Hepatoprotective and in vivo antioxidant effects of granulometric classes and decoction of Ficus dicranostyla Mildbread leaves powders against carbon tetrachloride-induced hepatotoxicity in Wistar rats.

Ficus dicranostyla is a plant from the Moraceae family commonly used in African countries for its nutritional value and its believed medicinal properties. Its antioxidant in vitro capacity and its richness in phenolic compounds have been previously demonstrated. This work aimed at evaluating the hepatoprotective and in vivo antioxidant activities of different granulometric fractions of the F. dicranostyla leaves against carbon tetrachloride-induced hepatotoxicity in rats. Powdery fractions (<125, 250-125, and ≥250 µm), and the unsieved powder, obtained from the F. dicranostyla leaves were water-dissolved and given orally to rats at the same dose (250 mg/kg body weight) before administering carbon tetrachloride intraperitoneally (1 mL/Kg bw). The lipid status parameters (total cholesterol, triglycerides, HDL-cholesterol, and LDL-cholesterol), hepatic toxicity through aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) in blood plasma, and antioxidant status by measuring the malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) in liver homogenate were performed. The activities of all parameters registered a significant (p < .05) alteration in CCl4-treated rats, which were significantly recovered toward an almost normal level in coadministered with Ficus dicranostyla leaf powder samples in a particle size-dependent manner. Results suggest that the smaller particle size of the powder fraction, as well as the decoction powder of Ficus dicranostyla, may be used as hepatoprotective and antioxidant agents.

Aqueous extract of Parkia biglobosa (Jacq.) R. Br. (Fabaceae) exerts antiepileptogenic, anti-amnesic, and anxiolytic-like effects in mice via mechanisms involving antioxidant and anti-inflammatory pathways.

Parkia biglobosa (Jacq.) R. Br. (Fabaceae) is a widely distributed tree, used in traditional medicine to treat amebiasis, hookworm infection, ascariasis, asthma, sterility, dental pain, headaches, cardiac disorders, and epilepsy. To date, no study on the effect of an aqueous extract of P. biglobosa on epileptogenesis and associated neuropsychiatric disorders has been undertaken. Therefore, this study aimed to investigate antiepileptogenic-, antiamnesic-, and anxiolytic-like effects of an aqueous extract of P. biglobosa using pentylenetetrazole (PTZ)-induced kindling in mice. Animals were divided into six groups of eight mice each. Thus, a PTZ group received distilled water (10 ml/kg, per os), a positive control group received sodium valproate (300 mg/kg, p.o.), and three test groups received the aqueous extract of P. biglobosa (80, 160, and 320 mg/kg, p.o.).In addition, a control group of eight mice receiving distilled water (10 ml/kg, p.o.) was formed. The treatments were administered to mice, 60 min before administration of PTZ (20 mg/kg, i.p.). These co-administrations were performed once daily, for 22 days. The number and duration of seizures (stages 1, 2, 3, and 4 of seizures) exhibited by each mouse were assessed for 30 min during the treatment period. Twenty-four hours following the last administration of the treatments and PTZ, novel object recognition and T-maze tests were performed to assess working memory impairment in mice, while the open field test was performed to assess anxiety-like behavior. After these tests, the animals were sacrificed, and the hippocampi were collected for biochemical and histological analysis. During the period of PTZ-kindling, the extract at all doses completely (p < 0.001) protected all mice against stages 3 and 4 of seizures when compared to sodium valproate, a standard antiepileptic drug. The extract also significantly (p < 0.001) attenuated working memory impairment and anxiety-like behavior. In post-mortem brain analyses, the extract significantly (p < 0.001) increased γ-aminobutyric acid (GABA) level and reduced oxidative stress and inflammation. Histological analysis showed that the aqueous extract attenuated neuronal degeneration/necrosis in the hippocampus. These results suggest that the extract is endowed with antiepileptogenic-, anti-amnesic-, and anxiolytic-like effects. These effects seem to be mediated in part by GABAergic, antioxidant, and anti-inflammatory mechanisms. These results suggest the merit of further studies to isolate the bioactive molecules responsible for these potentially therapeutically relevant effects of the extract.

Pathological and immunological evaluation of different regimens of praziquantel treatment in a mouse model of Schistosoma mansoni infection.

BACKGROUND: One of the considerable challenges of schistosomiasis chemotherapy is the inefficacy of praziquantel (PZQ) at the initial phase of the infection. Immature schistosomes are not susceptible to PZQ at the curative dose. Here, we investigated the efficacy of different PZQ regimens administered during the initial stage of Schistosoma mansoni infection in mice. METHODOLOGY/PRINCIPAL FINDINGS: Two months-old mice were individually infected with 80 S. mansoni cercariae and divided into one infected-untreated control group (IC) and four PZQ-treated groups: PZQ at 100 mg/kg/day for five consecutive days (group PZQ1), PZQ at 100 mg/kg/day for 28 days (group PZQ2), PZQ at 18 mg/kg/day for 28 days (group PZQ3) and a single dose of PZQ at 500 mg/kg (group PZQ4). The treatment started on day one post-infection (p.i), and each group of mice was divided into two subgroups euthanized on day 36 or 56 p.i, respectively. We determined the mortality rate, the parasitological burden, the hepatic and intestinal granulomas, the serum levels of Th-1, Th-2, and Th-17 cytokines, and gene expression. The treatment led to a significant (p < 0.001) reduction of worm burden and egg counts in the intestine and liver in groups PZQ2 and PZQ3. On 56th day p.i, there was a significant reduction (p < 0.001) of the number and volume of the hepatic granulomas in groups PZQ2 and PZQ3 compared to group PZQ1 or PZQ4. Moreover, in group PZQ3, the serum levels of IFN-γ, TNF-α, IL-13, and IL-17 and their liver mRNA expressions were significantly reduced while IL-10 and TGF-ß gene expression significantly increased. The highest mortality rate (81.25%) was recorded in group PZQ2. CONCLUSION/SIGNIFICANCE: This study revealed that the administration of PZQ at 18 mg/kg/day for 28 consecutive days was the optimal effective posology for treating S. mansoni infection at the initial stage in a murine model.

