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Acne is one of the most common skin conditions worldwide, with multifactorial origins it affects areas of the skin with hair follicles and sebaceous glands that become clogged. Bacterial incidence aggravates treatment due to resistance to antimicrobial agents and production of virulence factors such as biofilm formation. Considering the above, this study aims to conduct in vitro evaluations of the antibacterial activity of essential oils (EOs), alone and in combination, against Propionibacterium acnes, Staphylococcus aureus, and Staphylococcus epidermidis in planktonic and biofilm forms. This study also assessed the anti-inflammatory potential (TNF-α) and the effects of EOs on the viability of human keratinocytes (HaCaT), murine fibroblasts (3T3-L1), and bone marrow-derived macrophages (BMDMs). Of all EOs tested, 13 had active action against P. acnes, 9 against S. aureus, and 9 against S. epidermidis at concentrations of 0.125 to 2.0 mg/mL. Among the most active plant species, a blend of essential oil (BEOs) was selected, with Cymbopogon martini (Roxb.) Will. Watson, Eugenia uniflora L., and Varronia curassavica Jacq., the latter due to its anti-inflammatory action. This BEOs showed higher inhibition rates when compared to chloramphenicol against S. aureus and S. epidermidis, and higher eradication rates when compared to chloramphenicol for the three target species. The BEOs did not affect the cell viability of cell lines evaluated, and the levels of TNF-α decreased. According to these results, the BEOs evaluated showed potential for the development of an alternative natural formulation for the treatment of acne.
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The combination of a polyphenol, quercetin, with dasatinib initiated clinical trials to evaluate the safety and efficacy of senolytics in idiopathic pulmonary fibrosis, a lung disease associated with the presence of senescent cells. Another approach to senotherapeutics consists of controlling inflammation related to cellular senescence or "inflammaging", which participates, among other processes, in establishing pulmonary fibrosis. We evaluate whether polyphenols such as caffeic acid, chlorogenic acid, epicatechin, gallic acid, quercetin, or resveratrol combined with different senotherapeutics such as metformin or rapamycin, and antifibrotic drugs such as nintedanib or pirfenidone, could present beneficial actions in an in vitro model of senescent MRC-5 lung fibroblasts. A senescent-associated secretory phenotype (SASP) was evaluated by the measurement of interleukin (IL)-6, IL-8, and IL-1ß. The senescent-associated ß-galactosidase (SA-ß-gal) activity and cellular proliferation were assessed. Fibrosis was evaluated using a Picrosirius red assay and the gene expression of fibrosis-related genes. Epithelial-mesenchymal transition (EMT) was assayed in the A549 cell line exposed to Transforming Growth Factor (TGF)-ß in vitro. The combination that demonstrated the best results was metformin and caffeic acid, by inhibiting IL-6 and IL-8 in senescent MRC-5 cells. Metformin and caffeic acid also restore cellular proliferation and reduce SA-ß-gal activity during senescence induction. The collagen production by senescent MRC-5 cells was inhibited by epicatechin alone or combined with drugs. Epicatechin and nintedanib were able to control EMT in A549 cells. In conclusion, caffeic acid and epicatechin can potentially increase the effectiveness of senotherapeutic drugs in controlling lung diseases whose pathophysiological component is the presence of senescent cells and fibrosis.
