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.     

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.     

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.     

Acute and subchronic oral toxicities of Pu-erh black tea extract in Sprague-Dawley rats

Ethnopharmacological relevance

Pu-erh black tea, which is obtained by first parching crude green tea leaves and then undergoes secondary fermentation with microorganisms, has been believed to be beneficial beverages for health for nearly 2000 years in China, Japan and Taiwan area. But its potential toxicity when administered at a high dose as concentrated extracts has not been completely investigated.

The aim of the study

The present study was aimed at evaluating potential toxicity of Pu-erh black tea extracts (BTE) from acute and sub-chronic administration to male and female Sprague-Dawley (SD) rats.

Materials and methods

A single BTE dose of 10,000 mg/kg of body weight was administered by oral gavage for acute toxicity in SD rats. Four groups (10 males and 10 females per group) of dose levels of 1250, 2500, and 5000 mg/kg/day of the test article, as well as controls (distilled water) were tested as the subchronic toxicity study.

Results

No deaths and signs of toxicity occurred during the 14 days of the study. There were no test article related mortalities, body weight gain, feed consumption, clinical observation, organ weight changes, gross finding, clinical or histopathological alterations during the 91-day administration.

Conclusions

The LD₅₀ of BTE can be defined as more than 10,000 mg/kg, and a dose of 5000 mg/kg/day was identified as the no-observed-adverse-effect-level (NOAEL) in this study.     

Safety evaluation of tea (Camellia sinensis (L.) O. Kuntze) flower extract: assessment of mutagenicity, and acute and subchronic toxicity in rats

Ethnopharmacological relevance

Tea (Camellia sinensis (L.) O. Kuntze, Theaceae) flowers possess many physiological functions and have been used in traditional medicines for deodorization, skin care, cough suppressant and expectorant in China. However, there is a little information about its possible toxicity.

Aim of the study

The present investigation was carried out to evaluate the safety of tea flower extract by mutagenicity and acute and subchronic toxicity studies.

Materials and methods

Mutagenicity of tea flower extract was evaluated by the Ames test in Salmonella typhimurium strains TA97, TA98, TA100 and TA102 at concentrations of 0.008, 0.04, 0.2, 1.0, 5.0 mg/plate. In the acute toxicity study, Sprague-Dawley rats were administered a single dose of 12.0 g/kg of body weight by gavage, and were monitored for 14 days. In the subchronic toxicity study, tea flower extract was administered by gavage at doses of 1.0, 2.0 and 4.0 g/kg body weight daily for 13 weeks to Sprague-Dawley rats.

Results

In the Ames test, there was no mutagenic effect of tea flower extract (up to 5.0 mg/plate) towards four tested strains (TA97, TA98, TA100, TA102), with or without metabolic activation (S9). In the acute toxicity study, all animals gained weight and appeared active and normal, so the LD₅₀ value must be >12.0 g/kg body weight. In the subchronic toxicity study, no dose-related effects on survival, growth, hematology, blood chemistry, organ weights, or pathologic lesions were observed.

Conclusion

These results indicate that tea flower extract does not possess mutagenic potential, and that both acute and subchronic toxicity towards animals is very low. A no-observed adverse-effect level (NOAEL) for tea flower extract is 4.0 g/kg bw/day for rats under the conditions of this study.     

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.     

Evaluation of safety of the herbal formula Ojeok-san: Acute and sub-chronic toxicity studies in rats

Aim of the study

Ojeok-san (OJS; wuji powder in China and goshaku-san in Japan), a widely used herbal formula in traditional Korean medicine and Japanese herbal medicine (Kampo medicine), has been used to treat common cold and illnesses including fatigue and gastrointestinal disorders, but there is very little information on its safety. To provide information on the safety of OJS, we evaluated its acute and sub-chronic toxicity in rats.

