Acute and Sub‐Acute Oral Toxicity Assessment of the Hydroalcoholic Extract of Withania somnifera Roots in Wistar Rats

Withania somnifera is a widely used medicinal plant for several disorders. Toxicity studies on Withania somnifera are not available. Acute and sub‐acute oral toxicities of Withania somnifera root extract in Wistar rats were evaluated in the present study. In the acute toxicity study, WSR extract was administered to five rats at 2000 mg/kg, once orally and were observed for 14 days. No toxic signs/mortality were observed. In the sub‐acute study, WSR extract was administered once daily for 28 days to rats at 500, 1000 and 2000 mg/kg, orally. No toxic signs/mortality were observed. There were no significant changes (P < 0.05) in the body weights, organ weights and haemato‐biochemical parameters in any of the dose levels. No treatment related gross/histopathological lesions were observed. The present investigation demonstrated that the no observed adverse effect level was 2000 mg/kg body weight per day of hydroalcoholic extract of W. somnifera in rats and hence may be considered as non‐toxic. Copyright © 2012 John Wiley & Sons, Ltd.     

Acute and sub-chronic toxicity of HPLC fingerprinted extract of Conyza sumatrensis (Retz.) E.H. Walker in rodents

Ethnopharmacological relevance

Conyza sumatrensis (CS) is an extensively used medicinal herb in the tropics for varied ailments related to pain, inflammation and malaria. Though in constant folkloric use, scientific validations are proving valuable.

Aim of the study

Evaluate the safety profile of methanol extract from CS in mice and rats through acute and sub-chronic toxicity studies respectively.

Material and methods

Acute toxicity study involved the single oral administration of CS at 1000, 2000 and 3000 mg/kg in mice, while the sub chronic toxicity was carried upon in rats at doses 250, 500 and 1000 mg/kg/day for 28 days. Besides body weight, general behaviour and mortality, serum biochemical parameters and liver histology were assessed after 7 and 28 days for acute and sub-chronic study respectively. The parameters were again checked on days 14 and 56 in order to assess the recovery from damage, if any. HPLC fingerprinting of the aqueous and methanol extract was performed through C18 column using water: acetonitrile as mobile phase with observations at 240 nm.

Results

In the acute toxicity test, single oral dose of 1000, 2000 and 3000 mg/kg of CS did not result in any behavioural changes or mortality, indicating non toxicity. In sub-chronic toxicity studies in rats, no mortality was observed at 250, 500 and 1000 mg/kg/day when administered orally for a period of 28 days. Except Serum Glutamate Pyruvate Transaminase (SGPT) level in acute study and Alkaline Phosphatase (ALP), SGPT and Serum Glutamate Oxaloacetate Transaminase (SGOT) level in sub-chronic study, all the observational, haematological and biochemical parameters studied showed non-significant changes. Histological examination of liver did not reveal any treatment-related effects in any of the studies. Moreover, haematological and biochemical changes orchestrated by CS got normalised after 14 and 56 days post-treatment in acute and sub-chronic toxicity respectively. The HPLC fingerprint could resolve 11 and 28 peaks from aqueous and methanol extracts respectively.

Conclusion

The experiments indicate the methanol extract to be safe even at high and repeated doses in pre-clinical studies even though the constituents are more than in aqueous extract.     

Gastric cytoprotective anti-ulcer effects of the leaf methanol extract of Ocimum suave (Lamiaceae) in rats

The anti-ulcerogenic potential of the leaf methanol extract of Ocimum suave (Lamiaceae) was investigated using four methods of gastric lesion induction in experimental Wistar rats (150-200 g): (1) HCl/ethanol-induced gastric lesions, (2) Absolute ethanol-induced gastric lesions, (3) Indomethacin-HCl/ethanol-induced gastric lesions, (4) Pylorus ligation-induced gastric lesions. Administration of the extract of O. suave to the rats by oral route (75-500 mg/kg) dose-dependently prevented the formation of acute gastric lesions induced using the four experimental techniques. The dose-dependent reduction of lesion formation was in all cases accompanied by significant increases in gastric mucus production. At the dose of 250 mg/kg there was complete inhibition of gastric lesions induced using the HCl/ethanol solution. Pre-treatment, by intraperitoneal route, with indomethacin significantly reduced the ability of the extract to inhibit the formation of HCl/ethanol-induced lesions. When the rats were subjected to pylorus ligation, the dose of 500 mg/kg completely inhibited lesion formation but did not have any effect on gastric acid secretion compared with the controls. The mucus secretion promoting effect of the extract was most significant when the gastric environment was highly acidic. These results suggest that a new anti-ulcer therapy regimen may be formulated which does not require the use of antacids and anti-secretory agents.     

