Acute and sub-chronic toxicity of an aqueous extract of the leaves of Herniaria glabra in rodents

AIM OF THE STUDY: The present investigation was carried out to evaluate the safety of an aqueous extract of Herniaria glabra (caryophyllaceae) (HG) plant by determining its potential toxicity after acute and sub-chronic administration in rodents. MATERIALS AND METHODS: For the acute study, a lyophilized aqueous extract of HG plant was administered to adult IOPS OFA mice in single doses of 5-14.5 g/kg given by gavage. General behavior adverse effects and mortality were determined for up to 14 days. In the sub-chronic dose study, the HG-extract was administered orally at doses of 1, 2 and 4 g/kg daily for 90 days to Wistar rats. Selected 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 HG plant caused dose-dependent general behavior adverse effects and mortality. The no-observed adverse effect levels (NOAEL) of the HG extract was 5 g/kg and the lowest-observed adverse effect levels (LOAEL) was 5.5 g/kg. Mortality increased with increasing doses: the calculated LD50 was 8.50 +/- 0.42 g/kg in mice. In the sub-chronic study in rats, daily oral administration of the crude HG extract for up to 90 days resulted in a significant attenuation of the normal increase in the body weight. At the highest dose, the HG-extract caused a significant increase in erythrocytes, leukocytes (WBC), platelets, and eosinophils, but it had no effect on the differential WBC counts (lymphocytes, monocytes, neutrophils and basophils). Only at the highest dose, the HG-extract caused a significant increase in serum levels of the liver enzymes, alanine aminotransferase and aspartate aminotransferase, as well as serum creatinine, indicating toxic effect of the high dose of the extract on the liver and kidney. The organ toxicity was confirmed by histopathological examination, which showed centrolobular sinusoidal congestion, disruption of the central vein and hepatocellular necrosis in the liver, and interstitial and intraglomerular congestion, tubular atrophy, and inflammation in the kidney. This study also revealed the hypoglycemic activity of the HG-extract in normoglycemic rats. The suppression of the normal weight gain and the hypoglycemic action of HG-extract should be investigated further for possible therapeutic implications. CONCLUSIONS: Because of the relatively high NOAEL values in the acute study in mice, and lack of mortality or clinically significant changes in the biological (except for hypoglycemia) and hematological parameters in rats after 90 days of daily dosing, it may be concluded that the HG extract does not appear to have significant toxicity (except at high doses). In view of the doses consumed empirically in traditional medicine in Morocco, there is a wide margin of safety for the therapeutic use of Herniaria glabra.     

Acute and subacute toxicity of ethanol extracts from Salvia przewalskii Maxim in rodents

Aim

The present investigation was carried out to evaluate the safety of the lipid-soluble ethanol extracts from rhizome of Salvia przewalskii Maxim (SPM) by determining its potential toxicity after acute and subacute administration in rodents.

Materials and methods

For the acute study, SPM extract was administered to mice in single doses given by gavage, intramuscular and intraperitoneal route. General behavior adverse effects and mortality were determined for up to 14 days. In the subacute study, the extract was administered orally at doses of 0, 50 and 250 mg/kg daily for 30 days to rats. Body weight, heart rate, blood pressure, biochemical and hematological parameters were determined at the end of 0, 15 and 30 days of daily administration.

Results

In acute study, SPM extract caused dose-dependent general behavior adverse effects and mortality. The no-observed adverse effect levels (NOAEL) of the extract were 1723, 288 and 500 mg/kg, when given by gavage, intramuscular and intraperitoneal routes, respectively, and the lowest-observed adverse effect levels (LOAEL) were 1981, 840 and 781 mg/kg. Mortality increased with increasing doses, with LD₅₀ of 2547.8, 901.3 and 780.8 mg/kg for the oral, intramuscular and intraperitonal administration. In subacute study, daily oral administration of SPM extract for up to 30 days did not result in death or significant changes in the body weight, heart rate and blood pressure, hematological and mainly biological parameters. In biological analysis, some significant changes occurred, including total protein and albumin, glucose and triglycerides, indicating that SPM extract has lipid-modulating activity.

