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1.
Food Res Int ; 182: 114134, 2024 Apr.
Article En | MEDLINE | ID: mdl-38519156

Hesperidin is a phenolic compound usually found in citrus fruits, which is known for its anti-inflammatory and antioxidant properties. This bioactive compound has already been used to formulate medications to treat chronic venous insufficiency. In this work, through a system which allows the in-line coupling of the pressurized liquid extraction (PLE) and high-intensity ultrasound (HIUS) with solid phase extraction (SPE), and analysis by high-performance liquid chromatography with UV-Vis detector (HPLC-UV) in on-line mode, a method was developed to obtain, separate, and quantify hesperidin from the industrial waste of lime. An eco-friendly approach with water and ethanol as extraction solvents was used. Parameters such as temperature (80, 100, and 120 °C) and HIUS power (0, 200, and 400 W) were evaluated regarding hesperidin yield. In this context, the higher hesperidin yield (18.25 ± 1.52 mg/g) was achieved using water at a subcritical state (120 °C and 15 MPa). The adsorbent SepraTM C-18-E isolated hesperidin from the other extracted compounds employing 50% ethanol in the SPE elution. The possibility ofon-lineanalysis coupling a high-performance liquid chromatograph to an ultraviolet detector (HPLC-UV) system was studied and shown to be a feasible approach for developing integrated technologies. Conventional extractions and their antioxidant capacities were evaluated, highlighting the advantages of the HIUS-PLE-SPE extractive method. Furthermore, the on-linechromatographic analysis showed the potential of the HIUS-PLE-SPE- HPLC-UV system to quantify the extracted compounds in real time.


Calcium Compounds , Hesperidin , Oxides , Antioxidants , Water/chemistry , Ethanol
2.
Foods ; 12(17)2023 Sep 01.
Article En | MEDLINE | ID: mdl-37685216

Sunflower (Helianthus annuus L.) and African palm kernel (Elaeis guineensis Jacq.) are among the most cultivated in the world regarding oil extraction. The oil industry generates a large amount of meal as a by-product, which can be a source of nutrients and bioactive compounds. However, the physiological effects of bioactive compounds in such matrices are only valid if they remain bioavailable and bioactive after simulated gastrointestinal digestion. This study evaluated the chemical composition and antioxidant and prebiotic potential of de-oiled sunflower (DS) and de-oiled palm kernel (DP) meal after in vitro digestion. The DS sample had the highest protein content and the best chemical score, in which lysine was the limiting amino acid. Digested samples showed increased antioxidant activity, measured by in vitro methods. The digested DS sample showed a better antioxidant effect compared to DP. Moreover, both samples managed to preserve DNA supercoiling in the presence of the oxidizing agent. The insoluble fractions after digestion stimulated the growth of prebiotic bacterium, similar to inulin. In conclusion, simulated gastrointestinal digestion promoted in both matrices an increase in protein bioaccessibility and antioxidant capacity, pointing to a metabolic modulation favorable to the organism.

3.
Cells ; 12(2)2023 01 07.
Article En | MEDLINE | ID: mdl-36672191

NEK6 is a central kinase in developing castration-resistant prostate cancer (CRPC). However, the pathways regulated by NEK6 in CRPC are still unclear. Cancer cells have high reactive oxygen species (ROS) levels and easily adapt to this circumstance and avoid cell death by increasing antioxidant defenses. We knocked out the NEK6 gene and evaluated the redox state and DNA damage response in DU-145 cells. The knockout of NEK6 decreases the clonogenic capacity, proliferation, cell viability, and mitochondrial activity. Targeting the NEK6 gene increases the level of intracellular ROS; decreases the expression of antioxidant defenses (SOD1, SOD2, and PRDX3); increases JNK phosphorylation, a stress-responsive kinase; and increases DNA damage markers (p-ATM and γH2AX). The exogenous overexpression of NEK6 also increases the expression of these same antioxidant defenses and decreases γH2AX. The depletion of NEK6 also induces cell death by apoptosis and reduces the antiapoptotic Bcl-2 protein. NEK6-lacking cells have more sensitivity to cisplatin. Additionally, NEK6 regulates the nuclear localization of NF-κB2, suggesting NEK6 may regulate NF-κB2 activity. Therefore, NEK6 alters the redox balance, regulates the expression of antioxidant proteins and DNA damage, and its absence induces the death of DU-145 cells. NEK6 inhibition may be a new strategy for CRPC therapy.