Toxicity evaluation of a standardised 50% ethanol extract of Orthosiphon stamineus

Aim of the study

The present investigation was carried out to evaluate the safety of standardised 50% ethanol extract of Orthosiphon stamineus plant by determining its potential toxicity after acute and subchronic administration in rats.

Materials and methods

For acute toxicity study, up and down method (limit dose) was adapted. A single dose of 5000 mg/kg of the standardised 50% ethanol extract of O. stamineus was given orally to 5 healthy Sprague-Dawley (SD) female adult rats. The rats were observed for mortality and clinical signs for 3 h and then periodically for 14 days. While in the subchronic toxicity study, the extract was administered orally at doses of 1250, 2500 and 5000 mg/kg per day for 28 days to female and male SD rats, respectively. The animals were sacrificed, followed by examination of their organs and blood serum.

Results

In the acute toxicity study, standardised 50% ethanol extract of O. stamineus at a dose of 5000 mg/kg caused neither visible signs of toxicity nor mortality. All five rats survived until the end of observation period. While in subchronic toxicity, administration of the standardised 50% ethanol extract of O. stamineus at 1250, 2500, and 5000 mg/kg for 28 days did not produce any mortality and there were no significant differences in the general condition, growth, organ weights, heamatological parameters, clinical chemistry values, or gross and microscopic appearance of the organs from the treatment groups as compared to the control group.

Conclusions

Standardised 50% ethanol extract of O. stamineus 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 extract could be devoid of any toxic risk. The NOAEL for the standardised 50% ethanol extract of O. stamineus is 5000 mg/kg per day for 28 days.     

New Activities for Isolated Compounds from Convolvulus austro‐aegyptiacus as Anti‐ulcerogenic,Anti‐Helicobacter pylori and Their Mimic Synthesis Using Bio‐guided Fractionation

Bio‐guided fractionation of the total alcoholic extract of Convolvulus austro‐aegyptiacus was screened for its anti‐ulcerogenic activity, using an absolute‐ethanol‐induced ulcer model at 500 and 1000 mg/kg doses. Two compounds were isolated from the butanol extract of C. austro‐aegyptiacus and identified by ¹H and ¹³C nuclear magnetic resonance as scopoletin and scopolin. The isolated compounds (50 mg/kg) showed a remarkable anti‐ulcerogenic activity because they exhibited control‐ulcer protection by 16.7% and 90.8%, respectively. The acute toxicity study showed that the extract is highly safe; the median lethal dose (LD₅₀₎ was more than 4000 mg/kg. Moreover, the obtained results were confirmed by the sub‐chronic toxicity because the rats that have been administered 1000 mg/kg of the extract for 15 consecutive days showed no alteration in the liver and kidney functions. Copyright © 2015 John Wiley & Sons, Ltd.     

Acute and chronic toxicity of a lyophilised aqueous extract of Tanacetum vulgare leaves in rodents

AIM OF THE STUDY: The present investigation was carried out to evaluate the safety of an aqueous extract of tansy (Tanacetum vulgare L.) leaves by determining its potential toxicity after acute and chronic administration in rodents. MATERIALS AND METHODS: For the acute study, a lyophilized aqueous extract of tansy leaves was administered to mice in single doses of 0-13 g/kg given by gavage as well as intraperitoneal doses of 0-4.5 g/kg. General behavior adverse effects and mortality were determined for up to 14 days. In the chronic dose study, the extract was administered orally at doses of 0, 100, 300 and 600 mg/kg daily for 90 days to rats. Biochemical and hematological parameters were determined after 30 and 60 days, and then at the end of 90 days of daily administration. RESULTS: In the acute study in mice, the crude aqueous extract of tansy leaves caused dose-dependent general behavior adverse effects and mortality. The no-observed adverse effect levels (NOAEL) of the tansy extract were 7.0 g/kg and 1.0 g/kg, and the lowest-observed adverse effect levels (LOAEL) were 9.0 g/kg and 1.5 g/kg, when given by the oral and intraperitoneal routes, respectively. Mortality increased with increasing doses, with LD(50) of 9.9 g/kg and 2.8 g/kg for the oral and intraperitonal modes of administration, respectively. In the chronic study in rats, daily oral administration of the crude aqueous extract of tansy leaves for up to 90 days did not result in death or significant changes in the biological (except for hypoglycemia) and hematological parameters. CONCLUSIONS: Because of the relatively high NOAEL values in the acute study in mice, and lack of significant effect on biological and hematological parameters in rats after 90 days of daily doses, the tansy extract does not appear to have significant toxicity. In view of the dose of tansy consumed in traditional medicine, there is a wide margin of safety for the therapeutic use of the aqueous extract of Tanacetum vulgare leaves.     

