Acute and sub-chronic toxicity evaluation of the crude methanolic extract of Diospyros mespiliformis hochst ex a. Dc (ebenaceae) and its fractions.

Diospyros mespiliformis, commonly called Jackal berry or African ebony, belongs to the plant family, Ebenaceae. The roots, barks and leaves have been used traditionally to treat wide varieties of conditions, however, there is limited information and literature reports concerning the toxicity and safety of this plant. The present study was conducted to evaluate the acute and sub-chronic toxicity of the crude methanolic extract of Diospyros mespiliformis and its fraction in Wistar rats. Diospyros mespiliformis was extracted by methanol 96 %. The crude methanolic extract was then fractionated into low, average and high polar compounds using hexane, ethyl acetate and butanol respectively. For the acute toxicity study, the revised limit Dose Test of "Up and Down" procedure according to the OECD guideline was used to determine the median lethal dose (LD50) of the crude methanolic leaf and bark extracts using a single fixed dose (5 g/kg) of the extracts administered by oral-gavage sequentially to 5 female Wistar rats. The rats were observed for instant death and toxicity signs for 24 h and then daily for 14 days. In the sub-chronic toxicity study, the bark and leaf ethyl acetate fractions (extract) was administered orally at doses of 250, 500 and 750 mg/kg bw /day respectively for 28 days to healthy Wistar rats. At the end of the experimental period, body weight, certain haematological, serum biochemical and histopathological parameters were evaluated. Results showed that acute oral administration of crude methanolic extract of Diospyros mespiliformis (5 g/kg bw) produced neither mortality nor visible changes in behavior or any other physiological activities and indicated that the LD50 of crude methanolic leaf and bark extract was greater than 5 g/kg bw in Wistar Rats. In the 28-days repeated dose oral toxicity study, no significant toxic effects was detected in any of the parameters evaluated. In conclusion, the crude methanolic extract was found safe in the acute toxicity study and the ethyl acetate fraction of Diospyros mespiliformis in the sub chronic study in rats could be safe for therapeutic purposes over a period not exceeding 28 days.

Ebbo AA ，Sani D ，Suleiman MM ，Ahmad A ，Hassan AZ ... -  《Toxicology Reports》

Acute toxicity study and effect of prolonged administration (28 days) of crude ethanolic root extract of Diospyros mespiliformis Hochst (Ebenaceae) on clinical, haematological and biochemical parameters of albino rats.

Different parts of the plant Diospyros mespiliformis have been used traditionally for the treatment of ailments in Nigeria particularly among the Kamwe people of Michika local government area of Adamawa State where the root has been used as an anti-malarial for ages. Most of the uses have been without any scientific evidence and toxicological assessment. The present study aimed to determine acute toxicity profile as well as the effect of prolonged administration of the extract on clinical, haematological and biochemical parameters of albino rats. Thirty and twenty-five Wistar rats of both sexes and of varying weights were, respectively, used for acute toxicity study and prolonged administration study of crude ethanolic root extract of Diospyros mespiliformis. The rats used for both studies were each administered graded concentrations of the extract (100, 200, 400, 800 and 1600mg/kg) for acute toxicity testing and (50, 100, 200 and 400mg/kg) for the study of the effect of prolonged administration. The rats used for acute toxicity study were observed for a period of 24h for signs of toxicity and eventual death while parameters for prolonged study were recorded at weekly interval starting from day zero up to day 28 post administration. The extract produced an intraperitoneal LD50 of 570mg/kg. Body weight changes were not statistically significant (p>0.05) while haematological parameters (packed cell volume (PCV)), haemoglobin concentration (Hb), red blood cells (RBC), white blood cells (WBC) and differential leucocyte counts (DLC) were significantly modulated (p>0.05) after administration. Haematological indices (mean corpuscular volume (MCV)), mean corpuscular haemoglobin (MCH) and mean corpuscular haemoglobin concentrations (MCHC) were similarly modulated significantly (p>0.05). The extract appeared to be moderately toxic while prolonged administration improved the blood parameters of rats, suggesting that the plant׳s extract at lower doses can be used for a prolonged period, without deleterious effect on the haematological profile and serum enzymes.

Luka J ，Badau SJ ，Mbaya AW ，Gadzama JJ ，Kumshe HA ... -  《-》

Short-term administration of an aqueous extract of kalanchoe integra var. crenata (Andr.) Cuf leaves produces no major organ damage in Sprague-Dawley rats.