Prostatic Neoplasms, Castration-Resistant , Male , Humans , Prostatic Neoplasms, Castration-Resistant/genetics , Prostatic Neoplasms, Castration-Resistant/metabolism , Reactive Oxygen Species/metabolism , Cell Line, Tumor , Antioxidants/metabolism , NF-kappa B p52 Subunit/metabolism , Oxidation-Reduction , DNA Damage , NIMA-Related Kinases/genetics , NIMA-Related Kinases/metabolism
4.
J Food Biochem ; 46(12): e14383, 2022 12.
Article En | MEDLINE | ID: mdl-36181391

The growing value of industrial collagen by-products has given rise to interest in extracting them from different species of animals. Intrinsic protein structure variation of collagen sources and its hydrolysis can bring about different bioactivities. This study aimed to characterize and evaluate the differences in vitro biological potential of commercial bovine (BH), fish (FH), and porcine hydrolysates (PH) regarding their antioxidant and hypoglycemic activities. All samples showed percentages above 90% of protein content, with high levels of amino acids (glycine, proline, and hydroxyproline), responsible for the specific structure of collagen. The BH sample showed a higher degree of hydrolysis (DH) (8.7%) and a higher percentage of smaller than 2 kDa peptides (74.1%). All collagens analyzed in vitro showed inhibition of pancreatic enzymes (α-amylase and α-glucosidase), with the potential to prevent diabetes mellitus. The PH sample showed higher antioxidant activities measured by ORAC (67.08 ± 4.23 µmol Trolox Eq./g) and ABTS radical scavenging (65.69 ± 3.53 µmol Trolox Eq./g) methods. For the first time, DNA protection was analyzed to hydrolyzed collagen peptides, and the FH sample showed a protective antioxidant action to supercoiled DNA both in the presence (39.51%) and in the absence (96.36%) of AAPH (reagent 2,2'-azobis(2-amidinopropane)). The results confirmed that the source of native collagen reflects on the bioactivity of hydrolyzed collagen peptides, probably due to its amino acid composition. PRACTICAL APPLICATIONS: Our data provide new application for collagen hydrolysates with hypoglycemiant and antioxidant activity. These data open discussion for future studies on the additional benefits arising from collagen peptide consumption for the prevention of aging complications or hyperglycemic conditions as observed in chronic diseases such as diabetes mellitus type II (DM 2). The confirmation of these results can open new market areas for the use of collagen with pharmacological applications or to produce new supplements. Furthermore, provides a solution for waste collagen from meat industries and adds value to the product.


Antioxidants , Glucose , Animals , Cattle , Swine , Antioxidants/chemistry , Peptides/chemistry , Peptide Hydrolases , Collagen/chemistry , Amino Acids , Fishes/metabolism
5.
Plant Foods Hum Nutr ; 77(2): 233-240, 2022 Jun.
Article En | MEDLINE | ID: mdl-35553352

The consumption of sprouts has increased as the germination process causes changes in the chemical composition of the seeds, improving their nutritional value. The aim of this work was to compare the total phenolic content and antioxidant capacity of broccoli, lentils and wheat sprouts before and after in vitro digestion, and the total phenolic content and antioxidant capacity between seeds and sprouts. Broccoli and wheat showed no difference in total phenolic content before and after germination, while lentils showed a significant decrease in total phenolic content after germination. The antioxidant capacity of broccoli and wheat increased after germination. After simulated digestion, the total phenolic content and antioxidant activity of broccoli sprouts significantly decreased during digestion in the gastric phase compared to the sprouts before digestion. Lentil sprouts did not show a decrease in total phenolic content during the gastric phase of digestion compared to the sprouts before digestion. However, they showed a significant increase in total phenolic content during the enteric phase. Finally, wheat sprouts showed a significant increase in total phenolic content and antioxidant activity during the gastric phase of digestion compared to grain before digestion. The germination process may increase the antioxidant capacity of sprouts, although this is not always related to the phenolic compound.