Conclusions

SPM extract was found to be low or non-toxic when acute toxicities and subacute toxicities in rodents. In view of the doses of the components consumed in traditional medicine, there is a wide margin of safety for the therapeutic use.     

Acute and sub-chronic toxicity of a lyophilised aqueous extract of Centaurium erythraea in rodents

Ethnopharmacological relevance

An aqueous concoction made from centaury (Centaurium erythraea (L.) Rafn., (Gentianaceae) whole plant is used in the Moroccan traditional medicine for the treatment of diabetes, as well as a number of other diseases. No systematic study of the potential toxicity of the plant has been described.

Aim of the study

The present investigation was carried out to evaluate the safety of an aqueous extract of Centaurium erythraea whole plant (CE-extract) by determining its potential toxicity after acute and sub-chronic administration in rats and mice.

Materials and methods

For the acute study, the lyophilised CE-extract was administered to adult IOPS OFA mice in single oral doses of 1-15 g/kg given by gavage, and single intraperitoneal (i.p.) doses of 1-14 g/kg. General behavioral adverse effects, mortality, and latency of mortality were determined for up to 14 days. In the sub-chronic dose study, the CE-extract was administered orally at doses of 100, 600 and 1200 mg/kg daily for 90 days to Wistar rats. Body weight and selected biochemical and hematological parameters were determined every 30 days and at the end of 90 days of daily administration; sections of liver and kidney were examined histologically for any signs of organ damage at the end of the treatment.

Results

In the acute study in mice, there were no deaths or any signs of toxicity observed after oral administration of single doses of the CE-extract at any dose level up to the highest dose tested (15 g/kg), which was the no-observed-adverse-effect level (NOAEL). However, the mortality rate as well as the acute toxicity of the i.p. administered CE-extract increased progressively with increasing dose. The NOAEL for the i.p. dose was 6 g/kg while the lowest-observed-adverse-effect level (LOAEL) was 8 g/kg; the calculated acute toxicity (LD₅₀) of i.p. administered CE-extract in mice was 12.13 g/kg.In sub-chronic studies in rats, the CE-extract (administered orally at daily doses of 100, 600 and 1200 mg/kg for 90 days), did not cause any changes in hematological and biochemical parameters, except a small reduction of mean corpuscular volume, and a decrease in serum glucose and triglyceride levels at the higher doses. Histopathological examination of the liver and kidneys at the end of the study showed normal architecture suggesting no morphological disturbances.

Conclusions

Because of the lack of toxicity of the CE-extract given by the oral route, and relatively high NOAEL values for the i.p. dose in the acute study in mice, as well as lack of mortality or clinically significant adverse changes in the biological and hematological parameters, and the morphology of liver and kidneys in rats after 90 days of daily dosing, it may be concluded that the CE-extract is relatively non-toxic. Also, in view of the doses consumed empirically in traditional medicine in Morocco, there is a wide margin of safety for the therapeutic use of Centaurium erythraea.     

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.     

Anti-hyperglycaemic activity of the aqueous extract of Origanum vulgare growing wild in Tafilalet region

The effect of an aqueous extract of Origanum vulgare (OV) leaves on blood glucose levels was investigated in normal and streptozotocin (STZ) diabetic rats. In normal rats, the blood glucose levels were slightly decreased 6 h after a single oral administration (P<0.05) as well as 15 days after once daily repeated oral administration of aqueous OV extract (P<0.05) (20 mg/kg). After a single dose or 15 daily doses, oral administration of the aqueous extract (20 mg/kg) produced a significant decrease on blood glucose levels in STZ diabetic rats (P<0.001). In STZ rats, the blood glucose levels were normalised from the fourth day after daily repeated oral administration of aqueous OV extract (20 mg/kg) (P<0.001). However, this effect was less pronounced 2 weeks after daily repeated oral administration of OV extract. In addition, no changes were observed in basal plasma insulin concentrations after treatment in either normal or STZ diabetic rats indicating that the aqueous OV extract acted without changing insulin secretion. We conclude that an aqueous extract of OV exhibits an anti-hyperglycaemic activity in STZ rats without affecting basal plasma insulin concentrations.     

