RESUMO
2,2',4,4'-tetrabromodiphenyl ether (BDE47) is a foodborne environmental risk factor for depression, but the pathogenic mechanism has yet to be fully characterized. In this study, we clarified the effect of BDE47 on depression in mice. The abnormal regulation of the microbiome-gut-brain axis is evidenced closely associated with the development of depression. Using RNA sequencing, metabolomics, and 16s rDNA amplicon sequencing, the role of the microbiome-gut-brain axis in depression was also explored. The results showed that BDE47 exposure increased depression-like behaviors in mice but inhibited the learning memory ability of mice. The RNA sequencing analysis showed that BDE47 exposure disrupted dopamine transmission in the brain of mice. Meanwhile, BDE47 exposure reduced protein levels of tyrosine hydroxylase (TH) and dopamine transporter (DAT), activated astrocytes and microglia cells, and increased protein levels of NLRP3, IL-6, IL-1ß, and TNF-α in the brain of mice. The 16 s rDNA sequencing analysis showed that BDE47 exposure disrupted microbiota communities in the intestinal contents of mice, and faecalibaculum was the most increased genus. Moreover, BDE47 exposure increased the levels of IL-6, IL-1ß, and TNF-α in the colon and serum of mice but decreased the levels of tight junction protein ZO-1 and Occludin in the colon and brain of mice. In addition, the metabolomic analysis revealed that BDE47 exposure induced metabolic disorders of arachidonic acid and neurotransmitter 2-Arachidonoyl glycerol (2-AG) was one of the most decreased metabolites. Correlation analysis further revealed gut microbial dysbiosis, particularly faecalibaculum, is associated with altered gut metabolites and serum cytokines in response to BDE47 exposure. Our results suggest that BDE47 might induce depression-like behavior in mice through gut microbial dysbiosis. The mechanism might be associated with the inhibited 2-AG signaling and increased inflammatory signaling in the gut-brain axis.
Assuntos
Eixo Encéfalo-Intestino , Microbioma Gastrointestinal , Camundongos , Animais , Depressão/induzido quimicamente , Glicerol/farmacologia , Fator de Necrose Tumoral alfa , Disbiose/metabolismo , Interleucina-6 , Multiômica , Camundongos Endogâmicos C57BLRESUMO
The integrity and permeability of the intestinal epithelial barrier are important indicators of intestinal health. Impaired intestinal epithelial barrier function and increased intestinal permeability are closely linked to the onset and progression of various intestinal diseases. Sinapic acid (SA) is a phenolic acid that has anti-inflammatory, antihyperglycemic, and antioxidant activities; meanwhile, it is also effective in the protection of inflammatory bowel disease (IBD), but the specific mechanisms remain unclear. Here, we evaluated the anti-inflammatory of SA and investigated its potential therapeutic activity in LPS-induced intestinal epithelial barrier and tight junction (TJ) protein dysfunction. SA improved cell viability; attenuated epithelial permeability; restored the protein and mRNA expression of claudin-1, ZO-1, and occludin; and reversed the redistribution of the ZO-1 and claudin-1 proteins in LPS-treated Caco-2 cells. Moreover, SA reduced the inflammatory response by downregulating the activation of the TLR4/NF-κB pathway and attenuated LPS-induced intestinal barrier dysfunction by decreasing the activation of the MLCK/MLC pathway. This study demonstrated that SA has strong anti-inflammatory activity and can alleviate the occurrence of high intercellular permeability in Caco-2 cells exposed to LPS.
Assuntos
Ácidos Cumáricos/farmacologia , Mucosa Intestinal/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Transporte Ativo do Núcleo Celular , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Células CACO-2 , Sobrevivência Celular , Claudina-1/biossíntese , Progressão da Doença , Relação Dose-Resposta a Droga , Humanos , Inflamação , Lipopolissacarídeos/metabolismo , Ocludina/biossíntese , Permeabilidade , Junções Íntimas/metabolismo , Proteína da Zônula de Oclusão-1/biossínteseRESUMO
The present study investigated the effects of Lactobacillus plantarum YS2 (LP-YS2) that was isolated from yak yogurt on activated carbon-induced constipation in Kunming (KM) mice. The KM mice were orally administered LP-YS2 and reference strain Lactobacillus delbrueckii ssp. bulgaricus. Administration of LP-YS2 [1.0 × 109 cfu/kg of body weight (BW)] promoted gastrointestinal peristalsis and reduced the first black stool defecation time (129 min), which clearly defines attenuation of the voiding difficulty in mice with constipation. The LP-YS2 treatment also increased the serum level of motilin (MTL; 178.2 pg/mL), gastrin (69.4 pg/mL), acetylcholine (Ach; 30.1 pg/mL), substance P (SP; 57.6 pg/mL), and vasoactive intestinal peptide (VIP; 53.2 pg/mL) and reduced the somatostatin (SS, 32.6 pg/mL) levels compared with the L. delbrueckii ssp. bulgaricus treatment (MTL, 139.7 pg/mL; gastrin, 43.1 pg/mL; Ach, 15.9 pg/mL; SP, 43.6 pg/mL; VIP, 32.3 pg/mL; SS, 55.1 pg/mL) and the control (MTL, 105.3 pg/mL; gastrin, 26.7 pg/mL; Ach, 9.7 pg/mL; SP, 30.2 pg/mL; VIP, 21.0 pg/mL; SS, 70.5 pg/mL). The LP-YS2 treatment significantly increased the colonic mRNA and protein expression of c-Kit (CD117, cluster of differentiation 117; 2.87 times mRNA expression of the control group), stem cell factor (30.40 times mRNA expression of the control group), and glial cell-derived neurotrophic factor (29.97 times mRNA expression of the control group) in mice with constipation. In addition, LP-YS2 reduced the expression of transient receptor potential vanilloid 1 (0.42 times mRNA expression of the control group) and nitric oxide synthase (0.49 times mRNA expression of the control group) in constipated mice. These results demonstrate that LP-YS2 was able to attenuate the activated carbon-induced constipation in KM mice.