Antipyretic properties of the aqueous and ethanol extracts of the leaves of Ocimum suave and Ocimum lamiifolium in mice

Numerous plant species are used to treat ailments associated with pyrexia in the indigenous health care delivery system of Ethiopia. Notable among these are Ocimum suave and Ocimum lamiifolium. The objective of the present study was thus to evaluate the antipyretic effects of the aqueous and ethanol extracts of the leaves of Ocimum suave and Ocimum lamiifolium in mice. Rectal temperatures were recorded before and after inducing pyrexia as well as after administration of the respective extracts every half an hour for 3h. Parallel experiments were run with a standard antipyretic (acetylsalicylic acid) and the vehicle (distilled water). All the plant extracts showed antipyretic property with reasonable onset and duration of action. Both ethanol and aqueous extracts of Ocimum suave were observed to be more potent than those of Ocimum lamiifolium. Aqueous extract of Ocimum suave and ethanol extract of Ocimum lamiifolium were more potent than their other counterpart extracts. Time dependent antipyretic effect was also observed with some extracts; reduced with time with aqueous extract of Ocimum suave and increased with time with both extracts of Ocimum lamiifolium.     

Anti-inflammatory effects and acute toxicity of hydroethanolic extract of Jacaranda decurrens roots in adult male rats

Ethnopharmacological relevance

Jacaranda decurrens subsp. symmetrifoliolata Farias and Proença (Bignoniaceae) is a species traditionally used for the treatment of inflammatory diseases. However, until this moment, there is no scientific evidence of these effects.

Aim of study

To evaluate the anti-inflammatory effects of hydroethanolic root extract of Jacaranda decurrens in rats and to determine the safe of this plant after acute exposure.

Materials and methods

The acute toxicity of Jacaranda decurrens root extract (EJD) was evaluated by oral administration to male rats as single doses of 0; 500; 1000 or 2000 mg/kg body weight. General behavior and toxic symptoms were observed for 14 days. The anti-inflammatory activity was evaluated in carrageenan-induced inflammatory paw edema and myeloperoxidase activity in male rats.

Results

No signs of acute toxicity were observed, indicating that the LD₅₀ is greater than 2000 mg/kg. EJD (100 and 300 mg/kg) significantly reduced edema formation and at higher dose, the reduction was similar to dexamethasone. A significant decrease in myeloperoxidase activity was also observed.

Conclusions

The present study shows that Jacaranda decurrens extract has anti-inflammatory properties in rats without causing acute toxicity. These properties observed may be due to the presence of bioactive constituents such as ursolic acid.     

Toxicity evaluation of standardized extract of Gynostemma pentaphyllum Makino

Ethnopharmacological relevance

To evaluate the safety of standardized extract of Gynostemma pentaphyllum in rats.

Materials and methods

The water extract of Gynostemma pentaphyllum was prepared and standardized, the dry powder yielded 6% gypenosides. In the acute oral toxicity test, the single oral dose of 5000 mg/kg of Gynostemma pentaphyllum extract was given to female Sprague–Dawley rats. In subchronic toxicity test, the oral dose of 1000 mg/kg/day of the extract was given to rats in treatment and satellite groups for 90 days. Satellite groups of both sexes were kept for additional 28 days after 90-day treatment. Control rats received distilled water.

Results

Standardized extract of Gynostemma pentaphyllum did not cause death or any toxic signs in rats. The daily administration of the extract for 90 days did not produce lethal or harmful effects. Although certain hematological and blood chemistry values (i.e., neutrophil, monocyte, glucose, and serum alkaline phosphatase levels) were found to be statistically different from the control group, however; these values were within the ranges of normal rats.