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Senescencia Celular , Fibroblastos , Pulmón , Polifenoles , Humanos , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Senescencia Celular/efectos de los fármacos , Polifenoles/farmacología , Pulmón/patología , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Células A549 , Proliferación Celular/efectos de los fármacos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Metformina/farmacología , Ácidos Cafeicos/farmacología , Indoles/farmacología , Senoterapéuticos/farmacología , Línea Celular , Fenotipo Secretor Asociado a la Senescencia/efectos de los fármacos , Sirolimus/farmacología , Interleucina-8/metabolismo , Interleucina-8/genética , Factor de Crecimiento Transformador beta/metabolismo , PiridonasRESUMEN
Abstract Objectives: This paper aims to review data on the association of obesity and iron deficiency in children and adolescents, exposing the possible involvement of hepcidin and interleukin-6 (IL-6), obesity's inflammation biomarkers. Data source: Articles from PUBMED and WEB OF SCIENCE database with no chronological limit were reviewed to write this systematic review. Keywords such as children, obesity, iron deficiency, and hepcidin were used. After deleting duplicated and review articles, 91 were screened, and 39 were selected as eligible. Sixteen articles were included because they involved serum hepcidin levels in obese children and adolescents as outcomes. Summary of findings: Finally, those 16 articles were organized in two tables: one includes therapeutic interventions, and the other does not. As hepcidin was discovered in 2000, the first articles that presented serum hepcidin's quantification in obese children and adolescents, homeostasis iron markers, and their possible association with obesity's inflammatory environment began to be published in 2008. Conclusions: Obesity's chronic inflammation state leads to the production of IL-6, which acts as a signaling molecule for hepcidin synthesis, resulting in iron deficiency, which is common in obese children and adolescents who respond inadequately to iron supplementation. On the other hand, that population responds adequately to therapeutic intervention programs that lead to weight loss, guaranteeing iron homeostasis improvement. Therefore, perhaps it is time to discuss serum hepcidin level quantification as part of evaluating children and adolescents with iron deficiency, which could guide clinical choices that might lead to better therapeutic outcomes.
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Therapeutically targeting senescent cells seems to be an interesting perspective in treating chronic lung diseases, which are often associated with human aging. The combination of the drug dasatinib and the polyphenol quercetin is used in clinical trials as a senolytic, and the first results point to the relief of physical dysfunction in patients with idiopathic pulmonary fibrosis. In this work, we tested new combinations of drugs and polyphenols, looking for senolytic activity using human lung fibroblasts (MRC-5 cell line) with induced senescence. We researched drugs, such as azithromycin, rapamycin, metformin, FK-506, aspirin, and dasatinib combined with nine natural polyphenols, namely caffeic acid, chlorogenic acid, ellagic acid, ferulic acid, gallic acid, epicatechin, hesperidin, quercetin, and resveratrol. We found new effective senolytic combinations with dasatinib and ellagic acid and dasatinib and resveratrol. Both drug combinations increased apoptosis, reduced BCL-2 expression, and increased caspase activity in senescent MRC-5 cells. Ellagic acid senolytic activity was more potent than quercetin, and resveratrol counteracted inflammatory cytokine release during senolysis in vitro. In conclusion, dasatinib and ellagic acid and dasatinib and resveratrol present in vitro senolytic potential like that observed for the combination in clinical trials of dasatinib and quercetin, and maybe they could be future alternatives in the senotherapeutic field.
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Seborrheic dermatitis is a chronic inflammatory disease caused by Malassezia yeast species that affects the regions of the body where the sebaceous glands are present. The combined use of different essential oils (EOs) can increase their spectrum of action. Thus, the present study aimed to evaluate the action of EOs alone and in combination with each other on M. furfur, in planktonic and biofilm form, and their anti-inflammatory and mutagenic potential, in addition to the effects on the viability of cells lines. Of the 40 evaluated EOs, 22 showed activity against M. furfur at 0.5â-â2.0 mg/mL concentrations. Among the most active species, a blend of essential oils (BEOs) composed of Cymbopogon martini (Roxb.) Will. Watson (MIC = 0.5 mg/mL) and Mentha × piperita L. (MIC = 1.0 mg/mL) was selected, which showed a synergistic effect against yeast when evaluated through the checkerboard assay. The fungicidal activity was maintained by the addition of anti-inflammatory oil from Varronia curassavica Jacq. to BEOs. The BEOs also showed activity in the inhibition of biofilm formation and in the eradication of the biofilm formed by M. furfur, being superior to the action of fluconazole. Furthermore, it did not show mutagenic potential and did not interfere with the cell viability of both evaluated cell lines (HaCaT and BMDMs). TNF-α levels were reduced only by C. martini; however, this property was maintained when evaluating BEOs. BEOs had no effect on IL-8 levels. Thus, the BEOs may be indicated for alternative treatments against seborrheic dermatitis.