Materials and methods

The single and sub-chronic toxicity of OJS was examined using male and female Sprague-Dawley rats. The rats were treated with the OJS extract orally at the highest dose level of 2000 mg/kg/day body weight. After single administration, signs of toxicity were observed every hour for the first 6 h and every day for two weeks. In the sub-chronic toxicity study, OJS was administered for 13 weeks. Mortality, clinical signs, body weight changes, food and water consumption, ophthalmologic findings, urinalysis, hematological and biochemical parameters, gross findings, organ weights and histological markers were monitored during the study period.

Results

We found no mortality and no abnormality in clinical signs, body weight, and necropsy findings for any of the animals in the acute and sub-chronic toxicity study following oral administration of OJS.

Conclusion

OJS may not have any single dose toxicity. The lethal dose with a 50% mortality rate (LD₅₀) was over 2000 mg/kg. The no-observed adverse effects level (NOAEL) was considered to be 2000 and 1000 mg/kg/day for male and female rats, respectively.     

Evaluation of the sub-acute toxicity of the sclerotium of Lignosus rhinocerus (Cooke), the Tiger Milk mushroom

Ethnopharmacological relevance

Lignosus rhinocerus (known locally as ‘Tiger Milk mushroom’) is the most important medicinal mushroom used by the indigenous communities of Malaysia to treat fever, cough, asthma, cancer, food poisoning and as a general tonic. The sclerotium of the mushroom is the part with medicinal value. Lignosus rhinocerus was hitherto unexploited commercially because of limited supply. Recently, the mushroom was successfully cultivated.

Materials and methods

Sprague Dawley rats (5 rats/group/sex) were fed orally with 250, 500 and 1000 mg/kg TM02, 1000 mg/kg TM03 as well as 1000 mg/kg wild type Lignosus rhinocerus sclerotial powder. Sclerotial powder was orally administered once daily and consecutively for 28 days. Body weight of each animal was measured and any gross behavioral change was observed daily. Hematological and clinical biochemical parameters as well as histopathological analysis were carried out on 29th day.

Results

The results showed that oral administration of the sclerotial powder at daily dose of up to 1000 mg/kg had no adverse effect on the growth rate, hematological and clinical biochemical parameters (including renal and liver function parameters). Histological studies showed that the treatments did not induce any pathological changes in the liver, kidney, heart, spleen and lung of the animals.

Conclusion

In conclusion, our results show that there was no treatment-related sub-acute toxicity in rats following 28-days oral administration of 250, 500 and 1000 mg/kg TM02, 1000 mg/kg TM03 as well as 1000 mg/kg wild type Lignosus rhinocerus sclerotial powder. As the highest tested dose of 1000 mg/kg was not associated with any toxicity concern, the NOAEL dose is higher than 1000 mg/kg.     

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.     

Toxicological evaluation of the aqueous leaf extract of Moringa oleifera Lam. (Moringaceae)

Ethnopharmacological relevance

The rapid increase in consumption of herbal remedies worldwide has been stimulated by several factors, including the notion that all herbal products are safe and effective. However, over the past decade, several news-catching episodes in developed communities indicated adverse effects, sometimes life-threatening, allegedly arising as a consequence to taking herbal products or traditional medicines from various ethnic groups. Despite the popular use of Moringa oleifera for treating various disorders, there is limited or no scientific data available regarding safety aspects of this remedy, nor are there any documented toxicological studies that can be used to ascertain the safety index of its herbal preparation. Therefore, this present study aimed to carry out extensive toxicological evaluation of the aqueous leaf extract of Moringa oleifera.

Materials and Methods

In an acute toxicity test, male Wistar albino mice were orally administered an aqueous extract up to 6400 mg/kg and intraperitoneally up to 2000 mg/kg. A sub-chronic toxicity test was performed by daily administration with the extract at 250, 500 and 1500 mg/kg orally for 60 days. Control rats received distilled water. Sperm quality was analyzed, haematological and biochemical (liver enzymes, urea and creatinine) parameters were determined and a histopathological examination was carried out.