Conclusion

Standardized extract of Gynostemma pentaphyllum did not produce mortality or any abnormality in rats.     

Acute and chronic toxicological studies of Dimorphandra mollis in experimental animals

Dimorphandra mollis Benth. (Caesalpiniaceae), known as "faveira" or "fava d'anta" is a common plant in central Brazilian cerrado that is used mainly as a vasoprotector. Its main marker is rutin. The present study aimed to evaluate the security of Dimorphandra mollis dry extract in rodents. The extract presented a rutin content of 76+/-3%. Acute and chronic (180 days) toxicity was evaluated after per os administration. In acute toxicity, 3500 and 5000 mg/kg doses presented reversible effects. In chronic toxicity, 1000 and 2000 mg/kg doses did not provoke significant changes in body weight of the animals and in water and food consumption. Behavioral reversible changes and in blood count parameters (hemoglobin, hematocrit and red cells decrease and platelets increase in male in rats) were observed only in 2000 mg/kg dose. In biochemical evaluation, the results varied a lot considering doses and sex, without a linear profile. Some parameters showed a significant difference but without a clinical correlation. In histopathological examination, lung hemorrhage was observed in 2000 mg/kg dose. In conclusion, the study suggest that the extract is safe in a 1000 mg/kg dose, whereas for 2000 mg/kg dose further studies are needed. In long-term use, caution is required.     

Preclinical toxicological evaluations of the sclerotium of Lignosus rhinocerus (Cooke), the Tiger Milk mushroom

Ethnopharmacological relevance

Lignosus rhinocerus (Tiger Milk mushroom) is distributed in South China, Thailand, Malaysia, Indonesia, Philippines and Papua New Guinea. In Malaysia, it is the most popular medicinal mushroom used by the indigenous communities to relieve fever, cough, asthma, cancer, food poisoning and as a general tonic. In China, this mushroom is an expensive traditional medicine used to treat liver cancer, chronic hepatitis and gastric ulcers. The sclerotium of the mushroom is the part with medicinal value. This rare mushroom has recently been successfully cultivated making it possible to be fully exploited for its medicinal and functional benefits. The present study was carried out to evaluate the chronic toxicity of the sclerotial powder of Lignosus rhinocerus cultivar (termed TM02), its anti-fertility and teratogenic effects as well as genotoxicity.

Materials and methods

Sprague Dawley rats (10 rats/group/sex) were fed orally with 250, 500 and 1000 mg/kg of sclerotial powder of TM02. The sclerotial powder was orally administered once daily and consecutively for 180 days. At the completion of the oral feeding period, analysis of hematological and clinical biochemical parameters, urine profiles, organ weight as well as histopathological analysis were carried out. The effect of the sclerotial powder on fertility and its possible teratogenicity were examined by feeding rats orally with 100 mg/kg sclerotial powder consecutively for 7–8 weeks. Genotoxicity was evaluated by Ames test using Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537 and Escherichia coli WP2 uvrA.

Results

The results showed that oral administration of the sclerotial powder of the Lignosus rhinocerus cultivar at daily dose of up to 1000 mg/kg for 180 days had no adverse effect on the general clinical observations, body weight, hematology, clinical biochemistry, urinalysis, absolute organ weight as well as relative organ weight, nor induced histological changes in the organs. Oral administration of 100 mg/kg sclerotial powder of the Lignosus rhinocerus for 7–8 weeks did not affect the fertility of the rats nor induce teratogenic effect on their offspring. Lignosus rhinocerus sclerotial powder up to 5000 μg/plate in the presence and absence of metabolic activation did not cause gene mutations by base pair changes or frameshifts in the genome of the tester strains used.

Conclusion

Our results showed that the no-observed-adverse-effect level (NOAEL) dose of the sclerotial powder of Lignosus rhinocerus in 180-day chronic toxicity study is more than 1000 mg/kg. Oral feeding of the sclerotial powder at 100 mg/kg did not induce adverse effect on rats' fertility nor causing teratogenic effect on their offspring. In the reverse mutation Ames test, the sclerotial powder at all tested concentration did not show any genotoxicity.     

