Acute and subchronic toxicity profile of methanol extract of leaves of Fimbristylis miliacea (L.) Vahl.

Fimbristylis miliacea (L.) Vahl (Cyperaceae) is a grass like herb habitually breeds as weed in paddy fields and mostly disseminated in tropical or sub-tropical countries of south and south-east Asia, northern Australia, and west Africa. The plant has been traditionally used to treat fever as a form of poultice. However, no scientific study regarding its toxicity profile has been testified. The study has been carried out to determine the potential toxicity of the methanol extract from leaves of the Fimbristylis miliacea, employing the technique of acute and subchronic oral administration in mice. In the acute toxicity study according to OECD guideline 425, oral administration of FM methanol extract at single doses of 2000 and 5000 mg/kg in both sexes of Swiss albino mice was performed. Toxic symptoms, abnormal behavior, changes in body weight, and mortality were observed for 14 consecutive days. In subchronic toxicity study according to OECD guideline 407, plant extract was administered orally at doses of 100, 500, 1000, and 2000 mg/kg daily for 28 days. The general toxic symptoms, abnormal behavior, changes in body weight were observed daily. Biochemical analysis of serum, and histopathological examination of liver were performed at the end of the study. No mortality, abnormal behavior and urination, changes in sleep, food intake, adverse effect, and non-linearity in body weight have been recorded during acute toxicity study at the doses of 2000 and 5000 mg/kg. Also, in subchronic toxicity study, FM extract produced no mortality or any kind of adverse effects in regards of general behavior, body weight, urination, sleeping routine, and food intake. In case of analysis of thirteen different biochemical parameters, concentrations of aspartate transaminase (AST) and glucose were altered significantly in male and female mice in both acute and subchronic study. Total cholesterol and triglycerides at 5000 mg/kg.bw were changed in male mice in acute toxicity study. On the other hand, female mice had altered triglycerides in subchronic test. All other critical parameters were found unaffected. In subchronic test, histopathological examination of liver demonstrated cellular necrosis at 2000 mg/kg.bw in both male and female mice while minor necrosis was observed at 1000 mg/kg.bw. Thus, the no observed adverse effect level (NOAEL) can be assumed around 1000 mg/kg.bw. The present study suggests that treatment with FM extract does not reveal significant toxicity.

Roy R ，Liya IJ ，Roy J ，Basher MA ... -  《Toxicology Reports》

Antipyretic and anti-nociceptive effects of methanol extract of leaves of Fimbristylis miliacea in mice model.

Fimbristylis miliacea (L.) Vahl (Cyperaceae) is a grass like herb usually grows as a weed in rice fields and is mainly distributed in tropical or sub-tropical countries of south and south-east Asia, central America, northern Australia and west Africa. The plant has been traditionally used to treat fever as a form of poultice. The present study aimed to investigate antipyretic and anti-nociceptive effects of methanol extract of leaves of Fimbristylis miliacea in mice model. Antipyretic effect of Fimbristylis miliacea was examined using Baker's yeast induced hyperthermia test. Anti-nociceptive effect was investigated using acetic acid induced writhing test, formalin induced hind paw licking test and hot plate test. The extract at concentration of 400 mg/kg produced significant reduction in body temperature after 0.5 h of administration (4.12 °F, p ≤ 0.001) and continued to decrease (after 4 h, 5.92 °F, p ≤ 0.001). Extracts at 100 mg/kg and 200 mg/kg decreased the temperature by about 2.77 °F (from 99.47 °F to 96.7 °F) and 5.58 °F (98.2 °F-92.62 °F) respectively after 4 h whereas paracetamol dropped by about 7.2 °F (p ≤ 0.001). The extract showed significant decrease in number of writhes at all concentrations. Highest effect was found at 200 mg/kg having 35.7 writhes (p ≤ 0.001), much lower than control (89.2); standard drug diclofenac showed 23.2 writhes. Percent inhibition of writhing were 54.26 and 73.99 for 200 mg/kg and diclofenac respectively. The result of hind paw licking test also corroborated writhing test. Significant reduction in percent inhibition of licking was observed mainly in late phase. Percent inhibition of licking were 93.77 and 51.55 for 400 mg/kg extract and diclofenac respectively. In hot plate test, extract at 400 mg/kg showed significant increase in latency from 10.77 s to 13.59 s (p ≤ 0.05). Extract at this dose after 2 h demonstrated greater percent maximal effect (43.26%) compared to ketorolac (40.19%). The experiment confirmed the traditional use of F. miliacea in the treatment of fever with possible anti-nociceptive effects.

Roy R ，Ud Daula AFMS ，Akter A ，Sultana S ，Barek MA ，Liya IJ ，Basher MA ... -  《-》

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 ... -  《-》

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 ... -  《-》

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》