In Vitro Assessment of the Cercaricidal Activity of Sida acuta Burm. F. and Sida rhombifolia Linn. (Malvaceae) Hydroethanolic Extracts, Cytotoxicity, and Phytochemical Studies.

Despite the global efforts, schistosomiasis remains a public health problem in several tropical and subtropical countries. One of the major challenges in the fight against schistosomiasis is the interruption of the parasite life cycle. Here, we evaluated the anticercarial, cytotoxicity, and phytochemical profiles of Sida acuta (HESa) and Sida rhombifolia (HESr) hydroethanolic extracts (Malvaceae). Schistosoma mansoni cercaria was collected from fifteen Biomphalaria pfeifferi-infected snails. Twenty-five cercariae were incubated in duplicate with different concentrations (31.25-1,000 µg/mL) of HESa or HESr. The cercaria viability was monitored at 30 min time intervals for 150 min, and the concentration-response curve of each plant extract was used to determine their respective lethal concentration 50 (LC50). Additionally, the cytotoxicity profile of each plant extract was evaluated on the Hepa 1-6 cell line at a concentration range of 15.625-1,000 µg/mL using the WST-8 assay method and its inhibitory concentration 50 (IC50) was calculated. Moreover, phytochemical characterization of each plant extract was carried out by HPLC-MS. Both extracts exhibited cercaricidal activity in a time- and concentration-dependent manner. At 30 min time point, HESa (LC50 = 28.41 ± 3.5 µg/mL) was more effective than HESr (LC50 = 172.42 ± 26.16 µg/mL) in killing S. mansoni cercariae. Regarding the cytotoxicity effect of both extracts, the IC50 of HESa (IC50 = 109.67 µg/mL) was lower than that of HESr (IC50 = 888.79 µg/mL). The selectivity index was 3.86 and 5.15 for HESa and HESr, respectively. Fifteen compounds were identified from HESa and HESr after HPLC-MS analysis. N-Feruloyltyramine, a polyphenol, and thamnosmonin, a coumarin, were identified in both extracts. HESa and HESr displayed cercaricidal activity and were not toxic on Hepa 1-6 cell line. Based on the selectivity index of these extracts, S. rhombifolia extract could be more effective on S. mansoni cercariae than S. acuta extract. This study could provide baseline information for further investigations aiming to develop plant-based alternative drugs against S. mansoni.

Ziziphus jujuba (Rhamnaceae) Alleviates Working Memory Impairment and Restores Neurochemical Alterations in the Prefrontal Cortex of D-Galactose-Treated Rats.

Alzheimer's disease is a progressive cognitive dysfunction. However, pharmacological treatments are symptomatic and have many side effects, opening the opportunity to alternative medicine. This study investigated the antiamnesic effect of the aqueous extract of Ziziphus jujuba on D-galactose-induced working memory impairment in rats. Impairment of working memory was induced by subcutaneous (s.c.) injection of D-galactose (350 mg/kg/day) to rats for 21 days. These animals were then subjected to object recognition and Y-maze tests. Rats with confirmed memory impairment were treated per os (p.o.) with tacrine (10 mg/kg), aspirin (20 mg/kg, p.o.), extract (41.5, 83, and 166 mg/kg, p.o.), and distilled water (10 mL/kg, p.o.) daily for 14 days. At the end of the treatments, alteration in working memory was assessed using the above paradigms. Afterward, these animals were euthanized, and cholinergic, proinflammatory, and neuronal damage markers were analyzed in the prefrontal cortex. Rats administered D-galactose and treated with distilled water had impaired working memory (evidenced by decreased time spent on the novel object and discrimination index) and decreased spontaneous alternation in the Y-maze. D-galactose also decreased the levels of acetylcholinesterase and acetylcholine and increased the level of glial fibrillary acidic protein, ionized calcium-binding adapter molecule 1, tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1ß), interleukin 6 (IL-6), and interferon-gamma (IFN-γ). Treatment with the extract (166 mg/kg) reversed the time spent on the novel object and the discrimination index. It equally increased the percentage of spontaneous alternation. Neurochemical analysis revealed that the extract markedly alleviated acetylcholinesterase activity and neuroinflammation. These observations were corroborated by the reduction in neuronal loss. Taken together, these results suggest that Ziziphus jujuba aqueous extract possesses an antiamnesic effect. This effect seems to involve cholinergic and anti-inflammatory modulations. This, therefore, claims using this plant in the treatment of dementia in Cameroon subject to further studies and trials.

