Acute and sub-chronic toxicity studies of Benincasa hispida (Thunb.) cogniaux fruit extract in rodents.

The objective of the present study was to evaluate the safety of standardized 70% ethanolic extract of Benincasa hispida fruit pulp (HABH) in rodents. Chemical characterization of HABH has been done by GC-MS and dimethylsulfoxonium formyl methylide, l-(+)-ascorbic acid and 2,6-dihexadecanoate were identified as major compounds in the extract. Acute oral toxicity study of HABH was done according to the Organization for Economic Cooperation and Development (OECD) guideline, by 'up and down' method, using the limit test at 2000 mg/kg, body weight in mice and were observed up to 14 days. In sub-chronic oral toxicity study, HABH was administered to Wistar rats at doses of 1000, 200 and 40 mg/kg b. w. per day for 90 days. In acute toxicity study, there was no mortality and no behavioural signs of toxicity at the limit test dose level (2000 mg/kg b. w.). In sub-chronic oral toxicity study, there was no significant difference observed in the consumption of food and water, body weight and relative organ weights. Haematological, serum biochemical and urine analysis revealed the non-adverse effects of prolonged oral consumption of HABH. The histopathologic examination did not show any differences in vital organs. Based on our findings, HABH, at dosage levels up to 1000 mg/kg b. w., is non-toxic and safe for long term oral consumption.

Phytomedicinal relevance of South African Cucurbitaceae species and their safety assessment: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: South Africa has a very rich flora. Many of these species such as those in the Cucurbitaceae family are exploited as medicines for the treatment of various infections. AIM OF THE REVIEW: The aim of the review was to synthesize the existing but scattered literature of some plant species in the Cucurbitaceae family used as sources of medicines in South Africa. MATERIALS AND METHODS: A literature survey was carried out on the ethnopharmacology, phytochemistry, pharmacological relevance and safety assessment of the South African Cucurbitaceae used as medicines. RESULTS: A total of 11 plants namely; Coccinia rehmannii Cogn., Cucumis africanus L.f., Cucumis anguria L. var. longaculeatus J.H.Kirkbr., Cucumis myriocarpus Naudin subsp. myriocarpus, Cucumis zeyheri Sond., Cucumis metuliferus E. Mey ex Naudin, Kedrostis nana (Lam) Cogn., Lagenaria siceraria (Molina) Standl., Momordica balsamina L., Momordica charantia L., and Momordica foetida Schumach. and Thonn were identified. Various traditional medicinal uses for these plants, from common ailments to life-threatening infections were reported. Biological activities including antidiabetic, antioxidant, antimicrobial, anticancer, anti-inflammatory and hepatoprotective were reported. However, some of the plants have not been investigated for some of the biological activities related to their traditional uses. In addition, most of the studies were carried out using non-standardized extracts. Thus, only a few studies on their bioactive constituents exist. Common compounds identified within the species are hydroxycinnamic and hydroxybenzoic acids such as sinapic, gallic, vanillic and salicylic acids; flavonoids such as naringenin, quercetin, kaempferol and rutin; fatty acids such as linoleic, palmitoleic, myristic and stearic acids; the saponin glycosides, momordicin alkaloids and cucurbitacins. However, most of these compounds have not been tested for biological activities. Cucurbitacins were implicated as a major class of toxic compounds present in the plants resulting in poisoning and death. CONCLUSIONS: Adequate knowledge of the traditional use of these plants in medicine and the parts used are very important due to the presence of toxic substances and their wide usage. Proper screening of the safety of these plants and products derived from them calls for urgent attention.

Potential antimalarial activity of Coccinia barteri leaf extract and solvent fractions against Plasmodium berghei infected mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Coccinia barteri (Hook. F.) is traditional used in Southeast of Nigeria in management of fever. This study aimed to evaluate the antimalarial activities of hydro-methanol crude extract and solvent fractions of Coccinia barteri leaf. MATERIALS AND METHODS: Two animal models employed for the study were, 4-day suppressive and curative assays against chloroquine sensitive Plasmodium berghei NK65. Level of parasitaemia, mean survival time (MST), anal temperature and weight loss were measured to assess antimalarial efficacy of the extract/fractions. Chloroquine (10 mg kg-1) was used as positive control. Chemo-profile of extract was evaluated using GC-MS, HPLC techniques and standard phytochemical analysis. Preliminary toxicity test was done using modified Lorke's method. RESULTS: The crude extract (100-400 mg kg-1) and solvent fractions (20-80 mg kg-1) demonstrated antimalarial activity in both models compared to controls. Semi purified fractions of the extract produced stronger percentage chemosuppression and inhibition of parasite. The % inhibition of the fractions, hexane, chloroform, ethyl acetate and aqueous at 80 mg kg-1 were 96.0 0, 95.29, 89.86 and 96.00% respectively on day 8 (D8). While on D14, 100% parasite clearance, indicating cure was obtained for hexane, chloroform and aqueous fraction treatment groups, no death occurred in these groups. Ethyl acetate fraction treated groups lived longer but were not fully protected. Some marker compounds were identified. CONCLUSIONS: These results support the use of C. barteri as malaria remedy and potential source of antimalarial templates. Long acting parasitaemia reduction effect indicates its possible combination potential in poly-herbal combination therapy.

