Acute and sub-chronic toxicity profile of methanol leaf extract of Gouania longipetala in rats.

Gouania longipetala leaves are commonly used in folkloric medicine in Africa and other parts of the world for treatment of edema, febrifuges, veneral diseases, lumbago, heart diseases, diabetes mellitus malaria, etc. This study therefore evaluated safety profile of the methanol leaf extract of the plant using acute and sub-chronic studies in rat model. Acute toxicity test of the plant lasted for 48 h with oral administration of graded doses (100-4000 mg/kg) of Gouania longipetala extract (GLE) in rats. The rats were observed for signs of toxicity and death. The sub-chronic toxicity was evaluated by administration of different doses (2.5, 5 and 10 mg/kg) of GLE daily in feed for 90 days. On days, 30, 60 and 90, blood samples collected from the retro-orbital plexus of the eye of the rats were used for evaluation of serum biochemistry, hematology, lipid peroxidation and in vivo antioxidant activities. Histopathological evaluations of the kidney, liver, lungs and heart were also done. The acute toxicity test revealed no observable signs of toxicity or morbidity. Sub-chronic study showed that GLE significantly (p<0.05) increased relative liver weight on day 90 at 10 mg/kg. There were no significant variations in the hematological parameters of both GLE treated and untreated rats. The extract significantly (p<0.05) reduced total cholesterol, triglycerides, very low density lipoproteins and increased high density lipoproteins which was more prominent on day 90 at the dose of 10 mg/kg. The extract significantly (p<0.05) increased liver enzyme markers at the doses used. GLE also significantly (p<0.05) increased serum urea at the dose of 10 mg/kg on day 90. The extract caused dose-dependent and significant (p<0.05) increase in superoxide dismutase and decrease in malondiadehyde. Histopathological studies revealed degenerative changes in the kidney and liver. The results of the study suggest that Gouania longipetala is well tolerated in short term therapies, but may have long term toxic effects on the kidney and liver.

Ezeja MI ，Anaga AO ，Asuzu IU 《-》

Antidiabetic, antilipidemic, and antioxidant activities of Gouania longipetala methanol leaf extract in alloxan-induced diabetic rats.

Ezeja MI ，Anaga AO ，Asuzu IU 《-》

Biochemical and hematological effects of acute and sub-acute administration to ethyl acetate fraction from the stem bark Scutia buxifolia Reissek in mice.

Scutia buxifolia is a native tree of Southern Brazil, Uruguay, and Argentina, which is popularly known as "coronilha" and it is used as a cardiotonic, antihypertensive and diuretic substance. The aim of this study was to assess the acute and sub-acute toxicity of the ethyl acetate fraction from the stem bark Scutia buxifolia in male and female mice. The toxicity studies were based on the guidelines of the Organization for Economic Cooperation and Development (OECD-guidelines 423 and 407). In an acute study, a single dose of 2000 mg/kg of Scutia buxifolia was administered orally to male and female mice. Mortality, behavioral changes, and biochemical and hematological parameters were evaluated. In the sub-acute study, Scutia buxifolia was administered orally to male and female mice at doses of 100, 200, and 400mg/kg/day for 28 days. Behavioral changes and biochemical, hematological, and histological analysis were evaluated. The acute administration of Scutia buxifolia did not cause changes in behavior or mortality. Male and female mice presented decreased levels of platelets. Female mice presented decreased levels of leukocytes. On the other hand, in a sub-acute toxicity study, we observed no behavioral changes in male or female mice. Our results demonstrated a reduction in glucose levels in male mice treated to 200 and 400mg/kg of Scutia buxifolia. Aspartate aminotransferase (ASAT) activity was increased by Scutia buxifolia at 400mg/kg in male mice. In relation to the hematological parameters, male mice presented a reduction in hemoglobin (HGB) and hematocrit (HCT) when treated to 400mg/kg of plant fraction. Female mice showed no change in these parameters. Histopathological examination of liver tissue showed slight abnormalities that were consistent with the biochemical variations observed. Scutia buxifolia, after acute administration, may be classified as safe (category 5), according to the OECD guide. However, the alterations observed, after sub-acute administration with high doses of ethyl acetate fraction from the stem bark Scutia buxifolia, suggest that repeated administration of this fraction plant can cause adverse hepatic, renal, and hematological effects.

da Silva AR ，Moreira Lda R ，Brum Eda S ，de Freitas ML ，Boligon AA ，Athayde ML ，Roman SS ，Mazzanti CM ，Brandão R ... -  《-》

In vivo estrogenic-like activities of Gouania longipetala Hemsl. (Rhamnaceae) bark extracts in a post-menopause-like model of ovariectomized Wistar rats.

