Subacute Toxicity Test Research Articles

Safety assessment of Bauhinia cheilantha Bong. Steud leaves extract: acute, sub-acute toxicity, antioxidant, and antihemolytic evaluations.

Bauhinia cheilantha (Fabaceae), known popularly as pata-de-vaca and mororó has been largely recommended treating several diseases in folk medicine. However, information on safe doses and use is still scarce. The goal was to evaluate in-vitro antioxidant and antihemolytic and also acute and sub-acute toxicity effects of hydroalcoholic extract from B. cheilantha leaves (HaEBcl). The identification of the compounds in the HaEBcl was performed by ultra-performance liquid chromatography coupled with a diode array detector and quadrupole time-of-flight mass spectrometry. Antioxidant and hemolytic activity of HaEBcl was evaluated in vitro. To study acute toxicity, female mice received HaEBcl in a single dose of 300 and 2.000 mg/kg. Later, sub-acute toxicity was introduced in both female and male mice by oral gavage at 300, 1000, or 2000 mg/kg for 28 consecutive days. Hematological and biochemical profiles were created from the blood as well as from histological analysis of the liver. HaEBcl is rich in flavonoids (quercitrin and afzelin), has no hemolytic effects and moderate antioxidant effects in vitro. Acute toxicity evaluation showed that lethal dose (LD50) of HaEBcl was over 2000mg/kg. Sub-acute toxicity testing elicited no clinical signs of toxicity, morbidity, or mortality. The hematological and biochemical parameters discounted any chance of hepatic or kidney toxicity. Furthermore, histopathological data did not reveal any disturbance in liver morphology in treated mice. Results indicate that HaEBcl has no hemolytic and moderate antioxidant effects in vitro. In addition, HaEBcl dosage levels up to 2000mg/kg are nontoxic and can be considered safe for mammals.

Effects of Three Carbonaceous Nanomaterials on the Developmental Toxicity, Oxidative Stress, and Metabolic Profile in Zebrafish

As an important part of artificial nanomaterials, carbonaceous nanomaterials (CNMs) are widely applied in a plenty of areas such as energy, manufacturing and pharmaceutical industries. In the present study, the developmental toxicity, induced by three typical CNMs including graphene oxide (GO), carbon nanotube (CNT) and graphene oxide quantum dot (GOQD) was investigated in the typical model animal, zebrafish larva. The induced sub-acute toxicity at the low concentration of GO, CNT and GOQD was investigated in adult zebrafish, either. Moreover, the molecular mechanisms at the level of metabolomics were also explored. The results showed that there was a significant increase in reactive oxygen species (ROS), and mitochondrial membrane damage was caused by GO, CNT and GOQD in zebrafish larva. However, there was no significant developmental toxicity on zebrafish larva. The toxicity order in terms of the ROS increase and mitochondrial membrane damage was GOQD > CNT > GO. The chronic exposure at the typical environment-associated concentration (0.01 mg·L-1) of CNMs can induce gill and kidney cell senescence of adult zebrafish. Meanwhile, it can also inhibit total superoxide dismutase (T-SOD) activity in adult zebrafish in the subacute toxicity test (21 d) at the concentration of 0.01 mg·L-1. The metabolomics research revealed that the toxicity order at the environment-associated concentration acting on adult zebrafish was GOQD > CNT > GO; and it showed that fatty acids and proline turbulence may be responsible for one of the molecular mechanisms of T-SOD inhibition in adult zebrafish. This work can supply rationale to evaluate the potential risk of ecosystems and human health induced by the three typical CNMs.

In vivo Antimalarial, Antioxidant Activities and Safety of Carapa procera DC. (Meliaceae).

