Evaluation of the Antioxidant and Anti-Inflammatory Activities and Acute Toxicity of Caco Seed (Chrysobalanus icaco L.) in Murine Models.

Chysobalanus icaco L. (C. icaco) is a plant that is native to tropical America and Africa. It is also found in the southeast region of Mexico, where it is used as food and to treat certain diseases. This study aimed to carry out a phytochemical analysis of an aqueous extract of C. icaco seed (AECS), including its total phenol content (TPC), total flavonoid content (TFC), and condensed tannins (CT). It also aimed to examine the antioxidant and metal-ion-reducing potential of the AECS in vitro, as well as its toxicity and anti-inflammatory effect in mice. Antioxidant and metal-ion-reducing potential was examined by inhibiting DPPH, ABTS, and FRAP. The acute toxicity test involved a single administration of different doses of the AECS (0.5, 1, and 2 g/kg body weight). Finally, a single administration at doses of 150, 300, and 600 mg/kg of the AECS was used in the carrageenan-induced model of subplantar acute edema. The results showed that the AECS contained 124.14 ± 0.32 mg GAE, 1.65 ± 0.02 mg EQ, and 0.910 ± 0.01 mg of catechin equivalents/g dried extract (mg EC/g de extract) for TPC, TFC and CT, respectively. In the antioxidant potential assays, the values of the median inhibition concentration (IC50) of the AECS were determined with DPPH (0.050 mg/mL), ABTS (0.074 mg/mL), and FRAP (0.49 mg/mL). Acute toxicity testing of the AECS revealed no lethality, with a median lethal dose (LD50) value of >2 g/kg by the intragastric route. Finally, for inhibition of acute edema, the AECS decreased inflammation by 55%, similar to indomethacin (59%, p > 0.05). These results demonstrated that C. icaco seed could be considered a source of bioactive molecules for therapeutic purposes due to its antioxidant potential and anti-inflammatory activity derived from TPC, with no lethal effect from a single intragastric administration in mice.

Chemopreventive Effect of Cooked Chickpea on Colon Carcinogenesis Evolution in AOM/DSS-Induced Balb/c Mice.

Chickpeas are one of the most widely consumed legumes worldwide and they might prevent diseases such as cancer. Therefore, this study evaluates the chemopreventive effect of chickpea (Cicer arietinum L.) on the evolution of colon carcinogenesis induced with azoxymethane (AOM) and dextran sodium sulfate (DSS) in a mice model at 1, 7, and 14 weeks after induction. Accordingly, the expression of biomarkers-such as argyrophilic nucleolar organizing regions (AgNOR), cell proliferation nuclear antigen (PCNA), ß-catenin, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2)-was assessed in the colon of BALB/c mice fed diets supplemented with 10 and 20% cooked chickpea (CC). The results showed that a 20% CC diet significantly reduced tumors and biomarkers of proliferation and inflammation in AOM/DSS-induced colon cancer mice. Moreover, body weight loss decreased and the disease activity index (DAI) was lower than the positive control. Lastly, tumor reduction was more evident at week 7 in the groups fed a 20% CC diet. In conclusion, both diets (10% and 20% CC) exert a chemopreventive effect.

Sociodemographic inequalities in cardiovascular risk factors among adolescents from indigenous areas in Chiapas, Mexico / Desigualdades sociodemográficas como factores de riesgo cardiovascular para adolescentes de zonas indígenas de Chiapas, México / Desigualdades sociodemográficas como fatores de risco cardiovascular para adolescentes de áreas indígenas de Chiapas, México

Abstract: This study was aimed to determine the prevalence of cardiovascular risk factors among different sociodemographic groups of adolescents from indigenous communities in Chiapas, Mexico. A cross-sectional prevalence study was performed in urban and rural communities in the Tzotzil-Tzeltal and Selva regions of Chiapas. A sample of 253 adolescents was studied, of whom 48% were girls and 52% were boys. A descriptive analysis of quantitative variables was performed using measures of central tendency and dispersion. The prevalence of cardiovascular risk factors stratified by sex, geographical area, years of schooling, and ethnicity of the mothers was estimated. The prevalence of cardiovascular risk factors was analyzed in relation to the sociodemographic characteristics of the study population. Low HDL-c (51%) was the predominant cardiovascular risk factor. Girls had a higher prevalence of abdominal obesity, hypertriglyceridemia, and borderline total cholesterol than boys. High diastolic blood pressure was more prevalent in boys. Adolescents from urban areas had a higher prevalence of overweight/obesity and insulin resistance than adolescents from rural areas. The prevalence of overweight/obesity and abdominal obesity was higher in adolescents whose mothers had ≥ 7 years of schooling compared with adolescents with less educated mothers. Differences by maternal ethnicity also influenced the prevalence of insulin resistance. Among the main findings, this study associated sociodemographic and geographical inequalities with cardiovascular risk factors. Promoting a healthy lifestyle for this young population is absolutely necessary to prevent cardiovascular diseases in adulthood.