Brassica , Lens Plant , Antioxidants/analysis , Brassica/chemistry , Digestion , Germination , Lens Plant/chemistry , Phenols/analysis , Seeds/chemistry , Triticum
6.
Curr Res Food Sci ; 4: 662-669, 2021.
Article En | MEDLINE | ID: mdl-34622216

Phenolic compounds in crude extracts were obtained from defatted sunflower seed flour using sodium bisulfite and ethanol solutions as extracting agents. The antioxidant, antimicrobial, anti-proliferative, and DNA protective activities of the phenolic compounds in crude extract were analyzed. The phenolic compound contents were determined as chlorogenic acid (CGA) equivalent, presenting 11.57 and 15.44 g CGA eq/100g regarding the sodium bisulfite extract and ethanolic extract, respectively. The ORAC, DPPH, and ABTS methods were used to evaluate antioxidant activity. Both extracts presented antioxidant properties, considering that the ethanolic extract demonstrated higher values (EC50 0.36 g extract/g DPPH•). The antimicrobial action was analyzed as to the minimal inhibitory concentration (MIC) and the minimal bactericidal concentration (MBC) of 4 kinds of bacteria (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Bacillus subtilis). The ethanolic extract was effective against all of these microorganisms, out of which E. coli was the most sensitive, with a MIC of 11.6 mg CGA/mL. The ethanolic extract presented DNA protective activity without cytotoxic activity concerning in vitro anti-proliferative assay. These findings can be considered as initial evidence of the potential use of phenolic compounds obtained from sunflower seed flour as natural additives in the food industry.

7.
J Neurosci Res ; 99(12): 3325-3338, 2021 12.
Article En | MEDLINE | ID: mdl-34651324

Iron restriction during pregnancy can lead to iron deficiency and changes in the dopaminergic system in the adulthood of offspring, and restless legs syndrome (RLS) is closely related to these changes. Objectives: Analyze whether iron restriction during pregnancy would cause changes in the behavior, sleep, and dopaminergic system of the male offspring. In addition, we aimed to assess whether exercise would be able to modulate these variables. The pregnant rats (Wistar) were divided into four groups with different concentrations of iron in the diet: standard (St), supplementation (Su), restriction since weaning (R1), and restriction only during pregnancy (R2). After birth, the offspring were assigned to their respective groups according to the dams diet (St, Su, R1, and R2) and distributed into sedentary (SD) and exercised (EX) (for 8 weeks of training), reaching eight groups of offspring (O): OSt SD, OSt EX, OSu SD, OSu EX, OR1 SD, OR1 EX, OR2 SD, and OR2 EX. Sleep, behavior, and analysis of key genes of dopaminergic system (D2, DAT) were performed after 8 weeks. The results for trained offspring that the mother received supplementation diet were the most expressive, with increased freezing and the OR1 SD group showed an increase in DAT protein content. These changes may have been due to the association between the dams diet during pregnancy and the practice of exercise by the offspring. The different concentrations of iron during pregnancy caused changes in the offspring, however, they were not associated with fetal programming in the context of RLS.


Iron Deficiencies , Restless Legs Syndrome , Animals , Female , Iron , Male , Pregnancy , Rats , Rats, Wistar , Sleep
8.
Phytother Res ; 35(11): 6191-6203, 2021 Nov.
Article En | MEDLINE | ID: mdl-34494317

Cervical cancer is the fourth leading cause of cancer mortality in women worldwide. Beetroot (Beta vulgaris L.) has bioactive compounds that can inhibit the progression of different types of cancer. To analyze the antiproliferative effects of beet leaf and root extracts, we performed MTT, clonogenic survival, cell cycle analysis, Annexin/PI labeling, and western blotting. Here, we report that 10 and 100 µg/ml of root and leaf extracts decreased cell viability and potentiated rapamycin and cisplatin effects while decreased the number of large colonies, especially at 10 µg/ml (293.6 of control vs. 200.0 of leaf extract, p = .0059; 138.6 of root extract, p = .0002). After 48 hr, 100 µg/ml of both extracts led to increased sub-G1 and G0/G1 populations. In accordance, 100 µg/ml of root extract induced early apoptosis (mean = 0.64 control vs. 1.56 root; p = .048) and decreased cell size (p < .0001). Both extracts decreased phosphorylation and expression of mechanistic Target of Rapamycin (mTOR) signaling, especially by inhibiting ribosomal protein S6 (S6) phosphorylation, increasing cleaved poly(ADP-ribose) polysomerase 1 (PARP1) and Bcl-2-like protein 11 (BIM), and decreasing cyclin D1 expression, which regulates cell cycle progression. Here, we demonstrate that beetroot and leaf extracts could be an efficient strategy against cervical cancer.


