Toxicity assessment of saline extract and lectin-rich fraction from Microgramma vacciniifolia rhizome.

Microgramma vacciniifolia is broadly used in folk medicine but safety information is unavailable. Therefore, we evaluated the toxicity of a saline extract and a lectin-rich fraction of M. vacciniifolia rhizome. The extract showed hemolytic activity on mice erythrocytes at 1000 µg/mL, whereas the fraction promoted hemolysis (8.57-26.15%) at all tested concentrations (10-1000 µg/mL). Acute toxicity test in mice indicated an LD50 of >5000 mg/kg. Hematological alterations and increased serum alkaline phosphatase level were observed in the treated animals. Transaminases and urea levels increased in the groups treated with the extract or fraction at 5000 mg/kg. Leukocyte infiltration was observed in the liver of extract-treated animals and in the liver and lungs of mice treated with the fraction. The kidneys of animals treated with the fraction at 5000 mg/kg presented hydropic degeneration. The extract and fraction did not induce oxidative stress in the liver and did not show genotoxicity, as examined by micronucleus and comet assays. In conclusion, the preparations were not lethal to mice but caused some signs of toxicity, mainly the fraction. The results indicated the need to evaluate the toxicity of M. vacciniifolia rhizome in other models and in chronic assays.

Assessment of 28-day oral toxicity and antipyretic activity of the saline extract from Pilosocereus gounellei (Cactaceae) stem in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Pilosocereus gounellei is a plant found in the Brazilian Caatinga and is popular due to its traditional uses in the treatment of inflammation. The present study was conducted to investigate the sub-acute toxicity of the saline extract from the stem of P. gounellei. AIM OF THE STUDY: To evaluate the 28-day oral toxicity (through behavioral, biochemical, hematological, and morphological analysis) and the antipyretic activity of the extract in mice. MATERIALS AND METHODS: A single oral dose (250, 500, and 1000 mg/kg) was administered daily over 28 consecutive days to male and female mice. Body weight, food and water intake, blood biochemical and hematological parameters, and urine composition were recorded. Histopathological examinations of the liver, kidney, spleen, lungs, and heart were performed and oxidative stress in the organs was evaluated by lipid peroxidation, superoxide dismutase (SOD), catalase (CAT), and nitrite analysis. The antipyretic effect of the 500 mg/kg dose was assessed using a yeast-induced pyrexia model. RESULTS: Oral administration of the extract over 28 days did not affect body weight gain, food and water consumption, body temperature, and hematological parameters in male and female mice. Blood glucose, total cholesterol, and triglyceride levels in male and female mice were reduced. Protein in the urine and histological alterations in both the liver and lungs were detected in male and female mice treated with the highest dose of the extract. SOD levels in the liver and the spleen increased significantly in both sexes, whereas lipid peroxidation decreased in the spleen of male mice. The extract also exerted an antipyretic effect after the first 60 min of the evaluation until the end of the observation duration (180 min). CONCLUSION: The saline extract from the stem of P. gounellei did not present significant toxic effects over 28 consecutive days and demonstrated antipyretic activity when administered orally. Moreover, the results suggest that the extract has potential hypoglycemic and hypolipidemic effects. Future studies are needed to investigate its pharmacological potential.

Saline extract of Pilosocereus gounellei stem has antinociceptive effect in mice without showing acute toxicity and altering motor coordination.

People broadly use medicinal plants although their safety and efficacy are often neglected. Several Cactaceae plants are used for medicinal purposes, but Pilosocereus gounellei (xique-xique) has been little studied for their pharmacological properties. In this study, a saline extract from Pilosocereus gounellei stem was evaluated for acute toxicity, effects on motor function, and antinociceptive activity in mice. Thin-layer chromatography and high-performance liquid chromatography revealed the presence of flavonoids and reducing sugars. No death of mice was noted with oral treatments at 2000 and 5000 mg/kg. Body weight gain, food intake, and water consumption were not affected with treatment at 2000 mg/kg. The number of segmented leukocytes was higher in the treated mice than in control, and reduced serum levels of cholesterol and triglycerides were detected after both extract treatments. No histological alterations in the liver, heart, lung, kidney, and spleen were detected. Open field and rotarod tests showed that the extract did not affect motor function and exploratory activity. Antinociceptive activity was detected in acetic acid-induced writhing, tail-immersion, and formalin tests, indicating interference with both non-inflammatory and inflammatory pain. In conclusion, the P. gounellei extract has antinociceptive activity in mice without showing toxicity and altering motor coordination.

