Aphrodisiac and androgenic effects of the aqueous extract of the roots of Vepris afzelii on cyproterone acetate-induced hypogonadism in rat.

This work aimed to evaluate the effects of the aqueous extract of Vepris afzelii roots on a rat model of hypogonadism. Phytochemical screening and acute toxicity of the extract were performed using different procedures. Hypogonadism was induced orally in adult Wistar rats using cyproterone acetate (30 mg/kg) for ten days. Besides six normal rats (10 ml/kg of distilled water, normal control), 30 hypogonadal rats were subdivided into five groups of six animals each, receiving for 14 days: distilled water (10 ml/kg, hypogonadal control), testosterone (4 mg/kg/3days) and the extract of V. afzelii (100, 200 and 400 mg/kg). Sexual behavior, sperm parameters, testes function and structure were assessed. Compared to the normal controls, significant (p = 0.0000) increases in mount (24 ± 0.94 seconds vs. 1200 ± 00 seconds) and intromission (49.16 ± 10.85 seconds vs. 1200 ± 00 seconds) latencies, and post-ejaculatory interval (381.72 ± 37.55 seconds vs. 1200 ± 00 seconds) were observed in all groups receiving cyproterone acetate on day 0. Total inhibitions of mounts (63.50 ± 8.91 vs. 00 ± 00), intromissions (36.66 ± 3.51 vs. 00 ± 00) (p = 0.0000), ejaculations (2.83 ± 00 vs. 00 ± 00, p = 0.0002) frequencies and mean copulatory interval (627.30 ± 81.80 vs. 00 ± 00, p = 0.0000) were also observed in these groups. Moreover, decreases in daily sperm production (2.65 ± 0.19 vs. 1.17 ± 0.08, p = 0.0498), percentage of sperm mobility (78.64 ± 8.41 vs. 10.12 ± 2.32), serum testosterone level (8.39 ± 0.63 ng/dl vs. 1.68 ± 0.19 ng/dl), diameter of seminiferous tubules (111.97 ± 0.51 µm vs. 94.51 ± 0.57 µm) and height of germinal epithelium (46.58 ± 0.34 µm vs. 33.74 ± 0.66 µm) (p = 0.0000) associated with increases in sperm transit (3.13 ± 0.45 vs. 11.07 ± 1.45, p = 0.0000) were also observed in these groups. Interestingly, compared to hypogonadal control and day 0, the administration of V. afzelii extract induced significant (p = 0.0000) improvements in all these altered parameters with 400 mg/kg being the most active dose. These results, attributed to saponins, flavonoids, polyphenols and triterpenes detected in this plant's extract confirm its traditional usage and could be useful for the management of patients suffering from hypogonadism.

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.

Rotenoids and Isoflavones from Xeroderris stuhlmannii (Taub.) Mendonça & E.P. Souza and Their Biological Activities.

The phytochemical study of the ethanolic extract of the leaf of Xeroderris stuhlmannii led to the isolation of five hitherto unreported compounds including two isoflavones (1-2), and three rotenoids (3-5), along with eight known isoflavonoid derivatives (6-13) and one pterocarpan derivative (14). The structures of the new compounds and those of the known ones were established by the spectroscopic (1D and 2D NMR) and spectrometric (HRESIMS) techniques as well as a comparison of their spectroscopic data with those reported in the literature. The leaf extract, fractions, and isolated compounds were tested for their antibacterial effects against nine bacterial strains. Compounds 3, 8, 11, and 12 showed a significant antibacterial effect, with a minimum inhibitory concentration (MIC) value of 62.5 µg/mL each, against Salmonella typhi, Staphylococcus aureus, Klessiella pneumonae, and Escherichia coli, respectively. In addition, the leaf extract, fractions, and isolated compounds were tested for their antifungal effects against four fungal strains. The hexane fraction showed a significant antifungal effect with an MIC value of 125 µg/mL against Candida parasilosis, whereas compounds 3, 8, and 12 showed significant antifungal activity with an MIC value of 62.5 µg/mL, each against Candida parasilosis, Candida albicans, and Candida krusei, respectively.