Antineoplastic Agents, Phytogenic , Beta vulgaris , Uterine Cervical Neoplasms , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/therapeutic use , Apoptosis , Cell Proliferation , HeLa Cells , Humans , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Uterine Cervical Neoplasms/drug therapy
9.
Neoplasia ; 23(10): 1048-1058, 2021 Sep 17.
Article En | MEDLINE | ID: mdl-34543857

Lung cancer is the second leading cause of cancer death worldwide and is strongly associated with cisplatin resistance. The transcription factor signal transducer and activator of transcription 3 (STAT3) is constitutively activated in cancer cells and coordinates critical cellular processes as survival, self-renewal, and inflammation. In several types of cancer, STAT3 controls the development, immunogenicity, and malignant behavior of tumor cells while it dictates the responsiveness to radio- and chemotherapy. It is known that STAT3 phosphorylation at Ser727 by mechanistic target of rapamycin (mTOR) is necessary for its maximal activation, but the crosstalk between STAT3 and mTOR signaling in cisplatin resistance remains elusive. In this study, using a proteomic approach, we revealed important targets and signaling pathways altered in cisplatin-resistant A549 lung adenocarcinoma cells. STAT3 had increased expression in a resistance context, which can be associated with a poor prognosis. STAT3 knockout (SKO) resulted in a decreased mesenchymal phenotype in A549 cells, observed by clonogenic potential and by the expression of epithelial-mesenchymal transition markers. Importantly, SKO cells did not acquire the mTOR pathway overactivation induced by cisplatin resistance. Consistently, SKO cells were more responsive to mTOR inhibition by rapamycin and presented impairment of the feedback activation loop in Akt. Therefore, rapamycin was even more potent in inhibiting the clonogenic potential in SKO cells and sensitized to cisplatin treatment. Mechanistically, STAT3 partially coordinated the cisplatin resistance phenotype via the mTOR pathway in non-small cell lung cancer. Thus, our findings reveal important targets and highlight the significance of the crosstalk between STAT3 and mTOR signaling in cisplatin resistance. The synergic inhibition of STAT3 and mTOR potentially unveil a potential mechanism of synthetic lethality to be explored for human lung cancer treatment.

10.
Phytother Res ; 35(9): 5241-5258, 2021 Sep.
Article En | MEDLINE | ID: mdl-34132433

Beet (Beta vulgaris L.) has high nutritional value, containing bioactive compounds such as betalains and flavonoids. Scientific evidence points to the use of these natural compounds in the treatment of several types of cancer, such as prostate cancer, one of the main causes of morbidity and mortality in men. Here, we compared beet roots and leaves extracts, and their main compounds, apigenin, and betanin, respectively, in DU-145 and PC-3 prostate cancer cell lines. Both cells presented the proliferation decreased for beetroot and beet leaves extracts. The apigenin treatment also reduced the proliferation of both cell lines. Regarding cell migration, beet leaves extract was able to decrease the scratch area in both cell lines, whereas apigenin affected only PC-3 cells' migration. In colony formation assay, both extracts were effective in reducing the number of colonies formed. Besides, the beet leaves extracts and apigenin presented strong inhibition of growth-related signaling pathways in both cell lines, and the beetroot extract and betanin presented effects only in DU-145 cells. Furthermore, the extracts and isolated compounds were able to reduce the levels of apoptotic and cell cycle proteins. This study reveals that beet extracts have important anti-cancer effects against prostate cancer cells.