<b>Background and Objectives:</b> <i>Carapa procera</i> is a popular herb used by traditional healers in the western part of Burkina Faso. In a previous study, <i>Carapa procera </i>showed interesting antiplasmodial activity <i>in vitro </i>against <i>P. falciparum</i>. The present study aimed to evaluate its <i>in vivo</i> potential against malaria parasites and its safety in mice. <b>Materials and Methods:</b> The antimalarial activity of the ethanolic extract was evaluated on <i>Plasmodium berghei </i>Anka in the Naval Medical Research Institute (NMRI) mice using the Peters 4-day suppressive test. The acute toxicity was performed according to the Lorke method and sub-acute toxicity following the Seewaboon method. The polyphenols and flavonoids were determined by colorimetric methods. The antioxidant activity of the extract was evaluated <i>in vitro</i> by Ferric Reducing Antioxidant Power (FRAPP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) methods. <b>Results:</b> <i>Carapa procera</i> had a good antiplasmodial activity at a dose of 250 mg kg¹ b.wt. Phytochemical screening revealed the presence of polyphenols and flavonoids in the extracts. Soxhlet ethanolic extracts had the highest content in polyphenols and flavonoids. The antioxidant activity of Soxhlet ethanolic extracts was better than macerated extract by DPPH method and FRAP method. Besides, no mortality in mice was recorded with the soxhlet ethanolic extract. No toxic signs were observed in animals in the sub-acute toxicity test. <b>Conclusion:</b> <i>Carapa procera </i>soxhlet ethanolic stem bark extract had a good <i>in vivo</i> antimalarial activity against <i>Plasmodium berghei </i>infection in mice and the extract was relatively safe when administered orally in mice.

Subacute toxicological evaluation of AT-533 and AT-533 gel in Sprague-Dawley rats.

As a novel heat shock protein 90 inhibitor, AT-533 exhibits various biological activities in vitro, including anti-viral, anti-tumor and anti-inflammatory activities. Moreover, AT-533 gel, a gel dosage form of AT-533, has been suggested to have anti-keratitis and herpes simplex virus type-1 infection-induced effects on the skin lesions of animals. However, the safety evaluation of AT-533 and AT-533 gel has, to the best of our knowledge, not been examined in in vivo toxicological tests. Therefore, these toxicological tests were carried out in the present study. A 30-day subacute toxicity test for AT-533 was conducted at doses of 1, 2 and 4 mg/kg in Sprague-Dawley rats, while that for AT-533 gel was conducted using a single dose of 5 g/kg. The toxicological tests showed that a high-dose of AT-533 caused lethality and side effects in Sprague-Dawley rats. However, no mortality, loss of appetite and body weight, adverse reactions, or toxicologically relevant alterations in hematology, biochemistry and macroscopic findings (except for skin) occurred in rats exposed to low-dose AT-533 and single-dose AT-533 gel (5 g/kg) during a 30-day subacute dermic toxicity study. The aforementioned results suggested that AT-533 gel is non-toxic for Sprague-Dawley rats, as shown by a dermic subacute toxicity test and that except for slight skin irritation, AT-533 gel had almost no side effects when administered percutaneously for 30 days.

Toxicity Evaluation by Single and Repeated Administration of Yeast Hydrolysate DNF-10.

This study aimed at investigating the acute and subacute oral toxicity of yeast hydrolysate (DNF-10) in Sprague-Dawley rats. To determine the acute toxicity of DNF-10, it was orally administered to rats at a dose of 5,000 mg/kg. Furthermore, to determine subacute toxicity of DNF-10, it was orally administered to female and male rats at a dose of 1,000 mg/kg for 90 days. In the acute toxicity test, the experimental group did not show changes in body and organ weights compared to the corresponding weights in the control group. When compared to female controls, the DNF-10-treated female rats showed decreased red blood cell counts, haemoglobin, and total bilirubin levels; however, the parameters remained within the normal range. In the subacute toxicity test, DNF-10 administration significantly reduced body weight among male rats, which appears attributable to the anti-obesity effect of the compound. In the experimental groups, significant differences in some haematological parameters were considered as non-toxic because the results were within the normal range. These results suggest that DNF-10 is safe and non-toxic at single doses (5,000 mg/kg) and repeated doses (1,000 mg/kg).

Safety evaluation of Aloe vera soft capsule in acute, subacute toxicity and genotoxicity study.