In vitro and in vivo antiplasmodial activity of hydroethanolic bark extract of Bridelia atroviridis müll. Arg. (Euphorbiaceae) and lc-ms-based phytochemical analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Malaria is a life-threatening health problem worldwide and treatment remains a major challenge. Natural products from medicinal plants are credible sources for better anti-malarial drugs. AIM OF THE STUDY: This study aimed at assessing the in vitro and in vivo antiplasmodial activities of the hydroethanolic extract of Bridelia atroviridis bark. MATERIALS AND METHODS: The phytochemical characterization of Bridelia atroviridis extract was carried out by High-Performance Liquid Chromatography-Mass spectrometry (HPLC-MS). The cytotoxicity test on Vero cells was carried out using the resazurin-based assay while the in vitro antiplasmodial activity was determined on Plasmodium falciparum (Dd2 strain, chloroquine resistant) using the SYBR green I-based fluorescence assay. The in vivo assay was performed on Plasmodium berghei-infected rats daily treated for 5 days with distilled water (10 mL/kg) for malaria control, 25 mg/kg of chloroquine sulfate for positive control and 50, 100 and 200 mg/kg of B. atroviridis extract for the three test groups. Parasitaemia was daily monitored using 10% giemsa-staining thin blood smears. At the end of the treatment, animals were sacrificed, blood was collected for hematological and biochemical analysis while organs were removed for biochemical and histopathological analyses. RESULTS: The HPLC-MS analysis data of B. atroviridis revealed the presence of bridelionoside D, isomyricitrin, corilagin, myricetin and 5 others compounds not yet identified. Bridelia atroviridis exhibited good in vitro antiplasmodial activity with the IC50 evaluated at 8.08 µg/mL and low cytotoxicity with the median cytotoxic concentration (CC50) higher than 100 µg/mL. B. atroviridis extract significantly reduced the parasitemia (p < 0.05) with an effective dose-50 (ED-50) of 89 mg/kg. B. atroviridis also prevented anemia, leukocytosis and liver and kidneys impairment by decrease of transaminases, ALP, creatinine, uric acid, and triglycerides concentrations. As well, B. atroviridis extract decreased some pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6) levels and significantly improved the anti-inflammatory status (P < 0.01) of infected animals marked by a decrease of IL-10 concentration. These results were further confirmed by the improved of antioxidant status and the quasi-normal microarchitecture of the liver, kidneys and spleen in test groups. Overall, the hydroethanolic bark extract of Bridelia atroviridis demonstrated antimalarial property and justified its use in traditional medicine to manage malaria disease.

Effects of stem bark aqueous extract of Fagara tessmannii Engl (Rutaceae) on cardiovascular risks related to monosodium glutamate-induced obesity in rat: In vivo and in vitro assessments.

ETHNOPHARMACOLOGICAL RELEVANCE: Fagara tessmannii is a shrub of the African rainforests in South-West, Centre, South and East provinces in Cameroon. It is used in traditional medicine for the treatment of tumors, swellings, inflammation, gonorrhoea, schistosomiasis, antifungal, heart diseases and as anti-hypertensive. AIM OF THE STUDY: We investigated the potential effects of F. tessmannii on cardiovascular risk related to monosodium glutamate-induced obesity. MATERIALS AND METHODS: Monosodium glutamate (MSG, 4 mg/g/day) was injected subcutaneously to newborn Wistar rats for the four consecutive first days of their life and on the 6th, 8th and 10th day after birth. After 21 weeks, obese rats were treated orally with F. tessmannii (100 or 200 mg/kg/day), orlistat (10 mg/kg/day) or telmisartan (10 mg/kg/day) for 6 weeks. Body weight, obesity, body mass index (BMI), Lee index, insulin sensitivity and glucose tolerance, blood pressure, lipid profile as a Coronary Risk Index (CRI), and reactivity of isolated thoracic aorta were evaluated. RESULTS: In addition to significantly decrease body weight (17.60% and 20.34%), BMI, Lee's index, retroperitoneal fat, total adiposity, and coronary risk indicators, F. tessmannii has significantly decreased insulin resistance and hyperglycemia and high blood pressure observed in MSG-obese rats. The high contractility to phenylephrine as well as the hypersensitivity to sodium nitroprusside (a nitric oxide-donor), observed in MSG aortic rings were significantly reduced by the F. tessmannii extract. Enhanced serum Na+ and Cl- levels and decreased K+ observed in obese rats were also significantly reversed after F. tessmannii treatment. CONCLUSIONS: F. tessmannii fights against obesity and associated cardiovascular risks by modulating production and vascular responsiveness to vasoactive factors, monitoring premature aging. F. tessmannii promotes the loss of ectopic fat and other fatty tissues, the sensitivity of the peripherical tissues to insulin, the energy expenditure and the renovascular decompression and regulates ions movement which prevents hypertension.