Antihypertensive Effects of Aqueous Extract of Ricinodendron heudelotii (Baill.) Pierre (Euphorbiaceae) in Wistar Rat.

Ricinodendron heudelotii stem bark is commonly used in Cameroonian traditional medicine to treat cardiovascular diseases such as hypertension. The present study was designed to investigate the antihypertensive and antioxidant properties of the aqueous extract of Ricinodendron heudelotii in salt-induced hypertensive rats. Analysis by HPLC-ESI-Q-TOF-MS was used to identify various chemical components of the extract. A total of thirty rats were used for each test. High-salt hypertension was induced in rats by oral administration of NaCl for 12 weeks. Mean blood pressure (MBP) and heart rate (HR) were monitored by noninvasive methods. Oral administration of Ricinodendron heudelotii significantly (p < 0.01) reduced the increase of mean blood pressure (23.12%, 26.14%, and 24.34%) and heart rate (31.19%, 31.09%, and 26.98%), respectively, at the doses of 40, 20, and 6 mg/kg, compared to the hypertensive group. All the doses tested significantly reduced or/and ameliorated biochemical and oxidative stress parameters. Histological analysis showed that Ricinodendron heudelotii restored renal disorders induced by the administration of salt. The aqueous extract of Ricinodendron heudelotii exerts a cardioprotective effect, and the antihypertensive activity seems associated with an improvement in antioxidant status. Overall, the results justify and support the traditional use of Ricinodendron heudelotii.

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.

Antihypertensive Effects of the Vitex cienkowskii (Verbenaceae) Stem-Bark Extract on L-NAME-Induced Hypertensive Rats.

Vitex cienkowskii stem-bark is used in Cameroonian traditional medicine to treat cardiovascular diseases including hypertension. In previous studies, the methanol/methylene chloride stem-bark extract of Vitex cienkowskii (MMVC) showed a preventive activity in L-NAME-induced hypertension and improved blood pressure of spontaneously hypertensive rats. The present study investigated the curative effects in L-NAME-induced hypertensive rats (LNHR). Hypertension was induced in rats by oral administration of L-NAME (40 mg/kg/day) for 28 days. The animals were divided into 2 groups: one group of 5 rats receiving distilled water (10 ml/kg) and another 20 rats receiving L-NAME. At the end of 4 weeks of administration of L-NAME, the animals were divided into 4 groups of 5 rats each: one group of hypertensive rats receiving distilled water, another one receiving captopril (25 mg/kg), and two groups of hypertensive rats receiving MMVC at doses of 200 and 400 mg/kg, respectively. Body weight, food, and water intake were measured weekly. At the end of the treatment, blood pressure and heart rate were recorded by invasive method. Whole heart, left ventricle, kidneys, and liver were weighed. The effects of plant extract on lipid profile and oxidative stress markers, as well as markers of hepatic and renal functions were assessed spectrophotometrically according to well described protocols. Results show that L-NAME significantly increases the mean arterial blood pressure (MABP), atherogenic index, lipid profile, and creatinine and transaminase activities of normotensive rats. MMVC significantly reduced the blood pressure in LNHR. Body weight, food and water intake, left ventricular hypertrophy, antioxidant level, renal and hepatic markers, and lipid profile were improved by the treatment with MMVC. The curative effect of MMVC on L-NAME-induced hypertension is probably related to its antihypertensive, hypolipidemic, and antioxidant properties. These results confirmed the use of Vitex cienkowskii for the treatment of hypertension in traditional medicine.

Acute and sub-acute toxicity assessment of aqueous leaves extract of Crassocephalum crepidioides (Asteraceae) in Wistar rats.

