Evaluation of acute and subacute toxicity of aqueous extract of Crassocephalum rubens leaves in rats.

Crassocephalum rubens is found throughout tropical Africa including the Indian Ocean islands. The leaves are commonly eaten in form of soups and sauces in South-Western Nigeria, also in other humid zones of Africa. Traditionally, it is used as an antidote against any form of poisoning; used to treat stomach and liver complaints; and externally to treat burns, sore eyes, earache, leprosy and breast cancer. In this study, acute and subacute toxicity of aqueous extract of C. rubens leaves was evaluated in rats in order to assess its safety profile. In acute toxicity study, rats were given a single oral administration of aqueous extract of C. rubens leaves at graded doses (250-5000mg/kg). The animals were monitored for behavioural changes and possible mortality over a period of 24h and thereafter, for 14 days. In the subacute toxicity study, rats of both sexes were administered C. rubens orally at doses of 250mg/kg, 500mg/kg, 750mg/kg and 1000mg/kg body weight daily, for 28 days. Rats were observed weekly for any changes in general behaviour and body weights. In addition, other relevant parameters were assayed at the end of the main and reversibility study periods. There was no observed adverse effect; including mortality in the animals. The extract caused no significant difference in the body weights as well as organs weights of treated groups when compared with the control groups. Haematological and biochemical parameters also revealed no toxic effects of the extract on rats. Histological assessments were normal in liver and kidney. It can therefore be suggested based on the results from this study that aqueous extract of C. rubens leaves, at dosage levels up to 1000mg/kg, is non-toxic and could also offer protection on some body tissues. Aqueous extract of C. rubens could therefore, be considered safe. This study supports the application of Crassocephalum rubens in traditional medicine.

Adewale OB ，Onasanya A ，Anadozie SO ，Abu MF ，Akintan IA ，Ogbole CJ ，Olayide II ，Afolabi OB ，Jaiyesimi KF ，Ajiboye BO ，Fadaka AO ... -  《-》

Acute and sub-acute toxicity of the methanolic extract of Pteleopsis hylodendron stem bark.

Pteleopsis hylodendron is one of the most popular medicinal plants in Cameroon where it is used to treat measles, chickenpox, sexually transmitted diseases, female sterility, liver and kidney disorders as well as dropsy. To date there is no documented evidence corroborating its safety. This study thus aimed to determine the toxicity profile of the methanolic extract of Pteleopsis hylodendron. The acute and sub-chronic toxicity of the methanolic extract of Pteleopsis hylodendron were investigated by employing established methods. The acute toxicity study was done by administering single doses (2-8 g/kg body weight) of plant extract to adult mice. For the sub chronic toxicity study, doses (85-680 mg/kg bw) of plant extract were administered daily to adult rats during 28 days after which the effect on organs, the hematological and biochemical parameters was assessed. In mice, single oral administrations of the methanolic extract of Pteleopsis hylodendron caused dose-dependent general behaviour adverse effects and mortality. The LD50 values were 3.00 and 3.60 g/kg bw for males and females respectively. In rats, daily single oral doses of the methanolic extract of Pteleopsis hylodendron provoked significant (p < 0.05) growth retardation in rats at all tested doses after 28 days of dosing. Haematological parameters showed a significant decrease in white blood cells count and significant increases red blood cells count; irrespective of the sex, all biochemical parameters studied, except triglycerides significantly (p < 0.001) increased with dose. However, a dose-dependent significant (p < 0.007) increase in HDL was observed only in male rats. Increases in liver enzymes (ALT and AST), proteins and creatinine levels correlate the observed histopathological damages (i.e. inflammation and vascular congestions) in the liver and kidneys. The overall results of this study indicate that the methanolic extract of Pteleopsis hylodendron stem bark possesses hepatotoxic and nephrotoxic effects at doses ≥ 85 mg/kg bw, suggesting that this plant should be used with caution.

Nana HM ，Ngane RA ，Kuiate JR ，Mogtomo LM ，Tamokou JD ，Ndifor F ，Mouokeu RS ，Etame RM ，Biyiti L ，Zollo PH ... -  《-》

Safety evaluation (acute and sub-acute studies) of the aqueous extract of the leaves of Myrianthus arboreus P. Beauv. (Cecropiaceae) in Wistar rats.

Myrianthus arboreus P. Beauv (Cecropiaceae) is a medicinal plant distributed in forests and damp places of tropical Africa. Its leaves are widely used as food and/or for the treatment of various ailments including dysmenorrhoea, female infertility, tumors and diarrhea. However, to the best of our knowledge, no safety assessment of this plant has been reported yet. The present study aimed at evaluating the safety of the aqueous extract of leaves of Myrianthus arboreus (MAA) in Wistar rats through an acute and sub-acute oral administration. In acute oral toxicity, the test was performed according to the Organization for Economic Cooperation and Development (OECD) guidelines Nr. 423 (acute toxicity class method, ATC) with slight modifications. Female Wistar rats were orally treated with the aqueous extract of M. arboreus at the doses of 2000 and 5000mg/kg. In sub-acute toxicity study, using the OECD guidelines Nr. 407, the extract was administered by gavage at the doses of 20, 110 and 200mg/kg/day for 28 consecutive days. A single oral administration of 2000 or 5000mg/kg of the extract induced neither mortality nor exterior signs of toxicity indicating a LD50 >5000mg/kg. In sub-acute study, the extract decreased triglycerides, total cholesterol/high density lipoproteins ratio and atherogenic index of plasma in both sexes at all tested doses. Alanine transaminase decreased in both sexes at 200mg/kg and serum creatinine levels decreased at all tested doses in females. Moreover, significant increases in ovarian and uterine wet weights, red blood cell count, hematocrit, mean corpuscular hemoglobin and hemoglobin were observed at 200mg/kg in females. In males, this extract decreased white blood cell count, lymphocytes and relative weight of seminal vesicles and ventral prostate at 200mg/kg. The aqueous extract of Myrianthus arboreus leaves was non-toxic in acute administration and exhibited a relatively low toxicity potential on accessory sex organs in both sexes, and leukocytes in males following the repeated 28-days oral administration of the dose 200mg/kg.