Antihypertensive and antidiabetic activities of Erythrina senegalensis DC (Fabaceae) stem bark aqueous extract on diabetic hypertensive rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Erythrina senegalensis is traditionally used in Cameroon for its relaxing and hypoglycemic properties in the treatment of cardiovascular diseases and diabetes. AIM OF THE STUDY: High blood pressure and diabetes mellitus are frequently linked. These pathologies represent major risk factors for cardiovascular and renal diseases. The present study was designed to evaluate the antidiabetic and antihypertensive activity of the stem bark of Erythrina senegalensis aqueous extract in male hypertensive diabetic rats (HDR). MATERIALS AND METHODS: Hypertension and diabetes were induced by oral administration of sucrose (15%) and ethanol (40°) at doses of 1.5 g/kg and 5 g/kg respectively for 30 days, followed by an intravenous injection of streptozotocin (STZ; 40 mg/kg). A control group of 5 rats received distilled water (10 mL/kg) followed by intravenous injection of 0.9% NaCl (1 mL/100 g). HDR were divided into 4 groups of 5 rats each according to their blood glucose level and continued to receive ethanol in association with: distilled water (10 mL/kg); group I, metformin (200 mg/kg)+nifedipine (10 mg/kg); group II, plant extract (100 and 200 mg/kg) group IV and V, respectively for 28 days. At the end of the treatment, hemodynamic parameters were recorded by the direct method. Animals were sacrificed; blood and organs (aorta, heart, liver, and kidneys) were collected for biochemical and histological analysis. Phytochemistry and HPLC-DAD-HRESI-MS were used to determine the major compounds of the extract. RESULTS: The administration of sucrose, alcohol, and STZ resulted in a significant increase in blood glucose, hemodynamic parameters, and body weight loss. A significant decrease in pancreatic islets size, nitrite, GSH, SOD and catalase activity was observed in HDR. There was also a significant increase in serum triglycerides, total cholesterol, creatinine, bilirubin, and transaminases activity in HDR. The aqueous extract of E. senegalensis, as well as the metformin + nifedipine combination, significantly improved all these parameters. HPLC coupled to both diode array and mass spectrometry detectors revealed the presence of 15 compounds and 11 of them were identified. CONCLUSION: These results suggest that the aqueous extract of E. senegalensis possess antihypertensive, hypoglycemic, hypolipidemic, cardiomodulator and antioxidant properties involved in the improvement of the metabolic disorders found in HDR. This may be due at least in part to the presence of Erysenegalensein (D, O, N, E), Warangalone, senegalensin and 6,8-diprenylgenistein identified in the extract.

Efficacy of Sida pilosa Retz aqueous extract against Schistosoma mansoni - induced granulomatous inflammation in the liver and the intestine of mice: histomorphometry and gastrointestinal motility evaluation.

BACKGROUND: The macerate of Sida pilosa aerial parts is used empirically for the treatment of intestinal helminthiasis. Previous studies have shown that Sida pilosa aqueous extract (SpAE) has schistosomicidal, antioxidant, anti-inflammatory and anti-fibrotic activities in Schistosoma mansoni infection. This study was designed to evaluate the effect of SpAE on the granulomatous inflammation induced by S. mansoni in the liver and the intestine of mice by histomorphometry; as well as on the gastrointestinal motility. METHODS: To study the effect of SpAE on the liver and intestine histomorphometry and on the gastrointestinal motility, SpAE was administered at 200 mg/kg per os to S. mansoni-infected mice for 4 weeks. Praziquantel was used as reference drug. Prior to carrying out sacrifice, a batch of mice was subjected to gastrointestinal transit evaluation with 3% charcoal meal. After sacrifying another batch of mice, we performed histological and morphometric analyses of the liver and the ileum. We measured the following: total proteins, transaminases, malondialdehyde, nitrites, superoxide dismutase, catalase and reduced glutathione. The effect of SpAE (4, 8, 16 and 32 mg/mL) on the ileum contractile activity was evaluated either in the absence or in the presence of pharmacological blockers. RESULTS: SpAE induced a significant reduction of hepatosplenomegaly and intestine enlargement. The number of granulomas was reduced by 52.82% in the liver and 52.79% in the intestine, whereas the volume of hepatic granulomas decreased by 48.76% after SpAE treatment. SpAE also reduced (p < 0.001) the ileal muscular layer thickness. The levels of total proteins, transaminases, malondialdehyde, nitrites, superoxide dismutase, catalase and reduced glutathione were restored after treatment of infected mice with SpAE. A normalization of the gastrointestinal transit was also recorded after SpAE treatment. The effect of SpAE on intestinal motility was mediated via intracellular and extracellular calcium mobilization. CONCLUSION: Our findings provide evidence that SpAE improves granulomatous inflammation induced by S. mansoni both in the liver and in the intestine, as well as it re-establishes normal gastrointestinal transit. SpAE may be used for the development of alternative medicine against S. mansoni infection.

Neoboutonia melleri var velutina Prain: in vitro and in vivo hepatoprotective effects of the aqueous stem bark extract on acute hepatitis models.

BACKGROUND: Hepatitis is a liver inflammation caused by different agents and remains a public health problem worldwide. Medicinal plants are an important source of new molecules being considered for treatment of this disease. Our work aims at evaluating the hepatoprotective properties of Neoboutonia velutina, a Cameroonian medicinal plant. METHODS: The aqueous extract has been prepared using phytochemical methods. HepG2 cells were used to assess anti-inflammatory properties of the extract at different concentrations. Acute hepatitis models (Carbon tetrachloride and Concanavalin A) were performed in mice receiving or not receiving, different extract doses by gavage. Liver injury was assessed using histology, transaminases and pro-inflammatory markers. Extract antioxidant and radical scavenging capacities were evaluated. RESULTS: The extract led to a significant decrease in pro-inflammatory cytokine expression in vitro and to a remarkable protection of mice from carbon tetrachloride-induced liver injury, as shown by a significant decrease in dose-dependent transaminases level. Upon extract treatment, inflammatory markers were significantly decreased and liver injuries were limited as well. In the Concanavalin A model, the extract displayed weak effects. CONCLUSIONS: Taking into account underlying mechanisms in both hepatitis models, we demonstrate the extract's radical scavenging capacity. Neoboutonia velutina displays a potent hepatoprotective effect mediated through radical scavenging properties.