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Dermatitis Seborreica , Malassezia , Aceites Volátiles , Antifúngicos/farmacología , Aceites Volátiles/farmacología , Dermatitis Seborreica/tratamiento farmacológico , Antiinflamatorios/farmacologíaRESUMEN
OBJECTIVES: This paper aims to review data on the association of obesity and iron deficiency in children and adolescents, exposing the possible involvement of hepcidin and interleukin-6 (IL-6), obesity's inflammation biomarkers. DATA SOURCE: Articles from PUBMED and WEB OF SCIENCE database with no chronological limit were reviewed to write this systematic review. Keywords such as children, obesity, iron deficiency, and hepcidin were used. After deleting duplicated and review articles, 91 were screened, and 39 were selected as eligible. Sixteen articles were included because they involved serum hepcidin levels in obese children and adolescents as outcomes. SUMMARY OF FINDINGS: Finally, those 16 articles were organized in two tables: one includes therapeutic interventions, and the other does not. As hepcidin was discovered in 2000, the first articles that presented serum hepcidin's quantification in obese children and adolescents, homeostasis iron markers, and their possible association with obesity's inflammatory environment began to be published in 2008. CONCLUSIONS: Obesity's chronic inflammation state leads to the production of IL-6, which acts as a signaling molecule for hepcidin synthesis, resulting in iron deficiency, which is common in obese children and adolescents who respond inadequately to iron supplementation. On the other hand, that population responds adequately to therapeutic intervention programs that lead to weight loss, guaranteeing iron homeostasis improvement. Therefore, perhaps it is time to discuss serum hepcidin level quantification as part of evaluating children and adolescents with iron deficiency, which could guide clinical choices that might lead to better therapeutic outcomes.
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Anemia Ferropénica , Deficiencias de Hierro , Obesidad Infantil , Adolescente , Niño , Humanos , Obesidad Infantil/complicaciones , Hepcidinas , Interleucina-6 , Índice de Masa Corporal , Hierro , Inflamación , Biomarcadores , Anemia Ferropénica/complicaciones , Anemia Ferropénica/epidemiologíaRESUMEN
Soy isoflavones are considered important sources of bioactive compounds, but they are poorly absorbable, due to their large hydrophilic structures. Some biotransformation strategies have been used to convert the glycosidic form into aglycones, making them available for absorption. This study evaluated the potential of enzymatic and/or microbial fermentation combined bioprocesses in a soymilk extract before and after gastrointestinal in vitro digestion. Commercial ß-glucosidase (ET) and a mix of commercial probiotics (F) containing Lactobacillus acidophilus, Lactobacillus casei, Lactococcus lactis, Bifidobacterium bifidum, and Bifidobacterium lactis were used to biotransform the soymilk phenolic extract. An isoflavone profile was identified using HPLC-DAD, total phenolic content was identified using the Folin-Ciocalteu test, and antioxidant capacity was identified using ORAC and FRAP. Soymilk enzymatically treated (ET) followed by microbial fermentation (ET + T) resulted in better conversion of glycosylated isoflavones (6-fold lower than control for daidzin and 2-fold for genistin) to aglycones (18-fold greater than control for dadzein and genistein). The total phenolic content was increased (3.48 mg/mL for control and 4.48 mg/mL for ET + T) and the antioxidant capacity was improved with treatments of ET + T (120 mg/mL for control and 151 mg/mL with ORAC) and with FRAP (285 µL/mL for control and 317 µL/mL). After the in vitro digestion, ET + T samples resulted in a higher content of genistein (two-fold higher than control); also, increases in the total phenolic content (2.81 mg/mL for control and 4.03 mg/mL for ET + T) and antioxidant capacity measured with ORAC were greater compared to undigested samples. In addition, the isolated microbial fermentation process also resulted in positive effects, but the combination of both treatments presented a synergistic effect on soy-based products.