OBJECTIVES: Several studies establish the therapeutic properties of various plants which are sometimes a source of minerals, vitamins and phytochemical compounds. However, many studies evoked potential toxic of some. In Cameroon, Crassocephalum crepidioides (C.c) is used in folk medicine to treat several diseases, but there are not much informations about its toxicity. This study evaluate its acute and sub-acute toxicity. METHODS: Our study was undertaken to evaluate acute and sub-acute toxicity of aqueous leaves extract of C.c. The study was conducted using the OECD guidelines about oral toxicity's study. For acute toxicity, rats were administrated single oral dose of 5,000 mg/kg body weight (b.w) and monitored for death and weight impairment during seven days. In sub-acute toxicity, experimental rats received daily doses of 250,500 and 1,000 mg/kg b.w during 28 consecutive days. The toxics effects of the extract were assessed using anthropometric, haematological, biochemical parameters as well as histology of vital body's organs (liver, kidneys, lungs and spleen). RESULTS: lethal dose 50 (LD50) was find to be greater than 5,000 mg/kg b.w in rats. In sub-acute toxicity, we observed significant increase of body weight, food and water consumption with the maximums of 15.14, 24.52 and 28.86% respectively at 1,000 mg/kg b.w. There was no significant change in haematological parameters. However, we observed significant change in biochemical parameters. Furthermore, structural disorders were noticed in liver and kidneys of animals treated with C.c. CONCLUSION: Data obtained suggesting that C.c extract could be safe in single administration, but with toxic effects in repeated treatment.

In vivo effects of Rauvolfia vomitoria (Apocynaceae) ethanolic extract on sexual performance and reproductive activity in male rats.

Plants and plant-derived products have a long history in the treatment of sexual disorders. Rauvolfia vomitoria is one of such plant used traditionally for the enhancement of male sexual and reproductive activity. This study was carried out to elucidate the potential activity of R. vomitoria ethanolic extract on sexual behaviour and male reproductive function. Twenty-five male rats were assigned to five groups and orally treated with distilled water (control), sildenafil citrate (standard) and R. vomitoria ethanolic extract (50, 100 and 200 mg/kg BW) for 22 days. Sexual behaviour parameters such as mount latency (ML), intromission latency (IL), ejaculation latency (EL), mount frequency (MF), intromission frequency (IF), ejaculation frequency (IF) and post-ejaculatory interval (PEI) were recorded at day 0, 1, 8, 15 and 22. The reproductive function including reproductive organ weights, testicular histology and sperm parameters was also assessed. Results showed enhancement in sexual behaviour through significant reduction (p < .01) in ML, IL and PEI and significant increase (p < .01) in EL, MF IF and EF. The extract also caused an increase in sperm count, motility and transit. Present findings demonstrate the ability of R. vomitoria ethanolic extract to improve male sexual behaviour and reproductive activity in rats.

Eco-friendly synthesis, characterization, in vitro and in vivo anti-inflammatory activity of silver nanoparticle-mediated Selaginella myosurus aqueous extract.

INTRODUCTION: There is emerging interest in medicinal plants in the biomedical field, due to their multitude of chemicals which show anti-inflammatory, antimicrobial, antiviral, or antitumoral potential. Research on medicinal plants has shown that nanotechnology could offer new solutions in the quality control, delivery aspects, or in sustaining herbal biological activities. This work reports on the preparation and characterization of silver nanoparticle-mediated Selaginella myosurus plant extract. METHODS: Ultraviolet-visible spectroscopy, Fourier transform infrared spectroscopy, powder X-ray diffraction, energy dispersive X-ray spectroscopy, high-resolution scanning electron microscopy, high-resolution transmission electron microscopy, and selected area electron diffraction have been used to characterize the prepared silver nanoparticles. The synthetic stability was studied by varying concentrations and pH of reactants. Egg albumin denaturation and carrageenan-induced rat paw edema model were used to ascertain the anti-inflammation. RESULTS: Ultraviolet-visible spectroscopy gave plasmon resonance ranging between 420 and 480 nm while Fourier transform infrared spectroscopy proved nano interface functionalized with organics. The powder X-ray diffraction pattern is in agreement with silver and silver chloride nanoparticles of crystallite size 33.7 nm and 44.2 nm for silver and silver chloride, respectively. Energy dispersive X-ray spectroscopy enables elemental characterization of the particles consisting of silver and silver chloride among main elements. Spherical silver grain of 58.81 nm average size has been depicted with high-resolution scanning electron microscopy and high-resolution transmission electron microscopy. Inhibitions of 99% and 60% were obtained in vitro and in vivo, respectively. CONCLUSION: The albumin denaturation and carrageenan-induced rat hind paw edema model to assess the anti-inflammatory potential of generated nanoparticles suggests that the silver nanoparticles may act as reducing/inhibiting agents on the release of acute inflammatory mediators. Hence, this work clearly demonstrated that silver nanoparticles mediated-Selaginella myosurus could be considered as a potential source for anti-inflammatory drugs.