Kalanchoe intergra (Ki) leaf extract is an orally administered multipurpose plant medicine in Ghana and other parts of the world for the treatment of ulcers, pain and adenoma of the prostate gland. There is paucity of information concerning its short-term usage. The present study is aimed at conducting histopathological and biochemical studies in a 14-day sub-acute toxicity studies using female Sprague-Dawley rats. Crude extract of Ki leaves was prepared and freeze-dried. A 14-day sub-acute toxicity studies was conducted using 2 week old nulliparous and non-pregnant female Sprague-Dawley rats (120-150g). Reconstituted Ki was administered at a dosage of 900mgkg(-1) (high dose), 300mgkg(-1) with a control group receiving an equivalent volume of distilled water (as vehicle) by gastric lavage. Histopathological studies of major organs and blood chemistry analysis were performed on blood obtained via cardiac puncture into EDTA tubes after euthanisation. There was a significant decrease in urea (p<0.016) and creatinine levels (p<0.001) in both the high and low dose groups. There was an increase in ALP levels (P=0.01) in both the high and low dose groups. ALT and AST rather decreased significantly in both the high and low dose groups (p<0.0001). Histopathological results did not show any abnormalities in all the H&E stained paraffin sections. Thus the photomicrographs of the liver, kidney and heart were within histopathological limits. Ki leaf extract is non-toxic when administered by the oral route over a time period of 14 days at the above doses.

Asiedu-Gyekye IJ ，Antwi DA ，Awortwe C ，N'guessan BB ，Nyarko AK ... -  《-》

Comparative antimalarial, toxicity and mito-protective effects of Diospyros mespiliformis Hochst. ex A. DC. and Mondia whitei (Hook.f.) Skeels on Plasmodium berghei infection in mice.

Diospyros mespiliformis Hochst. ex A. DC. and Mondia whitei (Hook.f.) Skeels are traditionally used in Africa for the treatment of malaria. However, scientific evidence to substantiate this folkloric claim and their effects on liver mitochondria during malaria treatment have not been reported. This study investigated the efficacy of D. mespiliformis and M. whitei against chloroquine-sensitive and resistant strains of malarial parasites in mice. It also investigated the toxicity and protection against cellular organelles like mitochondria. Male Swiss mice were infected with a chloroquine resistant (ANKA) strain of Plasmodium berghei and were treated via oral gavage with methanol extracts of D. mespiliformis and M. whitei reconstituted in diluted dimethylsulfoxide as vehicle (DMSO, 5% v/v) for five consecutive days. Percentage parasite load and clearance were assessed by microscopy. The infected control was treated with the vehicle. Hematological indices were assessed using standard procedures. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were determined using assay kits. Hepatic mitochondria were isolated via centrifugation, and their permeability transition (mPT), ATPase (mATPase) activity and lipid peroxidation (mLPO) were determined spectroscopically. Liver tissue histology was carried out by standard laboratory procedures. Phytochemical analysis of both extracts were performed using LC-MS to identify the most prominent compounds from each of the extracts. After treatment on day 5, D. mespiliformis and M. whitei at 400 mg/kg decreased mean values for: percentage parasitemia (5.0 ± 1.0, 2.0 ± 0.2), increased Packed Cell Volume (PCV) (36.0 ± 1.4, 36.0 ± 0.0%) and platelets (2.0 ± 1.4, 2.0 ± 2.8 × 105mm3) relative to the untreated control (20.0 ± 5.2; 30.0 ± 0.0%; 1.4 ± 1.4 × 105 mm3, respectively). At the same dose, D. mespiliformis and M. whitei decreased ALT (8.0 ± 3.8, 24.2 ± 4.0U/L), AST (6.2 ± 0.8, 8.0 ± 0.9U/L) and ALP (56.0 ± 0.7, 51.0 ± 1.0U/L) activities compared to the infected control (77.0 ± 10.9U/L, 14.0 ± 0.7U/L and 76.0 ± 6.0U/L, respectively). Both D. mespiliformis and M. whitei reversed mPT opening, decreased mATPase enhancement and mLPO, relative to the control. Histopathology of the liver showed extensive hemorrhagic lesions and severe disseminated congestion in the infected control while both D. mespiliformis and M. whitei were well tolerated at the highest dose. The LC-MS analysis of D. mespiliformis showed the presence of betulinic acid, tocopherol and kaempferol with antimalarial and antioxidant properties while the M. whitei sample contained coumarin and chlorogenic acid that have antimalarial and hepato-protective properties. D.mespiliformis and M. whitei show antimalarial effects against resistant Plasmodium berghei infection, enhanced cell viability, mito-protection and are not toxic in mice.

Olanlokun JO ，Bodede O ，Prinsloo G ，Olorunsogo OO ... -  《-》

EVALUATION OF THE ACUTE AND SUBCHRONIC TOXICITY OF Aster tataricus L. F.

Peng WJ ，Xin RH ，Luo YJ ，Liang G ，Ren LH ，Liu Y ，Wang GB ，Zheng JF ... -  《-》