Assuntos
Constipação Intestinal/prevenção & controle , Lactobacillus plantarum/metabolismo , Iogurte/microbiologia , Animais , Antioxidantes/análise , Biomarcadores/análise , Peso Corporal , Bovinos , Carvão Vegetal/efeitos adversos , Colo/metabolismo , Constipação Intestinal/induzido quimicamente , Constipação Intestinal/terapia , Defecação , Trato Gastrointestinal/metabolismo , Trânsito Gastrointestinal/fisiologia , Intestino Delgado/metabolismo , Lactobacillus delbrueckii/metabolismo , Masculino , Camundongos , Óxido Nítrico Sintase/metabolismo , Peristaltismo/fisiologia , Substância P/metabolismoRESUMO
Yogurt from Xinjiang, China, is a traditional and naturally fermented food, and abundant microorganisms are produced during its fermentation process. In this study, we carried out in vivo animal experiments to explore the effect of a newly isolated lactic acid bacterial strain, Lactobacillus plantarum KSFY02 (LP-KSFY02), on oxidative aging. We used d-galactose to induce oxidative aging in mice and analyzed the serum and tissues of those mice using molecular biology detection methods. The results showed that LP-KSFY02 could inhibit the decreases in the thymic, cerebral, cardiac, liver, spleen, and kidney indices of mice caused by oxidative aging. The LP-KSFY02 strain increased activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione (GSH) and reduced levels of nitric oxide (NO) and malondialdehyde in the serum, liver, and spleen of the oxidative aging mice. Pathological observation demonstrated that LP-KSFY02 alleviated damage to the liver and spleen of oxidative aging mice. Quantitative PCR showed that LP-KSFY02 effectively upregulated mRNA expression of neuronal nitric oxide synthase (Nos1), endothelial nitric oxide synthase (Nos3), copper/zinc superoxide dismutase (Sod1), manganese superoxide dismutase (Sod2), catalase (Cat), heme oxygenase-1 (Hmox1), nuclear factor erythroid 2 related factor 2 (Nfe2l2), γ-glutamylcysteine synthetase (Gclm), and quinone oxidoreductase 1 (Nqo1) in mouse liver and spleen and downregulated expression of inducible nitric oxide synthase (Nos2). Western blot analysis revealed that LP-KSFY02 effectively upregulated protein expression of SOD1, SOD2, CAT, GSH1, and GSH2 in mouse liver and spleen tissues. Therefore, LP-KSFY02 can effectively prevent d-galactose-induced oxidative aging in mice. Its efficacy was superior to that of Lactobacillus delbrueckii ssp. bulgaricus (LDSB) and vitamin C, which are commonly used in the medical field as antioxidants. Thus, LP-KSFY02 is a high-quality strain with probiotic potential.
Assuntos
Envelhecimento/efeitos dos fármacos , Galactose/efeitos adversos , Lactobacillus plantarum/química , Probióticos/farmacologia , Substâncias Protetoras/farmacologia , Iogurte/microbiologia , Animais , Feminino , Fermentação , Lactobacillus plantarum/classificação , Masculino , Camundongos , Oxirredução , Estresse Oxidativo , Probióticos/química , Substâncias Protetoras/químicaRESUMO
BACKGROUND How to speed the recovery of viable myocardium in chronic total occlusion (CTO) patients after revascularization is still an unsolved problem. Breviscapine is widely used in cardiovascular diseases. However, there has been no study focused on the effect of breviscapine on viable myocardium recovery and left ventricular remodeling after CTO revascularization. MATERIAL AND METHODS We propose to recruit 78 consecutive coronary artery disease (CAD) patients with CTO during a period of 12 months. They will be randomly assigned to receive either breviscapine (40 mg) or placebo in the following 12 months. Blood tests, electrocardiogram, and Major Adverse Cardiac Events (MACE) will be collected at baseline and the follow-up visits at 1, 3, 6, 9, and 12 months. Low-dose dobutamine MRI will be applied for the assessment of viable myocardium, microcirculation perfusion, and left ventricular remodeling, and the concentrations of angiogenic cytokine, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) will be investigated at baseline and at 1- and 12-month follow-up. The recovery of viable myocardium after revascularization in CTO patients was the primary endpoint. Improvement of microcirculation perfusion, left ventricular remodeling, peripheral concentrations of VEGF and bFGF as well as MACE will be the secondary endpoints. RESULTS Breviscapine treatment obviously improve the recovery of viable myocardium, myocardial microcirculation perfusion, and left ventricular remodeling after revascularization in CTO patients, and reduce the occurrence of MACE. We also will determine if breviscapine increases the peripheral blood angiogenic cytokine concentrations of VEGF and bFGF. CONCLUSIONS This study will aim to demonstrate the effect of breviscapine on the recovery of viable myocardium and left ventricular remodeling in CTO patients after revascularization.