Antineoplastic Agents, Phytogenic/pharmacology , Beta vulgaris , Plant Extracts , Prostatic Neoplasms , Apoptosis , Beta vulgaris/chemistry , Betalains , Cell Line, Tumor , Cell Proliferation , Humans , Male , Plant Extracts/pharmacology , Plant Leaves/chemistry , Plant Roots/chemistry , Prostatic Neoplasms/drug therapy
11.
Molecules ; 26(7)2021 Apr 02.
Article En | MEDLINE | ID: mdl-33918290

Flavonoids represent an important group of bioactive compounds derived from plant-based foods and beverages with known biological activity in cells. From the modulation of inflammation to the inhibition of cell proliferation, flavonoids have been described as important therapeutic adjuvants against several diseases, including diabetes, arteriosclerosis, neurological disorders, and cancer. Cancer is a complex and multifactor disease that has been studied for years however, its prevention is still one of the best known and efficient factors impacting the epidemiology of the disease. In the molecular and cellular context, some of the mechanisms underlying the oncogenesis and the progression of the disease are understood, known as the hallmarks of cancer. In this text, we review important molecular signaling pathways, including inflammation, immunity, redox metabolism, cell growth, autophagy, apoptosis, and cell cycle, and analyze the known mechanisms of action of flavonoids in cancer. The current literature provides enough evidence supporting that flavonoids may be important adjuvants in cancer therapy, highlighting the importance of healthy and balanced diets to prevent the onset and progression of the disease.


Flavonoids/therapeutic use , Neoplasms/drug therapy , Animals , Clinical Trials as Topic , Flavonoids/administration & dosage , Flavonoids/chemistry , Flavonoids/pharmacology , Humans , Immunity/drug effects , Inflammation/pathology , Neoplasms/immunology , Signal Transduction/drug effects
12.
Int J Oncol ; 58(6)2021 06.
Article En | MEDLINE | ID: mdl-33846781

Lung cancer is the leading cause of cancer­associated death worldwide and exhibits intrinsic and acquired therapeutic resistance to cisplatin (CIS). The present study investigated the role of mTOR signaling and other signaling pathways after metformin (MET) treatment in control and cisplatin­resistant A549 cells, mapping pathways and possible targets involved in CIS sensitivity. MTT, flow cytometry, clonogenic assay, western blotting, proteomic analysis using the Stable Isotope Labeling by Amino acids in Cell culture (SILAC) approach and reverse transcription­quantitative PCR were performed. The results revealed that CIS treatment induced mTOR signaling pathway overactivation, and the mTOR status was restored by MET. MET and the mTOR inhibitor rapamycin (RAPA) decreased the viability in control and resistant cells, and decreased the cell size increase induced by CIS. In control cells, MET and RAPA decreased colony formation after 72 h and decreased IC50 values, potentiating the effects of CIS. Proteomics analysis revealed important pathways regulated by MET, including transcription, RNA processing and IL­12­mediated signaling. In CIS­resistant cells, MET regulated the apoptotic process, oxidative stress and G2/M transition. Annexin 4 (ANXA4) and superoxide dismutase 2 (SOD2), involved in apoptosis and oxidative stress, respectively, were chosen to validate the SILAC analysis and may represent potential therapeutic targets for lung cancer treatment. In conclusion, the chemosensitizing and antiproliferative effects of MET were associated with mTOR signaling and with potential novel targets, such as ANXA4 and SOD2, in human lung cancer cells.


Antineoplastic Combined Chemotherapy Protocols/pharmacology , Carcinoma, Non-Small-Cell Lung/drug therapy , Cisplatin/pharmacology , Drug Resistance, Neoplasm/drug effects , Lung Neoplasms/drug therapy , Metformin/pharmacology , A549 Cells , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Cisplatin/therapeutic use , Gene Expression Regulation, Neoplastic/drug effects , Humans , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Metabolic Networks and Pathways/drug effects , Metabolic Networks and Pathways/genetics , Metformin/therapeutic use , Signal Transduction/drug effects , Signal Transduction/genetics , TOR Serine-Threonine Kinases/metabolism
13.
Einstein (Sao Paulo) ; 18: eAO5665, 2020.
Article En, Pt | MEDLINE | ID: mdl-33295427

