Characteristics of biscuits containing different proportions of whole mung bean, wheat and rice brown flours.

A simplex-centroid design was used to evaluate the effect of proportions (0 to 100%) of whole wheat flour (WWF), whole mung bean flour (WMF) and whole rice flour (BRF) on the quality of cookies savory. The dough cut in the shape of a disks (37 mm × 2 mm) showed a 13% retraction in diameter when they contained exclusively WWF, it was less intense (5%) with BRF and null (0%) with WMF. The dough expansion occurred only vertically, the thicknesses of the WWF, WMF and BRF biscuits were 5.33, 2.79 and 2.13 times greater than the initial dough height, respectively. This characteristic showed high correlations with volumetric expansion (r = 0.95), specific volume (r = 0.90), hardness (r = 0.92), fracturability (r = 0.93) and spread factor (r = -0.96). BRF increased the value of the color difference of the biscuits up to 17.70, the effect of WMF was smaller (6.51). Only the radial expansion index correlated with the trough (r = 0.76), final viscosity (r = 0.79) and setback (r = 0.77) parameters. Considering the main desirable physical characteristics in savory biscuits, the highest global desirability obtained was for the proportion of 49% WWF, 24% WMF and 27% BRF.

Vitamin C and Phenolic Antioxidants of Jua (Ziziphus joazeiro M.) Pulp: A Rich Underexplored Brazilian Source of Ellagic Acid Recovered by Aqueous Ultrasound-Assisted Extraction.

Jua (juá in Portuguese) is an underexplored fruit from Brazil's northeast. This fruit is rich in antioxidant substances. However, there is a dearth of information about jua's bioactive potential. The present study evaluated two extraction methods (continuous agitation and ultrasound-assisted extraction-UAE) and employed three different solvents (water, ethanol, and acetone) to efficiently recover soluble phenolic compounds. Aqueous extracts obtained by UAE showed the highest total phenolic content (TPC) and antiradical activity. Besides being an eco-friendly procedure, extraction and/or solubility in an aqueous medium is also important for food application. Ellagic acids were the predominant phenolics (80%) found in aqueous jua pulp extract obtained by UAE, as determined by HPLC, while its TPC was 405.8 gallic acid equivalent per gram of fruit. This extract also exhibited a higher scavenging activity towards peroxyl radicals when compared to that of several other fruits from the literature, including grape, strawberry, cranberry, and walnuts, which are known references in terms of antioxidants. This is the first report that demonstrates jua pulp's potential as an alternative source of ellagic acid and other phenolic acids and flavonoids. Therefore, the outcome of this study provides new information that can be useful for functional food and nutraceutical industries.

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.

Anti-inflammatory mechanisms of fruits and by-products from Mauritia flexuosa, an exotic plant with functional benefits.

Mauritia flexuosa L., traditionally known as "buriti", exhibits chemoprotective properties including antioxidant, antithrombotic, and nutritional actions. The aim of this study was to examine the oral anti-inflammatory activity of epicarp, mesocarp and endocarp obtained from M. flexuosa fruits using in vivo models to verify physiological benefits. The anti-edematogenic action was determined using phlogistic agents to induce paw edema and peritonitis. Pro-inflammatory cytokines, cell migration of peritoneal cells, histological changes, and abdominal swelling induced by acetic acid were also investigated. Carrageenan-induced edema was found to be decreased in mice pre-treated with epicarp by 50.8%, 53.7% and 39.2% and mesocarp by 41.8%, 65.3% and 71.9% after 2, 3, and 4 hr stimuli, respectively. Edema initiated by specific agents such as compound 48/80, histamine, serotonin, and prostaglandin E2 were also reduced, and better outcomes were found against histamine-induced edema, as evidenced by the decline at all times analyzed (30-120 min) with both doses of water extract of mesocarp (500 or 1000 mg/kg). Mesocarp-pre-treatment reduced inflammatory tissue parameters such as number of peritoneal leukocytes and TNF-α levels, but only epicarp diminished abdominal pain. In summary, M. flexuosa fruits, especially mesocarp, exhibited oral physiological benefits and capacity to modify biochemical and cellular steps in the inflammatory cascade, indicating that dietary supplements containing these fruits may be combined with pharmacological tools to ameliorate or prevent diseases of inflammatory origin.

α-Phellandrene exhibits antinociceptive and tumor-reducing effects in a mouse model of oncologic pain.