Assuntos
Oclusão Coronária/terapia , Flavonoides/administração & dosagem , Revascularização Miocárdica/métodos , Remodelação Ventricular/efeitos dos fármacos , Oclusão Coronária/tratamento farmacológico , Oclusão Coronária/cirurgia , Método Duplo-Cego , Coração/efeitos dos fármacos , Coração/fisiopatologia , Humanos , Miocárdio , Estudos Prospectivos , Projetos de Pesquisa , Resultado do Tratamento , Disfunção Ventricular Esquerda/tratamento farmacológico , Disfunção Ventricular Esquerda/patologiaRESUMO
We investigated in vitro and in vivo antioxidant activity of Lactobacillus paracasei ssp. paracasei YBJ01 (LPSP-YBJ01) isolated and identified from fermented yogurt. Strain LPSP-YBJ01 had stress tolerance against acidity, bile salt, and osmotic pressure. Five in vitro antioxidant assays were used to evaluate antioxidant activity of LPSP-YBJ01, which could scavenge free radicals (2,2-diphenyl-1-picrylhydrazyl and hydroxyl) and superoxide anion in vitro. In addition, strain LPSP-YBJ01 had stronger antilipid peroxidation activity and weak reducing power in vitro. We measured in vivo antioxidant activity of LPSP-YBJ01 in an oxidation mouse model induced by d-galactose injection. Strain LPSP-YBJ01 significantly increased serum superoxide dismutase (SOD), glutathione peroxidase, and total-antioxidant capability, and inhibited generation of malondialdehyde in a dose-dependent manner. In addition, strain LPSP-YBJ01 also increased the hepatic and splenic protein expressions of some antioxidant enzymes such as catalase, Cu/Zn-SOD, and Mn-SOD in mice treated with d-galactose. Thus, LPSP-YBJ01 had antioxidant activity in vitro and in vivo and may be a useful probiotic.
Assuntos
Galactose/efeitos adversos , Lacticaseibacillus paracasei/metabolismo , Estresse Oxidativo , Animais , Antioxidantes/farmacologia , Catalase/metabolismo , Bovinos , Fermentação , Galactose/metabolismo , Glutationa Peroxidase/metabolismo , Lacticaseibacillus paracasei/isolamento & purificação , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Malondialdeído/metabolismo , Camundongos , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Probióticos/farmacologia , Superóxido Dismutase/metabolismo , Iogurte/microbiologiaRESUMO
This study investigated the enhanced antiproliferative effect of Lactobacillus casei strain Shirota (LcS) on geniposide actions in human oral squamous carcinoma HSC-3 cells. An MTT assay, flow cytometry, qPCR assay, western blot and HPLC were used for this study. The concentration of 1.0 × 106 CFU/mL of LcS had no effect on the HOK normal oral epithelial cells and HSC-3 cancer cells. The 25 and 50 µg/mL geniposide concentrations also had no impact on HOK normal oral epithelial cells, but they had remarkable inhibitory effects on the growth of HSC-3 cancer cells, which are enhanced in the presence of LcS. By the flow cytometry assay, the LcS-geniposide-H (1.0 × 106 CFU/mL LcS and 50 µg/mL geniposide)-treated HSC-3 cancer cells had the largest number of cells undergoing apoptosis compared to cells treated with other combinationsand obviously more than cells treated with only geniposide-H (50 µg/mL geniposide). Geniposide-H could increase the mRNA and protein expressions of caspase-3, caspase-8, caspase-9, Bax, p53, p21, IκB-α, Fas, FasL, TIMP-1, and TIMP-2 as well as decrease those of Bcl-2, Bcl-xL, HIAP-1, HIAP-2, NF-κB, COX-2, iNOS, MMP-2, and MMP-9 compared to other groups of cells, and LcS further enhanced these changes, with results that are greater than for the cells treated with only a high concentration of geniposide. The results of this study show thatLcS enhanced the antiproliferative effect of geniposide in HSC-3 cancer cells.