OBJECTIVE: To evaluate if different concentrations of iron in diets during pregnancy would interfere in the aerobic and anaerobic performance of the offspring, observed during 8-week swimming training and measured by lactate minimum test. METHODS: Pregnant rats were divided into four groups with different dietary iron concentrations: standard (40mg/kg), supplementation (100mg/kg), restriction since weaning, and restriction only during pregnancy (4mg/kg). After birth, the offspring were assigned to their respective groups (Standard Offspring, Supplementation Offspring, Restriction Offspring or Restriction Offspring 2). The lactate minimum test was performed at three time points: before starting exercise training, after 4 weeks and after 8 weeks of exercise training. RESULTS: The Restriction Offspring Group had a significant reduction in the concentration of lactate minimum and in swimming time to exhaustion, after 4 and 8 weeks of training as compared to before training. Therefore, the results showed the Restriction Offspring Group was not able to maintain regularity during training in lactate minimum tests. CONCLUSION: Our results suggested the Restriction Offspring Group showed a marked decrease in its performance parameters, which may have occurred due to iron restriction.


Physical Conditioning, Animal , Animals , Female , Iron , Male , Nutritional Status , Pregnancy , Rats , Swimming
14.
J Agric Food Chem ; 68(44): 12433-12443, 2020 Nov 04.
Article En | MEDLINE | ID: mdl-33095576

This study aims to isolate metal-binding peptides and synthesize promising amino acid sequences to potentially act as neuroprotective compounds in the future, targeting different mechanisms. Fractions of whey metal-binding peptides (Cu, Fe, and Zn) isolated by immobilized metal affinity chromatography showed different amino acid profiles according to the metal. The Cu-binding peptides presented roughly twofold increase in the in vitro antioxidant, as assessed by oxygen radical absorbance capacity and anticholinesterase activities over the hydrolysate. This is probably because of the higher concentration of aromatic and basic residues, the latter being crucial for binding to the anionic sites of acetylcholinesterase. Six peptide sequences were synthesized based on the metal-binding sites, molecular mass, hydrophobicity, and bioactivity probability. Among the synthetic peptides, the VF dipeptide stood out both for its in vitro antioxidant and anticholinesterase activities. This peptide, as well as the fraction of Cu-binding peptides, should be further studied because it may act through different mechanisms related to neurodegenerative diseases, in addition to the chelation of the excess of metals in the central nervous system.


Chelating Agents/chemistry , Copper/chemistry , Iron/chemistry , Neuroprotective Agents/chemistry , Peptides/chemistry , Whey/chemistry , Zinc/chemistry , Animals , Cattle , Chelating Agents/isolation & purification , Neuroprotective Agents/isolation & purification , Peptides/isolation & purification , Whey Proteins/chemistry
15.
Phytother Res ; 34(6): 1385-1396, 2020 Jun.
Article En | MEDLINE | ID: mdl-31989717

Beetroot is an herb used worldwide as a food product, raw material for food industry, ethanol production and source of food coloring. Beet leaves are an unconventional food with antioxidant properties, which might neutralize reactive oxygen species (ROS) induced by oxidized Low-Density Lipoprotein (LDL) present in dyslipidemias. This study aimed to elucidate the effects of beet leaves on the suppression of LDL oxidative processes. Beet leaves extract was produced, characterized, and tested for its antioxidant capacity using endothelial cells in vitro. A model of human umbilical vein endothelial cells was used in various tests, including viability assay, molecular analysis of antioxidant genes, ROS labeling, and macrophage adhesion assay. The extract improved the antioxidative protection of endothelial cells against different agents including oxidized LDL-cholesterol and H2 O2 . It acted on ROS directly due to its high content of natural antioxidants, but also due to the activation and improvement of cellular defenses such as Superoxide dismutase 1, Superoxide dismutase 2, and catalase. The inhibition of LDL-mediated oxidative effects on endothelial cells may turn this unconventional food a functional food with great potential for phytotherapy of atherosclerosis as an adjuvant for medicinal treatments.