Medical reports indicate a prevalence of pain in 50% of patients with cancer. In this context, this article investigated the antinociceptive activity of α-PHE using in vivo Sarcoma-180-induced hypernociception in mice to detail its mechanism(s) of antinociception under different conditions of treatment and tumor progression. Firsty, in vitro cytotoxic action was assessed using melanoma B-16/F-10 and S-180 murine cells and colorimetric MTT assays. For in vivo studies, acute treatment with α-PHE (6.25, 12.5, 25 and 50 mg/kg orally by gavage) was performed on the 1st day after S-180 inoculation. Subacute treatments were performed for 8 days starting on the next day (early protocol) or on day 8 after S-180 inoculation (late protocol). For all procedures, mechanical nociceptive evaluations were carried out by von Frey's technique in the subaxillary region peritumoral tissue (direct nociception) and in right legs of S-180-bearing mice (indirect nociception). α-PHE showed in vitro cytotoxic action on B-16/F-10 and S-180 (CI50 values of 436.0 and 217.9 µg/mL), inhibition of in vivo tumor growth (ranging from 47.3 to 82.7%) and decreased direct (peritumoral tissue in subaxillary region) and indirect (right leg) mechanical nociception in Sarcoma 180-bearing mice with early and advanced tumors under acute or subacute conditions of treatment especially at doses of 25 and 50 mg/kg. It improved serum levels of GSH as well as diminished systemic lipid peroxidation, blood cytokines (interleukin-1ß, -4, -6, and tumor necrosis factor-α). Such outcomes highlight α-PHE as a promising lead compound that combines antinociceptive and antineoplasic properties. Its structural simplicity make it a cost-effective alternative, justifying further mechanistic investigations and the development of pharmaceutical formulations. Moreover, the protocols developed and standardized here make it possible to use Sarcoma-180 hypernociception model to evaluate the capacity of new antinociceptive molecules under conditions of cancer-related allodynia.

Toxicological, chemopreventive, and cytotoxic potentialities of rare vegetal species and supporting findings for the Brazilian Unified Health System (SUS).

Caatinga flora which are found in a poor Brazilian region contain a substantial number of endemic taxa with biomedical and social importance for regional communities. This study examined the antioxidant and cytotoxic potential of 35 samples (extracts/fractions) from 12 Caatinga species and determined the antiproliferative and genotoxic action of dichloromethane fraction from Mimosa caesalpiniifolia stem bark (DC-Mca) on human and vegetal cells. Samples were assessed for chemopreventive ability, toxic effects on Artemia salina shrimp as well as cytotoxicity on tumor cell lines and erythrocytes. DC-Mca was also tested with respect to antiproliferative and genotoxic effects upon normal leukocytes and meristematic cells from A. cepa roots. Some extracts reduced free radical levels >95% and 7 samples exhibited a lethal concentration (LC) 50 < 100 µg/ml upon Artemia salina larvae. Eight samples displayed in vitro antitumor effects and three produced hemolysis. Data also demonstrated the pharmacological significance of bioactive extracts from Brazilian semi-arid region. There was no significant relationship between antioxidant, toxic, and antiproliferative activities, and that these properties were dependent upon the extractant. DC-Mca contained betulinic acid as main compound (approximately 70%), which showed higher (1) cytotoxic activity on cancer cell lines and dividing leukocytes, (2) reduced mitotic index of Allium cepa roots, and (3) induced cell cycle arrest and chromosomal bridges, thereby providing native promising sources for phytotherapy development. ABBREVIATIONS: ABTS: 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid); AcOH: ethyl acetate; ANOVA: analysis of variance; SUS: Brazilian Unified Health System; DC-Mca: dichloromethane fraction from Mimosa caesalpiniifolia stem bark; DMSO: dimethylsulfoxide; DPPH: 1,1-diphenyl-2-picrylhydrazyl; EC50: effective concentration 50%; EtOAc: ethyl acetate; FDA: Food and Drug Administration; GC-Qms: gas chromatograph quadrupole mass spectrometer; GI: genotoxic index; HCT-116: colon carcinoma line; HL-60: promyelocytic leukemia line; HPLC: high-performance liquid chromatography; HRAPCIMS: high resolution atmospheric pressure chemical ionization mass spectrum; IC50: inhibitory concentration 50%; LC50: lethal concentration 50%; MeOH = methyl alcohol; MI: mitotic index; MTT: 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide; MutI: mutagenic index; OVCAR-8 = ovarian carcinoma line; PBMC: peripheral blood mononuclear cells; RPMI-1640: Roswell Park Memorial Institute medium; SF-295: glioblastoma line; TEAC: trolox equivalent antioxidant capacity; TLC: thin-layer chromatography; Trolox: 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid.