Results

The LD₅₀ was estimated to be 1585 mg/kg. The extract did not elicit any significant difference (P ≥ 0.05) in sperm quality, haematological and biochemical parameters in the treated rats compared to the control. Moreover, there was no significant difference in weight gain of the control and treated animals although there was a dose-dependent reduction in food consumption of the animals treated with 250 to 1500 mg/kg extract.

Conclusions

Results obtained in this study suggest that the aqueous leaf extract of Moringa oleifera is relatively safe when administered orally.     

Acute and subacute toxicity of Cassia occidentalis L. stem and leaf in Wistar rats

Ethnopharmacological relevance

Cassia occidentalis L. (syn. Senna occidentalis; Leguminosae) has been used as natural medicine in rainforests and tropical regions as laxative, analgesic, febrifuge, diuretic, hepatoprotective, vermifuge and colagogo. Herein, we performed a pre-clinical safety evaluation of hydroalcoholic extract of Cassia occidentalis stem and leaf in male and female Wistar rats.

Materials and methods

In acute toxicity tests, four groups of rats (n = 5/group/sex) were orally treated with doses of 0.625, 1.25, 2.5 and 5.0 g/kg and general behavior, adverse effects and mortality were recorded for up to 14 days. In subacute toxicity assays, animals received Cassia occidentalis by gavage at the doses of 0.10, 0.50 or 2.5 g/kg/day (n = 10/group/sex) for 30 days and biochemical, hematological and morphological parameters were determined.

Results

Cassia occidentalis did not produce any hazardous symptoms or death in the acute toxicity test, showing a LD₅₀ higher than 5 g/kg. Subacute treatment with Cassia occidentalis failed to change body weight gain, food and water consumption and hematological and biochemical profiles. In addition, no changes in macroscopical and microscopical aspect of organs were observed in the animals.

Conclusions

Our results showed that acute or subacute administration of Cassia occidentalis is not toxic in male and female Wistar rats, suggesting a safety use by humans.     

In vivo antiulcer activity of the aqueous extract of Bauhinia purpurea leaf

Ethnopharmacological relevance

Bauhinia purpurea (Fabaceae) is a medicinal plant traditionally used to treat various ailments, including ulcers. In order to establish pharmacological properties of the leaf of Bauhinia purpurea, studies were performed on antiulcer activity of the plant's aqueous extract.

Materials and methods

The Bauhinia purpurea aqueous extract (BPAE) was prepared in the doses of 100, 500 and 1000 mg/kg. Antiulcer activity of BPAE was evaluated by absolute ethanol- and indomethacin-induced gastric ulcer, and pyloric ligation models. Acute toxicity was also carried out.

Results

BPAE, at the dose of 5000 mg/kg, did not cause any signs of toxicity to rats when given orally. Oral administration of BPAE exhibited antiulcer activity (p < 0.05) in all models used. However, the dose-dependent activity was observed only in the absolute ethanol-induced gastric ulcer model. Histological studies supported the observed antiulcer activity of BPAE. In pyloric ligation assay, BPAE increased the gastric wall mucus secretion.

Conclusions

The BPAE exhibits antiulcer activity, which could be due to the presence of saponins or sugar-free polyphenols, and, thus, confirmed the traditional uses of Bauhinia purpurea in the treatment of ulcers.     

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.     

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.     

Safety assessment of aqueous extract from leaf Smallanthus sonchifolius and its main active lactone, enhydrin

Ethnopharmacological Relevance

Leaves of Smallanthus sonchifolius (Poepp. & Endl.) H. Robinson (yacon) have been used since pre-Columbian times in the Andean region to prepare medicinal herbal tea with beneficial health properties. However, there are still disagreements about the safe use. This work was carried out to evaluate the toxicity profile of both, 10% decoction of yacon leaves and their major active lactone, enhydrin.