In vitro effects of aqueous extract from Maytenus senegalensis (Lam.) Exell stem bark on egg hatching, larval migration and adult worms of Haemonchus contortus.

BACKGROUND: Maytenus senegalensis is a common shrub which is scattered in tropical Africa. Different parts of this plant have been reported to be useful in traditional medicine against gastrointestinal disorders and intestinal worms. This study evaluated the anthelmintic activity of the aqueous stem bark extract of M. senegalensis using egg hatch assay (EHA), larval migration inhibition assay (LMIA) and adult worms' motility inhibition assay (AMIA). RESULTS: On EHA, the extract concentrations tested resulted in a significant (p < 0.01) inhibition of egg hatching in concentration-dependent manner and ranged between 31.86% at 75 µg.mL- 1 to 54.92% at 2400 µg.mL- 1 after a 48 h post-exposure with eggs. For the LMI assays, the aqueous extract of M. senegalensis showed a significant (p < 0.05) inhibition of larval migration in a concentration-dependent manner. The highest concentration used (2400 µg.mL- 1) showed a 37.77% inhibition. The use of polyvinyl polypyrrolidone (PVPP) indicated that tannins and flavonoids were partly involved in the effect since the larval migration was inhibited by 15.5%, but other biochemical compounds were also implicated. On AMIA, M. senegalensis was associated with a reduced worm motility after a 24 h post exposure compared to phosphate buffered saline as control (p < 0.05). By this time 66.66% of the worms' were found immotile or dead in the wells containing plant extract at 2400 µg.mL- 1. The Phytochemical analysis of aqueous extract of M. senegalensis by HPLC-ESI-MSn detected the presence of proanthocyanidins (20%) and flavonoids (> 50%). CONCLUSIONS: These in vitro results suggest the presence of some anthelmintic properties in M. senegalensis extract, which is traditionally used by small farmers in west and central Africa. These effects may be due to the flavonoids and proanthocyanidins present in the extract and need to be studied under in vivo conditions.

The aqueous extract of Albizia adianthifolia leaves attenuates 6-hydroxydopamine-induced anxiety, depression and oxidative stress in rat amygdala.

BACKGROUND: While the Albizia adianthifolia (Schumach.) W. Wright (Fabaceae) is a traditional herb largely used in the African traditional medicine as analgesic, purgative, antiinflammatory, antioxidant, antimicrobial, memory-enhancer, anxiolytic and antidepressant drug, there are no scientific data that clarify the anxiolytic and antidepressant-like effects in 6-hydroxydopamine (6-OHDA)-lesioned animal model of Parkinson's disease. This study was undertaken in order to identify the effects of aqueous extract of A. adianthifolia leaves on 6-hydroxydopamine-induced anxiety, depression and oxidative stress in the rat amygdala. METHODS: The effect of the aqueous extract of A. adianthifolia leaves (150 and 300 mg/kg, orally, daily, for 21 days) on anxiety and depression was assessed using elevated plus-maze and forced swimming tests, as animal models of anxiety and depression. Also, the antioxidant activity in the rat amygdala was assessed using assessed using superoxide dismutase, glutathione peroxidase and catalase specific activities, the total content of the reduced glutathione, protein carbonyl and malondialdehyde levels. Statistical analyses were performed using by one-way analysis of variance (ANOVA). Significant differences were determined by Tukey's post hoc test. F values for which p < 0.05 were regarded as statistically significant. Pearson's correlation coefficient and regression analysis were used in order to evaluate the connection between behavioral measures, the antioxidant defence and lipid peroxidation. RESULTS: 6-OHDA-lesioned rats exhibited the following: decrease of the exploratory activity, the percentage of the time spent and the number of entries in the open arm within elevated plus-maze test and decrease of swimming time and increase of immobility time within forced swimming test. Administration of the aqueous extract significantly exhibited anxiolytic- and antidepressant-like effects and also antioxidant potential in the rat amygdala. CONCLUSIONS: Our results suggest that the aqueous extract ameliorates 6-OHDA-induced anxiety and depression by attenuation of the oxidative stress in the rat amygdala. These pieces of evidence accentuate its use in traditional medicine.

