RESUMO
Maintaining the mucus layer is crucial for the innate immune system. Urolithin A (Uro A) is a gut microbiota-derived metabolite; however, its effect on mucin production as a physical barrier remains unclear. This study aimed to elucidate the protective effects of Uro A on mucin production in the colon. In vivo experiments employing wild-type mice, NF-E2-related factor 2 (Nrf2)-deficient mice, and wild-type mice treated with an aryl hydrocarbon receptor (AhR) antagonist were conducted to investigate the physiological role of Uro A. Additionally, in vitro assays using mucin-producing cells (LS174T) were conducted to assess mucus production following Uro A treatment. We found that Uro A thickened murine colonic mucus via enhanced mucin 2 expression facilitated by Nrf2 and AhR signaling without altering tight junctions. Uro A reduced mucosal permeability in fluorescein isothiocyanate-dextran experiments and alleviated dextran sulfate sodium-induced colitis. Uro A treatment increased short-chain fatty acid-producing bacteria and propionic acid concentration. LS174T cell studies confirmed that Uro A promotes mucus production through the AhR and Nrf2 pathways. In conclusion, the enhanced intestinal mucus secretion induced by Uro A is mediated through the actions of Nrf-2 and AhR, which help maintain intestinal barrier function.
Assuntos
Colite , Cumarínicos , Mucosa Intestinal , Fator 2 Relacionado a NF-E2 , Receptores de Hidrocarboneto Arílico , Animais , Fator 2 Relacionado a NF-E2/metabolismo , Receptores de Hidrocarboneto Arílico/metabolismo , Camundongos , Mucosa Intestinal/metabolismo , Cumarínicos/farmacologia , Colite/metabolismo , Colite/induzido quimicamente , Mucina-2/metabolismo , Mucina-2/genética , Humanos , Colo/metabolismo , Camundongos Endogâmicos C57BL , Transdução de Sinais/efeitos dos fármacos , Masculino , Microbioma Gastrointestinal , Camundongos Knockout , Sulfato de Dextrana , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Função da Barreira IntestinalRESUMO
BACKGROUND: Enzymatically modified isoquercitrin (EMIQ) is produced from rutin using enzymatic hydrolysis followed by treatment with glycosyltransferase in the presence of dextrin to add glucose residues. EMIQ is absorbed in the same way as quercetin, a powerful antioxidant reported to prevent disused muscle atrophy by targeting mitochondria and to have ergogenic effects. The present study investigated the effect of EMIQ on skeletal muscle hypertrophy induced by functional overload. METHODS: In Study 1, 6-week-old ICR male mice were divided into 4 groups: sham-operated control, sham-operated EMIQ, overload-operated control, and overload-operated EMIQ groups. In Study 2, mice were divided into 3 groups: overload-operated whey control, overload-operated whey/EMIQ (low dose), and overload-operated whey/EMIQ (high dose) groups. The functional overload of the plantaris muscle was induced by ablation of the synergist (gastrocnemius and soleus) muscles. EMIQ and whey protein were administered with food. Three weeks after the operation, the cross-sectional area and minimal fiber diameter of the plantaris muscle fibers were measured. RESULTS: In Study 1, functional overload increased the cross-sectional area and minimal fiber diameter of the plantaris muscle. EMIQ supplementation significantly increased the cross-sectional area and minimal fiber diameter of the plantaris muscle in both the sham-operated and overload-operated groups. In Study 2, EMIQ supplementation combined with whey protein administration significantly increased the cross-sectional area and minimal fiber diameter of the plantaris muscle. CONCLUSION: EMIQ, even when administered as an addition to whey protein supplementation, significantly intensified the fiber hypertrophy of the plantaris muscle in functionally overloaded mice. EMIQ supplementation also induced fiber hypertrophy of the plantaris in sham-operated mice.
Assuntos
Fibras Musculares Esqueléticas/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Quercetina/análogos & derivados , Animais , Suplementos Nutricionais , Hipertrofia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Quercetina/administração & dosagem , Quercetina/farmacologia , Proteínas do Soro do Leite/administração & dosagem , Proteínas do Soro do Leite/farmacologiaRESUMO
During high-intensity exercise, the concentration of ammonia is augmented in skeletal muscle. Ammonia activates phosphofructokinase and prevents oxidation of pyruvate to acetyl CoA, thus leading to exhaustion. Citrulline is an amino acid component of the urea cycle in the liver, along with ornithine and arginine. The aim of this study was to examine the effect of citrulline supplementation on fatigue and performance during high-intensity exercise. We constructed a swimming exercise protocol, in which mice were subjected to exhaustive swimming with a load of 5% body weight, and measured the time until exhaustion, the blood levels of lactate and ammonia, and the glycogen content of the gastrocnemius and biceps femoris muscles. Citrulline supplementation significantly increased the swimming time until exhaustion. Exercise-induced blood ammonia elevation was repressed by citrulline supplementation, and exercise-induced blood lactate increment in the citrulline-supplemented group was significantly lower than that in the non-supplemented group. Citrulline supplementation may facilitate the detoxification of ammonia via the urea cycle and inhibit additional glycolysis. Our findings suggest that citrulline supplementation may be useful for improving the exercise performance of athletes.
Assuntos
Citrulina/uso terapêutico , Suplementos Nutricionais , Fadiga/prevenção & controle , Condicionamento Físico Animal/fisiologia , Resistência Física/efeitos dos fármacos , Natação/fisiologia , Amônia/sangue , Animais , Citrulina/farmacologia , Fadiga/sangue , Ácido Láctico/sangue , Masculino , Camundongos , Camundongos Endogâmicos ICR , Resistência Física/fisiologiaRESUMO
Potent peroxidase-like activity of the ß-ketoenamine (1)-dicopper (II) complex (2) for the chemiluminescence (CL) of luminol either in the presence or absence of H(2)O(2) has been previously demonstrated by our group. In this study, the ß-ketoenamine (1) as the ligand unit for copper(II) was incorporated into the oligonucleotide (ODN) probes. It has been shown that the catalytic activity of the ODN probes conjugating the ligand-Cu(II) complex is activated by hybridization with the target DNA with the complementary sequence. Thus, this study has successfully demonstrated the basic concept for the sensitive detection of nucleic acids by CL based on the template-inductive activation of the catalytic unit for CL.