Materials and methods

In vitro cytotoxicity assays were performed with Hep-G2, COS1, CHO-K1 and Vero cell lines using a test of metabolic competence based upon assessment of mitochondrial performance. In vivo toxicity study was performed in adult Wistar rats. In the acute oral toxicity each group of rats was orally given a single dose of 10% decoction or enhydrin. General condition, behavior and mortality were recorded for up to 14 days post treatment. In subchronic toxicity studies, both products were given orally for 90 days to rats. Body weight and food intakes were observed weekly. Hematological, clinical chemistry parameters and organ weight were determined in all animals at the end of the experimental period.

Results

Cell viability decreased in a concentration dependent fashion when cells were incubated with 2–200 μg of 10% decoction and 0.015–7.5 μg of enhydrin. In acute study in rats, there were no deaths or signs of toxicity observed after oral administration of single doses of 10% decoction or enhydrin at any dose level up to the highest dose tested (14.0 g/kg and 0.32 g/kg, respectively). In subchronic studies in rats, both products administered orally for 90 days at daily doses of 0.07, 0.14 and 0.28 g 10% decoction/kg and 0.4, 0.8 and 8.0 mg enhydrin/kg, did not caused haematological, biochemical and histological alterations.

Conclusions

The results presented in this paper lead us to the conclusion that the use of 10% decoction and enhydrin is safe in rat at doses in which it is demonstrated the hypoglycaemic effect.     

Antidiabetic effect of Symplocos cochinchinensis (Lour.) S. Moore. in type 2 diabetic rats

Aim

Symplocos cochinchinensis (Lour.) S. Moore. is used in Indian system of traditional medicine to treat diabetes mellitus. The present study aims to investigate the antidiabetic efficacy of the hexane extract of Symplocos cochinchinensis leaves in high fat diet-low streptozotocin (STZ) induced type 2 diabetic rats.

Materials and methods

The doses for the study were fixed based on Irwin test. The hypoglycemic effect of the hexane extract of Symplocos cochinchinensis leaves were studied in normal rats. Oral glucose and insulin tolerance tests were carried out. The antihyperglycemic effect of the hexane extract at 250 and 500 mg/kg was studied in high fat diet-low STZ induced type 2 diabetic rats for 28 days.

Results

The extracts showed no adverse effects up to 5 g/kg concentration. In hypoglycemic study, after treatment with hexane extract at 250 and 500 mg/kg the blood glucose was mildly reduced. In oral glucose tolerance test, the treatment with the hexane extract at 250 and 500 mg/kg showed a highly significant reduction of 12.07% and 23.58% in plasma glucose levels, respectively 30 min after glucose load. The insulin tolerance test also showed improved insulin sensitivity after 60 min of insulin treatment. In high fat diet-low STZ induced type 2 diabetic rats, after 28 days treatment with the hexane extract at 250 and 500 mg/kg reduced the plasma glucose level by 17.04% and 42.10%, respectively. A significant reduction in plasma insulin, plasma and hepatic total cholesterol (TC), triglycerides (TG) and free fatty acids (FFA) and a significant increase in liver glycogen were observed in treated diabetic rats.

Conclusion

This study demonstrated the potential antidiabetic property of hexane extract of Symplocos cochinchinensis leaves on type 2 diabetes mellitus, thus justifying its traditional usage.     

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.     

Hepatoprotective and toxicological assessment of an ethnomedicinal plant Euphorbia fusiformis Buch.-Ham.ex D.Don

Aim of the study

The tubers of Euphorbia fusiformis Buch.-Ham.ex D.Don (Euphorbiaceae) are traditionally used in India by the Malayali tribes of Chitteri hills, Eastern Ghats, Tamil Nadu to treat liver disorders. The objective of the present study was to assess the hepatoprotective potential and biosafety of Euphorbia fusiformis tuber upon administration thereby justifying the traditional claims.

Materials and methods

The hepatoprotective potential of the ethanol extract of Euphorbia fusiformis tuber against rifampicin induced hepatic damage was investigated in Wistar albino rats. The acute and subchronic toxicity were assessed in mice and rats, respectively.

