Chemotherapeutic and Safety Profile of a Fraction from Mimosa caesalpiniifolia Stem Bark.

Mimosa caesalpiniifolia (Fabaceae) is used by Brazilian people to treat hypertension, bronchitis, and skin infections. Herein, we evaluated the antiproliferative action of the dichloromethane fraction from M. caesalpiniifolia (DFMC) stem bark on murine tumor cells and the in vivo toxicogenetic profile. Initially, the cytotoxic activity of DFMC on primary cultures of Sarcoma 180 (S180) cells by Alamar Blue, trypan, and cytokinesis block micronucleus (CBMN) assays was assessed after 72 h of exposure, followed by the treatment of S180-bearing Swiss mice for 7 days, physiological investigations, and DNA/chromosomal damage. DFMC and betulinic acid revealed similar in vitro antiproliferative action on S180 cells and induced a reduction in viable cells, induced a reduction in viable cells and caused the emergence of bridges, buds, and morphological features of apoptosis and necrosis. S180-transplanted mice treated with DFMC (50 and 100 mg/kg/day), a betulinic acid-rich dichloromethane, showed for the first time in vivo tumor growth reduction (64.8 and 80.0%) and poorer peri- and intratumor quantities of vessels. Such antiproliferative action was associated with detectible side effects (loss of weight, reduction of spleen, lymphocytopenia, and neutrophilia and increasing of GOT and micronucleus in bone marrow), but preclinical general anticancer properties of the DFMC were not threatened by toxicological effects, and these biomedical discoveries validate the ethnopharmacological reputation of Mimosa species as emerging phytotherapy sources of lead molecules.

Triplaris gardneriana seeds extract exhibits in vitro anti-inflammatory properties in human neutrophils after oxidative treatment.

ETHNOPHARMACOLOGICAL RELEVANCE: Triplaris gardneriana Wedd. (Polygonaceae family) is a plant species from Brazilian semiarid region which is used in local traditional medicine for the treatment of inflammatory conditions such as hemorrhoids. AIM OF THE STUDY: In this study, the in vitro anti-inflammatory activity of different concentrations of ethanolic extract from T. gardneriana seeds (EETg) was performed in order to contribute to the knowledge about etnomedicinal use of this plant species. MATERIALS AND METHODS: The anti-inflammatory properties were evaluated through different approaches, such as in vitro protein anti-denaturation test, scavenging of reactive oxygen species (ROS) and myeloperoxidase (MPO) inhibition in human neutrophils activated by phorbol-12-myristate-13-acetate (PMA). Besides that, molecular docking was performed to provide new insights about the interaction between the major phenolic components in the plant extract and MPO. RESULTS: EETg was characterized showing a total phenol content of 153.5 ± 6.3 µg gallic acid equivalent/mg extract, ability to remove hydrogen peroxide (H2O2) in a concentration-dependent manner and had a spectroscopic profile which suggests the presence of hydroxyl groups. EETg was able to prevent protein denaturation ranging from 40.17 to 75.09%. The extract, at 10 and 20 µg/mL, was able to modulate neutrophils pro-inflammatory functions, such as degranulation and burst respiratory. In both assays, the EETg had anti-inflammatory effect comparable to nonsteroidal anti-inflammatory drugs. Among the main phenolic compounds of EETg, quercitrin, quercetin and catechin showed the highest binding affinity in silico to MPO. CONCLUSION: This study demonstrated, for the first time, that the anti-inflammatory effect of T. gardneriana seeds occurs due to its modulatory effect on human neutrophil degranulation and free-radical scavenging activity.

Risk assessment of the antifungal and insecticidal peptide Jaburetox and its parental protein the Jack bean (Canavalia ensiformis) urease.

Jaburetox (JBTX) is an insecticidal and antifungal peptide derived from jack bean (Canavalia ensiformis) urease that has been considered a candidate for developing genetically modified crops. This study aimed to perform the risk assessment of the peptide JBTX following the general recommendations of the two-tiered, weight-of-evidence approach proposed by International Life Sciences Institute. The urease of C. ensiformis (JBU) and its isoform JBURE IIb (the JBTX parental protein) were assessed. The history of safe use revealed no hazard reports for the studied proteins. The available information shows that JBTX possesses selective activity against insects and fungi. JBTX and JBU primary amino acids sequences showed no relevant similarity to toxic, antinutritional or allergenic proteins. Additionally, JBTX and JBU were susceptible to in vitro digestibility, and JBU was also susceptible to heat treatment. The results did not identify potential risks of adverse effects and reactions associated to JBTX. However, further allergen (e.g. serum IgE binding test) and toxicity (e.g. rodent toxicity tests) experimentation can be done to gather additional safety information on JBTX, and to meet regulatory inquiries for commercial approval of transgenic cultivars expressing this peptide.