Resumen: El objetivo de este estudio fue estimar la prevalencia de los factores de riesgo cardiovascular entre diferentes grupos sociodemográficos de adolescentes de comunidades indígenas de Chiapas, México. Se realizó un estudio transversal de prevalencia en comunidades urbanas y rurales de las regiones Tzotzil-Tzeltal y Selva, en Chiapas. Participó una muestra de 253 adolescentes, en la cual el 48% eran niñas y el 52% niños. Se realizó un análisis descriptivo de las variables cuantitativas utilizando medidas de tendencia central y dispersión. Se estimó la prevalencia de los factores de riesgo cardiovascular, estratificados por sexo, área geográfica, nivel de estudios y etnia de las madres. Se analizó la prevalencia de los factores de riesgo cardiovascular con relación a las características sociodemográficas de la población estudiada. El HDL-c bajo (51%) fue el factor de riesgo cardiovascular predominante. Se observó una mayor prevalencia de obesidad abdominal, hipertrigliceridemia y colesterol total en las niñas que en los niños. La alta presión arterial diastólica prevaleció en los niños. Los adolescentes del área urbana tuvieron una mayor prevalencia de sobrepeso/obesidad y resistencia a la insulina que los del área rural. La prevalencia de sobrepeso/obesidad y obesidad abdominal fue mayor en los adolescentes cuyas madres tenían nivel de estudios ≥ 7 años que aquellos cuyas madres tenían bajo nivel de estudios. Las diferencias en la etnicidad materna también influyeron en la prevalencia de resistencia a la insulina. Entre las principales conclusiones de este estudio, se destacan las desigualdades sociodemográficas y geográficas entre los factores de riesgo cardiovascular. La promoción de un estilo de vida saludable entre la población joven es lo indicado para prevenir las enfermedades cardiovasculares en la edad adulta.

Resumo: O objetivo deste estudo foi determinar a prevalência de fatores de risco cardiovascular entre diferentes grupos sociodemográficos de adolescentes de comunidades indígenas em Chiapas, México. Foi realizado um estudo transversal de prevalência em comunidades urbanas e rurais das regiões de Tzotzil-Tzeltal e Selva de Chiapas. Foi estudada uma amostra de 253 adolescentes, sendo 48% meninas e 52% meninos. Foi realizada uma análise descritiva das variáveis quantitativas por meio de medidas de tendência central e dispersão. Foram estimadas as prevalências de fatores de risco cardiovascular, estratificadas por sexo, área geográfica, escolaridade e etnia das mães. A prevalência dos fatores de risco cardiovascular foi analisada em relação às características sociodemográficas da população estudada. O HDL-c baixo (51%) foi o fator de risco cardiovascular predominante. Prevalências mais elevadas de obesidade abdominal, hipertrigliceridemia e colesterol total limítrofe foram mais observadas em meninas do que em meninos. A pressão arterial diastólica elevada prevaleceu nos meninos. Adolescentes da área urbana apresentaram prevalências de sobrepeso/obesidade e resistência à insulina maiores do que os da área rural. A prevalência de sobrepeso/obesidade e obesidade abdominal foi maior nos adolescentes cujas mães possuíam escolaridade ≥ 7 anos do que naqueles indivíduos cujas mães tinham baixa escolaridade. As diferenças de etnia das mães também foram observadas na prevalência de resistência à insulina. Dentre as principais conclusões, foram encontradas, neste estudo, desigualdades sociodemográficas e geográficas entre fatores de risco cardiovascular. Promover estilos de vida saudáveis entre a população jovem é o ideal para prevenir doenças cardiovasculares na vida adulta.