Aloe vera has been widely used in health and nutritional supplements in Chinese herbal medicine. Furthermore, Aloe vera production has been an emerging industry for making cosmetics and functional food. However, the reported adverse effects raised questions as to whether Aloe vera and its products were safe enough to be used in medicine and health care. In view of this, the safety evaluation of Aloe vera products before marketing is very important. The present study aimed to assess the toxicological profile of Aloe vera soft capsule (ASC), through acute, subacute toxicity and genotoxicity tests. Male and female ICR mice were received by oral gavage 15000 mg/kg bodyweight of ASC in the acute toxicity test. Male and female SD rats were fed on diet blended with different doses of ASC (equivalent to 832.5, 1665 and 3330 mg/kg bodyweight of ASC) for the subacute toxicity test. In the acute toxicity study, no mortality or behavioral changes were observed, indicating the LD50 was higher than 15000 mg/kg bodyweight. In the subacute toxicity test, no significant changes were observed in bodyweight, food consumption, hematological, biochemical or histopathological parameters in the rats exposed. These data suggested that ASC used in this study did not produce any marked subacute toxic effects up to a maximum concentration of 3330 mg/kg bodyweight. In the genotoxicity study, ASC showed no mutagenic activity in the Ames test and no evidence of potential to induce bone marrow micronucleus or testicular chromosome aberrations in ICR mice exposed to 10000 mg/kg bodyweight. Collectively, ASC could be considered safe before it was marketed as a laxative and moistening health food.

Toxicological evaluation of aqueous extract of the traditional Chinese formula Qing Hao Gan Cao.

Qing Hao Gan Cao (QHGC), a Chinese medicinal formula containing Artemisia annua and Glycyrrhizae Radix et Rhizoma, has been used to treat sunstroke and as an antiviral agent for more than 800 years. It has not previously been subject to a toxicological safety evaluation in acute and subacute (28days) studies. Therefore, the acute and subacute toxicity of an aqueous extract of QHGC were evaluated in vivo. For the QHGC preparation, the botanical raw materials were crushed into pieces and mixed in the ratio of 10:1 in distilled water for 12 h, then boiling three times for 2 h each time. The three decoctions were mixed and filtered, then spray-dried with hot air at 160°C for 30 min, and stored at room temperature. For the acute toxicity test, 72.0 g/kg of QHGC extract was administered by gavage to male and female mice. Body weight, general observations, and autopsy results were recorded. No mortality or toxicity signs were observed during the studies. For the subacute toxicity test, 4.0, 8.0, or 16.0 g/kg/day of QHGC extract was administered to rats for 28 days. General observations and mortality, body weight, biochemical and hematological parameters, organ weight, and pathological morphology were analyzed. The acute and subacute toxicity studies did not show significant changes in body weight, general observations, hematology and biochemical parameters, organ weight, and liver, spleen, stomach, duodenum, testis, ovary, lung, heart, and kidney histopathological analyses. The consumption of QHGC aqueous extract can be considered safe within the conditions of this study.

Acute and subacute (28 days) oral toxicity studies of tucum almond oil (Bactris Setosa Mart.) in mice

Oils extracted from almonds are often used with particular interest due to their prospective health effects and benefits. Tucum is a Pantanal fruit widely consumed by local population and no in vivo toxicity studies regarding its safety are available in the literature to date. This study investigated the acute and subacute toxicity of tucum almond oil (TAO) in mice by evaluating its safety profile. For the acute (2000 mg/kg) and subacute (250, 500 and 1000 mg/kg) toxicity studies, TAO was administered orally to mice according to 425 and 407 Organization for Economic Cooperation and Development Guidelines, respectively. Food intake, body, and organ weight of animals were recorded. Signs of toxicity were assessed, and hematological, biochemical and histopathological analyses were performed. In the acute toxicity study, no mortality or behavioral changes were observed in mice treated with 2000 mg/kg, indicating that LD50 is higher than this dose. In the subacute toxicity test, the doses evaluated did not produce relevant changes in hematological, biochemical or histopathological parameters in the exposed animals. The data obtained suggest that TAO did not induce toxicity after exposure to a single or repeated doses and LD50 value may be considered to be more than 2000 mg/kg body weight.

Evaluation of the in vivo and in vitro safety profile of Cuscuta epithymum ethanolic extract.