Acute and sub-chronic oral toxicity profiles of the aqueous extract of Polygala fruticosa in female mice and rats

Polygala fruticosa (P.J. Bergius) is one of the most popular medicinal plants in South Africa but to date there is no documented evidence corroborating its safety. This study thus aimed to determine the toxicity profile of the aqueous extract of Polygala fruticosa by determining its effects after acute and sub-chronic oral administration in female mice and rats, respectively. In adult mice, single oral administrations of the aqueous extract of Polygala fruticosa (2–20 g/kg body weight) induced an increase in the incidence of general behavioural adverse effects. The mortality rate also increases with increasing dosage (LD₅₀ = 10.8 g/kg). In rats, daily single oral doses of Polygala fruticosa aqueous extract (0.1 and 1 g/kg) were well tolerated behaviourally after 31 days of dosing (LD₅₀ much higher than 1 g/kg) and induced no significant changes in body and organs weights. However, haematological and biochemical parameters showed a significant decrease in platelet count and significant increases in ALT, AST and creatinine levels suggesting disturbances of haemopoiesis, liver and kidney functions.     

Acute and chronic toxicity of the aqueous extract of Artemisia afra in rodents

Artemisia afra (Jacq. Ex. Willd), "African Wormwood" is widely used traditionally in South Africa with no literature evidence substantiating its safety. The aim of this study was to investigate the safety of the aqueous extract of Artemisia afra by determining its pharmaco-toxicological effects after acute and chronic administration in mice and rats, respectively. The aqueous extract mimicked the traditional decoction dosage form of Artemisia afra. In mice, single intraperitoneal injections of Artemisia afra-extract (1.5-5.5g/kg) induced a regular dose-dependent increase in the death rate and incidence of general behaviour adverse effects, while with single oral doses (2-24g/kg) the increases in incidence of general behaviour adverse effects and mortality rate were dose-independent. The LD(50s) after acute intraperitoneal and oral doses were 2.45 and 8.96g/kg, respectively. Rats given oral doses of Artemisia afra-extract (0.1 or 1g/kg/day) survived the 3 months of dosing (i.e. LD(50) much higher than 1g/kg), experienced no significant changes in general behaviour and haematological and biochemical parameters, except for transient decrease in AST activity. No significant changes were observed in organ weights, and histopathological results showed normal profile suggesting no morphological alterations. Collectively, the results indicate that Artemisia afra-extract is non-toxic when given acutely, has low chronic toxicity potential and, in high doses, may have a hepatoprotective effect.     

Teratogenic effects, acute and sub chronic toxicity of the leaf aqueous extract of Ocimum suave Wild (Lamiaceae) in rats

The aqueous extract from the leaves of Ocimum suave was evaluated for acute and sub chronic toxicity and teratogenic effects. Swiss mice were administered single oral doses of 2000, 4000, 6000 and 8000 mg/kg and monitored for death and body weight gained for 7 days (acute toxicity). In sub-acute toxicity, experimental rats, received daily doses of 250, 500 and 1000 mg/kg for 42 consecutive days and the toxic effects were assessed using biochemical and haematological data and histology of vital organs. In a teratogenic study, 1-day pregnant rats were administered orally 500 and 1000 mg/kg of extract daily for 21 consecutive days and 14th day corpora lutea and foetal implants and litter size at birth were noted. Reproductive performance of F(1) generation rats was studied by crossing them at maturity and recording the number, birth weight and physical presentation of the young offspring. Acute intake of extract up to 8000 mg/kg did not produce mortality or significant changes in general behaviour. Sub chronic treatment did not show any change in body and organ weights, feeding habits or behaviour between the control and the treated groups of both sexes. Haematological analysis and blood biochemistry revealed no toxicity effects of the extract. No gross abnormalities or histological changes were observed. Teratogenic and fertility studies did not reveal any toxic manifestations or foetal abnormalities. The leaf aqueous extract of Ocimum suave is non toxic in acute and sub chronic intake.     

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.     

