Improvement of microvascular complications in STZ-diabetic rats treated with Pterocarpus erinaceus Poir. extract.

Pterocarpus erinaceus Poir. from Fabaceae family is a medicinal plant traditionally used in decoction or infusion to treat diabetes mellitus. Although this plant is used in treating diabetes, studies on the effectiveness of its stem bark on the complications induced by chronic hyperglycemia have not been thoroughly addressed. Thus, this study was conducted to prove the efficacy of hydroethanolic extract of stem bark of P. erinaceus on type 2 diabetes and its complications, such as renal fibrosis and retinopathy in rats. STZ diabetics. The dry extract of P. erinaceus stem bark was obtained following the hydroethanolic extraction (v/v). Diabetes was induced with streptozocin in SD rats pretreated with fructose-lard for 20 days. Then, the serum and urinary biochemical parameters were evaluated at the start and the end of the treatment. Rats with blood glucose ≥350 mg/dL and significant proteinuria were selected and treated with P. erinaceus stem bark extract and glibenclamide for 3 weeks. A complete blood count and a histopathological examination of the retina and kidneys were performed at the end of the 41st day of treatment. The results showed that P. erinaceus extract at a dose of 500 mg/kg bw and glibenclamide at a dose of 0.6 mg/kg bw caused a significant decrease (p < 0.0001) in basal blood glucose in STZ diabetic rats during treatment and improved oral glucose intolerance. At the end of the experiment, the treated rats showed a normalization in body weight, food and water consumption. Evaluating of biochemical parameters showed a significant (p < 0.001) decrease in total cholesterol, LDL-C, triglycerides, TG/HDL-C ratio, CPK and oxidative stress in treated rats. No retinal and kidney abnormalities were observed on histological sections in rats treated with plant extract and glibenclamide. In contrast, macular edema and renal fibrosis were observed in the diabetic control group. The findings showed that extract at a dose of 500 mg/kg bw improves oral glucose intolerance, and inhibits lipid deposition and retinal and renal fibrosis. Therefore, the plant extract could be exploited in the production of herbal medicines to manage diabetes and its complications.

Anti-cholinesterase, anti-inflammatory and antioxidant properties of Combretum micranthum G. Don: Potential implications in neurodegenerative disease.

Background: Brain damage is a severe and common pathology that leads to life-threatening diseases. Despite development in the research, the medical evidence of the effectiveness of potential neuroprotective medicines is insufficient. As a result, there is an immense and urgent demand for promising medication. For millennia, herbal remedies were a fundamental aspect of medical treatments. Combretum micranthum (CM), a plant of the family Combretaceae in sub-Saharan Africa, has been utilized in folklore medicine to cure diverse human ailments. In order to develop a neuroprotective phytomedicine, the current research was undertaken to explore the antioxidant, anti-inflammatory, anticholinesterase and neuroprotective potential of CM extract. Methods: Colorimetric methods were used to determine CM antioxidant activity, in-vitro protein denaturation and membrane destabilization assays were used to evaluate its anti-inflammatory capacity, anticholinesterase activity was carried out using Ellman's method, and neuroprotective potential was assessed on brain homogenate stressed with ferric chloride and ascorbic acid (FeCl2-AA) by assessing the lipoperoxidation biomarker malondialdehyde (MDA). Results: In Ferric Reducing Antioxidant Power (IC50 = 27.15 ± 0.06 µg/mL) and Total Antioxidant Capacity (IC50 = 31.13 ± 0.02 µg/mL), CM extract demonstrated strong antioxidant activity. Anti-inflammatory effect were improved in heat-induced Egg albumin and BSA denaturation (IC 50 = 46.35 ± 1.53 and 23.94 ± 1.10 µg/mL) as well as heat and hypotonia induced membrane destabilization (IC 50 = 20.96 ± 0.11 and 16.75 ± 0.94 µg/mL).CM extract showed strong anticholinesterase activity (IC 50 = 59.85 ± 0.91 µg/mL). In an ex-vivo neuroprotective model, CM extract showed substantial inhibition (p < 0.001) of oxidative damage caused by FeCl2-AA in brain tissue. Conclusion: C. micranthum may be a good candidate for its probable neuroprotective potential. Its neuroprotective benefits might be attributed to its antioxidant, anti-inflammatory and anticholinesterase effects.