Evaluation of acute toxicity, genotoxicity and inhibitory effect on acute inflammation of an ethanol extract of Morus alba L. (Moraceae) in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Morus alba L. (white mulberry) is used in traditional medicine worldwide, including Brazil. The leaves of this plant are used to treat inflammatory disorders. Universal interest in this plant necessitates studies on the toxicological safety and scientific substantiation of the medicinal properties of M. alba. In previous work, we investigated the acute toxicity of orally administered M. alba ethanol extract in mice. AIM OF THE STUDY: This work was designed to investigate the ethanol extract obtained from M. alba leaves for acute toxicity when intraperitoneally administered, in vivo genotoxicity, and potential to reduce acute inflammation. In order to further investigate the constituents of the extract, we also obtained the high-performance liquid chromatography (HPLC) fingerprint of the extract. MATERIALS AND METHODS: Phytochemical analysis by thin layer chromatography (TLC) was performed and the results were used to obtain the HPLC fingerprint. Acute toxicity of 300 and 2000mg/kg b.w. i.p. doses administered to mice for 14 days was evaluated. Genotoxicity was evaluated by counting the number of micronucleated polychromatic erythrocytes in the blood of mice that either received or did not receive the extract at 75, 150 and 300mg/kg b.w. per os. The anti-inflammatory effect of the same doses administered per os was investigated using the carrageenan air pouch model. RESULTS: The TLC analysis of the extract revealed the presence of a remarkable amount of flavonoids and cinnamic acids. The HPLC fingerprint showed the presence of one major peak corresponding to chlorogenic acid and two smaller peaks corresponding to flavonoids. In the toxicity assays, there were no deaths or deviations in behavior of treated mice as compared to the control at any dose. However, biochemical, hematological, and histological analyses showed that intraperitoneal injection caused several forms of damage to the mice, which were not observed in case of oral administration, studied in our previous work. Oral administration of the extract did not result in genotoxicity and considerably reduced (58.6-65.6% inhibition) leukocyte migration in all doses evaluated, in comparison with the negative control. CONCLUSIONS: The ethanol extract from M. alba leaves administered intraperitoneally possesses a greater degree of toxicity in mice when compared to per os administration. The extract was not genotoxic when ingested by mice and exhibited a highly inhibitory effect against acute inflammation, which is probably linked to the presence of chlorogenic acid and flavonoids in the composition. This work contributes to the determination of safety of the medicinal use of M. alba leaves.

Evaluation of Toxicity and Antimicrobial Activity of an Ethanolic Extract from Leaves of Morus alba L. (Moraceae).

This work evaluated an ethanolic extract from Morus alba leaves for toxicity to Artemia salina, oral toxicity to mice, and antimicrobial activity. Phytochemical analysis revealed the presence of coumarins, flavonoids, tannins, and triterpenes in the extract, which did not show toxicity to A. salina nauplii. No mortality and behavioral alterations were detected for mice treated with the extract (300 and 2000 mg/kg b.w.) for 14 days. However, animals that received the highest dose showed reduced MCV and MCHC as well as increased serum alkaline phosphatase activity. In treatments with the extract at both 300 and 2000 mg/kg, there was a reduction in number of leukocytes, with decrease in percentage of lymphocytes and increase in proportion of segmented cells. Histopathological analysis of organs from mice treated with the extract at 2000 mg/kg revealed turgidity of contorted tubules in kidneys, presence of leukocyte infiltration around the liver centrilobular vein, and high dispersion of the spleen white pulp. The extract showed antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans, Candida krusei, Candida tropicalis, and Aspergillus flavus. In conclusion, the extract contains antimicrobial agents and was not lethal for mice when ingested; however, its use requires caution because it promoted biochemical, hematological, and histopathological alterations.

Lectin from Crataeva tapia Bark Improves Tissue Damages and Plasma Hyperglycemia in Alloxan-Induced Diabetic Mice.

Crataeva tapia is a plant popularly used for diabetes treatment, in Brazil. Progressive decline in renal and hepatic functions has been described in patients with diabetes mellitus, and mortality rate is increased in patients with chronic liver and renal disease. This study aimed to evaluate whether Crataeva tapia bark lectin (CrataBL) improves hyperglycemia and renal and hepatic damage in diabetic mice. CrataBL was purified by ion exchange chromatography on CM-cellulose, and intraperitoneal administration of CrataBL to alloxan-induced diabetic mice at dose of 10 mg/Kg/day and 20 mg/Kg/day for 10 days significantly reduced serum glucose levels by 14.9% and 55.9%, respectively. Serum urea, creatinine, aspartate aminotransferase, and alanine aminotransferase were also significantly reduced after treatment with both doses of CrataBL. Furthermore, histological analysis of liver, kidney, and pancreas revealed an improvement in the tissue morphology upon treatment with CrataBL. The results suggest that CrataBL has a beneficial hypoglycemic activity and improves the renal and hepatic complications of diabetes. Therefore, this lectin may be a promising agent for the treatment of diabetes, and this might be the basis for its use in the folk medicine as an alternative treatment to manage diabetes-related complications such as hyperglycemia and tissue damage.

Effect of semisolid formulation of persea americana mill (avocado) oil on wound healing in rats.