Potential hepatoxicity risk of the shell of Herpetospermum caudigerum Wall in rats based on 1H-NMR metabonomics.

The Herpetospermum caudigerum Wall (HCW) is a traditional Tibetan medicine and is widely used in clinical practice. However, the shell of the HCW (SHCW) has rarely been studied, and some researchers have suggested that the SHCW may be toxic. Therefore, in this study, SHCW was administered to rats at two doses (0.1 and 0.33 g/kg) once a day for 21 days. The hepatic stimuli induced by SHCW in rats were investigated for the first time by 1H-NMR-based metabolomics combined with histopathological observation and biochemical detection. Histopathological sections showed a certain degree of hepatocyte edema and hepatic sinus congestion in the liver tissue of the rats in the drug-administered group. Serum biochemical indicators revealed a significant increase in ALT, AST, and MDA, and a significant decrease in SOD. Metabolomic results showed that the metabolites in rats were changed after gavage administration of extracts from SHCW. By multivariate statistical analysis and univariate analysis, it was found that SHCW could cause the disorder of energy metabolism, oxidative stress and amino acid metabolism in rats, leading to liver damage. This comprehensive metabolomics approach demonstrates its ability to describe the global metabolic state of an organism and provides a powerful and viable tool for exploring drug-induced toxicity or side effects.

Acute and subacute toxicity of aqueous extract of the tuber of Kedrostis africana (L.) Cogn in Wistar rats.

Kedrostis africana (L.) Cogn (Cucurbitaceae) is used in South African traditional medicine and pharmacopoeia as an emetic, purgative and diuretic, and it is used against dropsy in the management of obesity. Aim of the study In this study, acute and subacute toxicity of aqueous extract of K. africanatuber was evaluated in male and female Wistar rats in order to assess its safety profile. Materials and methods In acute toxicity, the effects of a single oral dose (2,000 and 5,000 mg/kg) of aqueous extract was determined in both sexes. General behavior, adverse effects and mortality were determined for 3 h and then periodically for 14 days. The subchronic toxicity test was performed in rats. The effects of the extract in daily single oral administration at the doses of 200, 400 and 600 mg/kg for 28 days were determined. Food and water intakes were monitored daily while body weight was monitored on a weekly bases. Hematological, biochemical and organ parameters were determined at the end of the 28-day administration. Results In the acute study, a single administration of the aqueous extract at the doses of 2,000 and 5,000 mg/kg did not induce mortality. Thus, the LD50 of the aqueous extract of K. africana (AEKA) has been estimated to be higher than 5,000 mg/kg. In the subchronic study, daily oral administration of the AEKA did not result in death of the rats or significant changes in hematological or biochemical parameters at the highest dose of 600 mg/kg. No alteration was observed in body weight, food and water intake. Liver, kidney and heart histopathology did not reveal morphological alteration. Conclusions The results showed that the aqueous tuber extract of K. africana did not cause any death, nor did it cause abnormalities in necropsy and histopathology findings. There were no acute or subchronic toxicity observed, and this indicates that the plant extract could be considered safe for oral medication.

Cholestatic hepatitis due to Ecballium elaterium ingestion.

Ecballium elaterium is an herbaceous plant belonging to the Cucurbitaceae family. This plant is fairly common in the Mediterranean regions. It is frequently consumed in infusion, mixture of fruit or even in aerosol in cases of fever or flu. This plant is known for its respiratory and ocular toxicity. Hepatotoxicity has never been described in the literature. We report a case of acute cholestatic hepatitis due to Ecballium elaterium in a 39 years old patient, with no past medical history.

Combined toxicity of Cassia senna and Citrullus colocynthis in rats.

Body weight loss, inefficiency of feed utilization, diarrhea, ruffled hair and enterohepatonephrotoxicity were effects on male Wistar rats fed diet containing 10% Cassia senna or 10% Citrullus colocynthis ripe fruits for 6w. Rats fed a 1:1 mixture (5% + 5%) of fruits from these plants were more adversely affected and had deaths than rats fed the individual plants. The changes associated with the macrocytic hypochromic anemia and leukopenia were increased serum AST, ALT and ALP activities, increased urea, and decreased total protein, albumin and calcium. Serum bilirubin concentration did not change.

Effect of combined Citrullus colocynthis and Rhazya stricta use in Najdi sheep.

The effect of oral administration of 0.25 g/kg/day of Citrullus colocynthis fruits, 0.25 g/kg/day of Rhazya stricta leaves or mixture of the two plants at 0.25 g/kg/day of C. colocynthis fruits plus 0.25 g/kg/day of R. stricta leaves in Najdi sheep was examined. Oral administration of 0.25 g/kg/day of C. colocynthis fruits or 0.25 g/kg/day of R. stricta leaves for 42 days proved not fatal but that of the mixture of the two plants (0.25 g + 0.25 g/kg/day) proved fatal within 26 days with profuse diarrhea, dehydration, loss in condition, ataxia and recumbency, prior to death. These manifestations accompanied by enterohepatonephrotoxicity, gelatinization of the renal and epicardial fat and transudate in serous cavities were correlated with alterations in serum LDH and AST activities and concentrations of total protein, albumin, globulin, bilirubin, cholesterol and urea and hematology.