Antidiabetic and antioxidant potential of total extract and supernatant fraction of the roots of Anogeissus leiocarpus in HFD-fed and Streptozocin -induced diabetic rats.

The aim of this study was to evaluate the antidiabetic properties of hydro alcoholic extract and supernatant fraction of the roots of Anogeissus leiocarpus, a plant used by traditional healers to treat Diabetes mellitus. Diabetes mellitus was induced by a single intraperitoneal administration of Streptozocin to Sprague Dawley rats under a fructose-enriched fat diet. Diabetic rats were treated with 500 mg/kg of total extract and 100 mg/kg of supernatant. The antidiabetic activity was assessed by measuring blood glucose level, lipid profile, insulin and biochemical parameters together with the antioxidant potential. The administration of total extract and supernatant exhibited significant decrease (p < 0.01) of the blood glucose level in the diabetic rats after 7 days of treatment compared to the diabetic rats. A significant reduction in the serum concentrations of cholesterol (19.7 %) and triglycerides (56.7 %) was observed in the treated diabetic rats. The levels of insulin did not differ across all the groups. However, compared to diabetic rats, HOMA-IR (Homeostasis Model Assessment for Insulin-resistance) and HOMA-ß (Homeostasis Model Assessment for ß cell function) showed a statistical decrease in insulin resistance and an increase in pancreatic ß cell function in the treated diabetic rats. Moreover, total extract and supernatant significantly increased GSH level and decreased lipid peroxidation because of their antioxidant properties. In comparison, the supernatant fraction exerted stronger antidiabetic and antioxidant effects than the total extract. Hence, the roots of Anogeissus leiocarpus are a potent antidiabetic agent that can be developed as an alternative medicine for diabetes and its complications.

Genotoxicity Assessment and Protective Effect of Anogeissus leiocarpus Roots against Cyclophosphamide-Induced DNA Damage In Vivo.

BACKGROUND: Belonging to the family of Combretaceae, the roots of Anogeissus leiocarpus are traditionally used to treat diabetes, wounds, infections, pain, and gastrointestinal diseases. To our knowledge, no genotoxicity assessment of the plant was reported. Hence, this study was designed to evaluate the potential genotoxic and protective effects of extract of Anogeissus leiocarpus roots using the micronucleus test on mice bone marrow cells in vivo. METHODS: Three different concentrations (250, 500, and 1000 mg·kg-1) of hydroalcoholic extract of roots of A. leiocarpus were administered daily for 7 days per os to mice, and the genotoxicity was induced by the administration ip of cyclophosphamide. Genotoxicity and cytotoxicity were evaluated by counting, respectively, the number of micronucleated polychromatic erythrocytes and polychromatic erythrocytes to total erythrocytes in the bone marrow of mice. RESULTS: The administration of A. leiocarpus did neither increase the ratio of the polychromatic erythrocyte (PCE) nor the frequency of micronucleated PCE (MNPCE) significantly in the bone marrow cells of the mice, compared to the vehicle control animals. However, a significant increase in the incidence of MNPCE in the bone marrow cell of the cyclophosphamide-treated mice was found. Moreover, in the groups treated with the total extract of A. leiocarpus at different doses plus cyclophosphamide, there was a significant decrease (p < 0.0001) in MNPCEs compared to the positive controls, in a dose-dependent manner. CONCLUSION: This first finding reports that the extract of A. leiocarpus was neither genotoxic nor cytotoxic. However, it shows a protective effect against the genotoxicity and cytotoxicity induced by cyclophosphamide.

A 90-Day Oral Toxicity of Hydroethanolic Root Extract of Carissa spinarum in Wistar Rats.