Antiplasmodial activity of some phenolic compounds from Cameroonians Allanblackia.

BACKGROUND: Plasmodium falciparum, one of the causative agents of malaria, has high adaptability through mutation and is resistant to many types of anti-malarial drugs. This study presents an in vitro assessment of the antiplasmodial activity of some phenolic compounds isolated from plants of the genus Allanblackia. METHODS: Tests were performed on well plates filled with a fixed parasitized erythrocytes volume. Compounds to be tested were then added in wells. After incubation, tritiated hypoxanthine is added and the plates were returned to the incubator. After thawing, the nucleic acids are collected. Inhibitory Concentration 50 (IC50) was determined by linear interpolation. RESULTS: From Allanblackia floribunda, have been isolated and characterized 1,7-dihydroxyxanthone 1, macluraxanthone 4, morelloflavone 9, Volkensiflavone 10 and morelloflavone 7-O-glucoside 11; from Allanblackia monticola, α-mangosine 2, rubraxanthone 3, allaxanthone C 5, norcowanine 6, tovophiline A 7, allaxanthone B 8 and from Allanblackia gabonensis, 1,7-dihydroxyxanthone 1. Six of them were evaluated for their antimalarial properties. The most active compound, macluraxanthone, presented a very interesting activity, with an IC50 of 0.36 and 0.27 µg/mL with the F32 and FcM29 strains respectively. CONCLUSION: This work confirms that species of Allanblackia genus are medicinally important plants containing many biologically active compounds that can be used effectively as antiplasmodial.

Memory-enhancing activities of the aqueous extract of Albizia adianthifolia leaves in the 6-hydroxydopamine-lesion rodent model of Parkinson's disease.

BACKGROUND: Albizia adianthifolia (Schumach.) W. Wright (Fabaceae) is a traditional herb largely used in the African traditional medicine as analgesic, purgative, anti-inflammatory, antioxidant, antimicrobial and memory-enhancer drug. This study was undertaken in order to evaluate the possible cognitive-enhancing and antioxidative effects of the aqueous extract of A. adianthifolia leaves in the 6-hydroxydopamine-lesion rodent model of Parkinson's disease. METHODS: The effect of the aqueous extract of A. adianthifolia leaves (150 and 300 mg/kg, orally, daily, for 21 days) on spatial memory performance was assessed using Y-maze and radial arm-maze tasks, as animal models of spatial memory. Pergolide-induced rotational behavior test was employed to validate unilateral damage to dopamine nigrostriatal neurons. Also, in vitro antioxidant activity was assessed through the estimation of total flavonoid and total phenolic contents along with determination of free radical scavenging activity. Statistical analyses were performed using two-way analysis of variance (ANOVA). Significant differences were determined by Tukey's post hoc test. F values for which p<0.05 were regarded as statistically significant. Pearson's correlation coefficient and regression analysis were used in order to evaluate the association between behavioral parameters and net rotations in rotational behavior test. RESULTS: The 6-OHDA-treated rats exhibited the following: decrease of spontaneous alternations percentage within Y-maze task and increase of working memory errors and reference memory errors within radial arm maze task. Administration of the aqueous extract of A. adianthifolia leaves significantly improved these parameters, suggesting positive effects on spatial memory formation. Also, the aqueous extract of A. adianthifolia leaves showed potent in vitro antioxidant activity. Furthermore, in vivo evaluation, the aqueous extract of A. adianthifolia leaves attenuated the contralateral rotational asymmetry observed by pergolide challenge in 6-OHDA-treated rats. CONCLUSIONS: Taken together, our results suggest that the aqueous extract of A. adianthifolia leaves possesses antioxidant potential and might provide an opportunity for management neurological abnormalities in Parkinson's disease conditions.

