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.

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.

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.

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.