BACKGROUND: Herbal medication is a worldwide and ancient practice, mostly in developing countries, where a large part of the population is involved in this practice. Hence, studies must be conducted to evaluate their safety and efficiency to avoid or prevent toxicological risks due to their usage. In Togo, Carissa spinarum is a medicinal plant belonging to Apocynaceae family, used as an aphrodisiac or to heal some ailments including malaria, sickle cell anemia, hypertension, pain, and asthma. Notwithstanding its several ethnomedicinal benefits, just a few toxicological data associated with its chronic use are available. OBJECTIVE: Therefore, this study aims to assess the toxicity of an ethanolic root extract of Carissa spinarum in Wistar rats. METHODS: The 90-day oral toxicity process following OECD TG 408 guidelines is used. Male Wistar rats received Carissa spinarum root hydroethanolic extract at 500 and 1000 mg/kg for 90 days by oral gavage. Body weight changes, hematological and blood biochemical parameters, organ weight changes, malondialdehyde as a lipoperoxidation marker expressed according to tissue proteins, and histopathology of vital organs were assessed. RESULTS: No signs of toxicity or mortality were observed during the 90 days experiment. Hematological parameters have not shown any treatment-related abnormalities. According to biochemical parameters, an increase in the chloride ion level was observed at 1000 mg/kg (p < 0.01). There was no significant difference between the treated groups and the control group concerning the malondialdehyde concentration, body weight, and organ relative weight. No changes in necropsy and histopathology of vital organs associated with extract treatment were observed. CONCLUSION: The results indicated that an ethanolic root extract of Carissa spinarum does not cause adverse effects, which can lead to Wistar rats' death after 90-day oral administration at 500 and 1000 mg.

Antihyperlipidemic and antioxidant properties of hydro-alcoholic extracts from Anogeissus leiocarpus (Combretaceae).

Anogeissus leiocarpus (Combretaceae) is a medicinal plant used in Togo to treat diabetes mellitus and others diseases. The present study was undertaken to evaluate the antihyperlipidemic and antioxidant activities of total extract and fractions of roots of Anogeissus leiocarpus. The antihyperlipidemic activity of the total extract and the supernatant was performed in vivo by the fructose overload test in ICR mice. Antioxidant potential was determined in vitro by methods based on scavenging of DPPH∗, total antioxidant capacity and reducing power. After the screening, phenolic compounds and flavonoids were evaluated by the well-known colorimetric assay using respectively Folin-Ciocalteu reagent and aluminium chloride. The results obtained showed that the total extract and the supernatant significantly reduced the serum and liver levels of triglycerides and hence the level of VLDL-Cholesterol compared to hyperlipidemic mice. In vitro the total extract and fractions had the ability to scavenge free radicals, to reduce metal and possessed strong total antioxidant activity. Phytochemical screening revealed the presence of polyphenols, flavonoids, alkaloids, tannins and saponosides in the extract and fractions. And the supernatant fraction contained more polyphenolic compounds than others. From this study, it is concluded that the total extract and fraction of Anogeissus leiocarpus possessed strong antihyperlipidemic, antioxidant properties and were riched in polyphenols, which can be used in the treatment of diabetes mellitus' complications. Hence, the supernatant fraction was the most biologically active.

Cytotoxicity, Acute, and Subacute Study of Hydroalcoholic Root Extract of Carissa spinarum L. on Wistar Rats.

Carissa spinarum L. (Apocynaceae) is used traditionally, in Africa, to treat many diseases such as malaria, sickle cell anemia, epilepsy, helminthoses, and sexual weakness. The aim of this study is to investigate the cytotoxicity on Artemia salina, the acute and subacute (28 days) oral toxicity of C. spinarum hydroalcoholic root extract on Wistar rats. The cytotoxicity was performed on A. salina larvae. The acute and subacute toxicity was performed using Organization of Economic Cooperation and Development guideline. Malondiadehyde as lipoperoxidation marker was evaluated and expressed according to tissue proteins. The cytotoxicity has shown that the lethal concentration 50 (LC50) was 0.9 mg/mL. The limit test dose of 5000 mg/kg did not provoke death or toxicity signs. For the subacute toxicity, no signs of toxicity or mortality were observed during the experiment. Results of biochemical and hematological parameters have not shown any treatment-related abnormalities, except a significant decrease of alkaline phosphatase at 1000 mg/kg (P < .05) and an increase of chloride ion level at 500 mg/kg (P < .01). There was no significant difference between the treated group and the control group concerning the malondialdehyde concentration, the body weight, and the organs relative weight (P < .05), except for testis at 500 mg/kg (P < .05). According to our results, the hydroalcoholic extract of C. spinarum roots is safe when administrated at 500 mg and 1000 mg/kg to Wistar rats for 28 days.