Assuntos
Antineoplásicos Fitogênicos/metabolismo , Antineoplásicos Fitogênicos/farmacologia , Iridoides/metabolismo , Iridoides/farmacologia , Lacticaseibacillus casei/metabolismo , Biomarcadores Tumorais , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Caspases/genética , Caspases/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Bucais/genética , Neoplasias Bucais/metabolismoRESUMO
Kudingcha is a traditional Chinese tea, and insect tea is a special drink produced by the metabolism of insect larvae using the raw Kuding tea. Insect tea polyphenols (ITP) and its raw tea (Kuding tea) polyphenols (KTP) are high-purity polyphenols extracted by centrifuge precipitation. The present study was designed to compare the antioxidative effects of insect tea polyphenols (ITP) and its raw tea (Kuding tea) polyphenols (KTP) on d-galactose-induced oxidation in Kunming (KM) mice. KM mice were treated with ITP (200 mg/kg) and KTP (200 mg/kg) by gavage, and vitamin C (VC, 200 mg/kg) was also used as a positive control by gavage. After determination in serum, liver and spleen, ITP-treated mice showed higher superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione (GSH) activities and lower nitric oxide (NO), malonaldehyde (MDA) activities than VC-treated mice, KTP-treated mice and untreated oxidation mice (control group). By H&E section observation, the mice induced by d-galactose-induced oxidation showed more changes than normal mice, and oxidative damage appeared in liver and spleen tissues; ITP, VC and KTP improved oxidative damage of liver and spleen tissues, and the effects of ITP were better than VC and KTP. Using quantitative polymerase chain reaction (qPCR) and western blot experiments, it was observed that ITP could increase the mRNA and protein expression of neuronal nitric oxide synthase (nNOS), endothelial nitric oxide synthase (eNOS), manganese superoxide dismutase (Mn-SOD), cupro/zinc superoxide dismutase (Cu/Zn-SOD), catalase (CAT), heme oxygenase-1 (HO-1), nuclear factor erythroid 2 related factor 2 (Nrf2), gamma glutamylcysteine synthetase (γ-GCS), and NAD(P)H:quinone oxidoreductase 1 (NQO1) and reduce inducible nitric oxide synthase (iNOS) expression in liver and spleen tissues compared to the control group. These effects were stronger than for VC and KTP. Both ITP and KTP had good antioxidative effects, and after the transformation of insects, the effects of ITP were better than that of KTP and even better than VC. Thus, ITP can be used as an antioxidant and anti-ageing functional food.
Assuntos
Antioxidantes/química , Antioxidantes/farmacologia , Insetos/química , Polifenóis/química , Polifenóis/farmacologia , Chá/química , Animais , Antioxidantes/administração & dosagem , Biomarcadores/sangue , Expressão Gênica , Glutationa/sangue , Glutationa Peroxidase/sangue , Imuno-Histoquímica , Fígado/metabolismo , Fígado/patologia , Malondialdeído/sangue , Camundongos , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Óxido Nítrico/sangue , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase/metabolismo , Compostos Fitoquímicos/química , Polifenóis/administração & dosagem , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio/química , Superóxido Dismutase/sangueRESUMO
The aim of this study was to investigate the potential anti-inflammatory effect of Conyzacanadeusis methanol extract (CME) using a cell model of RAW264.7 murine macrophage cell stimulated with lipopolysaccharide (LPS)(1µg/ml). Co-treatment with different concentrations (10, 50 and 100µg/ml) of CME was concentration-dependently reduced the LPS-induced generation of prostaglandin E2 (PGE2), nitric oxide (NO) tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß and IL-6. In addition, CME also reduced the mRNA expressions of cyclooxygenase-2 (COX-2), inducible nitric oxide (iNOS), TNF-α, IL-1ß and IL-6 in LPS-stimulated RAW264.7 cells. These results suggested that CME showed an anti-inflammatory activity through reduced the mRNA expression of COX-2, iNOS, TNF-α IL-1ß and IL-6 and also decreased the productions of PGE2, NO, TNF-α IL-1ß and IL-6in LPS-stimulated RAW264.7 cells.
Assuntos
Anti-Inflamatórios/química , Inflamação/tratamento farmacológico , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Metanol/química , Extratos Vegetais/química , Solventes/química , Animais , Anti-Inflamatórios/isolamento & purificação , Sobrevivência Celular/efeitos dos fármacos , Fracionamento Químico , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Citocinas/genética , Citocinas/metabolismo , Dinoprostona/metabolismo , Relação Dose-Resposta a Droga , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Macrófagos/metabolismo , Camundongos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Fitoterapia , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Células RAW 264.7RESUMO
The preventive effect of polysaccharide of Larimichthys crocea swimming bladder (PLCSB) and the increase of this effect by use of resistant starch (RS3) as the carrier for PLCSB on azoxymethane (AOM) and dextran sulfate sodium (DSS)-inducing colon carcinogenesis in C57BL/6 mice has been studied. RS3 microspheres carrying PLCSB (RS3 + PLCSB) were produced and evaluated as a potentially improved colon carcinogenesis therapy for this study. The body weight, colon length, and colon weight of mice were determined, and colonic tissues were histologically observed. The serum levels of proinflammatory cytokines and the inflammation and apoptosis-related genes in colonic tissue were also tested. The PLCSB or RS3 + PLCSB significantly suppressed AOM and DSS-induced body weight loss, colon length shortening and decreased the colon weight to length ratio. PLCSB or RS3 + PLCSB reduced the levels of the serum pro-inflammatory cytokines IL-6, IL-12, TNF-α, and IFN-γ to a greater extent compared with the control mice, and the levels of RS3 + PLCSB were more close to the normal mice than PLCSB treated mice. Histopathological examination of sections of colon tissues showed that the RS3 + PLCSB group recovered well from colon carcinogenesis; however, the tissue sections of the stachyose + starch could reduce the necrosis degree. PLCSB significantly induced apoptosis in tissues of mice (p < 0.05) by up-regulating Bax, caspase-3, and caspase-9, and down-regulating Bcl-2. The expression of genes associated with inflammation-related NF-κB, iNOS, and COX-2 genes, was significantly down-regulated, and IκB-α was up-regulated (p < 0.05). These results suggest that PLCSB is a potent preventive against in vivo colon carcinogenesis and that PLCSB with an RS3 carrier could increase the preventative effect in mice.