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INTRODUCTION: Several studies demonstrated that deferoxamine, an iron chelator, can improve inflammatory alterations in adipose tissue induced by obesity. Obesity alterations in adipose tissue are also associated with tissue remodeling, and deferoxamine has anti-fibrosis action previously described in sites like the skin and liver. METHODS: In this work, we analyzed deferoxamine effects on adipose tissue fibro-inflammation during obesity induced by diet in mice. in vitro approaches with fibroblasts and macrophages were also carried out to elucidate deferoxamine activity. RESULTS: Our results demonstrated that in addition to exerting anti-inflammatory effects, reducing the cytokine production in adipose tissue of obese mice and by human monocyte differentiated in macrophage in vitro, deferoxamine can alter metalloproteinases expression and extracellular matrix production in vivo and in vitro. CONCLUSION: Deferoxamine could be an alternative to control fibro-inflammation in obese adipose tissue, contributing to the metabolic improvements previously described.
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Deferoxamina , Resistencia a la Insulina , Humanos , Animales , Ratones , Deferoxamina/farmacología , Deferoxamina/uso terapéutico , Deferoxamina/metabolismo , Tejido Adiposo , Obesidad/metabolismo , Inflamación/metabolismo , Hígado/metabolismo , Ratones Endogámicos C57BLRESUMEN
PURPOSE: To evaluate how the induction of liver damage by ischemia and reperfusion affects the adipose tissue of lean and obese mice. METHODS: Lean and diet-induced obese mice were subjected to liver ischemia (30 min) followed by 6 h of reperfusion. The vascular stromal fraction of visceral adipose tissue was analyzed by cytometry, and gene expression was evaluated by an Array assay and by RT-qPCR. Intestinal permeability was assessed by oral administration of fluorescein isothiocyanate (FITC)-dextran and endotoxemia by serum endotoxin measurements using a limulus amebocyte lysate assay. RESULTS: It was found that, after liver ischemia and reperfusion, there is an infiltration of neutrophils, monocytes, and lymphocytes, as well as an increase in the gene expression that encode cytokines, chemokines and their receptors in the visceral adipose tissue of lean mice. This inflammatory response was associated with the presence of endotoxemia in lean mice. However, these changes were not observed in the visceral adipose tissue of obese mice. CONCLUSIONS: Liver ischemia and reperfusion induce an acute inflammatory response in adipose tissue of lean mice characterized by an intense chemokine induction and leukocyte infiltration; however, inflammatory alterations are already present at baseline in the obese adipose tissue and liver ischemia and reperfusion do not injure further.
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Grasa Intraabdominal , Daño por Reperfusión , Animales , Inflamación , Hígado , Ratones , Obesidad/complicaciones , Obesidad/metabolismo , Daño por Reperfusión/metabolismoRESUMEN
Purpose: To evaluate how the induction of liver damage by ischemia and reperfusion affects the adipose tissue of lean and obese mice. Methods: Lean and diet-induced obese mice were subjected to liver ischemia (30 min) followed by 6 h of reperfusion. The vascular stromal fraction of visceral adipose tissue was analyzed by cytometry, and gene expression was evaluated by an Array assay and by RT-qPCR. Intestinal permeability was assessed by oral administration of fluorescein isothiocyanate (FITC)-dextran and endotoxemia by serum endotoxin measurements using a limulus amebocyte lysate assay. Results: It was found that, after liver ischemia and reperfusion, there is an infiltration of neutrophils, monocytes, and lymphocytes, as well as an increase in the gene expression that encode cytokines, chemokines and their receptors in the visceral adipose tissue of lean mice. This inflammatory response was associated with the presence of endotoxemia in lean mice. However, these changes were not observed in the visceral adipose tissue of obese mice. Conclusions: Liver ischemia and reperfusion induce an acute inflammatory response in adipose tissue of lean mice characterized by an intense chemokine induction and leukocyte infiltration; however, inflammatory alterations are already present at baseline in the obese adipose tissue and liver ischemia and reperfusion do not injure further.