Objective: Cuscuta epithymum (CE) is one of the most popular medicinal plants in the world. However, detailed information about its toxicity is not available. Hence, this study aimed to evaluate the safety profile of CE ethanolic extract in vitro and in vivo.Materials and Methods:The extract's in vitro toxicity profile was investigated on normal fibroblast and cervical cancer cells by cytotoxicity test. In the next step, acute oral and intraperitoneal (i.p.) toxicity of the CE extract was evaluated in Wistar rats and BALB/c mice, respectively. Sub-acute oral toxicity was also examined by administering repeated oral doses of the CE extract (50, 200, and 500 mg/kg) to Wistar rats for 28 days. Results:The CE extract exhibited a significant cytotoxicity on both normal (IC50 0.82 mg/ml, p<0.001) and cancer cells (IC50 1.42 mg/ml, p<0.001). Acute oral administration of a single dose of CE extract (175-5000 mg/kg) did not cause mortality; however, its i.p. administration caused mortality at doses greater than 75 mg/kg (i.p. LD50 154.8 mg/kg). In the sub-acute toxicity test, no significant effects in terms of weight change, organ weights, blood chemistry, or kidney pathology were observed. However, at 200 and 500 mg/kg doses, the CE extract significantly increased liver pathological scores compared to the control group (p<0.05 and p<0.01, respectively).Conclusion:CE exhibited toxicities in i.p. acute and repeated oral dose administrations. It showed identical cytotoxicity against normal and cancer cells. This herb must be prescribed cautiously by traditional medicine practitioners.

Immunomodulatory Activity of the Marine Sponge, Haliclona (Soestella) sp. (Haplosclerida: Chalinidae), from Sri Lanka in Wistar Albino Rats: Immunosuppression and Th1-Skewed Cytokine Response.

Natural secondary metabolites of sponges of the genus Haliclona are associated with an array of biological activity with therapeutic usage. We investigated the immunopharmacological properties of a presumably novel marine sponge species from Sri Lanka, Haliclona (Soestella) sp. Sponge material was collected from southern Sri Lanka by scuba diving. Sponge identification was based on spicule and skeleton morphology using light microscopy. Selected in vivo and ex vivo tests investigated nonfunctional and functional immunomodulatory activity of the Haliclona (Soestella) sp. crude extract (HSCE) in the Wistar rat model. Compared to the controls, rats orally gavaged daily for 14 consecutive days with 15 mg/kg dose of the HSCE manifested a significant reduction of immune cell counts of total WBCs (by 17%; p < 0.01), lymphocytes (38%), platelets (52%), splenocytes (20%), and bone marrow cells (BMC; 60%) (p < 0.001), with a concurrent increase in the neutrophil : lymphocyte ratio (p < 0.05); RBC counts abated by 53% (p < 0.001). A significant reduction of the splenosomatic index was evident with the 10 and 15 mg/kg doses (p < 0.001). Rat plasma TNF-α cytokine level was augmented by tenfold (p < 0.001), IL-6 level by twofold (p < 0.01) with the 15 mg/kg HSCE treatment, while IL-10 was detectable in rat plasma only with this treatment; the corresponding Th1 : Th2 cytokine ratio (TNF-α : IL-10) was indicative of an unequivocal Th1-skewed cytokine response (p < 0.01). Ex vivo bone marrow cell and splenocyte proliferation were significantly and dose dependently impaired by HSCE (IC50 0.719 and 0.931 μg/mL, respectively; p < 0.05). Subacute toxicity testing established that HSCE was devoid of general toxic, hepatotoxic, and nephrotoxic effects. In conclusion, HSCE was orally active, nontoxic, and effectively suppressed nonfunctional and functional immunological parameters of Wistar rats, suggestive of the potential use of the HSCE as an immunosuppressant drug lead.

