (300 mg/kg/day) and compared with control group receiving only distilled water. All drugs were administered per os and at the end of the experiment that lasted for four consecutive weeks, blood pressure was measured by invasive method and blood samples were collected for the determination of the lipid profile. The heart and aorta were collected, weighed and used for both histological analysis and determination of NO tissue content. RESULTS: Acute intravenous administration of C. zeylanicum extract (5, 10 and 20 mg/kg) to L-NAME-induced hypertensive rats provoked a long-lasting decrease in blood pressure. Mean arterial blood pressure decreased by 12.5%, 26.6% and 30.6% at the doses of 5, 10 and 20 mg/kg, respectively. In chronic administration, MECZ and captopril significantly prevented the increase in blood pressure and organs' weights, as well as tissue histological damages and were able to reverse the depletion in NO tissue's concentration. The MECZ also significantly lower the plasma level of triglycerides (38.1%), total cholesterol (32.1%) and LDL-cholesterol (75.3%) while increasing that of HDL-cholesterol (58.4%) with a significant low atherogenic index (1.4 versus 5.3 for L-NAME group). CONCLUSION: MECZ possesses antihypertensive and organ protective effects that may result from its ability to increase the production of the endogenous NO and/or to regulate dyslipidemia.

Endothelium/Nitric Oxide Mediates the Vasorelaxant and Antihypertensive Effects of the Aqueous Extract from the Stem Bark of Mammea africana Sabine (Guttiferae).

This study evaluates the vasorelaxant and antihypertensive effects of the aqueous extract from the stem bark of M. africana (AEMA). AEMA was tested in vitro on intact or endothelium-denuded rats' aorta rings precontracted with KCl or norepinephrine in absence or in presence of L-NAME or glibenclamide. The effect of a single concentration (300 µg/mL) of AEMA was also examined on the concentration-response curve of KCl. In vivo, the antihypertensive effects of AEMA (200 mg/kg/day) were evaluated in male Wistar rats treated with L-NAME (40 mg/kg/day) for 4 weeks. AEMA relaxed aorta rings precontracted with NE or KCl with respective EC50 values of 0.36 µg/mL and 197.60 µg/mL. The destruction of endothelium or pretreatment of aorta rings with L-NAME shifted the EC50 of AEMA from 0.36 µg/mL to 40.65 µg/mL and 20.20 µg/mL, respectively. The vasorelaxant activity of M. africana was significantly inhibited in presence of glibenclamide. AEMA also significantly inhibited the concentration-response curve of KCl. Administered orally, AEMA induced acute and chronic antihypertensive effects and normalized renal NO level. These results show that the vasorelaxant activity of AEMA might be mediated by the activation of the NO-cGMP-ATP-dependent potassium channels pathway and might predominantly account for its antihypertensive effect.

A dimeric triterpenoid glycoside and flavonoid glycosides with free radical-scavenging activity isolated from Rubus rigidus var. camerunensis.

The aerial part of Rubus rigidus var. camerunensis (Rosaceae) is used to treat respiratory and cardiovascular disorders in the Cameroonian traditional medicine. The ethanol extract exhibited more potent antioxidant activity (E(max)s of 119% and 229% activity on DPPH and ß-carotene test) than aqueous extract. Bioactivity-guided fractionation of the ethanol extract based on free radical-scavenging assay (DPPH assay) afforded five flavonoid glycosides (four flavonol glycosides and an anthocyanin) and three glucosides of 19α-hydroxyursane-type triterpenoid (two monomeric and one dimeric triterpenoids). The flavonoids were identified as kaempferol 3-O-(2″-O-E-p-coumaroyl)-ß-D-glucopyranoside (1), kaempferol-3-O-ß-D-glucopyranoside (astragalin, 2), kaempferol-3-O-α-L-arabinofuranoside (juglanin, 3), quercetin-3-O-ß-D-glucopyranoside (isoquercitrin, 4), pelargonidin-3-O-ß-D-glucopyranoside (callistephin, 5). The three triterpenoids were 2α, 3ß, 19α, 23-tetrahydroxyurs-12-ene-28-O-ß-D-glucopyranosyl ester (nigaichigoside F(1), 6), 2α, 3ß, 19α-trihydroxyurs-12-ene-23-carboxyl-28-O-ß-D-glucopyranosyl ester (suavissimoside R(1), 7) as monomeric triterpenoids and coreanoside F(1) (8) as a dimeric triterpenoid. The flavonoids exhibited potent antioxidant activities (66 to 93.56% against DPPH radical) and they were also active on ß-carotene test. Coreanoside F(1) exhibited a 63% antioxidant activity, meanwhile the other two triterpenoids showed a weak activity. Three important facts on structure-activity relationship were observed: Compound 8, a dimeric triterpenoid glycoside, strongly enhanced antioxidant activity of its monomers, compound 3 with 3-O-α-L-arabinofuranyl has much more potent activity than compound 2 with 3-O-ß-D-glucopyranosyl, and antocyanin (5) is more potent than its corresponding flavonol glycosides.

Renal effects of Mammea africana Sabine (Guttiferae) stem bark methanol/methylene chloride extract on L-NAME hypertensive rats.

OBJECTIVE: The present study aims at evaluating the effects of methanol/methylene chloride extract of the stem bark of Mammea africana on the renal function of L-NAME treated rats. MATERIAL AND METHODS: Normotensive male Wistar rats were divided into five groups respectively treated with distilled water, L-NAME (40 mg/kg/day), L-NAME + L-arginine (100 mg/kg/day), L-NAME + captopril (20 mg/kg/day) or L-NAME + M. africana extract (200 mg/kg/day) for 30 days. Systolic blood pressure was measured before and at the end of treatment. Body weight was measured at the end of each week. Urine was collected 6 and 24 h after the first administration and further on day 15 and 30 of treatment for creatinine, sodium and potassium quantification, while plasma was collected at the end of treatment for the creatinine assay. ANOVA two way followed by Bonferonni or one way followed by Tukey were used for statistical analysis. RESULTS: M. africana successfully prevented the rise in blood pressure and the acute natriuresis and diuresis induced by L-NAME. When given chronically, the extract produced a sustained antinatriuretic effect, a non-significant increase in urine excretion and reduced the glomerular hyperfiltration induced by L-NAME. CONCLUSIONS: The above results suggest that the methanol/methylene chloride extract of the stem bark of M. africana may protect kidney against renal dysfunction and further demonstrate that its antihypertensive effect does not depend on a diuretic or natriuretic activity.