Acute oral toxicity and genotoxicity assessment of the essential oil from Croton pulegiodorus Baill (Euphorbiaceae) leaves in mice.

Essential oils obtained from Croton pulegiodorus leaf are renowned for their biological activities; however, data on their toxicity are limited. Therefore, this study aimed to evaluate the acute oral toxicity and genotoxicity of a C. pulegiodorus leaf essential oil (CPLEO). Chemical characterization of CPLEO was conducted by gas chromatography coupled to mass spectrometry (GC-MS). In vitro assay was performed to verify the hemolytic capacity of the oil in mice erythrocytes. Next, an acute oral toxicity study was conducted on female mice at CPLEO doses of 2000, 1000, 500, 250, 100, and 50 mg/kg. Hematological, biochemical, and histopathological markers were assessed in mice from groups were no death occurred. Relative consumption of water and food and the weight of animals and their organs were also recorded. Finally, a genotoxicity analysis was performed using the micronucleus and comet assays. The extraction yield of CPLEO was 1.149% and its major compounds were ascaridole (23.18%), eucalyptol (17.20%), camphor (14.20%), p-cymene (7.91%), α-terpineol (4.69%), and isobornyl acetate (4.57%). CPLEO showed a hemolytic effect only at high concentrations (185.5-1000 mg/mL). It showed acute oral toxicity in mice with a LD50 of 460.42 mg/kg. CPLEO (50-250 mg/kg) caused some significant changes in hematological and biochemical parameters. Histopathological evaluation indicated alterations in liver and kidneys but transaminases, urea and creatinine levels remained like the negative control. CPLEO administration impaired weight gain and reduced water and food consumption. Finally, it was not genotoxic by both comet and micronucleus tests. The results highlight the need for attention when choosing doses to evaluate the bioactivities of CPLEO.

Assessment of acute toxicity, genotoxicity, and anti-inflammatory activity of SteLL, a lectin from Schinus terebinthifolia Raddi. Leaves, in mice.

ETHNOPHARMACOLOGY RELEVANCE: Schinus terebinthifolia Raddi (Anacardiaceae), known as Brazilian pepper tree, stands out as a medicinal plant widely used in traditional medicine. The leaves are popularly used as anti-inflammatory agent and to relieve inflammatory conditions such as bronchitis, ulcers, and wounds, for example. AIM OF THE STUDY: The present study evaluated the acute toxicity, genotoxicity, and anti-inflammatory activity of S. terebinthifolia leaf lectin (SteLL) in mice (Mus musculus). MATERIALS AND METHODS: In the acute toxicity assay, the animals were treated intraperitoneally (i.p.) or orally (per os) with a single dose of 100 mg/kg. Genotoxicity was assessed by the comet and micronucleus assays. Carrageenan-induced peritonitis and paw edema models were used to evaluate the anti-inflammatory effects of SteLL (1, 5 and 10 mg/kg, i.p.). RESULTS: No animal died and no signs of intoxication or histopathological damage were observed in the acute toxicity assay. Genotoxic effect was not detected. In peritonitis assay, SteLL reduced in 56-69% leukocyte migration to the peritoneal cavity; neutrophil count decreased by 25-32%, while mononuclear cell count increased by 67-74%. SteLL promoted a notable reduction of paw edema after 4 h (61.1-63.4%). Morphometric analysis showed that SteLL also decreased the thickness of epidermal edema (30.2-40.7%). Furthermore, SteLL decreased MPO activity, plasma leakage, NO release, and modulated cytokines in both peritoneal fluid and paw homogenate. CONCLUSION: SteLL did not induce acute toxicity or genotoxicity in mice and stands out as a promising candidate in the development of new phytopharmaceuticals with anti-inflammatory action.

The lectin from Schinus terebinthifolia leaf (SteLL) reduces immobility of mice on the tail suspension test dependent on the monoaminergic and nitric oxide signaling.

Depression underlies a common psychiatric disorder that has been rising in the diagnosis of long-term disabilities worldwide. Natural products have been studied as an antidepressant and anxiolytic agents aiming to make available new options for the daily basis treatment of those psychological disorders. SteLL is a lectin extracted from Schinus terebinthifolia leaf that has been revealed as an antimicrobial, immunomodulatory, antitumor, and antinociceptive agent. Nonetheless, the efficacy of SteLL in the treatment of depression has not yet been explored. In view of this, the aim of this study was to investigate the effect of SteLL in an acute protocol for symptoms of depression using the tail suspension test (TST) to assess despair. Administration of SteLL (1, 2 e 4 mg/kg) significantly diminished the immobility time of animals in the TST and this anti-immobility action was dependent on the carbohydrate-recognizing domain (CRD) since the prior incubation with casein (an inhibitor of SteLL carbohydrate-binding property) blocked the effect. SteLL effect was also reversed by pre-treatment with pharmacological antagonists of α2-adrenoceptor, 5-HT2A/2C serotonin receptor, and D1 dopamine receptor as well as by a selective inhibitor of iNOS (aminoguanidine). l-arginine, a precursor of NO, potentiated SteLL anti-immobility effect. In a subacute evaluation, the anti-immobility effect of SteLL persisted after seven days of treatment. Our findings suggest a role of SteLL in the modulation of depression mostly through monoaminergic and nitric oxide signaling.