Bidens pilosa Ethylene acetate extract can protect against L-NAME-induced hypertension on rats.

BACKGROUND: Essential hypertension is mainly caused by endothelial dysfunction which results from nitric oxide (NO) deficiency. The present study was design to evaluate the protective effect of Bidens pilosa ethylene acetate extract (Bp) on L-NAME induced hypertension and oxidative stress in rats. METHODS: Male Wistar rats were used to induce hypertension by the administration of L-NAME (a non-pecific nitric oxide inhibitor) (50 mg/kg/day). The others groups were receiving concomitantly L-NAME plus Bp extract (75 and 150 mg/kg/day) or losartan (25 mg/kg/day). All the treatments were given orally for 4 weeks. At the end of the treatment, the hemodynamic parameters were recorded using the direct cannulation method. The effects of the extract on lipid profile, kidney and liver functions as well as oxidative stress markers were evaluated by colorimetric method. Results were expressed as the mean ± SEM. The difference between the groups was compared using one-way analysis of variance (ANOVA) followed by the Duncan's post hoc test. RESULTS: Animals receiving L-NAME presented high blood pressure, normal heart rate and lipid profile as well as NO depletion, liver and kidney injuries and oxidative stress. The concomitant treatment with L-NAME and Bp or losartan succeeded to prevent the raised of blood pressure and all the other injuries without affecting the heart rate. CONCLUSION: These results confirm the antihypertensive effects of Bidens pilosa and highlight its protective properties in L-NAME model of hypertension in rat, probably due to the presence of Quercetin 3,3 '-dimethyl ether 7-0-ß-D-glucopyranoside.

Antidiabetic Effects of Aqueous and Dichloromethane/Methanol Stem Bark Extracts of Pterocarpus soyauxii Taub (Papilionaceae) on Streptozotocin-induced Diabetic Rats.

AIM OF THE STUDY: The aim is to evaluate the hypoglycemic and antidiabetic effects of aqueous and CH2Cl2/CH3OH stem bark extracts of Pterocarpus soyauxii Taub in normal and diabetic rats. MATERIALS AND METHODS: Streptozotocin (STZ)-induced diabetic and normal adult Wistar rats were orally administered with aqueous and CH2Cl2/CH3OH plant extracts of P. soyauxii at various doses (38-300 mg/kg) in a single administration. In addition, STZ-induced diabetic rats received prolonged daily administration for 14 days. Glibenclamide (GB) (10 mg/kg) was used as reference treatment. In acute test, fasting blood glucose was followed for 5 h. In subacute test, body weight, food and water intakes, and blood glucose were followed weekly and serum biochemical parameters evaluated after 14 days treatment. RESULTS: Acute administration of aqueous and CH2Cl2/CH3OH stem bark extracts moderately decreased fasting blood glucose compared to GB, significantly in normal rats (P < 0.05 to P < 0.01) but, as GB, not significantly in diabetic rats. Prolonged treatments in diabetic rats with aqueous and CH2Cl2/CH3OH extracts reduced blood glucose to an extent, respectively, superior or similar to GB. Moreover, P. soyauxii also significantly (P < 0.01) reduced weight loss, and diabetes increased serum triglycerides, total cholesterol, and transaminases (alanine aminotransferase/aspartate aminotransferase) elevations. CONCLUSION: P. soyauxii Taub stem bark extracts have possible value for antidiabetic oral medication. SUMMARY: Aqueous and Dichloromethane/Methanol stem bark extracts of Pterocarpus soyauxii Taub have potent (compared to Glibenclamide) antidiabetic effects in STZ-diabetic rats, with specific kinetics and dose-responses.Moderate hypoglycemia effects upon acute P. soyauxii administration.Potent anti-hyperglycemic effects of sub-acute P. soyauxii administration in STZ-diabetic rats.Potent anti-hyperlipidemic effects of sub-acute P. soyauxii administration in STZ-diabetic rats.Improved hepatic and renal serum parameters after sub-acute P. soyauxii administration in STZ-diabetic rats.P. soyauxii extracts may be useful for oral treatment of diabetes and related metabolic disorders. Abbreviations Used: CH2Cl2/CH3OH: Dichloromethane/Methanol; STZ: Streptozotocin; GB: Glibenclamide; AE: Aqueous extract; OE: Organic extract; FeCl3: Iron (III) chloride; NaCl: Sodium chloride; K3Fe(CN)6: Potassium ferricyanide; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; H: Hour; BW: Body weight, W1 and W2: Weeks 1 and 2; CHOD: Cholesterol oxidase; GPO: Glycerol-3 Phosphate oxidase; PAP: Phenol + Aminophenazone.

Safety assessment of the aqueous extract of the flowers of Nymphaea lotus Linn (Nymphaeaceae): Acute, neuro- and subchronic oral toxicity studies in albinos Wistar rats.