Nephroprotective effect of Combretum micranthum G. Don in nicotinamide-streptozotocin induced diabetic nephropathy in rats: In-vivo and in-silico experiments.

ETHNOPHARMACOLOGICAL RELEVANCE: Combretum micranthum G. Don (CM) is extensively used in traditional medicine throughout West Africa and commonly known as "long-life herbal tea" or "plant to heal". Further, traditional healers frequently use the title plant to mitigate of renal disorders. AIM OF THE STUDY: To explore the nephroprotective property of standardised hydroalcoholic extract of Combretum micranthum in nicotinamide-streptozotocin induced diabetic nephropathy in rats. In addition, in-silico computational experiments were performed with bioactive compounds of the title plant against PPARα and PPARγ. MATERIAL AND METHODS: Male rats were made diabetic by a single intraperitoneal (ip) injection of STZ (50 mg/kg), 15 min after ip administration of NA (100 mg/kg) dissolved in normal saline. The diabetic rats received CM extract (200 and 400 mg/kg p.o.) daily, for eight weeks. Body weights and blood glucose (non-fasting and fasting) of rats were measured weekly. Daily food and water consumption were also measured. After 8 weeks of treatment, urine biochemical parameters such as N-Acetyl-ß-D-Glucosaminidase (NAG), urea (UR), uric acid (UA), creatinine (CRE), and serum markers of diabetes, kidney damage and liver damage such as insulin, lipid parameters), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transferase (γGT), albumin (Alb), magnesium (Mg2+), calcium (Ca2+), phosphorus (P), were estimated. Blood glycosylated hemoglobin (HbA1C) were also estimated. kidney and liver were used for biochemical estimation of oxidative stress markers such as lipid peroxidation, superoxide dismutase (SOD) activity and glutathione peroxidase (GPx) activity. The kidney and pancreas were used for histopathological study. Further, HPLC chemoprofiling of CM extract and in-silico molecular simulation experiments were performed. RESULTS: At the end of eight weeks, renal damage induced by the consequence of prolong diabetic condition was confirmed by altered levels of serum and urine kidney and liver function markers, oxidative stress markers and histopathological variations in kidney. Treatment with CM extract ameliorated the diabetes mellitus-induced renal biochemical parameters and histopathological changes. Further, HPLC-UV & MS experiments revealed that CM extract contains several bioactive compounds including hyperozide (62.35 µg/mg of extract) and quercitrin (19.07 µg/mg of extract). In-silico experiment exhibited cianidanol (-17.133), epicatechin (-15.107) exhibited higher docking score against PPARα and luteoforol (-11.038), epigallocatechin (-10.736) against PPARγ. Based on docking and drug likeness score, four bioactive compounds were selected for molecular dynamic experiments. Cianidanol and epigallocatechin out of the 30 compounds are concluded as a potential candidate for the treatment of DN through activating PPARα and PPARγ target protein. CONCLUSIONS: Taken together, the present study provided the scientific footage for the traditional use of Combretum micranthum.

Toxicological Studies of Hydroethanolic Leaf Extract of Launaea taraxacifolia (Willd) Amin Ex C. Jeffrey on Wistar Rats.

Launaea taraxacifolia (Asteraceae) is a widely used vegetable in West Africa. It is used in traditional healing of many diseases such as hypertension, anemia, diabetes, and bleeding. The aim of this study is to investigate the cytotoxicity and the acute and subacute (28 days) oral toxicity of L. taraxacifolia hydroethanolic leaves extract on male Wistar rats. The LC50 values of L. taraxacifolia on brine shrimp were 0.142 ± 0.11 mg/mL. The limit test dose of 5000 mg/kg did not provoke death or toxicity signs in the rats tested during the observation period. For 28 days subacute toxicity at 500 and 1000 mg/kg body weight, no signs of toxicity or mortality were observed during the experiment. There was no significant difference between the treated groups and the control group concerning the body and the relative organs weight (P > .05). Results of biochemical and hematological parameters did not show any treatment-related abnormalities. According to our results, the hydroethanolic extract of L. taraxacifolia leaves, at 500 and 1000 mg/kg body weight, is safe when administrated to male Wistar rats for 28 days.