Pharmacological and physicochemical profile of arylacetamides as tools against human cancers.

Arylacetamides are widely used as synthetic intermediates to obtain medicinal substances. This work evaluated in vitro antiproliferative activity of ten 2-Chloro-N-arylacetamides on human normal and cancer cells and detailed in vivo toxicological and anticancer investigations. Initially, cytotoxic colorimetric assays were performed using tumor lines, peripheral blood mononuclear cells (PBMC) and erythrocytes. Compounds 2, 3 and 4 were tested for acute toxicity (50, 150 and 300 mg/kg) and for subacute antitumoral capacity in HCT-116 colon carcinoma-bearing xenograft mice for 15 days at 25 mg/kg/day. Most compounds revealed cytotoxic action on tumor lines and PBMC, but activity on human erythrocytes were not detected. Molecular dipole moment, lipophilicity and electronic constant of aryl substituents had effects upon in vitro antiproliferative capacity. More common in vivo acute behavioral signals with compounds 2, 3 and 4 were muscle relaxation, reduction of spontaneous locomotor activity and number of entries in closed arms and increased number of falls andtime spent in open arms, suggesting diazepam-like anxiolytic properties. Decrease of grabbing strength and overall activity were common, but palpebral ptosis and deaths occurred at 300 mg/kg only. Compounds 2 and 3 reduced colon carcinoma growth (21.2 and 27.5%, respectively, p < 0.05) without causing apparent signals of organ-specific toxicity after subacute exposure. The structural chemical simplicity of arylacetamides make them cost-effective alternatives and justifies further improvements to enhance activity, selectivity and the development of pharmaceutical formulations.

Toxicological findings about an anticancer fraction with casearins described by traditional and alternative techniques as support to the Brazilian Unified Health System (SUS).

ETHNOPHARMACOLOGICAL RELEVANCE: Extracts, essential oils and molecules from Casearia sylvestris have popularly shown pharmacological actions against chronic diseases, as anxiety, inflammation, cancer and dyslipidemia. In the context of antitumoral therapy, we investigated in vitro, ex vivo and in vivo toxicological changes induced by a Fraction with Casearins (FC) and its component Casearin X isolated from C. sylvestris on animal and vegetal cells, and upon invertebrates and mammals. MATERIAL AND METHODS: Cytotoxicity was carried out using normal lines and absorbance and flow cytometry techniques, Artemia salina nauplii, Danio rerio embryos and meristematic cells from Allium cepa roots. Acute and 30 days-mice analysis were done by behavioral, hematological and histological investigations and DNA/chromosomal damages detected by alkaline Cometa and micronucleus assays. RESULTS: FC was cytotoxic against lung and fibroblasts cells and caused DNA breaks, loss of integrity and mitochondrial depolarization on ex vivo human leukocytes. It revealed 24 h-LC50 values of 48.8 and 36.7 µg/mL on A. salina nauplii and D. rerio embryos, reduced mitotic index of A. cepa roots, leading to cell cycle arrest at metaphase and anaphase and micronuclei. FC showed i.p. and oral LD50 values of 80.9 and 267.1 mg/kg body weight. Subacute i.p. injections induced loss of weight, swelling of hepatocytes and tubules, tubular and glomerular hemorrhage, microvesicular steatosis, lung inflammatory infiltration, augment of GPT, decrease of albumin, alkaline phosphatase, glucose, erythrocytes, and lymphocytes, and neutrophilia (p > 0.05). FC-treated animals at 10 mg/kg/day i.p. caused micronuclei in bone marrow and DNA strand breaks in peripheral leukocytes. CONCLUSIONS: This research postulated suggestive side effects after use of FC-related drugs, demonstrating FC as antiproliferative and genotoxic on mammal and meristematic cells, including human leukocytes, teratogenicity upon zebrafish embryos, myelosuppression, clastogenicity, and morphological and biochemical markers indicating liver as main target for FC-induced systemic toxicity.