Background Nymphaea lotus Linn (N. lotus) is a medicinal plant widely used in Cameroon popular medicine, to treat neuropsychiatric conditions, male sexual disorders or as food supplement. However, scientific data on the pharmacotoxic profile of this plant are not available. The safety of N. lotus was assessed in acute, neuro- and subchronic toxicity studies by following the OECD guidelines. Effectively, no data have been published until now in regard to its safety on the nervous system. Methods Aqueous extract of N. lotus at doses of 200, 400 and 600 mg/kg body weight (BW) was evaluated for nitrites contents and orally administered to rats daily for 28 days (5 male, 5 female per group). The control group received distilled water (10 mL/kg) and a satellite group was used to observe reversal effects. Neurotoxicity of the plant was determined using open field test for motor coordination, ataxia and gait analysis. Clinical signs and state of livelihood were recorded during the 24 h, then for 28 days of treatments. At the end of 28-day period, animals were anesthetized and decapitated. The whole brain was homogenized for neurobiochemical analysis. Blood samples were collected with or without anticoagulant for hematological examinations and serum analysis. Specimens of liver, kidney, testis, ovaries, and brain were fixed in 10 % formalin and processed for histopathological examinations. Results Our findings indicate dose-dependent elevation of nitrites contents in the flowers aqueous extract of N. lotus. Acute toxicity study revealed no signs of toxicity neither at the dose 2,000 mg/kg nor at 5,000 mg/kg. Thus the LD50 value of aqueous extract of N. lotus flowers is superior to 5,000 mg/kg. The repeated administration of N. lotus during 28 days, induced no signs of neurobehavioral changes in male, but female rats exhibited dose-dependent response in the open field test, suggesting sex and dose-relative psychotropic effects of N. lotus. The evaluation of neurobiochemistry revealed consistent rise of brain cholesterol by 44.05 %; 158.10 % and 147.62 % respectively in male rats treated with the doses of 200, 400 and 600 mg/kg. In female rats, these levels were significantly increased (p<0.001) only at the dose of 600 mg/kg compared to control. This trend persisted after 14 days withdrawal. Brain potassium and calcium concentrations were increased in all rats compared to their respective control receiving distilled water, suggesting transmembrane current stabilizing properties of brain cells by our extract. Further, serum biochemical analysis demonstrated that 28-day administration of N. lotus flowers increased depending on the dose and sex, the levels of serum urea, proteins, creatinine and bilirubin and reduced γ-glutamyltransferase (GGT) and alkaline phosphatase (ALP) activities. These results suggest liver alterations that are endowed by lower liver relative weight and histology damages observed in female rats treated with the dose of 600 mg/kg of our extract. We also observed a rise in the low-density lipoprotein (LDL) fraction and AI of male rats undergoing N. lotus treatment. In female rats, the latter remains unaltered, confirming the dose- and sex-dependent response of our extract. The levels of white blood cells (WBC) and granulocytes were higher in male irrespective to their control, revealing stimulatory properties of the male hematopoietic system. Such variations (sex- and dose-dependent) are without biological relevance for the majority of the biochemical parameters evaluated, indicating a wide margin of safety for the traditional use of N. lotus. The alkaloids, nitrites and phytosterols contained in N. lotus flowers extract may probably account for its neuroprotective, anti-oxidant, and immunoboosting properties. Conclusions N. lotus do not possesses neurotoxicity but is able to induce behavioral changes in rats. Therefore, the application of this plant as either drug or supplementary food should be carefully considered.

Oxidised palm oil and sucrose induced hyperglycemia in normal rats: effects of Sclerocarya birrea stem barks aqueous extract.

BACKGROUND: Consumption of foods rich in carbohydrates and fats, result in an increase in obesity and consequently type 2 diabetes. The present study was carried out to evaluate the effects of oxidised palm oil and sucrose (SOPO +S) on some metabolic parameters and to investigate the effects of aqueous extract from barks of Sclerocarrya birrea on SOPO + S induced damages. METHODS: During 16 weeks, animals received every day a supplement of oxidised palm oil (10 %) and 10 % sucrose as drinking water). Control rat received standard diet and drinking water without sucrose. At the end of this period, animal presenting intolerance in glucose test and insensitivity to insulin were continuously feed with hypercaloric diet along with the administration of the plant extract (150 or 300 mg/kg) or glibenclamide (10 mg/kg) during three weeks. OGTT was performed; insulin sensitivity was assessed by performing insulin tolerance test and determining insulin sensitivity index (Kitt). Several parameters were evaluated including body weight, abdominal fat mass, blood glucose levels, blood pressure, serum lipid profile, and serum transaminases (ALT and AST). Oxidative parameters were measured by MDA levels, nitrites levels, SOD levels, reduced glutathione content and by enzyme activities of SOD and catalase. RESULTS: Animal receiving a supplement of oxidised palm oil and sucrose showed hyperglycaemia, glucose intolerance, insulin resistance and a significant increase in body weight and abdominal fat mass compared to normal rats. In addition, there was a significant increase of SOD in aorta and heart, nitrites in liver and kidney, malondialdehyde (MDA) in heart, liver and kidney. It was also observed a significant reduction in the activities of the SOD and catalase in liver, kidney and reduced glutathione levels in heart. Concomitant treatment of plant extract with SOPO + S brought glycaemia and blood pressure towards normal value, restored glucose tolerance and insulin sensitivity. The plant extract prevent the increase or decrease in the activity of the enzyme depending to the organ, reduced MDA and nitrites levels. CONCLUSION: These results highlighted the hyperglycaemic and oxidant character of SOPO + S diet and confirm the hypoglycaemic, and antioxidant action of sclerocarya birrea aqueous extract in diabetes.