The in vivo toxicity evaluation of leaf and root methanolic extracts of Tephrosia vogelii Hook.f using animal model

BackgroundTraditionally, herbal medicines are commonly used to cure several diseases since immemorial of human life. Nevertheless, the safety of some traditionally used medicinal plants is uncertain. Since Tephrosia vogelii Hook.f is a traditionally used medicinal plant, the effects of its extracts were evaluated on lethality (LD50) and sub-acute toxicity in this study.MethodsPhytochemistry screening and an in vivo toxicity evaluation of leaf and root methanolic extracts of T. vogelii using laboratory albino rats were conducted. Methanolic extracts of doses 600, 1200, 2000 and 5000 mg/kg body weights were administered single dose in rats to observe deaths within 72 h in order to determine the LD50. Methanolic extracts doses of 600, 1200 and 2000 mg/kg body weights were consecutively administered for 14 days in order to evaluate sub-acute toxicity.ResultsTannins, steroids, terpenoids, flavonoids and saponins were identified in the phytochemical screening. The LD50 experiments revealed zero deaths of rats for the administered doses, 600 to 5000 mg/kg body weight. Histopathological examination of liver and kidney for sub-acute toxicity test showed safety at all doses except root methanolic extracts dose of 2000 mg/kg which exhibited necrosis and vacuolation of liver cells on the 14th day. Nonetheless, hepatic necrosis and hepatic vacuolation disappeared upon time elongation without dose administration to 28th day.ConclusionThe conducted toxicity evaluation of methanolic leaf and root extracts in albino rats revealed no deleterious effects, henceforth, suggesting that T. vogelii could be safe to users using it as a medicinal plant.

Acute and Subacute Oral Toxicity Studies and Anti-Sickling Activity Assessment of FACA® Syrup

Sickle cell disease remains a major public health problem in Burkina Faso and Africa. For the management of this pathology in young children, the Institute for Research in Health Sciences has developed an herbal drug called FACA® syrup. The objective of this study was to verify the safety and pharmacological efficacy of this formulation for its use in the management of sickle cell disease. Acute and subacute oral toxicity tests were performed on Wistar rats in accordance with Organization for Economic Cooperation and Development test guidelines and anti-sickling activity of FACA® syrup was evaluated according to the Emmel test. In the acute test, FACA® syrup didn’t cause mortality or any behavioral change at dose of 2000 mg/kg/b.w suggesting that the test product estimated LD50 is 5000 mg/kg b.w. The results of subacute toxicity study indicate that the daily administration of FACA® syrup during 28 days did not result in significant change on physical, haematological and biochemical parameters up to dose of 1000 mg/kg b.w. The evaluation of effect of FACA® syrup in vitro on sickling revealed that, FACA® syrup possesses a real antisickling activity. Regarding these results FACA® syrup would be considered as safe in both acute and subacute exposure and could be used in the management of sickle cell diseases.&#x0D; Keywords: FACA® syrup, oral toxicity, sickle cell anemia, Antisickling activity

Acute and Subacute Toxicity Studies of the Aqueous Extract from Haloxylon scoparium Pomel (Hammada scoparia (Pomel)) by Oral Administration in Rodents.

Materials and Methods Acute toxicity test was performed on Swiss albino mice at a single oral dose of 1-10 g/kg for 14 consecutive days. General behavioral adverse effects, mortality, and latency of mortality were determined. In the subacute study, the Haloxylon scoparium Pomel extract was administered orally at doses of 500, 1000, and 2000 mg/kg daily for 30 days to Wistar rats. Body weight and selected biochemical and hematological parameters were determined at the end of the experiment. Sections of livers and kidneys were removed for histological studies. Results Acute toxicity study showed that the oral LD50 value of Haloxylon scoparium Pomel extract was 5000 mg/kg. The subacute toxicity study of Haloxylon scoparium Pomel extract at doses 500, 1000, and 2000 mg/kg did not produce any observable symptoms of toxicity and no significant variation in body weight, organ weights, food, and water consumption or mortality in all treated rats. However, the administration of the Haloxylon scoparium Pomel extract to rats at 500 mg/kg and 1000 mg/kg showed a significant decrease in platelets. Moreover, only at the highest dose (2000 mg/kg), the extract caused a significant increase in red blood cells and hemoglobin. Our results showed that subacute treatments with Haloxylon scoparium Pomel extract at doses of 1000 mg/kg and 2000 mg/kg significantly elevated alkaline phosphatase and triglycerides. Histological studies showed that the subacute treatments of rats with Haloxylon scoparium Pomel extracts, at the doses 1000 and 2000 mg/kg, induced some histopathological changes in the livers but a slight changing in kidneys. Conclusion Our results indicated low acute toxicity of the aqueous extract of Haloxylon scoparium Pomel. Furthermore, daily oral administration of Haloxylon scoparium Pomel extract caused some damages to the livers of rats treated with high doses, expressed by an increase in some enzyme activities such as ALP. Regarding the renal function, we did not find remarkable toxicity in the subacute treatment with Haloxylon scoparium Pomel extracts at doses 1000 and 2000 mg/kg. However, further toxicity assessments should be done to ascertain the safety or the toxicity of this valuable plant species “Haloxylon scoparium pomel” in subchronic treatments.