Proteomic Analysis Reveals Differential Expression Profiles in Idiopathic Pulmonary Fibrosis Cell Lines.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, irreversible lung disorder of unknown cause. This disease is characterized by profibrotic activation of resident pulmonary fibroblasts resulting in aberrant deposition of extracellular matrix (ECM) proteins. However, although much is known about the pathophysiology of IPF, the cellular and molecular processes that occur and allow aberrant fibroblast activation remain an unmet need. To explore the differentially expressed proteins (DEPs) associated with aberrant activation of these fibroblasts, we used the IPF lung fibroblast cell lines LL97A (IPF-1) and LL29 (IPF-2), compared to the normal lung fibroblast cell line CCD19Lu (NL-1). Protein samples were quantified and identified using a label-free quantitative proteomic analysis approach by liquid chromatography-tandem mass spectrometry (LC-MS/MS). DEPs were identified after pairwise comparison, including all experimental groups. Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Protein-Protein Interaction (PPI) network construction were used to interpret the proteomic data. Eighty proteins expressed exclusively in the IPF-1 and IPF-2 clusters were identified. In addition, 19 proteins were identified up-regulated in IPF-1 and 10 in IPF-2; 10 proteins were down-regulated in IPF-1 and 2 in IPF-2 when compared to the NL-1 proteome. Using the search tool for retrieval of interacting genes/proteins (STRING) software, a PPI network was constructed between the DEPs and the 80 proteins expressed exclusively in the IPF-2 and IPF-1 clusters, containing 115 nodes and 136 edges. The 10 hub proteins present in the IPP network were identified using the CytoHubba plugin of the Cytoscape software. GO and KEGG pathway analyses showed that the hub proteins were mainly related to cell adhesion, integrin binding, and hematopoietic cell lineage. Our results provide relevant information on DEPs present in IPF lung fibroblast cell lines when compared to the normal lung fibroblast cell line that could play a key role during IPF pathogenesis.

Quercetin Regulates Key Components of the Cellular Microenvironment during Early Hepatocarcinogenesis.

Hepatocellular carcinoma (HCC) is a health problem worldwide due to its high mortality rate, and the tumor microenvironment (TME) plays a key role in the HCC progression. The current ineffective therapies to fight the disease still warrant the development of preventive strategies. Quercetin has been shown to have different antitumor activities; however, its effect on TME components in preneoplastic lesions has not been fully investigated yet. Here, we aimed to evaluate the effect of quercetin (10 mg/kg) on TME components during the early stages of HCC progression induced in the rat. Histopathological and immunohistochemical analyses showed that quercetin decreases the size of preneoplastic lesions, glycogen and collagen accumulation, the expression of cancer stem cells and myofibroblasts markers, and that of the transporter ATP binding cassette subfamily C member 3 (ABCC3), a marker of HCC progression and multi-drug resistance. Our results strongly suggest that quercetin has the capability to reduce key components of TME, as well as the expression of ABCC3. Thus, quercetin can be an alternative treatment for inhibiting the growth of early HCC tumors.

Modification of In Vitro and In Vivo Antioxidant Activity by Consumption of Cooked Chickpea in a Colon Cancer Model.

Chickpea has been classified as a nutraceutical food due to its phytochemical compounds, showing antioxidant, anti-inflammatory, and anticancer activity. To investigate this, we evaluated the effect of cooking on the nutritional and non-nutritional composition and the in vitro and in vivo antioxidant activity of chickpea seed. The latter was determined by the variation in the concentration of nitric oxide (NO), oxidized carbonyl groups (CO), malondialdehyde (MDA), and the expression of 4-hydroxy-2-nonenal (4-HNE) in the colon of male BALB/c mice fed with a standard diet with 10 and 20% cooked chickpea (CC). We induced colon cancer in mice by administering azoxymethane/dextran sulfate sodium (AOM/DSS); for the evaluation, these were sacrificed 1, 7, and 14 weeks after the induction. Results show that cooking does not significantly modify (p < 0.05) nutritional compounds; however, it decreases the concentration of non-nutritional ones and, consequently, in vitro antioxidant activity. The in vivo evaluation showed that animals administered with AOM/DSS presented higher concentrations of NO, CO, MDA, and 4-HNE than those in animals without AOM/DSS administration. However, in the three evaluated times, these markers were significantly reduced (p < 0.05) with CC consumption. The best effect on the oxidation markers was with the 20% CC diet, demonstrating the antioxidant potential of CC.

Protective Effect of Chickpea Protein Hydrolysates on Colon Carcinogenesis Associated With a Hypercaloric Diet.

OBJECTIVE: Colon cancer occupies the third place in incidence worldwide; eating habits, in particular, consumption of hypercaloric diets, are relevant in its etiopathogenesis. On the other hand, foods can also modulate carcinogenesis: for example, proteins, which when hydrolyzed release peptides with biological activities, and legumes, especially, chickpea, represent a good source of hydrolysates. The objective of this work was to verify the inhibitory effect of chickpea hydrolyzed protein on azoxymethane (AOM)-induced carcinogenesis in mice fed a hypercaloric diet. METHODS: We hydrolyzed chickpea protein by pepsin, pancreatin, and a combined pepsin-pancreatin system, to test its anticarcinogenic and hypercaloric activity in mice that had consumed a hypercaloric diet or a normal diet but were injected with azoxymethane (AOM). RESULTS: A concentrate (70% proteins) was obtained from chickpea seeds (18.5% proteins), and extensive hydrolysates were obtained at 15 minutes, in all tested enzyme systems. The greatest activity was evidenced in the hydrolysates obtained with pepsin-pancreatin at 90 minutes. Animals that consumed the hypercaloric diet had a higher concentration of cholesterol and a higher atherogenic index, which were significantly reduced with the administration of chickpea protein hydrolysates with a dose-response effect (10, 20, or 30 mg/kg), whereas no effect was observed in animals that consumed the normal diet. In animals given AOM, aberrant crypts were observed, at a higher rate in animals that consumed the hypercaloric diet; with the consumption of hydrolysates by the animals that consumed either diet, the number of aberrant crypts was reduced with the 3 doses tested, and the effect was better in those animals fed the hypercaloric diet. The best effect in all tests was with 30 mg/kg body weight. CONCLUSION: The consumption of chickpea protein hydrolysates might confer a protective effect against colon carcinogenesis.