Acute and chronic toxicological studies of Ajuga iva in experimental animals

Ajuga iva (L.) Schreber (AI), is widely used in the Moroccan pharmacopoeia as a panacea (cure-all), and specifically for gastrointestinal disorders and diabetes, and as an anthelmintic. No toxicological investigations have been carried out on this plant. We have previously observed that single oral doses (2-14 g/kg) of a lyophilised aqueous extract of AI (AI-extract) in mice or daily oral administration of 10 mg/kg of AI-extract in rats for 2 weeks did not result in any adverse effects. We have now evaluated AI-extract for its behavioural and pharmaco-toxicological effects after acute and chronic administration by the oral and intraperitoneal routes in rats and mice. No toxicity was observed in mice after single oral doses of as high as 14 g/kg of the AI-extract. However, single intraperitoneal injections of the AI-extract (1500-5500 mg/kg BW) produced a dose-dependent increase in adverse effects in the general behaviour and the mortality rate; the LD50 of acute intraperitoneal dose was 3.6 g/kg. In chronic toxicological studies in rats, the AI-extract (administered orally at daily doses of 100, 300 and 600 mg/kg for 3 months), did not cause any changes in haematological and biochemical parameters, with the exception of a transient rise in platelet counts and a short-term decrease in serum glucose levels. Histopathological examination of the brain, liver and the kidneys at the end of the study (3 months) showed normal architecture suggesting no morphological disturbances.     

藏药仁青常觉的毒理学实验研究

目的:观察藏药仁青常觉的毒理作用。方法:急性毒性实验:以一日最大耐受量测定小鼠灌胃仁青常觉的急性毒性实验。长期毒性试验:给大鼠灌胃给药3个不同剂量的仁青常觉,低剂量组(0.350g/kg)、中剂量组(0.700g/kg)和高剂量组(1.400g/kg),连续90天,空白对照组ig蒸馏水,观察大鼠一般状况、体重、摄食量,测定给药90天及停药15天血液生化指标、脏器系数、解剖学及病理组织。结果:测得小鼠最大耐受量大于30g/kg(此剂量相当于临床成人拟日服剂量的2142倍),未发现任何不良反应及死亡现象;各剂量组连续给药90天,未发现死亡,动物生长发育良好,外观正常,行为活动无异常,主要脏器系数、血液生化、血象等指标与空白对照组比较均无显著性差异。结论:通过实验,未发现明显毒性反应,证明临床剂量是安全的。     

Mineral constituents and toxicological profile of Jateorhiza macrantha (Menispermaceae) aqueous extract

Ethnopharmacological relevance

Jateorhiza macrantha is a medicinal plant used in popular medicine to treat several diseases, including cardiovascular disorders. To date, there is no documented report available on the toxicological profile of this medicinal plant.

The aim of the study

The present study was carried out to investigate the mineral content and the safety of the oral administration of the leaf aqueous extract of Jateorhiza macrantha in mice.

Materials and methods

The presence of Ca, Mg, K, Na, Cu, Mn, Fe and Zn in the extract was analyzed using Atomic Absorption Spectrophotometer. In the acute toxicity study, Male and female Balb-C mice were administered single doses of 2.5 and 5 g/kg of body weight by gavage, and were monitored for 7 days. In the subacute toxicity study, the extract was administered by gavage at doses of 150, 300 and 600 mg/kg body weight daily for 6 weeks to mice (8 mice/dose/sex). After this period of treatment, 5 mice per sex and per group were sacrificed. The rest of animals per group were observed without any treatment for 2 weeks. After the treatments, some biochemical and hematological parameters were analyzed.

Results

Our findings indicate the presence of all mineral elements tested. Acute study indicates no signs of toxicity at the doses used. The LD₅₀ value is >5.00 g/kg body weight, since there was no death registered at that dose. In subacute study, hematological and biochemical parameters showed a significant decrease in platelet and significant increases in ALT and AST in both sexes and creatinin levels only in male suggesting that some compounds of the plant extract were responsible of disturbances of hematopoiesis, liver and kidney functions.

Conclusions

Our results show that Jateorhiza macrantha acute toxicity towards animals is very low. However, in subacute administration, this extract induces slight injuries on hematopoiesis, liver and kidney functions, suggesting its use with caution.     

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.     