Assuntos
Neoplasias do Colo/prevenção & controle , Perciformes/metabolismo , Polissacarídeos/uso terapêutico , Amido/química , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Azoximetano/farmacologia , Peso Corporal/efeitos dos fármacos , Neoplasias do Colo/induzido quimicamente , Neoplasias do Colo/patologia , Citocinas/metabolismo , Sulfato de Dextrana/toxicidade , Regulação para Baixo/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Mediadores da Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Perciformes/sangue , Polissacarídeos/química , Regulação para Cima/efeitos dos fármacosRESUMO
Ulcerative colitis (UC) is a chronic gastrointestinal disease that results from repeated inflammation and serious complications. Sinapic acid (SA) is a hydroxycinnamic acid present in a variety of plants that has antioxidant, anti-inflammatory, anticancer, and other protective effects. This study investigated the antifibrotic effect of SA on chronic colitis induced by dextran sulfate sodium salt (DSS) in mice. We observed that SA could significantly reduce clinical symptoms (such as improved body weight loss, increased colon length, and decreased disease activity index score) and pathological changes in mice with chronic colitis. SA supplementation has been demonstrated to repair intestinal mucosal barrier function and maintain epithelial homeostasis by inhibiting activation of the NLRP3 inflammasome and decreasing the expression of IL-6, TNF-α, IL-17A, IL-18, and IL-1ß. Furthermore, SA could induce the expression of antioxidant enzymes (Cat, Sod1, Sod2, Mgst1) by activating the Nrf2/keap1 pathway, thus improving antioxidant capacity. Additionally, SA could increase the protein expression of downstream LC3-II/LC3-I and Beclin1 and induce autophagy by regulating the AMPK-Akt/mTOR signaling pathway, thereby reducing the production of intestinal fibrosis-associated proteins Collagen-I and α-SMA. These findings suggest that SA can enhance intestinal antioxidant enzymes, reduce oxidative stress, expedite intestinal epithelial repair, and promote autophagy, thereby ameliorating DSS-induced colitis and intestinal fibrosis.
RESUMO
Sinapic acid (SA) is renowned for its many pharmacological activities as a polyphenolic compound. The cause of polycystic ovary syndrome (PCOS), a commonly encountered array of metabolic and hormonal abnormalities in females, has yet to be determined. The present experiment was performed to evaluate the antifibrotic properties of SA in rats with letrozole-induced PCOS-related ovarian fibrosis. SA treatment successfully mitigated the changes induced by letrozole in body weight (BW) (p < .01) and relative ovary weight (p < .05). Histological observation revealed that SA reduced the number of atretic and cystic follicles (AFs) and (CFs) (p < .01), as well as ovarian fibrosis, in PCOS rats. Additionally, SA treatment impacted the serum levels of sex hormones in PCOS rats. Luteinizing hormone (LH) and testosterone (T) levels were decreased (p < .01, p < .05), and follicle-stimulating hormone (FSH) levels were increased (p < .05). SA administration also decreased triglyceride (TG) (p < .01) and total cholesterol (TC) levels (p < .05) and increased high-density lipoprotein cholesterol (HDL-C) levels (p < .01), thereby alleviating letrozole-induced metabolic dysfunction in PCOS rats. Furthermore, SA treatment targeted insulin resistance (IR) and increased the messenger RNA (mRNA) levels of antioxidant enzymes in the ovaries of PCOS rats. Finally, SA treatment enhanced the activity of peroxisome proliferator-activated receptor-γ (PPAR-γ), reduced the activation of transforming growth factor-ß1 (TGF-ß1)/Smads, and decreased collagen I, α-smooth muscle actin (α-SMA), and connective tissue growth factor (CTGF) levels in the ovaries of PCOS rats. These observations suggest that SA significantly ameliorates metabolic dysfunction and oxidative stress and ultimately reduces ovarian fibrosis in rats with letrozole-induced PCOS.
RESUMO
An ultrasensitive label-free electrochemical sensor based on a homemade imprinted polypyrrole (PPy) polymer film was prepared to achieve quantitative determination of Lactobacillus rhamnosus GG (LGG). The LGG-imprinted polymer (LIP) film was deposited on a portable screen-printed electrode (SPE) via electropolymerization, which constituted an independent integrated system. The main preparation parameters of the LIP sensor were investigated to obtain optimal performance. Under optimized conditions, the peak current response of the LIP sensor showed a linear relationship with the logarithmic value of LGG concentration in the range from 101 to 109 CFU mL-1 and a detection limit of 5 CFU mL-1. The proposed LIP sensor has achieved efficient, ultrasensitive, highly selective, and cost-effective detection of LGG and can be further developed for practical applications in the quality inspection and development of probiotic products.