Acute and subchronic oral toxicity assessments of Combretum micranthum (Combretaceae) in Wistar rats.

BACKGROUND: Combretum micranthum (CM) (Combretaceae) is widely used in traditional medicine throughout West Africa for the treatment of diabetes, hypertension, inflammation, malaria and liver ailments. In our recent research we demonstrated that CM has nephroprotective potentials in diabetes mellitus, hypertension and renal disorders. However, to the best of our knowledge, no systematic study concerning its toxicity profile has been reported. AIM OF THE STUDY: The study carried out to evaluates the potential toxicity of the hydroalcoholic extract from leaves of the CM, through the method of acute and sub-chronic oral administration in rats. MATERIALS AND METHODS: During the acute toxicity study, male and female rats were orally administrated with CM extract at single doses of 5000 mg/kg (n = 5/group/sex). Abnormal behaviour, toxic symptoms, weight, and death were observed for 14 consecutive days to assess the acute toxicity. For sub-chronic toxicity study, the extract was administered orally at doses of 500 and 1000 mg/kg (n = 5/group/sex) daily to Wistar rats for 28 days. The general behaviour and body weight of the rats was observed daily. A biochemical, haematological, macroscopical and histopathological examinations of several organs were conducted at the end of the treatment period. The CM extract was subjected to Fourier transform infrared spectrophotometric examination in order to detect the presence or absence of cyanide toxic compounds. RESULTS: The absence of absorbance peaks between the 2220-2260 cm-1 region of FT-IR spectrum of CM, indicating the absence of cyanide groups. This suggested that the CM extract may not contain toxic substances. During the acute toxicity test, no mortality or adverse effects were noted at the dose of 5000 mg/kg. In the subchronic study, the CM extract induced no mortality or treatment-related adverse effects with regard to body weight, general behaviour, relative organ weights, hematological, and biochemical parameters. Histopathological examination of vital organs showed normal architecture suggesting no morphological alterations. CONCLUSION: The present study revealed that oral administration of CM extract for 28 days, at dosage up to 1000 mg/kg did not induce toxicological damage in rats. From acute toxicity study, the median lethal dose (LD50) of the extract was estimated to be more than 5000 mg/kg.

Nephroprotective activity of Combretum micranthum G. Don in cisplatin induced nephrotoxicity in rats: In-vitro, in-vivo and in-silico experiments.

Nephrotoxicity is known to be a major complication during cisplatin chemotherapy in cancer patients. In the present study, the protective effect of a hydroalcoholic extract of Combretum micranthum (CM) against cisplatin (CP)-induced renal damage was evaluated using in-vitro human embryonic kidney (HEK)-293 cells and in-vivo experiments. Further, in-silico molecular docking and dynamic experiments were carried out with bioactive compounds of the title plant against nuclear factor kappa B (NF-κB) and soluble epoxide hydrolase (sEH). Incubation of HEK-293 cells with cisplatin resulted in a significant increase in cell death with changes in normal cellular morphology. Co-treatment of HEK-293 cells with CP and CM extract at varying concentrations resulted in significant enhancement of cell growth compared to CP treatment indicating the cytoprotective activity of CM with an EC50 8.136 µg/mL. In vivo nephroprotective activity was evaluated by administering CM (200 and 400 mg/kg, p.o) to rats for 10 days followed by single intraperitonial injection of CP (7.5 mg/kg) on the 5th day of the experiment. Nephrotoxicity induced by CP was apparent by elevated levels of serum and urine kidney function markers, transaminases, oxidative stress markers and histopathological alterations in kidney. Pre-treatment with CM normalized the renal function at both the doses by ameliorating the CP-induced renal damage markers, oxidative stress and histopathological variations. In-silico studies showed that, out of the thirty bioactive compounds, isovitexin and gallic acid exhibited a higher docking score of -22.467, -21.167 kcal/mol against NF-κB. Cianidanol and epicatechin exhibited a higher docking score of -14.234, -14.209 kcal/mol against sEH. The protective effect of CM extract in CP-induced nephrotoxicity might be attributed to its antioxidant, anti-inflammatory activity by inhibiting NF-κB and sEH upregulation.