Hypoglycemic and hypolipidemic effects of the aqueous fresh leaves extract of Clerodendrum capitatum in Wistar rats

Diabetes mellitus, the most common endocrine disorder of carbohydrate metabolism, is treated in the African traditional phytotherapies with the cold water decoction of Clerodendrum capitatum (CC). In the current study, the hypoglycemic and hypolipidemic effects of fresh leaves aqueous extract of CC were studied in four groups of six adult Wistar rats per group and weighting 120-150 g, by administering graded oral doses (100, 400 and 800 mg/kg/day) of the extract for 14 days. On the 15th day, the fasted rats were anesthetized under inhaled halothane and blood samples obtained through cardiac puncture. Phytochemical analysis of CC extract was conducted using standard procedures while the preliminary acute oral toxicity study was also conducted using limit dose test of Up and Down Procedure at a limit dose of 5000 mg/kg body weight/oral route. Results of the study showed CC to cause significant (p<0.05, p<0.001) dose dependent hypoglycemic and hypolipidemic effects but had no effect on the pattern of weight gain in the treated rats. Although no lethal effect was recorded with CC oral administration for up to 5000 mg/kg body weight/oral route, but there was an associated transient somatomotor and behavioral toxicities. Phytochemical results revealed the presence of saponins, flavonoids, alkaloids, tannin, glycosides and reducing sugars in the extract. Thus, the folkloric use of Clerodendrum capitatum in the treatment of suspected type 2 diabetics has a positive correlation with scientific data generated in this study.     

Acute and subchronic oral toxicity studies of Nelumbo nucifera stamens extract in rats

Ethnopharmacological relevance

Since the use of Nelumbo nucifera stamens in herbal medicines as well as in cosmetic products are highly prevalent in Thailand and increasing worldwide, acute and subchronic toxicity studies to confirm the safe use of Nelumbo nucifera stamens are warranted.

Aim of the study

Acute and subchronic oral toxicity studies of Nelumbo nucifera stamens extract in rats were performed in the present study in order to evaluate its safety.

Materials and methods

In acute toxicity study, Nelumbo nucifera stamens extract was administered by oral gavage to Sprague-Dawley rats (5 males and 5 females) at a dose of 5000 mg/kg. In subchronic toxicity study, the extract at doses of 50, 100, and 200 mg/kg/day were given orally to groups of rats (6 rats/dose/sex) for 90 consecutive days.

Results

The extract at a dose of 5000 mg/kg produced no treatment-related signs of toxicity or mortality in any of the animals tested during 14 days of the study. In the repeated dose 90-day oral toxicity study, there was no significant difference in body weight between the control and all treatment groups with the exception of the body weight of the female group treated with 200 mg/kg/day of the extract which was statistically significantly less than that of its control counterpart on day 90 but the percent weight changes of both groups were almost similar. Some statistically significant differences in hematological and biochemical parameters as well as in some internal organ weights of both male and female rats treated with the extract at the highest dose were observed. However, no abnormality of internal organs was observed in both gross and histopathological examinations.

Conclusions

These results suggest that the oral lethal dose of Nelumbo nucifera stamens extract for male and female rats is in excess of 5000 mg/kg and the no-observed-adverse-effect level (NOAEL) of the extract for both male and female rats is considered to be 200 mg/kg/day.     

Toxicological evaluation of acute and sub-chronic ingestion of hydroalcoholic extract of Solanum cernuum Vell. in mice

Ethnopharmacological relevance

Solanum cernuum Vellozo is a Brazilian shrub or small tree, restricted to Southwest states of the country. It has been widely used for the treatment of many ailments. The pharmacological activity of the extract on gastric ulcer has been the major therapeutic target proposed by the population investigated.

Materials and methods

In the acute toxicity test was used increasing doses of the extract (2, 4, 8, 12, 16, 20 and 25 g of extract per kilogram of body weight). The animal behavior was observed from 5 h after a single administration of the extract and subsequently monitored daily until the fourteenth day, beyond the calculation of the estimated LD50 of the extract. In the test sub-chronic toxicity was used two doses of the extract (0.1 and 1.4 g/kg) and the parameters analyzed over 31 days were: body weight, food intake, behavior, respiratory rate, movement and mortality of animals. After anesthesia, blood samples were collected for hematological and biochemical analysis. The animals were euthanized followed by macroscopic analysis of the stomach and intestine. Liver, lungs and kidneys were removed, weighed and analyzed histopathologically.