Hypolipidemic, antioxidant and anti-atherosclerogenic effects of aqueous extract of Zanthoxylum heitzii stem bark in diet-induced hypercholesterolemic rats.

OBJECTIVE: To evaluate anti-dyslipidemic, antioxidant and anti-atherosclerogenic properties of this extract in diet-induced hypercholesterolemic rat, a model of metabolic syndrome-induced atherosclerosis and associated cardiovascular diseases. METHODS: Normocholesterolemic (NC) male rats were divided into six groups (n=10) and fed a high-cholesterol (HC) diet for 30 days (5 groups), or normal rat chow (normal control group). Rats given a HC diet also received distilled water (disease control), the potent hypocholesterolemic agent with anti-atherosclerotic activity atorvastatin (2 mg/kg, positive control), or one of the three doses of Zanthoxylum heitzii stem bark aqueous extract tested (225, 300 and 375 mg/kg) concomitantly for four months. Signs of general toxicity, body temperature and weight, and water and food intake were monitored in live animals. After sacrifice, lipid profiles and oxidative stress markers were assessed in the blood and liver, aorta, and feces, and histopathological analysis of aorta was performed. RESULTS: Plant extract prevented the elevation of aortic total cholesterol and triglycerides, and hepatic low density lipoprotein, very low density lipoprotein, and total cholesterol. Lipid peroxidation (TBARS) was decreased and aortic atherosclerotic plaque formation prevented. CONCLUSIONS: These observations strongly suggest that stem bark aqueous extract of Zanthoxylum heitzii has anti-atherosclerogenic properties, at least partly mediated by antioxidant and hypolipidemic effects.

Compounds from Sorindeia juglandifolia (Anacardiaceae) exhibit potent anti-plasmodial activities in vitro and in vivo.

BACKGROUND: Discovering new lead compounds against malaria parasites is a crucial step to ensuring a sustainable global pipeline for effective anti-malarial drugs. As far as we know, no previous phytochemical or pharmacological investigations have been carried out on Sorindeia juglandifolia. This paper describes the results of an anti-malarial activity-driven investigation of the fruits of this Cameroonian plant. METHODS: Air-dried fruits were extracted by maceration using methanol. The extract was fractionated by flash chromatography followed by column chromatography over silica gel, eluting with gradients of hexane-ethyl acetate mixtures. Resulting fractions and compounds were tested in vitro against the Plasmodium falciparum chloroquine-resistant strain W2, against field isolates of P. falciparum, and against the P. falciparum recombinant cysteine protease falcipain-2. Promising fractions were assessed for acute toxicity after oral administration in mice. One of the promising isolated compounds was assessed in vivo against the rodent malaria parasite Plasmodium berghei. RESULTS: The main end-products of the activity-guided fractionation were 2,3,6-trihydroxy benzoic acid (1) and 2,3,6-trihydroxy methyl benzoate (2). Overall, nine fractions tested against P. falciparum W2 and falcipain-2 were active, with IC50 values of 2.3-11.6 µg/ml for W2, and 1.1-21.9 µg/ml for falcipain-2. Purified compounds (1) and (2) also showed inhibitory effects against P. falciparum W2 (IC50s 16.5 µM and 13.0 µM) and falcipain-2 (IC50s 35.4 and 6.1 µM). In studies of P. falciparum isolates from Cameroon, the plant fractions demonstrated IC50 values of 0.14-19.4 µg/ml and compounds (1) and (2) values of 6.3 and 36.1 µM. In vivo assessment of compound (1) showed activity against P. berghei strain B, with mean parasitaemia suppressive dose and curative dose of 44.9 mg/kg and 42.2 mg/kg, respectively. Active fractions were found to be safe in mice after oral administration of 7 g/kg body weight. CONCLUSIONS: Fractions of Sorindeia juglandifolia and two compounds isolated from these fractions were active against cultured malaria parasites, the P. falciparum protease falcipain-2, and in a rodent malaria model. These results suggest that further investigation of the anti-malarial activities of natural products from S. juglandifolia will be appropriate.

Antipyretic and antinociceptive effects of Nauclea latifolia root decoction and possible mechanisms of action.

CONTEXT: Nauclea latifolia Smith (Rubiaceae) is a small tree found in tropical areas in Africa. It is used in traditional medicine to treat malaria, epilepsy, anxiety, pain, fever, etc. OBJECTIVE: The aim of this study was to investigate the effects of Nauclea latifolia roots decoction on the peripheral and central nervous systems and its possible mechanisms of action. MATERIALS AND METHODS: The analgesic investigation was carried out against acetic acid-induced writhing, formalin-induced pain, hot-plate and tail immersion tests. The antipyretic activity was studied in Brewer's yeast-induced pyrexia in mice. Rota-rod test and bicuculline-induced hyperactivity were used for the assessment of locomotor activity. RESULTS: Nauclea latifolia induced hypothermia and had antipyretic effects in mice. The plant decoction produced significant antinociceptive activity in all analgesia animal models used. The antinociceptive effect exhibited by the decoction in the formalin test was reversed by the systemic administration of naloxone, N(ω)-L-nitro-arginine methyl ester or glibenclamide. In contrast, theophylline did not reverse this effect. Nauclea latifolia (antinociceptive doses) did not exhibit a significant effect on motor coordination of the mice in Rota-rod performance. Nauclea latifolia protected mice against bicuculline-induced behavioral excitation. DISCUSSION AND CONCLUSION: Overall, these results demonstrate that the central and peripheral effects of Nauclea latifolia root decoction might partially or wholly be due to the stimulation of peripheric opioid receptors through the action of the nitric oxide/cyclic monophosphate guanosin/triphosphate adenosine (NO/cGMP/ATP)-sensitive- K(+) channel pathway and/or facilitation of the GABAergic transmission.