Results

The ethanol extract of tubers (250 mg/kg p.o.) showed remarkable hepatoprotective effect against rifampicin induced hepatic damage in Wistar albino rats. The degree of protection was measured using the biochemical parameters serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), gamma glutamyl transpeptidase (GGTP), alkaline phosphatase (ALP), total bilirubin and total protein. Treatment with ethanolic extract prior to the administration of rifampicin significantly (P < 0.05 to P < 0.001) restored the elevated levels of the said parameters on a par with the control group. The single dose LD₅₀ was found to be 10,000 mg/kg bw when administered orally in mice. Subchronic toxicity studies in rats with oral doses of 125, 250 and 500 mg/kg exhibited no significant changes in body weight gain, general behavior, hematological and biochemical parameters. The histological profile of liver and kidney also indicated the non-toxic nature of this drug.

Conclusion

The ethanol extract of Euphorbia fusiformis tubers may have potential therapeutic value in the treatment of liver disorders and is safer to use even at higher doses when taken orally.     

Analgesic effects and anti-inflammatory properties of the crude methanolic extract of Schwenckia americana Linn (Solanaceae)

Aim of the study

To evaluate analgesic effect and anti-inflammatory properties of Schwenckia americana (Solanaceae), a medicinal plant used for treating rheumatic pains and swelling in North-western Nigeria.

Materials and methods

Three doses (25 mg/kg, 50 mg/kg and 100 mg/kg) of the crude methanolic extract of Schwenkia americana were evaluated for analgesic and anti-inflammatory activities using acetic acid induced writhing test, formalin induced nociception, and formalin induced hind paw oedema in rats.

Results

All doses (25, 50, 100 mg/kg) of the extract tested were effective. The extract at the tested doses produced a percentage inhibition of the acetic acid induced abdominal constriction of (53.3, 58.0 and 86.7%), respectively. A percentage inhibition of the formalin induced nociception of 44.00, 56.04, and 56.04% (early phase) and 33.00, 36.63 and 59.71% (late phase) was also produced. The inhibition of oedema formation increased with increasing dosage from 25 to 100 mg/kg. The crude extract produced a statistically significant analgesic and anti-inflammatory activity comparable to the effect of standard drug (10 mg/kg Piroxicam).

Conclusion

This study demonstrated the potential analgesic and anti-inflammatory properties of crude methanolic extract of Schwenkia americana thus justifying its traditional usage.     

Acute and subacute toxicity of Schinus terebinthifolius bark extract

Ethnopharmacological relevance

Schinus terebinthifolius Raddi (Anacardiaceae) has long been used in traditional Brazilian medicine, especially to treat inflammatory and haemostatic diseases.

Aim of the study

The objective of this study was to evaluate the acute and subacute toxicity (45 days) of Schinus terebinthifolius via the oral route in Wistar rats of both sexes.

Materials and methods

For the acute toxicity test, the dried extract of Schinus terebinthifolius bark was administered in doses from 0.625 to 5.0 g/kg (n = 5/group/sex) and in the subacute toxicity test the following doses were used: 0.25, 0.625 and 1.5625 g/kg/day (n = 13/group/sex), for 45 consecutive days.

Results

In the acute toxicity test, Schinus terebinthifolius did not produce any toxic signs or deaths. The subacute treatment with Schinus terebinthifolius did not alter either the body weight gain or the food and water consumption. The hematological and biochemical analysis did not show significant differences in any of the parameters examined in female or male groups, except in two male groups, in which the treatment with Schinus terebinthifolius (0.25 and 0.625 g/kg) induced an increase of mean corpuscular volume values (2.9 and 2.6%, respectively). These variations are within the physiological limits described for the specie and does not have clinical relevance.

Conclusion

The acute and subacute administration of the dried extract of Schinus terebinthifolius bark did not produced toxic effects in Wistar rats.