Potential Antidepressant Activity of Areca catechu Nut via Elevation of Serotonin and Noradrenaline in the Hippocampus of Rats

The current study was aimed at investigating the potential antidepressant activity of Areca catechu nut ethanol extract and its various fractions using behavioral (acute and sub‐chronic forced swim tests) and biochemical (monoamines and their metabolite levels using high performance liquid chromatography) tests. The areca nut ethanol extract and its aqueous fraction exhibited antidepressant activity in both acute and sub‐chronic forced swim tests (IC₅₀ ~ 50 and 20 mg/kg, respectively), which was further confirmed by unaltered locomotor (horizontal and vertical) activities of rats in the activity cage. Phytochemical analysis revealed that saponins of areca nut may be the active component in its antidepressant action. The rats treated sub‐chronically with areca nut extract displayed toxic effects, whereas its active aqueous fraction was non‐toxic, indicating the presence of different constituents for antidepressant and toxic effects. In the hippocampus of rats, the areca nut extract (50 mg/kg) and aqueous fraction (20 mg/kg) caused a significant elevation of serotonin (around 35%) and noradrenaline (around 30%) compared with the control (261 ± 25 and 512 ± 29 ng/g, respectively). In conclusion, the areca nut possesses potential antidepressant effect via the elevation of serotonin and noradrenaline. Copyright © 2012 John Wiley & Sons, Ltd.     

Evaluation of toxicity of Calophyllum brasiliense stem bark extract by in vivo and in vitro assays

Ethnopharmacological relevance

Calophyllum brasiliense Camb., Clusiaceae, is commonly known as “guanandi” and its stem bark is used in Brazilian traditional medicine to treat rheumatism, vein problems, hemorrhoids and gastric ulcers. The aim of this study was to evaluate the toxicity of hexane extract of Calophyllum brasiliense stem bark (HECb) using in vitro and in vivo experimental models.

Materials and methods

In vitro toxicity was evaluated by Alamar Blue cytotoxicity assay and micronucleus test, using Chinese hamster ovary (CHO-k1) epithelial cells. in vivo toxicity was evaluated by oral acute and subchronic toxicity assays. In the oral acute toxicity screening, a single dose of HECb was administered to mice at doses ranging from 250 to 1000 mg/kg. In the subchronic study, HECb was administered orally for 30 days to Wistar rats at doses of 100 mg/kg and 500 mg/kg. Phytochemical analyses were performed by HPLC/UV–vis, secondary metabolites were quantified by spectrophotometric methods.

Results

HECb presented IC₅₀=119.94±4.31 µg/mL after a 24 h cytotoxicity test using CHO-k1 cells, showing low cytotoxicity. However, when the cells were exposed to HECb for 72 h, the IC₅₀ value was 8.39±2.00 µg/mL, showing in this case, a pronounced cytotoxic effect. In the oral acute toxicity studies, doses up to 500 mg/kg of HECb did not cause any changes in both male and female mice. At 1000 mg/kg, male mice showed signs typical of depression and stimulation that were reversed at 72 h. Besides, female mice were more sensitive to the toxic effect of HECb at 1000 mg/kg, which initially presented typical agitation signals, followed by depression signals, leading to death of all the animals at 24 h. In subchronic assay with rats, HECb administered orally at doses of 100 and 500 mg/kg did not cause significant changes in all clinical parameters evaluated. Histopathological analyses showed no deleterious effect in the vital organs of rats. Preliminary phytochemical analysis revealed the presence of phenolic compounds, steroids, and volatile coumarins. Analysis by HPLC showed two major peaks characteristic of chromanones.

Conclusions

In vitro toxicological tests showed that HECb exhibited cytotoxicity especially after 72 h of exposition, and mutagenicity on the highest tested dose. The in vivo studies demonstrated that HECb produced some toxicity signs at the highest dose tested, particularly, in the acute toxicity test but showed no significant signs of toxicity in the subchronic assay. Based on these and previous pharmacological studies, it is possible to say that HECb did not exhibit significant toxicity at its effective dose. This suggests that HECb is relatively safe in humans at its effective dose.     

Acute and subchronic oral toxicity of Coriolus versicolor standardized water extract in Sprague-Dawley rats

Ethnopharmacological relevance

Coriolus versicolor, which is known as Yun Zhi, is one of the commonly used Chinese medicinal herbs. Recent studies have demonstrated its antitumor activities on cancer cells which led to its widespread use in cancer patient. However, little toxicological information is available regarding its safety. The present study evaluated the potential toxicity of Coriolus versicolor standardized water extract after acute and subchronic administration in rats.