Quercetin Reverses Rat Liver Preneoplastic Lesions Induced by Chemical Carcinogenesis.

Quercetin is a flavonoid widely studied as a chemopreventive agent in different types of cancer. Previously, we reported that quercetin has a chemopreventive effect on the liver-induced preneoplastic lesions in rats. Here, we evaluated if quercetin was able not only to prevent but also to reverse rat liver preneoplastic lesions. We used the modified resistant hepatocyte model (MRHM) to evaluate this possibility. Treatment with quercetin was used 15 days after the induction of preneoplastic lesions. We found that quercetin reverses the number of preneoplastic lesions and their areas. Our results showed that quercetin downregulates the expression of EGFR and modulates this signaling pathway in spite of the activated status of EGFR as detected by the upregulation of this receptor, with respect to that observed in control rats. Besides, quercetin affects the phosphorylation status of Src-1, STAT5, and Sp-1. The better status of the liver after the treatment with quercetin could also be confirmed by the recovery in the expression of IGF-1. In conclusion, we suggest that quercetin reversed preneoplastic lesions by EGFR modulation and the activation state of Src, STAT5, and Sp1, so as the basal IGF-1.

Hypocholesterolemic and Anticarcinogenic Effect of Vicia faba Protein Hydrolyzates.

In recent years, the consumption of vegetal-source proteins has been studied to determine their preventing effect on the development of several chronic diseases. The initial purpose of this report was to determine the effect of a hypercholesterolemic diet (HCD) given to mice, alone or with azoxymethane (AOM), on various obesity biochemical biomarkers, as well as on the induction of colon aberrant crypts (aberrant crypt foci; ACF). At the end of the 5-week assay, animals fed the HCD showed alterations in the level of total cholesterol, high- and low-density lipoproteins, and in the Atherogenic Index; besides, a significant elevation was observed in the number of ACF. Our second aim was to examine the effect of a Faba Protein Hydrolyzate (FPH) on mice fed the HCD. We first obtained protein hydrolyzates from the seeds of Vicia faba, determined the in vitro antioxidant potential with two tests, and, subsequently, evaluated the effect on obesity biomarkers and on the number of ACF. In the first case, we found that, generally, the best protective effect was obtained with the low dose of FPH (10 mg/kg) administered to animals fed the HCD, and injected AOM. With respect to the number of ACF, we observed that this dose was more effective, inhibiting such lesions to almost the level determined for the normocholesterolemic diet (NCD). Therefore, our results demonstrated the relevance of a HCD to develop anomalies in obesity biomarkers in mouse, as well as to increase the number of precarcinogenic lesions. Our results also showed a protective response with the administration of FPH, particularly with a specific dose, suggesting the need for extending research on the matter by widening the spectra of doses, in order to clearly define its potential to counteract the damage induced by the HCD, as well as to confirm if antioxidation in mice was involved in such an effect.

Nutrient and nonnutrient components of legumes, and its chemopreventive activity: a review.

Legumes in combination with other products are the staple food for a large part of the world population, especially the low-income fragment, because their seeds provide valuable amounts of carbohydrates, fiber, and proteins, and have an important composition of essential amino acids, the sulphured amino acids being the limiting ones. Furthermore, legumes also have nonnutritional compounds that may decrease the absorption of nutrients or produce toxic effects; however, it has been reported that depending on the dose, these nonnutritional compounds also have different bioactivities as antioxidant, hypolipidemic, hypoglycemic, and anticarcinogenic agents, which have been proven in scientific studies. It has been observed that in countries with a high consumption of legumes, the incidence of colorectal cancer is lower. Some studies have shown that legume seeds are an alternative chemopreventive therapy against various cancers especially colon; this was verified in various animal models of induced by azoxymethane, a colon specific carcinogenic compound, in which a diet was supplemented with different concentrations of beans, lentils, chickpeas, or soybeans, mostly. These studies have proven the anticancer activity of legumes in early stages of carcinogenesis. Therefore, it is important to review the information available to elucidate the chemopreventive mechanisms of action of legume compounds.