In vivo and in vitro toxicological evaluations of aqueous extract from Cecropia pachystachya leaves

ABSTRACT Cecropia pachystachya leaves are popularly used to treat asthma and diabetes. Despite the widespread consumption of this plant, there are few scientific studies regarding its toxicological potential. In order to conduct a thorough study concerning the potential adverse effects, the aim of this study was to assess acute and subacute toxicity tests of crude aqueous extract from C. pachystachya leaves (CAE-Cp) using in vivomodel, as well as in vitro cytotoxicity, genotoxicity and antioxidant activity. In addition, genotoxicity, and cytotoxicity of chlorogenic acid (CGA) and cytotoxicity of isoorientin (ISOO) were also evaluated. The antioxidant activity was verified by DPPH, cytotoxicity using sulforhodamine B (SRB) assay and genotoxicity by comet assay on V79 cells. The phytochemical analysis of CAE-Cp detected flavonoids and tannins, CGA and ISOO as the major compounds utilizing HPLC. The total flavonoid content (6.52 mg/g EQ) and antioxidant activity (EC50 = 62.15 µg/ml) of CAE-Cp were determined. In vitro evaluations with CAE-Cp showed genotoxic effects at 0.31 to 2.5 mg/ml and an expressive cytotoxicity on HT-29 (IC50 = 4.43 µg/ml) cells. CGA was genotoxic against V79 cells at 0.07 mg/ml and cytotoxic against to HT-29 (IC50 = 71.70 µg/ml), OVCAR-3 (IC50 = 80.07 µg/ml), MCF-7 (IC50 = 45.58 µg/ml) and, NCI-H460 (IC50 = 71.89 µg/ml) cancer cell lines. Wistar rats treated with a single dose (2,000 mg/kg) CAE-Cp decreased hemoglobin levels after 14 days, although no significant toxicity was observed in animals after 28 days. In view of the in vitro cytotoxicity and genotoxicity detected, further studies are necessary to establish the safe use of CAE-Cp.

Acute and subacute toxicity evaluation of aqueous extracts of Carpobrotus edulis in Sprague Dawley rats

Carpobrotus edulis is a common medicinal plant used in Southern Africa. Despite its extensive use in herbal medicine, there is no documented scientific evidence corroborating its safety. This study aims to evaluate the acute and subacute toxic effects of the aqueous extracts of Carpobrotus edulis in Sprague Dawley rats. In acute toxicity testing, three healthy female Sprague Dawley rats were exposed to Carpobrotus edulis aqueous extract per step at any of the four fixed dose levels of 300, 600, 1200 and 2000mg/Kg body weight. The Sprague Dawley rats were observed clinically for any signs of toxicity. A 28-day subacute toxicity testing was carried out on thirty-two Sprague Dawley rats grouped in four experimental groups of eight animals each. Group A received 100mg//kg of the extract, Group B received 300mg/kg while Group C received 1000mg/kg. Group D was a negative control group and received distilled water. Bodyweight, feed and water intake were measured at weekly intervals. Blood for biochemical analysis was collected on the last day of the study period. Gross pathological and histopathological examination was done on all experimental rats. There were no clinical signs suggestive of toxicity on all doses used in acute toxicity testing. The LD50 of the aqueous extract of Carpobrotus edulis was estimated to be above 2000mg/kg. On subacute toxicity testing, there were no significance differences (P&lt;0.05) on body weight changes, feed and water intake in all experimental groups. The serum biochemical results also did not show any significant variation among all the experimental groups. Gross pathology and histopathology examination of the selected organ tissues revealed no differences between control and treated Sprague Dawley Rats. It is concluded from the study that the aqueous extracts of Carpobrotus edulis are potentially safe.