Tetra-acetylajugasterone a new constituent of Vitex cienkowskii with vasorelaxant activity.

Tetra-acetylajugasterone C (TAAC) was found to be one of the naturally occurring compounds of the Cameroonian medicinal plant Vitex cienkowskii which is responsible for a vasorelaxant activity of an extract of this plant. The evaluation of the underlying mechanisms for the relaxing effect of TAAC was determined using aortic rings of rats and mice. TAAC produced a concentration-dependent relaxation in rat artery rings pre-contracted with 1µM noradrenaline (IC50: 8.40µM) or 60mM KCl (IC50: 36.30µM). The nitric oxide synthase inhibitor l-NAME (100µM) and the soluble guanylate cyclase inhibitor ODQ (10µM) significantly attenuated the vasodilatory effect of TAAC. TAAC also exerted a relaxing effect in aorta of wild-type mice (cGKI(+/+); IC50=13.04µM) but a weaker effect in aorta of mice lacking cGMP-dependent protein kinase I (cGKI(-/-); IC50=36.12µM). The involvement of calcium channels was studied in rings pre-incubated in calcium-free buffer and primed with 1µM noradrenaline prior to addition of calcium to elicit contraction. TAAC (100µM) completely inhibited the resulting calcium-induced vasoconstriction. The same concentration of TAAC showed a stronger effect on the tonic than on the phasic component of noradrenaline-induced contraction. This study shows that TAAC, a newly detected constituent of Vitex cienkowskii contributes to the relaxing effect of an extract of the plant. The effect is partially mediated by the involvement of the NO/cGMP pathway of the smooth muscle but additionally inhibition of calcium influx into the cell may play a role.

Analgesic and antiinflammatory activities of the ethyl acetate fraction of Bidens pilosa (Asteraceae).

Bidens pilosa is an Asteraceae widely used in traditional medicine for the treatment of various ailments including pain and inflammation. The present work was undertaken to assess the analgesic and antiinflammatory properties of the ethyl acetate fraction of methylene chloride/methanol (1:1) extract of leaves of Bidens pilosa at the gradual doses of 50, 100 and 200 mg/kg in mice and rats, respectively. The analgesic properties of Bidens pilosa were investigated using the acetic acid writhing, hot plate, capsaicin and formalin-induced pain models. This was followed by a study of the antiinflammatory properties using carrageenan, dextran, histamine and serotonin to induce acute inflammation in rat hind paw. The extract provided a significant (p < 0.01) reduction in pain induced by all four models of nociception. It also presented significant (p < 0.05) antiinflammatory activity in all four models of acute inflammation. These results show that the ethyl acetate fraction of methylene chloride/methanol (1:1) of Bidens pilosa has both analgesic and antiinflammatory properties. The qualitative analysis of the fraction by the high-performance liquid chromatography (HPLC) fingerprint revealed the presence of two flavonoids, namely quercetin and iso-okanin, known to have antiinflammatory and antinociceptive properties, which could be responsible for the analgesic and antiinflammatory effects observed.

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.

Pentacyclic triterpenoids and ceramide mediate the vasorelaxant activity of Vitex cienkowskii via involvement of NO/cGMP pathway in isolated rat aortic rings.

