Genotoxicity and maternal-fetal safety of the dried extract of leaves of Azadirachta indica A. Juss (Meliaceae) in Wistar rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Azadirachta indica A. Juss (Meliaceae), popularly known as "neem", is used for the treatment of rheumatism, cancer, ulcers, diabetes, respiratory problems, among others. This species is present on six continents and contains more than 400 bioactive compounds. Practically all parts of the plant are used in the treatment of diseases. Although it is widely used, no study has evaluated the safety of this species throughout the gestational period in Wistar rats. AIM OF THE STUDY: To evaluate the genotoxicity and the effect of treatment with dried extract of leaves of Azadirachta indica on maternal toxicity and fetal development. MATERIALS AND METHODS: The dried extract of leaves of A. indica was obtained by spray drying after percolation of the plant material in 30% ethanol (w/w). The total flavonoids and rutin contents of the extract were determined by spectrophotometric method and HPLC-DAD, respectively. Pregnant Wistar rats (n = 40) were divided into four groups (n = 10/group): one control and three groups treated with dried extract of leaves of A. indica at doses of 300, 600 or 1200 mg/kg. Treatments were carried out from gestational day (GD) 0-20. During gestation, clinical signs of toxicity, weight gain, feed and water consumption of the dams were evaluated. On GD 21, rats were euthanized and cardiac blood was collected. Liver, kidneys, lung, heart, uterus, ovaries and bone marrow were collected. Reproductive performance parameters, histopathological analysis, biochemistry and genotoxicity were evaluated. Fetuses were evaluated for external morphology, skeletal and visceral changes. RESULTS: The total flavonoid content of the extract ranged from 2.64 to 3.01%, and the rutin content was 1.07%. There was no change in body mass gain, food and water consumption between the evaluated groups. There was also no difference between the groups in terms of biochemical parameters, reproductive performance, histopathological analysis of the mother's organs and genotoxicity. Supernumerary ossification sites of the sternum were observed, and other skeletal and visceral alterations were not significant. CONCLUSIONS: The treatment did not induce maternal toxicity, it was neither embryotoxic nor fetotoxic. The extract was not potentially genotoxic, and at a dose of 1200 mg/kg, it caused changes in the ossification of the sternum.

Tissue healing changes on wounds in rats after treatment with Hancornia speciosa latex in cream-gel formulation.

PURPOSE: Hancornia speciosa latex has shown pharmacological potential in wound healing processes due to its angiogenic, osteogenic, and anti-inflammatory activities. The aims of this study were to carry out a cream-gel formulation with 5, 10 and 25% of H. speciosa serum latex and to evaluate its potential to stimulate the skin regeneration in rats' wounds. METHODS: One hundred and twenty rats were divided into five groups: neutral control with saline (G1), cream-gel based on H. speciosa latex serum at 5% m/v (G2), cream-gel at 15% m/v (G3), cream-gel at 25% m/v (G4), and cream-gel (G5). The animals were euthanized at three, seven, 14 and 21 days after the injury induction, and some parameters were analyzed: wound contraction, necrosis, fibrin, polymorphonuclear and mononuclear infiltrates, fibroblast, angiogenesis, hemorrhage, and collagen. RESULTS: The therapeutic treatment with cream-gel at 15 and 25% is beneficial in the inflammatory phase of healing processes since it increased the angiogenesis and proliferation of mononuclear infiltrations in wounds. Regarding wound contraction, the treatment with cream-gel (5 and 15%) induced a higher rate of contraction in the proliferative phase. The 15% cream-gel formulation stimulated a greater production of collagen in the injured tissues. CONCLUSIONS: H. speciosa cream-gel is a low-cost herbal medicine which can aid in tissue repair.