Materials and methods

In acute toxicity study, Coriolus versicolor water extract was administered by oral gavage to Sprague-Dawley (SD) rats (6 males, 6 females) at single doses of varying concentrations 1250, 2500 and 5000 mg/kg. In subchronic toxicity study, the extract was administered orally at doses of 1250, 2500 and 5000 mg/kg/day for 28 days to male and female SD rats respectively. General behavior, adverse effects and mortality were determined throughout the experimental period. Haematological and biochemical parameters, relative organ weights and histopathological were evaluated at the end of the experiment.

Results

There were no mortality and signs of toxicity in acute and subchronic toxicity studies. In the single dose acute toxicity and repeated dose 28-day subchronic toxicity studies, there were no significant difference in body weight, relative organ weight, haematological parameters, clinical chemistry, gross pathology and histopathology between treatment and control groups.

Conclusions

Coriolus versicolor water extract did not cause remarkable adverse effect in SD rats. The oral lethal dose of Coriolus versicolor water extract is more than 5000 mg/kg and no-observed-adverse-effect level (NOAEL) of the extract for both male and female rats is 5000 mg/kg per day for 28 days.     

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

Ethnopharmacological relevance

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.

Materials and Methods

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.

Results

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.

Conclusions

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.     

Evaluation of the developmental toxicity of the aqueous extract from Trigonella foenum-graecum (L.) in mice

Aim of the study

The use of medicinal plant products to treat various ailments is a common practice in many developing countries. However, a lack of information on the adverse effects of these plants raises questions on their safety and possible adverse side effects. This study was undertaken to evaluate the potential toxic effects of fenugreek seeds on pregnant mice and foetal development.

Materials and methods

Lyophilized aqueous extract from fenugreek seeds (LAE-FS) was administered to mated female mice during the entire period of pregnancy, at doses of 500 and 1000 mg/kg/day. Females were examined for standard parameters of reproductive performance. Foetuses were weighed and examined for externally visible malformations.

Results

In pregnant females, there were no obvious symptoms of toxicity, LAE-FS-related deaths or macroscopic abnormalities. Developmental toxicity in offspring included an increase in the foetal death rate, a decrease in the litter size, and a reduction in the foetal body weight. In addition there was an increase in the incidence of morphological abnormalities.

Conclusions

Based on these results, it was concluded that fenugreek seeds extract may have deleterious toxic effects on reproductive performance and potential teratogenic effects in foetuses.     

Acute and sub-chronic toxicity study of standardized extract of Fumaria indica in rodents

Ethnopharmacological relevance

Despite Fumaria indica (FI) widespread medicinal uses in the Indian traditional medicine, no systematic study of the potential toxicity of the plant has been described.

Aim of the study

To assess acute and sub-chronic toxicity of a 50% ethanolic extract of FI in mice and rats respectively.

Materials and methods

In acute toxicity study, Swiss strain albino mice of either sex were administered orally FI doses of 1, 2.5 and 5 g/kg and observed for behavioural changes and mortality, if any. In sub-chronic toxicity study, Charles Foster albino rats of either sex were administered two doses of FI i.e., 100 and 400 mg/kg, p.o. for 30 consecutive days. During 30 days of treatment, rats were observed for any change in body weight and daily food and water intake. After 30 days, rats were sacrificed for haematological, biochemical and histopathology study. Control animals were administered 0.3% carboxymethyl cellulose (CMC) suspension by oral route.

Results

There was no mortality or abnormal behaviour, observed in acute toxicity study in mice at all the three dose levels. In sub-chronic toxicity study, FI did not produce any significant change in body weight and daily food and water intake of rats when compared to vehicle treated rats. Further, haematological and biochemical parameters were also found normal. Histopathological study revealed normal architecture of kidney and liver of FI treated rats.

Conclusions

FI extract, provisionally standardized on its fumarate contents, seems to fulfill a preclinical criterion necessary for its further development as a clinically useful adaptogen.     

Acute and sub-chronic oral toxicity studies of an aqueous stem bark extract of Pterocarpus soyauxii Taub (Papilionaceae) in rodents

Pterocarpus soyauxii Taub (Papilionaceae) is used in Cameroonian traditional medicine and pharmacopoeia to treat hypertension, diabetes, gastrointestinal parasitizes and cutaneous diseases.