Antioxidant and nephroprotection activities of Combretum micranthum: A phytochemical, in-vitro and ex-vivo studies.

Management of chronic renal failure is exceedingly expensive. Despite of encouraging experimental outcomes, there is a lack of potent nephroprotective drugable molecules in a clinics or market. To develop a nephroprotective phytomedicine, the present study was designed to do a literature survey on reported phytochemical and biological analysis of Combretum micranthum and to carry out chemoprofiling, in-vitro antioxidant and ex-vivo nephroprotective capacity of the title plant. The phytochemical and biological activity survey of C. micranthum has reveals the presence of many bioactive compounds such as flavonoids, terpenoids, steroids and alkaloids with many biological activities. Phytochemical investigation re-confirmed the presence of these compounds. Hydroalcoholic extract of C. micranthum (CM extract) showed a strong antioxidant activity by scavenging AAPH, DPPH, nitric oxide, hydrogen peroxide and chelating metal ions. CM extract exhibited significant (P < 0.001) dose dependent inhibition of ferric chloride-ascorbic acid induced lipid peroxidation. Diabetic nephropathy is a serious and common complication leading to end stage renal disease. Therefore, in the present study, glucose-induced toxicity was also studied in human embryonic kidney cells (HEK-293) as an in vitro model for diabetic nephropathy. The results showed that exposure of cells to high glucose (100 mM) for 72 h significantly reduced the cell viability resulting in morphological changes such as cell shrinkage, rounded cell shape and cytoplasmic vacuolation. Treatment with CM extract at 10 and 25 µg/mL resulted in significant improvement in cell viability from 10 to 23% compared to the high glucose control. This study demonstrated the potential antioxidant and nephroprotective properties of C. micranthum, justifying its traditional use in the treatment of various diseases.

In vivo and in vitro toxicological evaluation of the hydroalcoholic leaf extract of Ageratum conyzoides L. (Asteraceae).

ETHNOPHARMACOLOGICAL RELEVANCE: In African traditional medicine, Ageratum conyzoides has been used as purgative, febrifuge, anti-ulcer and wound dressing. To date there is no safety information about long term use of Ageratum conyzoides which contains pyrrolizidine alkaloids, a class of hepatotoxic and carcinogenic phytochemicals. This study aims to evaluate the 90 days subchronic toxicity and in vitro toxicity of Ageratum conyzoides. MATERIALS AND METHODS: Three groups of 8 rats (4 males and 4 females) received distilled water (control), 500 and 1000 mg/kg of the extract daily for 90 consecutive days by oral gavage. The animals were observed daily for abnormal clinical signs and death. Body weight, relative organ weight, haematological and biochemical parameters of blood as well as heart, kidney, liver and spleen tissues histology were evaluated. RESULTS: After 90 days administration, Ageratum conyzoides increased significantly (p<0.05) the relative weight of the liver, the spleen and kidney as compared to control group. Ageratum conyzoides increased also significantly (p<0.05) ALP, ALT, AST and blood glucose. Furthermore, an increase in the number of platelets associated with a normocytic and normochromic anaemia was observed. The cytotoxicity, determined by the MTT test and neutral red assay, has shown that the cytotoxicity of hydroalcoholic extract of Ageratum conyzoides and its total alkaloids was very close. CONCLUSIONS: Our results have shown that Ageratum conyzoides at 500 and 1000 mg/kg can induce liver, kidney and haematological disorders. These toxics effects can be attributed to its total alkaloids especially to pyrrolizidine alkaloids which are present in this plant.