Antioxidants/therapeutic use , Endothelial Cells/metabolism , Oxidative Stress/drug effects , Plant Extracts/chemistry , Plant Leaves/chemistry , Antioxidants/pharmacology , Beta vulgaris/chemistry , Humans
16.
J Endocrinol ; 244(1): 71-82, 2020 01 01.
Article En | MEDLINE | ID: mdl-31557728

The mTOR/S6Ks signaling is one of the intracellular pathways important for metabolic control, acting both peripherally and centrally. In the hypothalamus, mTOR/S6Ks axis mediates the action of leptin and insulin and can modulate the expression of neuropeptides. We analyzed the role of different S6Ks isoforms in the hypothalamic regulation of metabolism. We observed decreased food intake and decreased expression of agouti-related peptide (AgRP) following intracerebroventricular (icv) injections of adenoviral-mediated overexpression of three different S6Ks isoforms. Moreover, mice overexpressing p70-S6K1 in undefined periventricular hypothalamic neurons presented changes in glucose metabolism, as an increase in gluconeogenesis. To further evaluate the hypothalamic role of a less-studied S6K isoform, p54-S6K2, we used a Cre-LoxP approach to specifically overexpress it in AgRP neurons. Our findings demonstrate the potential participation of S6K2 in AgRP neurons regulating feeding behavior.


Feeding Behavior/drug effects , Glucose/metabolism , Protein Isoforms/pharmacology , Ribosomal Protein S6 Kinases, 90-kDa/pharmacology , Ribosomal Protein S6 Kinases/pharmacology , Agouti-Related Protein/metabolism , Animals , Eating/genetics , Hypothalamus/metabolism , Mice , Signal Transduction/genetics , TOR Serine-Threonine Kinases/metabolism
17.
Plant Foods Hum Nutr ; 75(1): 54-62, 2020 Mar.
Article En | MEDLINE | ID: mdl-31838616

Pomegranate (Punica granatum) is known to contain polyphenols with many potential health benefits, including anti-tumoral, anti-inflammatory, and anti-microbial properties. It has been used in popular medicine for cancer treatment, which still represents the major cause of cancer-related deaths in men worldwide. Importantly, pomegranate peels are valuable by-products of the food industry that are rich in polyphenols. Here we report a comparison between juice and peel aqueous extracts in prostate cancer DU-145 and PC-3 cell lines. Both extracts were able to inhibit the proliferation, migration and colony formation of those cells, although peel extracts presented more robust effects compared to juice. Besides, the growth-related mTOR/S6K signaling pathway presented strong inhibition after pomegranate extracts treatment. This study presents evidence that both juice and isolated peel extracts from promegate fruit have important anti-cancer effects against prostate cancer cells, modulating the mTOR/S6K signaling pathway.


Pomegranate , Prostatic Neoplasms , Cell Line , Cell Proliferation , Fruit , Humans , Male , Plant Extracts , Proto-Oncogene Proteins c-akt , Signal Transduction , TOR Serine-Threonine Kinases
18.
Einstein (Säo Paulo) ; 18: eAO5665, 2020. graf
Article En | LILACS | ID: biblio-1142869

ABSTRACT Objective: To evaluate if different concentrations of iron in diets during pregnancy would interfere in the aerobic and anaerobic performance of the offspring, observed during 8-week swimming training and measured by lactate minimum test. Methods: Pregnant rats were divided into four groups with different dietary iron concentrations: standard (40mg/kg), supplementation (100mg/kg), restriction since weaning, and restriction only during pregnancy (4mg/kg). After birth, the offspring were assigned to their respective groups (Standard Offspring, Supplementation Offspring, Restriction Offspring or Restriction Offspring 2). The lactate minimum test was performed at three time points: before starting exercise training, after 4 weeks and after 8 weeks of exercise training. Results: The Restriction Offspring Group had a significant reduction in the concentration of lactate minimum and in swimming time to exhaustion, after 4 and 8 weeks of training as compared to before training. Therefore, the results showed the Restriction Offspring Group was not able to maintain regularity during training in lactate minimum tests. Conclusion: Our results suggested the Restriction Offspring Group showed a marked decrease in its performance parameters, which may have occurred due to iron restriction.


