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Safer analgesic drugs remain a hard challenge because of cardiovascular and/or gastrointestinal toxicity, mainly. So, this study evaluated in vivo the antiproliferative actions of a fraction with casearins (FC) from Casearia sylvestris leaves against human colorectal carcinomas and antihyperalgesic effects on inflammatory- or opiate-based pain relief and oncologic pain in Sarcoma 180 (S180)-bearing mice. Moreover, docking investigations evaluated the binding among Casearin X and NMDA(N-methyl-D-aspartate)-type glutamate receptors. HCT-116 colorectal carcinoma-xenografted mice were treated with FC for 15 days. Antinociceptive assays included chemically induced algesia and investigated mechanisms by pharmacological blockade. Intraplantar region S180-bearing animals received a single dose of FC and were examined for mechanical allodynia and behavior alterations. AutoDock Vina determined molecular interactions among Cas X and NMDA receptor subunits. FC reduced tumor growth at i.p. (5 and 10 mg/kg) and oral (25 mg/kg/day) doses (31.12-39.27%). FC reduced abdominal pain, as confirmed by formalin and glutamate protocols, whose antinociception activity was blocked by naloxone and L-NAME (neurogenic phase) and naloxone, atropine, and flumazenil (inflammatory phase). Meanwhile, glibenclamide potentiated the FC analgesic effects. FC increased the paw withdrawal threshold without producing changes in exploratory parameters or motor coordination. Cas X generated a more stable complex with active sites of the NMDA receptor GluN2B subunits. FC is a promising antitumor agent against colorectal carcinomas, has peripheral analgesic effects by desensitizing secondary afferent neurons, and inhibits glutamate release from presynaptic neurons and/or their action on cognate receptors. These findings emphasize the use of clerodane diterpenes against cancer-related pain conditions.
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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 (37â mm × 2â 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.
Assuntos
Fabaceae , Oryza , Vigna , Farinha , Triticum , DurezaRESUMO
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.
Assuntos
Antioxidantes , Ziziphus , Antioxidantes/análise , Antioxidantes/farmacologia , Ácido Ascórbico , Brasil , Ácido Elágico , Extratos Vegetais , Polifenóis/análise , ÁguaRESUMO
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.
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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.
Assuntos
Analgésicos/farmacologia , Antineoplásicos/farmacologia , Dor do Câncer/tratamento farmacológico , Monoterpenos Cicloexânicos/farmacologia , Melanoma Experimental/tratamento farmacológico , Sarcoma 180/tratamento farmacológico , Animais , Dor do Câncer/etiologia , Dor do Câncer/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Citocinas/metabolismo , Feminino , Glutationa/metabolismo , Mediadores da Inflamação/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Camundongos , Limiar da Dor , Sarcoma 180/complicações , Sarcoma 180/metabolismo , Sarcoma 180/patologia , Carga Tumoral/efeitos dos fármacos , Células Tumorais CultivadasRESUMO
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.
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Anti-Inflamatórios/farmacologia , Arecaceae/química , Edema/tratamento farmacológico , Inflamação/tratamento farmacológico , Leucócitos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/química , Edema/induzido quimicamente , Feminino , Frutas/química , Inflamação/induzido quimicamente , Inflamação/imunologia , Camundongos , Extratos Vegetais/química , Fator de Necrose Tumoral alfa/metabolismoRESUMO
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.
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Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Plantas Medicinais/química , Antineoplásicos Fitogênicos/química , Antioxidantes/química , Brasil , Ciclo Celular/efeitos dos fármacos , Células Cultivadas , Citotoxinas/química , Citotoxinas/farmacologia , Dano ao DNA , Ecossistema , Ecotoxicologia , Humanos , Cloreto de Metileno/química , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Plantas Medicinais/classificação , Plantas Medicinais/toxicidadeRESUMO
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⯵g/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 267.1â¯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 (pâ¯>â¯0.05). FC-treated animals at 10â¯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.
Assuntos
Antineoplásicos Fitogênicos/toxicidade , Casearia , Diterpenos Clerodânicos/toxicidade , Animais , Brasil , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cricetulus , Embrião não Mamífero/efeitos dos fármacos , Feminino , Fibroblastos/efeitos dos fármacos , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Medicina Tradicional , Meristema/citologia , Camundongos , Cebolas , Testes de Toxicidade , Peixe-ZebraRESUMO
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.
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Anacardiaceae/química , Antioxidantes/análise , Compostos Fenólicos/análise , Fenômenos Químicos , Compostos FitoquímicosRESUMO
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.(AU)