Análises físico-químicas, fenólicos e antioxidantes de polpa de ciriguela (Spondias purpurea L. ) / Physical-chemical analysis, phenolics and antioxidant of ciriguela pulp (Spondias purpurea L. )

O Brasil é o maior produtor de frutas in natura, dentre os frutos produzidos está a Spondias purpúrea L. bastante consumida in natura tal como parte de outros produtos. Desta forma, objetivou-se elaborar a polpa de ciriguela e avaliar suas características físico-químicas, compostos fenólicos e antioxidantes. Os frutos foram despolpados e realizadas as análises físico-químicas (conforme IAL), os compostos fenólicos e antioxidantes foram determinados por espectrofotometria. A polpa apresentou pH de 3,5, acidez de 0,76% em ácido cítrico, 14,74ºBrix de sólidos solúveis, 28,76 mg/100g de vitamina C, 800 EAG mg/100 g de compostos fenólicos e 26,19 mg/ml de antioxidantes. Com os resultados obtidos, evidencia-se que a polpa de ciriguela tem benefícios não apenas nutricionais como é uma boa fonte de compostos fenólico e antioxidante.

Preclinical anticancer effectiveness of a fraction from Casearia sylvestris and its component Casearin X: in vivo and ex vivo methods and microscopy examinations.

ETHNOPHARMACOLOGICAL RELEVANCE: Casearia sylvestris (Salicaceae) is found in South America and presents antiulcerogenic, cytotoxic, antimicrobial, anti-inflammatory and antihypertensive activities. AIM OF THE STUDY: To assess the in vivo and ex vivo antitumor action of a fraction with casearins (FC) and its main component - Casearin X-isolated from C. sylvestris leaves. MATERIALS AND METHODS: Firstly, Sarcoma 180 bearing Swiss mice were treated with FC and Cas X for 7 days. Secondly, BALB/c nude animals received hollow fibers with colon carcinoma (HCT-116) or glioblastoma (SF-295) cells and were treated with FC for 4 days. On 5th day, proliferation was determined by MTT assay. RESULTS: FC 10 and 25mg/kg/day i.p. and 50mg/kg/day oral and Cas X 25mg/kg/day i.p. and 50mg/kg/day oral revealed tumor growth inhibition rates of 35.8, 86.2, 53.7, 90.0 and 65.5% and such tumors demonstrated rare mitoses and coagulation necrosis areas. Similarly, FC reduced multiplying of HCT-116 and SF-295 cells when evaluated by the Hollow Fiber Assay (2.5 and 5mg/kg/day i.p. and 25 and 50mg/kg/day oral), with cell growth inhibition rates ranging from 33.3 to 67.4% (p<0.05). Flow cytometry experiments revealed that FC reduced membrane integrity and induced DNA fragmentation and mitochondrial depolarization (p<0.05). CONCLUSIONS: FC and Cas X were efficient antitumor substances against murine and human cancer cells and caused reversible morphological changes in liver, kidneys and spleens, emphasizing clerodane diterpenes as an emerging class of anticancer molecules.

Biomedical properties and potentiality of Lippia microphylla Cham. and its essential oils.

Lippia microphylla Cham. (Verbenaceae) is an endemic underexploited Brazilian vegetal. This work reviewed the biological potentialities of Lippia microphylla, emphasizing the properties of essential oils (EOs) and analyzed scientific indicators about genus Lippia and L. microphylla. Databases from 1948 to the present were searched and a software (vantage point 7.1) associated with Derwent Innovation Index was used to identify the indicators of the genus Lippia, and biological activities and compounds in the L. macrophylla species. Ethnopharmacological records report use of L. microphylla leaves to treat gastrointestinal disorders, influenza, bronchitis, cough, nasal congestion, and sinusitis during vaporization, whose aromatic volatile oils are rich in monoterpenes, especially cineole, terpineol, and thymol. Other EOs have larvicidal activity on Aedes aegypti larvae, and antifungal, antibacterial and cytotoxic and antitumor action on human and murine cancer cells. Brazil is the country with more articles about Lippia species, but it deposited only 9 patents since 1993. Most of the publications about L. microphylla are concentrated in food and chemical sciences. This bioprospection helps to choice areas of interest for capital investment and to give support for Brazilian Institutions to establish cooperation and improve technological impact at the point of view of creation and innovation.

Assessing chemical constituents of Mimosa caesalpiniifolia stem bark: possible bioactive components accountable for the cytotoxic effect of M. caesalpiniifolia on human tumour cell lines.