RESUMO Objetivo: Avaliar parâmetros aeróbios e anaeróbios da prole de ratas alimentadas com diferentes dietas de ferro durante a prenhez, por meio do teste de lactato mínimo. Métodos: As ratas prenhes foram divididas em quatro grupos com diferentes concentrações de ferro na dieta: padrão (40mg/kg), suplementação (100mg/kg), restrição desde o desmame e restrição apenas durante a gravidez (4mg/kg). Após o nascimento, os filhotes foram designados para seus respectivos grupos (Prole Padrão, Prole Suplementação, Prole Restrição ou Prole Restrição 2). O teste de lactato mínimo foi realizado em três momentos: antes de iniciar o treinamento físico, após 4 semanas e após 8 semanas de treinamento físico. Resultados: O Grupo Prole Restrição apresentou redução significativa na concentração do lactato mínimo e no tempo de natação até a exaustão, após 4 e 8 semanas de treinamento em relação ao período antes do início do treinamento. Assim, o Grupo Prole Restrição não foi capaz de manter regularidade durante o treinamento nos testes de lactato mínimo. Conclusão: Os resultados sugerem que o Grupo Prole Restrição apresentou diminuição acentuada nos parâmetros de desempenho, o que pode ter ocorrido devido à restrição de ferro.


Animals , Male , Female , Pregnancy , Rats , Physical Conditioning, Animal , Swimming , Nutritional Status , Iron
19.
Plant Foods Hum Nutr ; 74(2): 232-234, 2019 Jun.
Article En | MEDLINE | ID: mdl-30993531

Obesity is an important public health concern and is directly related with chronic noncommunicable diseases that affect the health of millions of people around the world. This study was held to verify the short-term effects related to the consumption of freeze-dried red beet leaves on biochemical and anthropometrical parameters of volunteers with overweight/obesity and dyslipidemia. Participants (n = 36) were divided at random into two groups. The control group (CG) received nutritional guidance only, and the intervention group (IG) received nutritional guidance and consumed 2.8 g of freeze-dried red beet leaves for four weeks. Biochemical tests and anthropometric measurements were collected, before and after intervention. The distribution of the characteristics between groups was similar. Parameters related to body weight and body mass index (BMI) had a significant reduction in the two groups (p = 0.05). Significant reduction on LDL-cholesterol was found only for the IG (p < 0.01). These data suggest a potential effect of consumption of red beet leaves on the health of individuals with overweight or obesity.


Beta vulgaris/metabolism , Dietary Supplements , Dyslipidemias/diet therapy , Functional Food , Obesity/diet therapy , Overweight/diet therapy , Body Mass Index , Body Weight , Cholesterol, LDL/blood , Fasting , Female , Freeze Drying , Humans , Male , Pilot Projects , Plant Leaves/metabolism , Random Allocation , Weight Loss
20.
Ultrason Sonochem ; 48: 151-162, 2018 Nov.
Article En | MEDLINE | ID: mdl-30080537

The combination of ultrasound and pressurized liquid extraction (UAPLE) was evaluated for the extraction of phenolic compounds from pomegranate peels (Punica granatum L.). The influence of several variables of the process on extraction yield, including solvent type (water, ethanol + water 30, 50 and 70% v:v), temperature (50-100 °C), ultrasound power (0-800 W at the generator, or 0-38.5 W at the tip of the probe), mean particle size (0.68 and 1.05 mm), and number of cycles (1-5), were analyzed according to the yield of 20 different phenolic compounds. The most suitable temperatures for the extraction of phenolic compounds using water were from 70 to 80 °C. In general, 100 °C was not adequate since the lowest extraction yields were observed. Results suggested that ultrasound had a greater impact on extraction yields using large particles and that intermediate ultrasound power (480-640 W at the generator, or 23.1-30.8 W at the tip of the probe) produced the best results. Using small particles (0.68 mm) or large particles (1.05 mm), extraction with ultrasound was 1 cycle faster. Ultrasound may have offset the negative effect of the use of large particles, however, did not increase the yield of phenolic compounds in any of the cases studied after five cycles. Additionally, the continuous clogging problems observed with small particles were avoided with the use of large particles, which combined with ultrasound allowed consistent operation with good intra and inter-day reproducibility (>95%). Using samples with large particle size, the best extraction conditions were achieved with water extraction solvent, 70 °C extraction temperature, ultrasound power at 480 W, and 3 cycles, yielding 61.72 ±â€¯7.70 mg/g. UAPLE demonstrated to be a clean, efficient and a green alternative for the extraction of phenolic compounds from pomegranate peels. These findings indicate that UAPLE has a great potential to improve the extraction of bioactive compounds from natural products.


Lythraceae/chemistry , Phenols/isolation & purification , Sonication , Particle Size , Pressure , Solvents/chemistry , Temperature , Water/chemistry
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