Safety assessment of essential oils from Xylopia aethiopica (Dunal) fruit from Nigeria

Introduction: The essential oils of Xylopia aethiopica fruits have been reported to possess numerous biochemical effects. However, no toxicological data is available regarding the safety evaluation of the essential oils from the plant spice. The present study was performed to evaluate the safety of essential oils from X. aethiopica (XAEO) fruit by acute and sub-acute oral toxicity studies in experimental rodents.&#x0D; Methods: In assessing the safety of XAEO, acute and sub-acute oral toxicity tests were performed following OECD guidelines 425 and 407, respectively, with slight modifications. At the end of each test, hematological and biochemical analysis of the collected blood was performed. Histopathological examination of vital organs of the animals was conducted for gross findings and for comparison to controls.&#x0D; Results: In acute oral toxicity, signs of toxicity were observed in the initial period of the experiment which culminated in the death of the mice before the end of the experiment. The sub-acute test observations indicated that generally, there were no significant differences (p&amp;lt;0.05) up to the high dose level compared to the controls.&#x0D; Conclusion: This study demonstrated the tolerability of XAEO administered daily for 28 days up to 450 mg/kg dose.

Toxicity and antidiabetic activity of ethanolic extract of Sphagneticola trilobata (L.) Pruski flower in rats

Ethnopharmacological relevancePlants are the source of medication for preventive, curative, protective or promotive purposes. Medicinal plants are an important source for generating of novel phytomedicine. They provide profound therapeutic benefits, more affordable treatments, effectiveness, less side effects and relatively low cost or less expensive and globally competitive. Using plant derived medicine is also relatively safe compared to synthetic medicines. Many plants have proved to successfully aid in the treatment of ailments including Sphagneticola triolobata (L.) Pruski. Aim of studyThis study was therefore, designed to investigate acute and subacute toxicities, antidiabetic activity and also antioxidant activity of flower extract from S. triolobata (L.) Pruski. MethodsThis research investigates the toxicity and antidiabetic activity of Sphagnelicola trilobata (L.) Pruski flower ethanolic extract in rats. Acute toxicity was determined by a single oral administration of S. trilobata extract of 1500, 2000, and 2500 mg/kg body weight; and subacute toxicity by oral administration every two days for 14 days. Signs of toxicity and mortality were observed during 24 h and for 14 days. Hematological values and blood chemistry were also characterized. The antidiabetic activity was examined by orally administering S. trilobata extract of 250 mg/kg body weight to streptozotocin-induced diabetic rats on a daily basis for eight weeks; and the body weight, blood glucose, serum insulin, and lipid profiles were determined. The antioxidant activity of the extract was assessed by 1, 1-diphenyl-2-picryl-hydrazyl free radical scavenging assay. Results and conclusionThe results demonstrated a median lethal dose (LD50) greater than 2500 mg/kg since there was no sign of toxicity and mortality in acute and subacute toxicity testing. The high LD50 indicated that S. trilobata flower ethanolic extract is safe for treatment of diabetes. There was no significant change in the body weight, hematological values, and blood chemistry of treated rats, compared with the control group. The diabetes-induced rats showed a significant reduction in blood glucose and triglyceride (p < 0.05). Meanwhile, the antioxidant activity of S. trilobata extract was lower than that of standard ascorbic acid.

Anti-diabetic properties of genistein-chromium (III) complex in db/db diabetic mice and its sub-acute toxicity evaluation in normal mice