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Animales , Ratones , Daño por Reperfusión/veterinaria , Interleucina-6 , Endotoxinas/análisis , Grasa Intraabdominal/fisiopatología , Inhibidores del Factor de Necrosis Tumoral/análisisRESUMEN
Structured lipids (SL) containing behenic acid have been produced in order to obtain low-calorie lipids for foods; however, the development of a high nutritional value and a stable nanoemulsion carrier system for these SL is an interesting breakthrough for this field of research, improving technologic and biological potential for food application. In this sense, the aim of this study was to evaluate the stability of a nanoemulsion containing SL NeSL (produced with olive oil, soybean oil and fully hydrogenated crambe oil), the behavior during in vitro digestion and the effects on biomarkers involved in the obesity in cell models. The samples showed good stability throughout storage (30 days) under refrigeration and room temperature and after the gastric digestion phase compared to the controls (nanoemulsion of olive and soybean oil). After the intestinal phase, there was an increase in oil droplet size and zeta potential, a characteristic of coalescence. In the lipid accumulation model in adipocytes, the highest concentration (50 µL/mL) of NeSL resulted in 42% less lipid accumulation, compared to the control. Furthermore, the sample was able to reduce inflammatory cytokines produced by macrophages provoked by LPS (lipopolysaccharide). The combination of the oils in NeSL resulted in a fatty acid profile with beneficial health properties, which may have contributed to less lipid accumulation and improved inflammatory parameters. This SL in the form of a nanoemulsion, may be used as a partial fat substitute in low-calorie food products.
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Ingestión de Energía , Aceite de Soja , Biomarcadores , Emulsiones , Humanos , ObesidadRESUMEN
Sucralose is a widely consumed non-nutritive sweetener (NNS). Studies have shown that some NNS can favor weight gain by altering the intestinal microbiota, satiety hormone production, or aspects related to glucose homeostasis. In this study, we investigated the effects of ad libitum sucralose consumption in mice fed with normal or high-fat diet (HFD) for an extended period (16 weeks). Weight gain, final body composition, energy expenditure, intestinal and pancreatic hormone production, and endotoxemia during a voracity test, as well as liver and skeletal muscles were evaluated after 16 weeks. We observed that sucralose supplementation reduced weight gain in HFD-fed mice but did not change weight gain in mice fed with normal diet. The evaluation of HFD mice showed that sucralose supplementation resulted in improvements in glycemic homeostasis, hepatic steatosis, and increased energy expenditure. Our results suggest that sucralose consumption promotes different outcomes in relation to weight gain when combined with different diets, which may explain the controversial data in previous studies, and can be considered in future clinical research aimed at clarifying the impact of NNS consumption on human health.
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Glucemia/metabolismo , Dieta Alta en Grasa/efectos adversos , Metabolismo Energético/efectos de los fármacos , Sacarosa/análogos & derivados , Edulcorantes/farmacología , Aumento de Peso/efectos de los fármacos , Animales , Apetito/efectos de los fármacos , Composición Corporal/efectos de los fármacos , Endotoxemia/metabolismo , Hígado Graso/metabolismo , Microbioma Gastrointestinal/efectos de los fármacos , Humanos , Intestinos/metabolismo , Hígado/metabolismo , Masculino , Ratones , Músculo Esquelético/metabolismo , Sacarosa/farmacologíaRESUMEN
BACKGROUND: New formulations for topical treatment of ulcerative colitis with budesonide inclusion complex (BUDHP-ß-CD) and poloxamers (PL) were developed for future clinical use. AIMS: This study evaluated the efficacy of such novel formulations in a rat model of colitis. METHODS: The PL-BUDHP-ß-CD systems were prepared by direct dispersion of the complex (BUD concentration 0.5 mg mL-1) in solutions with PL407 or PL403. Male Wistar rats underwent TNBS-induced colitis and were treated for 5 days by a rectal route, as follows: BUD 1: BUDHP-ß-CD + PL407 (18%); BUD 2: BUDHP-ß-CD + PL407 (20%); BUD 3: BUDHP-ß-CD + PL407 (18%) + PL403 (2%); BUD 4: plain BUD; BUD 5: BUDHP-ß-CD; C1: HP-ß-CD + PL407 (18%); C2: HP-ß-CD + PL407 (20%); C3: HP-ß-CD + PL407 (18%) + PL403 (2%); C4: saline. A negative control group without colitis was also used. Colitis was assessed via myeloperoxidase (MPO) activity, and macroscopic and microscopic damage score in colon tissues. Protein levels of TNF-α, IL-1ß, IL-10 and endogenous glucocorticoids were obtained using ELISA. RESULTS: BUDHP-ß-CD poloxamer formulations had similar MPO activity when compared with the negative control group. All formulations presented lower MPO activity than BUDHP-ß-CD and plain BUD (p < 0.001). BUD 2 produced lower microscopic score values than plain BUD and BUDHP-ß-CD (p < 0.01). All formulations with BUDHP-ß-CD poloxamers reduced TNF-α levels (p < 0.05). CONCLUSION: Novel budesonide inclusion complex formulations improved microscopic damage and reduced colonic MPO activity and TNF-α levels.