Assuntos
Lacticaseibacillus rhamnosus , Impressão Molecular , Polímeros , Pirróis , Eletrodos , Técnicas Eletroquímicas , Limite de DetecçãoRESUMO
In this paper, the potassium cobalt hexacyanoferrate (II), K2CoFe(CN)6, with peroxidase-like activity was used for the fabrication of a novel label-free Lactobacillus rhamnosus GG (LGG) electrochemical immunosensor. The K2CoFe(CN)6 nanocubes were made by a simple hydrothermal method and followed by low-temperature calcination. In addition to structural characterization, the peroxidase-mimicking catalytic property of the material was confirmed by a chromogenic reaction. It is known that H2O2 can oxidize electroactive thionine molecules under the catalysis of horseradish peroxidase (HRP). In this nanozyme-based electrochemical immunoassay, due to the steric hindrance, the formation of immune-complex of LGG and LGG antibody on the modified GCE inhibits the catalytic activity of the peroxidase mimics of K2CoFe(CN)6 and thus reduced the current signal. Therefore, the developed electrochemical immunosensor achieved quantitative detection of LGG. Under optimal conditions, the linear range of the sensor was obtained from 101 to 106 CFU mL-1 with a minimum detection limit (LOD) of 12 CFU mL-1. Furthermore, the immunosensor was successfully applied in the quantitative detection of LGG in dairy product samples with recoveries ranging from 93.2% to 106.8%. This protocol presents a novel immunoassay method, which provides an alternative implementation pathway for the quantitative detection of microorganisms.
Assuntos
Técnicas Biossensoriais , Lacticaseibacillus rhamnosus , Nanopartículas Metálicas , Peroxidase , Imunoensaio/métodos , Técnicas Biossensoriais/métodos , Peróxido de Hidrogênio/química , Nanopartículas Metálicas/química , Ouro/química , Peroxidase do Rábano Silvestre/química , Técnicas Eletroquímicas/métodos , Limite de DetecçãoRESUMO
Polycystic ovarian syndrome (PCOS) is one of the commonest endocrinopathies in childbearing women. The research was conducted to assess the impact of Irpex lacteus polysaccharide (ILP, 1000 mg/kg) on the letrozole (1 mg/kg)-induced PCOS model in female rats. Metformin (Met, 265 mg/kg) as the positive control. The study suggested that ILP restored the estrous cycle in rats with PCOS as well as lowered relative ovarian weight and body weight, in comparison to normal. Rats with PCOS showed improvement in ovarian structure and fibrosis when given ILP. ILP decreased the testosterone (T), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), total cholesterol (TC), luteinizing hormone (LH), homeostasis model assessment-insulin resistance (HOMA-IR), fasting blood glucose (FBG), and insulin (INS) levels and elevated the follicle-stimulating hormone (FSH) and estrogen (E2) levels in PCOS rats. In addition, ILP increased the content of superoxide dismutase (SOD) in serum and the antioxidant enzymes (Prdx3, Sod1, Gsr, Gsta4, Mgst1, Gpx3, Sod2 and Cat) expression levels in the ovaries and decreased the serum expression of malondialdehyde (MDA). In addition, ILP treatment slowed down the process of the fibrosis-associated TGF-ß1/Smad pathway and downregulated α-smooth muscle actin (α-SMA) and connective tissue growth factor (CTGF) levels in PCOS rats ovaries. According to these findings, ILP may be able to treat letrozole-induced PCOS in rats by ameliorating metabolic disturbances, sex hormone levels, oxidative stress, and ovarian fibrosis.
RESUMO
Tris (1,3-dichloro-2-propyl) phosphate (TDCPP) has neurotoxicity, but its mechanism remains unclear. Evidence recently showed that ferroptosis might be associated with TDCPP-induced neurotoxicity. To explore the role and underlying mechanism of ferroptosis in TDCPP-induced neurotoxicity, the occurrence of ferroptosis was examined in mice and PC12 cells upon TDCPP exposure. The mechanism of TDCPP-induced ferroptosis was clarified in vitro combined with the RNA sequencing assay. The in vivo results showed that orally TDCPP exposure (100 mg/kg, 30 d) inhibited the learning and memory ability of mice, reduced hippocampus neurons, induced malondialdehyde (MDA) accumulation, and decreased glutathione (GSH) and superoxide dismutase (SOD) levels in the hippocampus. Moreover, TDCPP exposure (100 mg/kg, 30 d) altered the ferroptosis and autophagy-related protein abundances in the hippocampus. The in vitro results showed that TDCPP exposure (0, 5, 20, 50, 100, and 200 µM) for 24 h induced dose-dependent cell death in PC12 cells, and the cell death was ameliorated by the co-treatment with ferrostatin-1 (1 µM, 24 h). Similarly, TDCPP exposure (0, 50, 100, and 200 µM) for 24 h increased the levels of MDA and LPO, but decreased the reduced GSH in PC12 cells. Furthermore, TDCPP exposure (0, 50, 100, and 200 µM) for 24 h altered the ferroptosis and autophagy-related protein abundances in PC12 cells. The RNA-sequencing revealed that TDCPP exposure (100 µM, 24 h) induced mitophagy activation in SH-SY5Y cells. Meanwhile, the in vitro experiments confirmed that TDCPP exposure (0, 50, 100, and 200 µM) for 24 h increased abundances of mitophagy-related protein phosphatase and tensin homolog induced kinase 1(PINK1), Parkinson protein 2 E3 ubiquitin-protein ligase (PARKIN), inositol 1,4,5-trisphosphate receptor type 1 (IP3R1), and voltage-dependent anion channel 1 (VDAC1) in PC12 cells. Moreover, TDCPP treatment (100 µM, 24 h) increased the mitochondrial recruitment of PARKIN, decreased the mitochondrial membrane potential (MMP) level, and increased the Fe2+ level in mitochondria. In addition, decreased ATP levels and increased reactive oxygen species (ROS) levels were observed in PC12 cells upon TDCPP exposure (0, 50, 100, and 200 µM) for 24 h. In summary, ferroptosis was associated with TDCPP-induced neurotoxicity, and the mechanism might be related to PINK1/PARKIN-mediated mitophagy initiated by mitochondrial damage.