Antihypertensive and antioxidant effects of Allanblackia floribunda Oliv. (Clusiaceae) aqueous extract in alcohol- and sucrose-induced hypertensive rats.

AIM OF THE STUDY: Allanblackia floribunda Oliv. (Clusiaceae), an evergreen tree of the rain-forest has long been used in traditional African medicine to treat hypertension. The aim of this study was to evaluate the protective effect of Allanblackia floribunda aqueous extract on alcohol- and sugar-induced hypertension in rats. MATERIAL AND METHODS: Alcohol-induced hypertensive rats (AHR) were obtained by oral administration of ethanol (3g/kg/day) while sucrose (5, 6 and 7% in drinking water) was used for sucrose-induced hypertensive rat (SuHR). Both models of animals concomitantly received either aqueous extract (200 or 400mg/kg; p.o.) or nifedipine (10mg/kg; p.o.) all along the 8 weeks of experiment. Blood pressure and heart rate were measured using the direct cannulation method. The effects of the plant extract on lipid profile, oxidative stress markers, as well as on kidney and liver functions were evaluated at the end of the treatment by the colorimetric method. RESULTS: At the doses of Allanblackia floribunda (200 and 400mg/kg/day) significantly prevented (21.74; 26.65% and 11.71; 24.58% of reduction) the increase in mean blood pressure on AHR and SuHR, respectively. Administration of the plant extract at the dose of 400mg/kg led to the prevention of total cholesterol (42.82%), HDL-cholesterol (36.59%) and triglycerides (9.67%) increase in serum lipid in AHR as compared to the untreated AHR. In SuHR, the extract significantly prevented the high concentrations of total cholesterol (44.08%) and triglycerides (33.05%) induced by sucrose treatment as compared to the untreated SuHR, without affecting that of HDL-cholesterol. Allanblackia floribunda (200 and 400mg/kg) also prevented the increase in atherogenic index by 54.45 and 42.94% in AHR and by 23.70 and 44.32% in SuHR, respectively. Allanblackia floribunda (400mg/kg) prevented the increase in bilirubine (19.59 and 16.56%), urea (33.36 and 28.2%), ALT (29.55 and 33.09%) and AST (36.28 and 37.12%) of AHR and SuHR, respectively. Treatment with plant extract significantly prevented the increase of superoxide dismutase (SOD), malondialdehyde (MDA) and catalase and the decrease of reduced glutathione (GSH) concentration in aorta, heart, kidney and liver of AHR and SuHR. CONCLUSION: These results demonstrate that the aqueous extract of Allanblackia floribunda can prevent alcohol- and sugar-induced hypertension and oxidative stress in rats. These findings could therefore justify its use in traditional medicine.

Sclerocarya birrea (Anacardiaceae) stem-bark extract corrects glycaemia in diabetic rats and acts on beta-cells by enhancing glucose-stimulated insulin secretion.

Sclerocarya birrea is a plant widely used as traditional medication for the treatment of diabetes in sub-Saharan regions. However, the mechanism of action is unknown and only hypoglycaemic effects of S. birrea extract (SBE) in diabetic rats have been reported to date. Here, we tested aqueous extracts of S. birrea on insulin-secreting INS-1E cells and isolated rat islets. Following 24 h of treatment at 5 microg/ml, the extract markedly potentiated glucose-stimulated insulin secretion. Neither basal insulin release nor non-nutrient stimulation was affected. The potentiation of the secretory response at stimulatory glucose appeared after 12 h of treatment. No acute effects were observed and, at the effective concentration, SBE was safe regarding cell integrity and differentiation. The mechanism of action of the SBE was related to glucose metabolism as both ATP generation and glucose oxidation were enhanced following the 24-h treatment. In streptozotocin-induced diabetic rats, SBE administration corrected glycaemia and restored plasma insulin levels after 2 weeks of treatment. These data show direct action of S. birrea on insulin-secreting cells and favour further delineation for use of the plant in the management of diabetes.

Acute and chronic anti-inflammatory properties of the stem bark aqueous and methanol extracts of Sclerocarya birrea (Anacardiaceae).

Sclerocarya birrea is used in folk medicine for the treatment of inflammatory disorders. The effect of the stem bark aqueous and methanol extracts of S. birrea (150 or 300 mg/kg) was evaluated on carrageenan-, histamine- or serotonin-induced paw oedema in rats. The methanol extract of S. birrea (300 mg/kg) being the most active, exhibited a maximum inhibition of 75.45 and 55.31% on carrageenan- and histamine-induced inflammation, respectively. When administered at 300 mg/kg, the methanol extract of S. birrea also exhibited 80.68% inhibition on the 10th day and 54.43% inhibition on the 21st day in formalin- or complete Freund's adjuvant (CFA)-induced paw oedema in rats. GSH level was significantly increased (75.14%), while MAD level was significantly decreased (31.22%) in the liver of CFA rats treated with S. birrea (300 mg/kg). The results suggest that the anti-inflammatory activity of the aqueous and methanol extracts of S. birrea is due to the inhibition of histamine and prostaglandin pathways and to its antioxidant activity.