Aim of the study

The present investigation was carried out to evaluate the safety of an aqueous stem bark extract of Pterocarpus soyauxii by determining toxicity after acute and sub-chronic oral administration in male and female rodents.

Materials and methods

The acute toxicity test was conducted in mice. An aqueous extract of barks was administrated by gavage in single doses of 2.5-12.5 g/kg. General behaviour and mortality were examined for up to 7 days. The sub-chronic toxicity test was performed in rats. The plant extract was administered by daily gavage of 150-600 mg/kg for 42 days. Body weight, food and water intakes were followed weekly. Haematological, biochemical and organ parameters were determined at the end of the 42-day administration.

Results

In the acute study in mice, oral administration of the aqueous extract of Pterocarpus soyauxii caused dose-dependent general behaviour adverse effects and mortality. The no-observed adverse effect level (NOAEL) of the extract was 5.0 g/kg. The lowest-observed adverse effect level (LOAEL) was 7.5 mg/kg. Mortality increased with the dose, LD₅₀ was > 10.75 g/kg for the mouse. In the sub-chronic study in rats, daily oral administration of the aqueous extract of Pterocarpus soyauxii did not result in death or significant changes in haematological or biochemical parameters, excepted increased hepatic catalase activity (P < 0.05) at the dose of 600 mg/kg. No alteration was observed in body weight, food and water intake. Liver, kidney, lung and pancreas histopathology did not reveal morphological alteration.

Conclusions

The results showed that the aqueous stem bark extract of Pterocarpus soyauxii Taub had very low toxicity in oral acute high dose administration and no toxicity in oral sub-chronic low dose administration and indicate that the plant could be considered safe for oral medication.     

Acute toxicity study of Aspidopterys obcordata aqueous extract in Sprague-Dawley rats

OBJECTIVE: To examine the acute toxicity of an aqueous extract of Aspidopterys obcordata(A. obcordata) in Sprague Dawley rats.METHODS: The rats were orally administered a dose of 5000 mg/kg body weight and observed continuously for 6 h and then daily for 14 days. Control rats were administered distilled water. The effect of the extract on general behavior, body weight, and food and water intake were measured.After 14 days, the rats were sacrificed and their organs(liver, heart, spleen, lungs, kidney, adrenal glands, ovaries, and testes) were removed for macroscopic examination. The body and organ weights in addition to hematology(e.g., hemoglobin and white blood cell counts) and clinical blood biochemistry(e.g., albumin and bilirubin) were also examined.RESULTS: There were no deaths recorded, and the rats treated with A. obcordata showed no signs of toxicity. All measured parameters in rats treated with A. obcordata were unaffected when compared with those in control rats. The acute toxicity(LD_(50))was estimated to be 5000 mg/kg body weight.CONCLUSION: Our results demonstrate the safety of an acute oral administration of an aqueous extract of A. obcordata in rats and indicate that future subacute and long-term toxicity testing of A. obcordata is warranted.     

Toxicology evaluation of standardized methanol extract of Gynura procumbens

Aims of the study

Gynura procumbens (Merr.), which is known as “Sambung nyawa”, is widely used in South East Asian countries in the traditional treatment of many ailments. However, there is little toxicological information available regarding safety following repeated exposure.The present investigation describes the toxicity of a methanol extract of Gynura procumbens leaves in rats.

Materials and methods

For acute toxicity studies, a methanol extract of Gynura procumbens was orally administered to Sprague–Dawley rats (female and male) at a dose range of 1000–5000 mg/kg. For sub-chronic toxicity studies, the rats were orally administered the methanol extract of Gynura procumbens at the doses of 125, 250, and 500 mg/(kg day) for a period of 13 weeks. The animals were sacrificed, followed by examination of their organs and blood serum.

Results and conclusions

Administration of the methanol extract from Gynura procumbens leaves at 1000–5000 mg/kg did not produce mortality or significant changes in the general behaviour, body weight, or organ gross appearance of rats. There were no significant differences in the general condition, growth, organ weights, haematological parameters, clinical chemistry values, or gross and microscopic appearance of the organs from the treatment groups as compared to the control group. Therefore, the NOAEL for the Gynura procumbens methanol extract is 500 mg/(kg day) administered orally for 13 weeks.