Assuntos
Ferroptose , Retardadores de Chama , Neuroblastoma , Síndromes Neurotóxicas , Trifosfato de Adenosina , Animais , Proteínas Relacionadas à Autofagia , Glutationa/metabolismo , Humanos , Receptores de Inositol 1,4,5-Trifosfato , Malondialdeído , Camundongos , Mitofagia/fisiologia , Compostos Organofosforados , Fosfatos/metabolismo , Proteínas Quinases/metabolismo , RNA , Ratos , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Tensinas/metabolismo , Ubiquitina-Proteína Ligases/genética , Canal de Ânion 1 Dependente de VoltagemRESUMO
Tea seed saponins (TSS) are oleanolane-type pentacyclic triterpenoid saponin mixtures with various pharmacological effects. We aimed to explore the effects of a total of 4 weeks intragastric administration of TSS (140 mg/kg·day) combined with aerobic exercise (AE) on lipid metabolism and its associated oxidative stress in HFD-induced obese mice and to investigate the possible molecular mechanisms. TSS + AE intervention significantly reduced body weight and the adiposity index (including subcutaneous, epididymal, perirenal, and abdominal adipose) in obese mice; improved dyslipidemia by lowering serum TC, TG, and LDL-c levels; and increased HDL-c levels. TSS + AE intervention significantly improved hepatic steatosis by inhibiting lipogenetic Acc, Srebp1c, and Scd1 and upregulating lipolysis genes (Pgc1α, Pgc1ß, Pparα, and Cpt1). TSS + AE intervention increased the hepatic protein expression of p-AMPK, SIRT1, and PGC-1α, as well as PPAR-γ and GLUT-4 in skeletal muscle compared with expression in the HFD group. In addition, TSS + AE also modulated oxidative stress in obese mice, which was indicated by the increased serum and liver levels of SOD, GSH, and T-AOC and decreased ROS and MDA levels. These results suggest that TSS + AE intervention can reduce fat accumulation and improve HFD-induced lipid metabolism disorders and oxidative stress. PRACTICAL APPLICATIONS: Obesity is a metabolic disease induced by excess nutritional intake and insufficient energy expenditure. Dietary modifications combined with aerobic exercise are currently an effective method for weight loss. Tea seed saponins (TSS) are a variety of biologically active oleanolane-type pentacyclic triterpenoid saponins that naturally exist in tea seeds. Few articles have focused on the effects and mechanisms of TSS combined with aerobic exercise (AE) in regulating lipid metabolism and improving oxidative damage in vivo. Using an HFD-induced obese mice model to explore the mechanism of TSS + AE in regulating lipid metabolism and its associated oxidative stress damage will help provide reliable data for the application of dietary nutrition combined with AE in anti-obesity.