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2-Hidroxipropil-beta-Ciclodextrina/farmacología , Budesonida/farmacología , Colitis Ulcerosa/tratamiento farmacológico , Hidrogeles/farmacología , Poloxámero/farmacología , Animales , Modelos Animales de Enfermedad , Combinación de Medicamentos , Masculino , Ratas , Ratas WistarRESUMEN
The World Health Organization declared the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-associated disease (coronavirus disease 2019 - COVID-19) as a pandemic in March 2020. COVID-19 is characterized by cytokine storm, acute respiratory distress syndrome (ARDS), and systemic inflammation-related pathology and already kills more than 1.5 million of people worldwide. Since aged and obese COVID-19 patients exhibit an enhanced inflammatory status, they represent a high-risk cluster for rapidly progressive clinical deterioration. These individuals present comorbid disorders and immunosenescence that may promote viral-induced cytokine storm and expression of molecules acting as virus receptor as angiotensin I converting enzyme 2 (ACE2) and CD26 (dipeptidyl-peptidase 4), resulting in respiratory failure and increased morbidity and mortality. A better knowledge of SARS-CoV-2 infection in inflammatory-associated high-risk population is essential in order to develop the therapies needed to combat or prevent severe COVID-19. Here, we review the pathogenesis and clinical implications of inflammatory disorders and disease markers associated to senescence in COVID-19 patients and the emerging evidence to argue that a high intake of polyphenols may have a protective effect on SARS-CoV-2 illness severity.
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Alterations in iron homeostasis are well described in obese patients. The effects of iron chelators on adipose tissue and other organs affected by obesity have been the interest of experimental studies, both in vivo and in vitro. The aim of this review was to update the available information indicating the potential of iron chelators as adjuvant drugs in the management of obesity and its comorbidities. The pharmacological actions of iron chelators, mainly deferoxamine, deferasirox, and deferiprone, on adipose tissue and liver alterations associated with obesity, were reviewed. Renal and other organ modifications observed in experimental obesity models (endotoxemia, ß-cell function, and systemic inflammation) were included, as well as data from clinical studies that were relevant to this review. The experimental results obtained with iron chelators showed their potential in the control of obesity-induced alterations in the adipose tissue and liver. However, knowledge about the possible systemic effects on endotoxemia and low-grade inflammation in obesity models is still lacking. In endotoxemia in humans, data obtained did not corroborate the anti-inflammatory effect described in experimental models. Clinical and experimental data reveal renal, ß-cell protection and inhibition of advanced glycation end products, which have long-term benefits in obesity. Experimental models of obesity demonstrated the beneficial effects of iron chelators on the adipose tissue, liver, kidneys, and ß-cells. Hence, clinical studies could be designed to evaluate the potential of iron chelators as a therapeutic option in the management of obesity.