BackgroundIn this study, chromium (III) complex was synthesized from genistein (GEN) which had good hypoglycemic activity and inorganic chromium (III) element, and its hypoglycemic activity and sub-acute toxicity were studied. MethodsThe genistein-chromium (III) complex was synthesized by chelating chromium with genistein in ethanol and its structure was determined by LC–MS, atomic absorption spectroscopy, UV–vis spectroscopy, infrared spectroscopy, elemental and thermodynamic analysis. The anti-diabetic activity of the complex was assessed in db/db mice and C57 mice by daily oral gavage for 4 weeks. The sub-acute toxicity test was carried out on KM mice with this complex. ResultsThe molecular structure of this complex was inferred as a complex [CrGEN3] formed by three ligands and one chromium element. The complex could significantly improve the body weight of db/db mice, fasting blood glucose, random blood glucose, organ index, glycogen levels and the performance of OGTT (Oral Glucose Tolerance Test) and ITT (Insulin Tolerance Test) in db/db mice (p < 0.05). The morphology of liver, kidney, pancreas and skeletal muscle also had obviously improvement and repairment. Effects on serum indices and antioxidant enzymes activities of db/db mice showed that the serum profiles and antioxidant ability of complex group had significant improvement compared with the diabetic control group (p < 0.05 or p < 0.01), and some indices even returned to normal levels. In addition, this complex did not produce any hazardous symptoms or deaths in sub-acute toxicity test. High dose of [CrGEN3] had no significant influence on serum indices and antioxidant capacity in normal mice, and the organ tissues maintained organized and integrity in the sub-acute toxicity study. ConclusionThe study of the genistein-chromium (III) complex showed that the complex had good hypoglycemic activity in vivo, and did not have the potential toxicity. These results would provide an important reference for the development of functional hypoglycemic foods or pharmaceuticals.

Evaluation of HIV1 GP 120-CD4 Binding Inhibition Potentials of the Stem Bark Extracts of Diospyros mespiliformis

The study was conducted to evaluate the HIV1 gp120-CD4 binding inhibitory potential of crude aqueous, methanol and petroleum ether extracts of Diospyros mespiliformis. The extracts were obtained by Soxhalet extraction. Phytochemical screening, gp120-CD4 binding inhibitory potential, and sub-acute toxicity tests were carried out using standard techniques. Total of six phyto-constituents were identified in the extracts; flavonoids, alkaloids and balsams in aqueous extract, while flavonoids, alkaloids, tannins, balsams, steroids and cardiac glycosides in methanol extract, and flavonoids, alkaloids in the petroleum ether extract. Mean percentage inhibitions of the extracts of Diospyros mespiliformis against HIV-1 gp120-CD4 binding were recorded at various concentrations of the extracts, with 10% inhibition was recorded at 125µg/ml in aqueous extract, 13% and 18% inhibitions were recorded at 250 and 125µg/ml in methanol extract respectively, while 3% inhibition was found in 125µg/ml of petroleum ether extract respectively. Physical signs of toxicity; weight changes, hair loss, diarrhea, and weakness of the body of the laboratory animals treated with 250 and 125mg/kg were observed. There was no significant difference (P&gt;0.05) in serum Aspartate Amino Transferase (AST) and Alkaline Phosphatase (ALP). There were no signs of Inflammation observed in the tissues of animals treated with all the extracts. It can be concluded that the methanol extracts possessed higher anti gp120-CD4 binding activity and extracts were non- toxic to the animals.

Acute and subacute oral toxicity assessment of dry encapsulated and non-encapsulated green coffee fruit extracts

The coffee fruit is a high source of bioactive compounds such as phenolic acids and methylxanthines, comprising chlorogenic acids and caffeine, respectively. Extract from this matrix may be used as supplement or active ingredient of functional foods, energy drinks, cosmetics or drugs. Safety of caffeine- and chlorogenic acid-rich encapsulated and non-encapsulated hydroethanolic extracts from green coffee fruit (GCFE) was assessed by acute and subacute toxicity tests. In the acute test, oral single dosage until 1000 mg/kg per body weight (bw) did not show any adverse effect on both female and male mice according to the Hippocratic screening and clinical parameters for a period of 14 days. While the oral median lethal dose of non-encapsulated GCFE was 5000 mg/kg bw/day, that of encapsulated GCFE was not detectable likely due to the delayed release of caffeine and other compounds from GCFE. Non-encapsulated GCFE displayed a stimulating effect at a dose of 1000 mg/kg bw/day after 30 min of oral administration, but not after 60 min. Daily consumption of encapsulated GCFE for 30 days showed no adverse effect in male rats even at the highest dose. Extrapolating this value of no-observed-adverse-effect level (1000 mg/kg bw/day) to human consumption, a human equivalent dose of 189 mg/kg bw/day or 11.34 g/day could be estimated for encapsulated GCFE considering a 60 kg adult body weight.