ETHNOPHARMACOLOGICAL RELEVANCE: Vitex cienkowskii Kotschy & Peyritsch is a deciduous tree, prescribed by Cameroonian traditional healers as one of the most popular plant widely used in many disorders including cardiovascular diseases. The preliminary pharmacological studies carried out on Vitex cienkowskii showed its vasorelaxant activities on guinea-pig aortic rings. AIM OF THE STUDY: The present work evaluated the vasorelaxant activity of extract and isolated compounds from Vitex cienkowskii. MATERIALS AND METHODS: Rat aortic rings were used to evaluate the in vitro vascular effect of the extract. The antioxidant activity was determined by measuring the reduction of the free radical 1,1-diphenyl-1-picryl-hydrazyl (DPPH). RESULTS: Vitex cienkowskii induced significant relaxation in a concentration- and endothelium-dependent manner (EC(50)=12.12 µg/ml, CH(2)Cl(2)-MeOH, 1:1) and did not produce a vasorelaxant effect on contraction evoked by KCl (60 mM). In order to determine its mode of action, Vitex cienkowskii-induced relaxant effect was evaluated in the presence of indomethacin (10 µM), L-NAME (100 µM), ODQ (1 µM) and SQ22356 (100 µM). Relaxation was significantly blocked by L-NAME and ODQ. These results indicate that Vitex cienkowskii-mediated relaxation is endothelium dependent, probably due to NO release, and the consequent activation of vascular smooth muscle soluble guanylate cyclase (sGC), a signal transduction enzyme that forms the second messenger cGMP. Bio-guided study of Vitex cienkowskii allowed the isolation of the known pentacyclic triterpenoids and a ceramide. It is the first report of salvin A, maslinic acid and a ceramide from Vitex cienkowskii. The activity induced by these compounds indicated that they may be partly responsible for the vasorelaxant effect of the plant extract. A dose of 40 mg/kg of CH(2)Cl(2)-MeOH (1:1) extract administered intravenously induced a decrease of mean arterial pressure but did not affect the heart rate. Moreover the plant extracts were found to be highly active in the DPPH radical scavenging assay. CONCLUSION: Vitex cienkowskii extract possesses antioxidant property, vasorelaxing, and hypotensive effect linked to the endothelium related factors, where nitric oxide is involved.

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.

Anti-inflammatory and anti-nociceptive activities of the stem bark extracts from Allanblackia monticola STANER L.C. (Guttiferae).

THE AIM OF THIS STUDY: was to assess the anti-inflammatory and mechanism of action of Allanblackia monticola (Guttiferae). The anti-inflammatory activity "in vivo" of the methylene chloride/methanol extract, methanol and methylene chloride fractions of stem barks of Allanblackia monticola, administered orally at doses of 37.5; 75; 150 and 300 mg/kg, was evaluated on carrageenan-induced oedema in rats to determine the most active fraction. Indomethacin, inhibitor of cyclo-oxygenase was used as reference drug. The effects of the most active fraction were then examined on the rat paw oedema caused by histamine, serotonin, arachidonic acid and dextran followed by its ulcerogenic effect. The results showed that the methylene chloride fraction of Allanblackia monticola was more effective on the oedema caused by the carrageenan. The anti-nociceptive activity of the methylene chloride fraction was assessed using the acetic acid-induced abdominal constriction model, formalin test and hot plate test. At 150 mg/kg, Allanblackia monticola caused maximum inhibitions of inflammation induced by carrageenan (83.33%), by histamine (42.10%), by dextran (40.29%) and by arachidonic acid (64.28%). Allanblackia monticola (75-300 mg/kg) did not cause significant modification of the oedema induced by serotonin. Concerning the anti-nociceptive properties of the plant, the methylene chloride fraction (75-300 mg/kg) caused a dose-dependent inhibition on abdominal contractions induced by acetic acid (32.34-77.37%) and significantly inhibited the inflammatory pain caused by formalin (40.71-64.78%). Allanblackia monticola did not increase the latency time in the hot plate test. Like indomethacin (10mg/kg), the fraction at the dose of 150 mg/kg caused ulceration of the gastric mucous membrane in treated rats. These results show that Allanblackia monticola has an anti-inflammatory and analgesic activities with gastric ulcerative side effects.