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Quelantes del Hierro/farmacología , Obesidad/tratamiento farmacológico , Animales , Homeostasis/efectos de los fármacos , Humanos , Hierro/metabolismo , Quelantes del Hierro/uso terapéutico , Obesidad/complicaciones , Obesidad/metabolismo , Obesidad/patologíaRESUMEN
BACKGROUND: Gliomas are aggressive and resilient tumors. Progression to advanced stages of malignancy, characterized by cell anaplasia, necrosis, and reduced response to conventional surgery or therapeutic adjuvant, are critical challenges in glioma therapy. Relapse of the disease poses a considerable challenge for management. Hence, new compounds are required to improve therapeutic response. As hydrolyzed rutin (HR), a compound modified via rutin deglycosylation, as well as some flavonoids demonstrated antiproliferative effect for glioblastoma, these are considered potential epigenetic drugs. OBJECTIVE: The purpose of this study was to determine the antitumor activity and evaluate the potential for modifying tumor aggressivity of rutin hydrolysates for treating both primary and relapsed glioblastoma. METHODS: The glioblastoma cell line, U251, was used for analyzing cell cycle inhibition and apoptosis and for establishing the GBM mouse model. Mice with GBM were treated with HR to verify antitumor activity. Histological analysis was used to evaluate HR interference in aggressive behavior and glioma grade. Immunohistochemistry, comet assay, and thiobarbituric acid reactive substance (TBARS) values were used to evaluate the mechanism of HR action. RESULTS: HR is an antiproliferative and antitumoral compound that inhibits the cell cycle via a p53- independent pathway. HR reduces tumor growth and aggression, mainly by decreasing mitosis and necrosis rates without genotoxicity, which is suggestive of epigenetic modulation. CONCLUSION: HR possesses antitumor activity and decreases anaplasia in glioblastoma, inhibiting progression to malignant stages of the disease. HR can improve the effectiveness of response to conventional therapy, which has a crucial role in recurrent glioma.
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Anaplasia/complicaciones , Anaplasia/prevención & control , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/tratamiento farmacológico , Glioblastoma/complicaciones , Glioblastoma/tratamiento farmacológico , Rutina/farmacología , Rutina/uso terapéutico , Animales , Apoptosis/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Humanos , Hidrólisis , Ratones , Recurrencia , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoRESUMEN
PURPOSE: Maternal obesity can program the offspring, increasing the risk of overweight and obesity in adult life. Guarana (Paullinia cupana) is a Brazilian plant that has weight-reducing effects. Thus, this study aimed to evaluate the effects of Guarana on metabolic and inflammatory parameters in mice programmed by maternal obesity. METHODS: Swiss female mice were divided into two groups: control and high fat (HF), who received a standard diet or a high-fat diet (HFD), respectively, for 8 weeks prior to mating, gestation, and lactation. After post-natal day (PN) 21, the offspring of the HF group were subdivided into three groups: HF without treatment; HF early treatment, offspring treated with Guarana (1 g/kg bodyweight) in PN25-PN30; HF late treatment, offspring treated with Guarana (1 g/kg bodyweight) in PN65-PN75. Basal energy expenditure, the lipid profile and fasting glucose levels were determined. Body composition was evaluated by dissecting adipose tissue depots. Gene expression was analyzed using real-time PCR. RESULTS: During mating, the weight of HF females increased; after lactation, their adipose tissue depots and fasting glycemic levels also increased. The offspring of the HF group showed an increased body weight at PN21. At PN80, in the mice treated with Guarana (with both treatments), VO2 and energy expenditure increased, adipose tissue depots decreased, and the expression of leptin, IL-6, TNF-α, and MCP-1 decreased compared with that in the HF group. CONCLUSIONS: Guarana treatment at both stages of life reversed some of the alterations developed by the offspring of HF animals in adult life.
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Inflamación/metabolismo , Fenómenos Fisiologicos Nutricionales Maternos , Obesidad/metabolismo , Paullinia , Extractos Vegetales/farmacología , Efectos Tardíos de la Exposición Prenatal/metabolismo , Animales , Modelos Animales de Enfermedad , Femenino , Masculino , Ratones , Extractos Vegetales/administración & dosificación , Extractos Vegetales/metabolismo , EmbarazoRESUMEN
Obesity is a health problem worldwide, and energy imbalance has been pointed out as one of the main factors responsible for its development. As mitochondria are a key element in energy homeostasis, the development of obesity has been strongly associated with mitochondrial imbalance. Polyphenols are the largest group of phytochemicals, widely distributed in the plant kingdom, abundant in fruits and vegetables, and have been classically described as antioxidants owing to their well-established ability to eliminate free radicals and reactive oxygen species (ROS). During the last decade, however, growing evidence reports the ability of polyphenols to perform several important biological activities in addition to their antioxidant activity. Special attention has been given to the ability of polyphenols to modulate mitochondrial processes. Thus, some polyphenols are now recognized as molecules capable of modulating pathways that regulate mitochondrial biogenesis, ATP synthesis, and thermogenesis, among others. The present review reports the main benefits of polyphenols in modulating mitochondrial processes that favor the regulation of energy expenditure and offer benefits in the management of obesity, especially thermogenesis and mitochondrial biogenesis.