Gouania longipetala is commonly used in Cameroonian traditional medicine to manage women fertility and menopausal complaints. However, despite this use, the estrogenic properties of G. longipetala have not been studied until now. The present study was aimed to assess estrogenic activities of the stem bark aqueous (GLA) and ethanolic (GLE) extracts of G. longipetala in post-menopause-like model of ovariectomized (Ovx) Wistar rats. Animals were either sham-operated or Ovx. 84 days after ovariectomy, animals were divided into seven groups of five animals and were daily treated for 28 days with distilled water (10 mL/kg) for group 1, 2% solution of Tween 80 (10 mL/kg) for group 2, estradiol valerate (1 mg/kg) for group 3, GLA (45 or 180 mg/kg) and GLE (40 or 160 mg/kg) for groups 4 to 7 respectively. Sham-operated animals daily received distilled water (10 mL/kg). During the experimental period, the body weight was registered every week. At the day 29, blood pressure was registered by invasive method while uterine and vagina morphometry as well as body, uterine and abdominal fat weights changes were analyzed. Serum levels of total cholesterol, triglycerides, HDL-cholesterol and LDL-cholesterol were determined. Moreover, oxidative stress markers such as nitrites, reduced glutathione (GSH) and malondialdehyde (MDA) were measured in homogenized liver and aorta. Compared with the sham control, vagina and uterine dystrophy and elevated blood pressure were observed in Ovx rats treated with vehicles. Biochemical parameters showed a significant increase of total cholesterol, triglycerides, LDL-cholesterol and MDA as well as a significant decrease of nitrites and GSH in Ovx animals treated with vehicle as compared to sham group. GLA and GLE displayed estrogen-like effects on vagina and did not affect uterine wet weight and epithelial height compared with vehicle groups. Both extracts displayed anti-atherogenic properties by reducing AI, AIP and LDL-cholesterol level as compared to vehicles groups. GLA and GLE significantly prevented the increase of MDA induced by ovariectomy as compared to rats treated with vehicles. This study showed that GLA and GLE exhibited estrogenic effects by providing vaginal lubrication, by modulating blood pressure and improving lipid profile, oxidative status and endothelial function and may not have an undesirable influence on the endometrium in ovariectomized rats.

Paul Désiré DD ，Yolande Sandrine MN ，Danielle Claude B ，Mireille K ，Oumarou Bibi-Farouck A ，Théophile D ，Pierre K ... -  《-》

Acute and subacute toxicity and chemical constituents of the hydroethanolic extract of Verbena litoralis Kunth.

Verbena litoralis Kunth is a native species of South America, popularly known as gervãozinho-do-campo or erva-de-pai-caetano. It is used in gastrointestinal disorders, as detoxifying the organism, antifebrile properties and amidaglitis. To identify the chemical constituents of the hydroethanolic extract obtained from the aerial parts of V. litoralis and to evaluate the acute and sub-acute toxicity in male and female rats. The single dose (2000 mg/kg) of the extract was administered orally to male and female rats. In the subacute study the extract was given at doses of 100, 200 and 400 mg/kg during 28 days orally. Biochemical, hematological and histological analyzes were performed, oxidative stress markers were tested and chemical constituents were identified through UHPLC-ESI-HRMS RESULTS: Six classes of metabolites were identified: iridoids glycosides, flavonoids, phenylpropanoids-derived, phenylethanoid-derived, cinnamic acid-derived and triterpenes. In the acute treatment, the extract was classified as safe (category 5), according to the OECD guide. Our results demonstrated that subacute administration of the crude extract of V. litoralis at 400 mg/kg resulted in an increase in AST in males, whereas ALT enzyme showed a small increase in males that received 200 mg/kg and 400 mg/kg of the extract. The extract of the aerial parts of Verbena litoralis did not present significant toxicity when administered a single dose. However, when different doses were administered for 28 days, were observed changes in hematological, biochemical and histological parameters in rats.

de Lima R ，Guex CG ，da Silva ARH ，Lhamas CL ，Dos Santos Moreira KL ，Casoti R ，Dornelles RC ，da Rocha MIUM ，da Veiga ML ，de Freitas Bauermann L ，Manfron MP ... -  《-》