Assuntos
Metabolismo dos Lipídeos , Saponinas , Camundongos , Animais , Dieta Hiperlipídica/efeitos adversos , Saponinas/farmacologia , Camundongos Obesos , Obesidade/tratamento farmacológico , Obesidade/etiologia , Obesidade/metabolismo , Estresse Oxidativo , Exercício Físico , Chá , Triterpenos Pentacíclicos/farmacologiaRESUMO
Abnormal production and degradation of amyloid beta (Aß) in the brain lead to oxidative stress and cognitive impairment in Alzheimer's disease (AD). Cirsium japonicum var. maackii (CJM) is widely used as an herbal medicine and has antibacterial and anti-inflammatory properties. This study focused on the protective effect of the ethyl acetate fraction from CJM (ECJM) on Aß 25-35-induced control mice. In the T-maze and novel object recognition test, ECJM provided higher spatial memory and object recognition compared to Aß 25-35 treatment alone. In the Morris water maze test, ECJM-administered mice showed greater learning and memory abilities than Aß 25-35-induced control mice. Additionally, ECJM-administered mice experienced inhibited lipid peroxidation and nitric oxide production in a dose-dependent manner. The present study indicates that ECJM improves cognitive impairment by inhibiting oxidative stress in Aß 25-35-induced mice. Therefore, CJM may be useful for the treatment of AD and may be a potential material for functional foods.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/toxicidade , Cirsium/química , Disfunção Cognitiva/tratamento farmacológico , Fragmentos de Peptídeos/toxicidade , Extratos Vegetais/farmacologia , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/fisiopatologia , Animais , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Extratos Vegetais/químicaRESUMO
This study investigated the antiasthmatic and anti-inflammatory effects of Lactobacillus plantarum-CQPC11 (LP-CQPC11) on ovalbumin (OVA)-induced asthmatic Balb/c mice. Administration of different doses of LP-CQPC11 (105 , 107 , and 109 colony-forming unit [CFU]/mouse) effectively reduced airway hyperresponsiveness (AHR) and the lung W/D ratio in asthmatic mice. LP-CQPC11 treatment reduced the accumulation of inflammatory cells in the BALF and attenuated histologic edema in asthmatic mice. Administration of LP-CQPC11 decreased the serum levels of OVA-specific IgE, IgE, and OVA-specific IgG1. LP-CQPC11 treatment decreased the levels of inflammatory cytokines (TNF-α, IL-4, IL-13, IL-5, and IL-6) in the BALF of asthmatic mice. In addition, LP-CQPC11 also elevated the mRNA levels of Foxp3 and T-bet and decreased the mRNA levels of Gata3 and RORγt in asthmatic mice lungs. Administration of LP-CQPC11 also reduced OVA-induced oxidative stress by improving the activities of GSH-Px, SOD, and catalase in the lungs. Finally, LP-CQPC11 treatment also significantly decreased the activation of the NF-κB pathway to modulate the inflammatory reaction in the lungs of asthmatic mice. The results from this study clearly demonstrated that oral administration of LP-CQPC11 exhibited outstanding activity in attenuating OVA-induced asthma in a mouse model. Furthermore, LP-CQPC11 may be an effective microecologic agent in preventing allergic asthma in the future. PRACTICAL APPLICATIONS: Allergic asthma is a common chronic inflammation-associated respiratory disease. Lactic acid bacteria (LAB) are known as a health product involved in modulating immune tolerance and play important roles in disease prevention and treatment. Many studies have reported that LAB, as probiotics, exhibits great antioxidation, anticancer, and anti-inflammatory activities and have health benefits in gastrointestinal disorders. In fact, human studies have confirmed that Lactobacillus rhamnosus strains have an effective activity to reduce the risk of allergic asthma. LP-CQPC11 was isolated from Sichuan pickled cabbages (a type of LAB-fermented vegetable product, also called Sichuan paocai) and was reported to reduce d-galactose-induced aging in mice in our previous study. However, the antiasthmatic and anti-inflammatory activities of LP-CQPC11 are unclear. The current study investigated the antiasthmatic and anti-inflammatory effects of LP-CQPC11 on OVA-induced asthmatic Balb/c mice.
Assuntos
Asma , Lactobacillus plantarum , Administração Oral , Animais , Asma/tratamento farmacológico , Líquido da Lavagem Broncoalveolar , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/efeitos adversosRESUMO
Background: Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility in women. Rhamnocitrin (Rha) has anti-inflammatory and antioxidant actions. The WNT1-inducible-signaling pathway protein 2 (Wisp2) and nuclear factor (NF)-κB are involved in fibrosis in many diseases. We aimed to elucidate the role of Rha in fibrosis of PCOS and the underlying mechanisms. Methods: Dehydroepiandrosterone (DHEA)-incubated ovarian granulosa KGN cells were treated by Rha. Cell proliferation was detected with cell counting kit-8 (CCK-8) and 5-ethynyul-2'-deoxyuridine (EdU) staining. The levels of Wisp2 and transforming growth factor-ß1 (TGF-ß1) in supernatant were measured by enzyme-linked immunosorbent assay (ELISA). We observed α-smooth muscle actin (α-SMA) protein by immunofluorescence (IF). The levels of fibrosis factors were determined using Western blot. We observed p65 nuclear translocation with confocal microscopy. We used Wisp2 overexpression and knockdown in cells treated with DHEA or Rha to validate Wisp2 function. Interaction between Wisp2 and NF-κB, as well as Wisp2 and PPARγ, were assessed by co-immunoprecipitation assay, luciferase reporter assay and chromatin immunoprecipitation (ChIP). Results: The results showed that Rha elevated the reduced proliferation of DHEA-treated cells. In addition, Rha reversed the decreased Wisp2 and the increased TGF-ß1 in supernatant. The proteins CTGF, α-SMA, Collagen I, TGF-ß1, p-Smad2, and p-Smad3 were up-regulated while Wisp2, Sirt1, and PPARγ were down-regulated by DHEA treatment, which were reversed by Rha. Meanwhile, DHEA up-regulated p-IKBa and p-p65 and promoted p65 nuclear translocation, which were inhibited by Rha. These effects of Rha were antagonized by Wisp2 knockdown and were mimicked by Wisp2 overexpression. We confirmed the protein interaction between Wisp2 and NF-κB, along with Wisp2 and PPARγ. Conclusions: Wisp2-mediated PPARγ/NF-κB/TGF-ß1/Smad2/3 signaling contributes to Rha-improved ovarian granulosa cells fibrosis, suggesting Rha as a novel agent for the treatment of PCOS.