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Polifenoles/farmacología , Animales , Humanos , Inmunidad Innata , Análisis por Micromatrices , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Biogénesis de Organelos , Especies Reactivas de Oxígeno/metabolismo , Termogénesis/efectos de los fármacosRESUMEN
No scientific report proves the action of the phytochemicals from the mangrove tree Rhizophora mangle in the treatment of diabetes. The aim of this work is to evaluate the effects of the acetonic extract of R. mangle barks (AERM) on type 2 diabetes. The main chemical constituents of the extract were analyzed by high-performance liquid chromatography (HPLC) and flow injection analysis electrospray-iontrap mass spectrometry (FIA-ESI-IT-MS/MS). High-fat diet (HFD)-fed mice were used as model of type 2 diabetes associated with obesity. After 4 weeks of AERM 5 or 50 mg/kg/day orally, glucose homeostasis was evaluated by insulin tolerance test (kiTT). Hepatic steatosis, triglycerides and gene expression were also evaluated. AERM consists of catechin, quercetin and chlorogenic acids derivatives. These metabolites have nutritional importance, obese mice treated with AERM (50 mg/kg) presented improvements in insulin resistance resulting in hepatic steatosis reductions associated with a strong inhibition of hepatic mRNA levels of CD36. The beneficial effects of AERM in an obesity model could be associated with its inhibitory α-amylase activity detected in vitro. Rhizophora mangle partially reverses insulin resistance and hepatic steatosis associated with obesity, supporting previous claims in traditional knowledge.
Asunto(s)
Resistencia a la Insulina , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Extractos Vegetales/farmacología , Polifenoles/farmacología , Rhizophoraceae/química , Animales , Biomarcadores , Glucemia , Cromatografía Líquida de Alta Presión , Dieta Alta en Grasa , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Redes y Vías Metabólicas , Ratones , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/etiología , Extractos Vegetales/química , Extractos Vegetales/farmacocinética , Polifenoles/química , Polifenoles/farmacocinética , Sustancias Protectoras/química , Sustancias Protectoras/farmacocinética , Sustancias Protectoras/farmacología , Espectrometría de Masa por Ionización de Electrospray , Espectrometría de Masas en TándemRESUMEN
SCOPE: The potential effects of yerba mate (YM) on mitochondrial biogenesis and thermogenesis are evaluated. METHODS AND RESULTS: The in vitro effects of YM on mitochondrial respiration are assessed in C2C12 cells. The expression of genes related to mitochondrial biogenesis and thermogenesis are analyzed by quantitative PCR. The in vivo experiments are performed on mice fed a high-fat diet (HFD) and treated with YM extract. Indirect calorimetry was performed, and the expression of genes and proteins related to mitochondrial biogenesis, thermogenesis, and de novo lipogenesis is determined by quantitative PCR and western blot. Our in vitro data indicate that YM increases mtDNA copy number as well as mitochondrial spare respiratory capacity and coupling efficiency. The gene expression profile reinforces this evidence, indicating a modulation of genes downstream of Ampk. In vivo, it is found that YM partially prevents diet-induced obesity by increasing energy expenditure and enhancing mitochondrial biogenesis via the AMPK/SIRT1/PGC1α pathway. CONCLUSIONS: YM stimulates mitochondriogenesis and Ucp expression, leading to an increase in the spare respiratory capacity and energy dissipation. These effects may help to better understand the potential use of YM for obesity treatment.