Results

In the acute toxicity test was observed a dose-dependent mortality and the value of estimated LD50 was 14.50 g/kg. In the hematological and biochemical analyses there were significant increase in the activities of AST and ALT indicating liver toxicity, but the extract was not able to alter food intake, body weight and organ weights after 31 days of treatment and it did not produce significant histopathological changes.

Conclusion

Therefore we can consider the hydroalcoholic extract of Solanum cernuum Vell as practically non-toxic in acute administration and safe in the sub-chronic administration, as hepatotoxicity was observed only with the highest dose used, not with the dose routinely used by the native population.     

Toxicity of Nerium oleander and Rhazya stricta in Najdi sheep: hematologic and clinicopathologic alterations

The toxic effects of oral administration of 0.25 g/kg Nerium oleander leaves, 0.25 g/kg Rhazya stricta leaves or their mixture at 0.25 g/kg N. oleander leaves plus 0.25 g/kg R. stricta leaves on Najdi sheep were investigated. Daily oral dosing of R. stricta leaves for 42 days was not fatal to sheep while single oral doses of either N. oleander leaves or the mixture with R. stricta leaves proved fatal to animals within 24 hours with dyspnea, grunting, salivation, grinding of the teeth, ruminal bloat, frequent urination, ataxia and recumbency prior to death. The main lesions were widespread congestion or hemorrhage, pulmonary cyanosis, emphysema, bronchotracheal froths, and hepatonephropathy. The clinical and pathological changes were correlated with alterations in serum LDH and AST activities and concentrations of cholesterol, bilirubin, urea, total protein, albumin, and globulin and hematological values.     

In vitro anti HSV-1 and HSV-2 activity of Tanacetum vulgare extracts and isolated compounds: an approach to their mechanisms of action

Herpes simplex viruses (HSV-1 and HSV-2) are responsible for long-term latent infections in humans, with periods of recurring viral replication associated to lesions around the lips, eyes, mucous membrane of the oral cavity or the genitals. The lack of an effective vaccine, the moderate to high toxicity of the available synthetic antiherpes compounds and the appearance of resistant viral strains emphasize the need for new inhibitors. Tanacetum vulgare, commonly known as tansy, has been used for treating rheumatic pain, skin eruption and diuretic conditions as well as an anthelmintic, antihypertensive, stimulant, emmenagogue, carminative, antiseptic, antihypertensive, antispasmodic and antioxidant agent. The anti HSV-1 activity of tansy aerial parts, ethyl acetate extract and the isolated compound parthenolide, has been reported recently. In this work, through a comprehensive mechanistic-based antiherpetic activity study, it was revealed that constituents other than parthenolide are responsible for the antiviral activity of tansy.     

Toxicological studies on Stryphnodendron adstringens

This study was carried out to determine the acute toxicity of total barbatim?o extract (LD(50)) after oral administration to mice, and its effect on certain biochemical parameters in plasma of rats after 30 days of administration. The LD(50) value of the extract was 2699 mg/kg. A daily oral administration of extracts at 800 and 1600 mg/kg doses for 30 days caused a decrease in body weight, thymic involution, and an increase of plasma glucose and aspartate aminotransferase levels in the animals. The results showed that the extract administered in a prolonged period produced toxic effects in the experimental animals.     

Oral subchronic toxicity of aqueous crude extract of Plantago australis leaves

The toxic effects of chronic oral administration (60 days) of aqueous crude extract (AE) of Plantago australis Lam. (Plantaginaceae) in rats at doses of 850 and 1700 mg/kg on biochemical (ALT, AST, creatinine, urea, glucose, alkaline phosphatase, total proteins and albumin), hematological (complete hemogram), and histopathological (heart, lung, liver, kidney, esophagus, stomach and gut) parameters were studied. All biochemical and hematological parameters were found to be in the normal range, but ALT in animals that received AE of 850 mg/kg was higher. Histopathological analysis of organs, especially the liver did not present alterations.