Effect of Bridelia ferruginea Benth (Euphorbiaceae) ethyl acetate and acetone fractions on insulin resistance in fructose drinking mice.

ETHNOPHARMACOLOGICAL RELEVANCE: The root of Bridelia ferruginea is traditionally used as a treatment for type 2 diabetes. The present study was investigated to evaluate the effect of Bridelia ferruginea root bark fractions on some markers of type 2 diabetes on fructose drinking mice. MATERIALS AND METHODS: Mice received a solution of fructose 15% during 42 days ad libitum; at the 15th day to the 42nd day, they received distilled water for fructose drinking control group, metformin 50 mg/kg per day or fractions 50 mg/kg per day for treatment groups. The normal control group received only distilled water during the experiment. After 6 weeks of experiment, OGTT, fasting blood glucose, plasma insulin, triglycerides (TG), total cholesterol, AST and ALT levels were measured. RESULTS: Fructose drinking control group (F) showed significant (p<0.001) increase of glucose tolerance, plasma levels of total cholesterol, triglycerides and insulin index for insulin resistance (Homeostasis Model Assessment ratio HOMA-IR) as compared to normal control mice. In treated groups, there was a significant reduction of glucose intolerance respectively 74% (p<0.001), 25% (p<0.5) and 92% (p<0.001) for ethyl acetate fraction, acetone fraction and metformin at the same dose of 50 mg/kg per day during 4 weeks administration. In ethyl acetate fraction and metformin treated groups, biochemical parameters and insulin index were significantly (p<0.001) lower than that of fructose drinking control group. CONCLUSIONS: This indicates that Bridelia ferruginea root bark ethyl acetate fraction improved insulin resistance as metformin significantly in type 2 diabetes.

Survey of pesticide application on vegetables in the Littoral area of Togo.

Vegetable production in Togo is seriously affected by pests attack. To reduce damage, farmers indiscriminately use pesticides. Various studies have reported high concentrations of pesticide residues more than acceptable limits in vegetables and other edible food. The aim of the presented study is to study the attitudes and practices developed by vegetable growers about pesticides applications. A standardized questionnaires which included socio-professional factors, provisions and operations concerning the use of varieties of pesticides were addressed to 150 growers in vegetable farms along the Littoral of Togo. In order to complete data concerning pesticides, seven runoff private companies and agents of the 'Direction de la Protection des Végétaux' were interviewed. Data were statistical treated using Sphinx Plus. The survey showed that vegetable growers have an acceptable educational level (36% have more than 7 years of formal education) to exploit instructions concerning pesticide use, but more than 97% do not use recommended tools. Only 21% of them received training for pesticide use. Moreover, 84% of them did not usually wear gloves, and less than 30% used oro-nasal masks. Failure to observe minimum intervals between pesticide application and sale is worrying because extremely hazardous (Carbofuran and Cadusaphos) or moderately toxic (Cypermethrin, Dimethoate, Endosulfan, Chlorpyrifos-ethyl, Fipronil) are the products currently used. The presented study indicates that pesticides application in the survey area represents a potential risk for the environment, farmers and consumers. More investigations are needed to quantify pesticides residues on the vegetables currently con,umed and moreover, to determine the potential effect of those products on human and animals health.

Acute and sub-chronic (28days) oral toxicity evaluation of hydroethanolic extract of Bridelia ferruginea Benth root bark in male rodent animals.

The present investigation was carried out to evaluate the safety of hydro-ethanol extract of Bridelia ferruginea Benth (Euphorbiaceae) root bark. For acute toxicity study, a single dose of 2000 and 5000 mg/kg of the B. ferruginea root bark extract was given orally to healthy male Wistar rats and Balb/c mice. The animals were observed for mortality and clinical signs for 3 h and then daily for 14 days. In the sub-chronic toxicity study, the extract was administered orally at doses of 250, 500 and 1000 mg/kg/day for 28 days to male Wistar rats. Animals were sacrificed to examine their organs, and urine and blood serum were analyzed. In the acute toxicity study, B. ferruginea root bark extract caused neither significant visible signs of toxicity, nor mortality in Wistar rats and Balb/c mice. In sub-chronic toxicity study, administration of the B. ferruginea root bark extract at 250, 500, and 1000 mg/kg for 28 consecutive days to Wistar rats did not produce mortality. No significant differences were found in relative organ weights, biochemical studied parameters in treated groups compared to control group. No obvious histological changes were observed in organs of B. ferruginea extract treated animals compared to controls.