The aim of this study was to evaluate the wound-healing activity of a semisolid formulation of avocado oil, SSFAO 50%, or avocado oil in natura, on incisional and excisional cutaneous wound models in Wistar rats. An additional objective was to quantify the fatty acids present in avocado oil. On the 14th day, a significant increase was observed in percentage wound contraction and reepithelialization in the groups treated with 50% SSFAO or avocado oil compared to the petroleum jelly control. Anti-inflammatory activity, increase in density of collagen, and tensile strength were observed inSSFAO 50% or avocado oil groups, when compared to control groups. The analysis of the components of avocado oil by gas chromatography detected the majority presence of oleic fatty acid (47.20%), followed by palmitic (23.66%), linoleic (13.46%) docosadienoic (8.88%), palmitoleic (3.58%), linolenic (1.60%), eicosenoic (1.29%), and myristic acids (0.33%). Our results show that avocado oil is a rich source of oleic acid and contains essential fatty acids. When used in natura or in pharmaceutical formulations for topical use, avocado oil can promote increased collagen synthesis and decreased numbers of inflammatory cells during the wound-healing process and may thus be considered a new option for treating skin wounds.

Antileishmanial activity of warifteine: a bisbenzylisoquinoline alkaloid isolated from Cissampelos sympodialis Eichl. (Menispermaceae).

Leishmania (L.) chagasi is the etiological agent of visceral leishmaniasis, an important endemic zoonosis in the American continent, as well as in many other countries in Asia, Africa, and Mediterranean Europe. The treatment is difficult due to the high toxicity of the available drugs, high costs, and emergence of resistance in the parasites. Therefore, there is an urgent need for new leishmanicidal agents. The bisbenzylisoquinoline alkaloids have been related to antibacterial, antiprotozoal, and antifungal activities. The aim of this study was to evaluate the growth inhibitory activity of warifteine (bisbenzylisoquinoline alkaloid) against L. chagasi promastigotes in axenic cultures and the occurrence of drug-induced ultrastructural changes in the parasite. This bisbenzylisoquinoline alkaloid was isolated from the leaves and roots of Cissampelos sympodialis Eichl. (Menispermaceae), a plant commonly used for the treatment of various diseases in Brazilian folk medicine. Using the purified warifteine, the 50% inhibitory concentration (IC50) was determined at 0.08 mg/mL after 72 h in culture, inducing significant changes in the parasite morphology, like aberrant multisepted forms and blebs in the plasma membrane. In conclusion, warifteine represents an attractive candidate for future pharmacological studies aiming new leishmanicidal drugs.

Effect of a Semisolid Formulation of Linum usitatissimum L. (Linseed) Oil on the Repair of Skin Wounds.

The purpose of this study was to investigate the effects of a semisolid formulation of linseed oil, SSFLO (1%, 5%, or 10%) or in natura linseed oil on skin wounds of rats. We used wound models, incisional and excisional, to evaluate, respectively, the contraction/reepithelialization of the wound and resistance to mechanical traction. The groups (n = 6) treated with SSFLO (1% or 5%) began the process of reepithelialization, to a significant extent (P < .05), on the sixth day, when compared to the petroleum jelly control group. On 14th day for the groups treated with SSFLO (1% or 5%), 100% reepithelialization was found, while in the petroleum jelly control group, this was only 33.33%. Our study showed that topical administration of SSFLO (1% or 5%) in excisional wounds allowed reepithelialization in 100% of treated animals. Therefore, a therapeutic potential of linseed oil, when used at low concentrations in the solid pharmaceutical formulations, is suggested for the process of dermal repair.

Antimicrobial Activity of Indigofera suffruticosa.

Various organic and aqueous extracts of leaves of Indigofera suffruticosa Mill (Fabaceae) obtained by infusion and maceration were screened for their antibacterial and antifungal activities. The extracts were tested against 5 different species of human pathogenic bacteria and 17 fungal strains by the agar-solid diffusion method. Most of the extracts were devoid of antifungal and antibacterial activities, except the aqueous extract of leaves of I. suffruticosa obtained by infusion, which showed strong inhibitory activity against the Gram-positive bacteria Staphylococcus aureus with a minimal inhibitory concentration (MIC) of 5000 microg ml(-1). The MIC values to dermatophyte strains were 2500 microg ml(-1) against Trichophyton rubrum (LM-09, LM-13) and Microsporum canis. This study suggests that aqueous extracts of leaves of I. suffruticosa obtained by infusion can be used in the treatment of skin diseases caused by dermatophytes.

Embryotoxicity in vitro with extract of Indigofera suffruticosa leaves.

Aqueous extract of leaves of Indigofera suffruticosa (AELIs) were studied for adverse effects in preimplantation mouse embryos. Two-cell mouse embryos were cultured for 94 h in human tubal fluid medium (HTF), and AELIs at a concentration of 5 or 10 mg/ml. On Day 4 of culture, morulae and blastocysts were collected for morphological analysis of blastomeres. We found that embryos exposed to the higher concentration of AELIs (10 mg/ml) did not develop and all embryos persisted at the two-cell stage. Those embryos exposed to the lower concentration (5 mg/ml) showed development until morula, blastocyst and hatched blastocyst stages that were similar to the controls. These results suggest that use of AELIs may be hazardous to humans who make use of it in folk medicine.