Awounfack CF ，Ateba SB ，Zingue S ，Mouchili OR ，Njamen D ... -  《-》

90 Days toxicological assessment of hydroethanolic leaf extract of Ipomoea asarifolia (Desr.) Roem. and Schult. (Convolvulaceae) in rats.

Ipomoea asarifolia (Convolvulacae), commonly known as "morning glory" is found across West Africa. Preparations of the plant are used traditionally for the treatment of diverse ailments including diabetes, neuralgia, arthritic pain and stomach ache. This study was designed to assess the safety profile of the hydroethanolic leaf extract of I. asarifolia through a 90-day subchronic toxicity study in rats. I. asarifolia was administered p.o. at doses of 40, 200 and 1000mg/kg to separate groups of rats for 90 days. Distilled water was given p.o. to rats in the control group. Some set of rats in each group were left for additional 30 days without administration of the extract for reversibility study. Animals were weighed weekly and relevant parameters were assayed at the end of the main and reversibility study periods. There was no significant change (p>0.05) in the body weight of rats, and food and water intake in I. asarifolia treated groups compared with control. I. asarifolia (40-1000 mg/kg) significantly but reversibly reduced (p<0.05, 0.001) sperm motility and count. The extract did not generally cause significant change (p>0.05) in the weight of vital organs and haematological parameters except in the case of reversible reduction in the level of haemoglobin and red blood cell count (p<0.01; 40 mg/kg). The level of biochemical parameters and electrolytes were not significantly changed (p>0.05) except for the reversible reduction in the level of aspartate aminotransferase (AST; p<0.0001; 200 and 1000 mg/kg) and increase in the level of Na(+) (p<0.01; 200 mg/kg). The level of kidney reduced glutathione (GSH) was reversibly increased (p<0.01; 1000 mg/kg) while the level of enzymatic and non-enzymatic in vivo antioxidants was generally comparable and not significantly different (p>0.05) from control in respect of all other vital organs. Histological presentations were generally normal in respect of the liver, kidneys, brain, heart, lungs, pancreas, spleen and testes. The findings in this study suggest that the hydroethanolic leaf extract of I. asarifolia is relatively safe administered orally for an extended period with potential renal in vivo antioxidant activities. However, the extract may cause reversible male sterility, anaemia and hypernatraemia.

Akindele AJ ，Unachukwu EG ，Osiagwu DD 《-》

Acute and sub-chronic toxicity studies of the aqueous extract from leaves of Cistus ladaniferus L. in mice and rats.

Cistus ladaniferus L. (C.ladaniferus) (Cistaceae) is an aromatic shrub native to the Mediterranean region. The leaves are widely used in traditional medicine throughout Morocco for the treatment of various diseases including, diabetes, diarrhea, inflammation, and skin ailments. However, to the best of our knowledge, no systematic study concerning its toxicity profile has been reported. The study carried out evaluates the potential toxicity of the aqueous extract from leaves of the C.ladaniferus (CL extract) shrub, through the method of acute and sub-chronic oral administration in mice and rats. During the acute toxicity study, male and female mice were orally administrated with CL aqueous extract at single doses of 500, 1000, 2000, 3000 and 5000mg/kg (n = 5/group/sex). Abnormal behavior, toxic symptoms, weight, and death were observed for 14 consecutive days to assess the acute toxicity. During the sub-chronic toxicity study, the aqueous extract was administered orally at doses of 500, 700 and 1000mg/kg (n = 6/group) daily to Wistar rats of both sexes for 90 days. The general behavior of the rats was observed daily, and their body weight was recorded weekly. A urinalysis, biochemical analysis, hematological analysis, macroscopic examination and histopathological examination of several organs were conducted at the end of the treatment period. During the acute toxicity test, when mice were administered doses of 3000 and 5000mg/kg, the CL extract produced a 10-30% mortality rate, respectively, and induced signs of toxicity. However, no mortality or adverse effect was noted at the doses of 1000 and 2000mg/kg. The median lethal dose (LD50) of the extract was estimated to be more than 5000mg/kg. In the subchronic study, the CL extract induced no mortality or treatment-related adverse effects with regard to body weight, general behavior, relative organ weights, urine, hematological, and biochemical parameters. Histopathological examination of vital organs showed normal architecture suggesting no morphological alterations. Moreover, the CL extracts improved lipid profile and exhibited a significant hypoglycemic effect in all doses tested in rats. The results of the present study suggest that treatment with the CL extract for 13 weeks does not appear to produce significant toxicity, except at high dose. Therefore, the use of appropriate levels of the CL extract as a traditional medicine remedies should have a wide margin of safety for its therapeutic use.

El Kabbaoui M ，Chda A ，El-Akhal J ，Azdad O ，Mejrhit N ，Aarab L ，Bencheikh R ，Tazi A ... -  《-》