Mimosa caesalpiniifolia is a native plant of the Brazilian northeast, and few studies have investigated its chemical composition and biological significance. This work describes the identification of the first chemical constituents in the ethanolic extract and fractions of M. caesalpiniifolia stem bark based on NMR, GC-qMS and HRMS analyses, as well as an assessment of their cytotoxic activity. GC-qMS analysis showed fatty acid derivatives, triterpenes and steroid substances and confirmed the identity of the chemical compounds isolated from the hexane fraction. Metabolite biodiversity in M. caesalpiniifolia stem bark revealed the differentiated accumulation of pentacyclic triterpenic acids, with a high content of betulinic acid and minor amounts of 3-oxo and 3ß-acetoxy derivatives. Bioactive analysis based on total phenolic and flavonoid content showed a high amount of these compounds in the ethanolic extract, and ESI-(-)-LTQ-Orbitrap-MS identified caffeoyl hexose at high intensity, as well as the presence of phenolic acids and flavonoids. Furthermore, the evaluation of the ethanolic extract and fractions, including betulinic acid, against colon (HCT-116), ovarian (OVCAR-8) and glioblastoma (SF-295) tumour cell lines showed that the crude extract, hexane and dichloromethane fractions possessed moderate to high inhibitory activity, which may be related to the abundance of betulinic acid. The phytochemical and biological study of M. caesalpiniifolia stem bark thus revealed a new alternative source of antitumour compounds, possibly made effective by the presence of betulinic acid and by chemical co-synergism with other compounds.

Cytotoxic and toxicological effects of phthalimide derivatives on tumor and normal murine cells.

Eleven phthalimide derivatives were evaluated with regards to their antiproliferative activity on tumor and normal cells and possible toxic effects. Cytotoxic analyses were performed against murine tumors (Sarcoma 180 and B-16/F-10 cells) and peripheral blood mononuclear cells (PBMC) using MTT and Alamar Blue assays. Following, the investigation of cytotoxicity was executed by flow cytometry analysis and antitumoral and toxicological potential by in vivo techniques. The molecules 3b, 3c, 4 and 5 revealed in vitro cytotoxicity against Sarcoma 180, B-16/F-10 and PBMC. Since compound 4 was the most effective derivative, it was chosen to detail the mechanism of action after 24, 48 and 72 h exposure (22.5 and 45 µM). Sarcoma 180 cells treated with compound 4 showed membrane disruption, DNA fragmentation and mitochondrial depolarization in a time- and dose-dependent way. Compounds 3c, 4 and 5 (50 mg/kg/day) did not inhibit in vivo tumor growth. Compound 4-treated animals exhibited an increase in total leukocytes, lymphocytes and spleen relative weight, a decreasing in neutrophils and hyperplasia of spleen white pulp. Treated animals presented reversible histological changes. Molecule 4 had in vitro antiproliferative action possibly triggered by apoptosis, reversible toxic effects on kidneys, spleen and livers and exhibited immunostimulant properties that can be explored to attack neoplasic cells.

Teor de fenóis e flavonoides, atividades antioxidante e citotóxica dasfolhas, frutos, cascas dos frutos e sementes de Piptadenia moniliformisBenth (Leguminosae – Mimosoideae) / Phenols, flavonoids and antioxidant and cytotoxic activity of leaves, fruits, peel of fruits and seeds of Piptadenia moniliformis Benth (Leguminosae - Mimosoideae)

The total phenol and flavonoid content, in addition to the antioxidant and cytotoxic activities, of extracts and fractions of Piptadenia moniliformis was determined. This honey plant species is commonly known as "catanduba" or "angico de bezerro". The aqueous fraction derived from the peels of the fruits exhibited the highest antioxidant activity, remaining comparable to the standard value, and there was a general correlation between this activity and the phenol and flavonoid content. The antioxidant potential of this species provides a basis for future developments in herbal medicines and cosmetics. Only the hydro alcoholic extract, the dichloromethane fractions and the ethyl acetate fractions showed moderate cytotoxicity.

Foram determinados o teor de fenóis e flavonoides, as atividades antioxidante e citotóxica dos extratos e frações de Piptadenia moniliformis. Essa é uma espécie melitófila comumente conhecida como "catanduba" ou "angico de bezerro". Das frações testadas, a fração aquosa das cascas dos frutos apresentou a maior atividade antioxidante, com valor comparável ao padrão, e no geral houve correlação do teor de fenóis e flavonoides com essa atividade. Os resultados do potencial antioxidante para essa espécie fornecem subsídios para futuros trabalhos que visem o desenvolvimento de fitoterápicos e cosméticos. Quanto à atividade citotóxica apenas o extrato hidroalcoólico e as frações diclorometano e acetato de etila demonstraram moderada citotoxicidade.