Gastroprotective Effect of Hydroalcoholic Extract of Aloe buettneri.

Aloe buettneri A. Berger is commonly used in traditional Togolese medicine to treat inflammatory and gastric ulcers. The present study examined the gastro-protection effect of the hydro-alcoholic extract of A. buettneri on mucus production and gastric pH. A gastric ulcer is induced by ethanol 95° alone (1 mL/kg body weight), after pre-treatment with indomethacin (300 mg/kg) or by utilising L-NAME (40 mg/kg IV). In addition gastric mucus was removed by scraping and subsequently weighed. The experiment focused entirely on rats that had been subjected to fasting. The hydro-alcoholic extract of A. buettneri (500 mg/kg) significantly inhibited ulcers that were induced by ethanol, indomethacin or L-NAME pre-treatment. A. buettneri was shown to increase the production of gastric mucus. Furthermore L-arginine significantly decreased the size of the induced ulcers. The results achieved in the study carried out suggest that A. buettneri posses gastro-protective properties.

In vitro inhibitory effect of West African medicinal and food plants on human cytochrome P450 3A subfamily.

AIM OF THE STUDY: In Africa, medicinal plants are used intensively and concomitantly with allopathic medicines in the treatment of opportunity diseases by many patients or by healthy person to prevent diseases. However, there is little information about the interactions between medicines and botanical products used currently in West Africa area. Therefore, the aim of the present investigation is to study the effect of some plant products on CYP3A4, CYP3A5 and CYP3A7, three individual enzymes of CYP3A subfamily, in vitro. MATERIALS AND METHODS: Teas and ethanolic extracts of medicinal, food and co-administered plants were evaluated on CYP3A4, CYP3A5 and CYP3A7 individual enzymes in vitro using fluorometric assays. RESULTS: Extracts of adjuvant plants such as Aframomum cuspidatum, and Aframomum melegueta, as well as one medicinal plant (Harrisonia abyssinica) inhibited CYP3A4, CYP3A5 and CYP3A7 activity more than 90%. Phyllanthus amarus showed high inhibition of CYP3A5 and CYP3A7. Food plants (Solanum macrocarpon and Talinum triangulare) inhibited CYP3A4 and CYP3A5 less than 20%. CONCLUSION: These results indicate that plants tested in this study affect in vitro the activity of the main three CYP3A subfamily enzymes. These active plants could interfere with the metabolism at phase I of conventional drugs in vivo as well act as pharmacoenhancers in herbal mixtures.

Effect of Tectona grandis on phenylhydrazine-induced anaemia in rats.

Traditional oral report indicates that Tectona grandis is used in the treatment of anaemia in Togo. For this purpose, the extract of T. grandis leaves is evaluated on anaemia model of rat induced by intraperitoneal injection of phenylhydrazine at 40 mg/kg for 2 days. Oral administration of T. grandis extract at 1 g/kg/day and 2 g/kg/day, to the rats previously treated with phenylhydrazine, increased the concentration of haemoglobin, red blood cells number, haematocrit and reticulocytes rate. Moreover, the extract of T. grandis enhanced the osmotic resistance of the red blood cells that confirm the important presence of young red blood cells. These results support partially the traditional use of T. grandis in the treatment of anaemia.

The effect of Mangifera indica stem bark and Pluchea ovalis roots on tracheal smooth muscle in vitro.

Aqueous extract of the stem bark of Mangifera indica and ethanolic extract of the roots of Pluchea ovalis has been studied on rat tracheal smooth muscle in vitro. The extract of M. indica at 1, 2 and 4 mg/ml and that of P. ovalis at 0.25, 0.5 and 1 mg/ml relaxed, dose-dependently, the rat tracheal smooth muscle strip previously contracted by acetylcholine at 0.055 mmol/l.