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1.
Dig Dis Sci ; 68(7): 2981-2996, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36867295

RESUMO

BACKGROUND: Sodium butyrate (NaB) is a short-chain fatty acid produced by intestinal microbial fermentation of dietary fiber, and has been shown to be effective in inhibiting ulcerative colitis (UC). However, how NaB regulates inflammation and oxidative stress in the pathogenesis of UC is not clear. AIMS: The purpose of this study was to use a dextran sulfate sodium salt (DSS)-induced murine colitis model, and determine the effects of NaB and the related molecular mechanisms. METHODS: Colitis model was induced in mice by administration of 2.5%(wt/vol) DSS. 0.1 M NaB in drinking water, or intraperitoneal injection of NaB (1 g/kg body weight) was given during the study period. In vivo imaging was performed to detect abdominal reactive oxygen species (ROS). Western blotting and RT-PCR were used to determine the levels of target signals. RESULTS: The results showed that NaB decreases the severity of colitis as determined by an improved survival rate, colon length, spleen weight, disease activity index (DAI), and histopathological changes. NaB reduced oxidative stress as determined by a reduction in abdominal ROS chemiluminescence signaling, inhibition of the accumulation of myeloperoxidase and malondialdehyde, and restoration of glutathione activity. NaB activated the COX-2/Nrf2/HO-1 pathway by increasing the expressions of COX-2, Nrf2, and HO-1 proteins. NaB inhibited the phosphorylation of NF-κB and activation of NLRP3 inflammasomes, and reduced the secretion of corresponding inflammatory factors. Furthermore, NaB promoted the occurrence of mitophagy via activating the expression of Pink1/Parkin. CONCLUSIONS: In conclusion, our results indicate that NaB improves colitis by inhibiting oxidative stress and NF-κB/NLRP3 activation, which may be via COX-2/Nrf2/HO-1 activation and mitophagy.


Assuntos
Colite Ulcerativa , Colite , Camundongos , Animais , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ácido Butírico/farmacologia , Sulfato de Dextrana/toxicidade , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Mitofagia , Ciclo-Oxigenase 2/metabolismo , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/patologia , Colite Ulcerativa/patologia , Transdução de Sinais , Estresse Oxidativo , Cloreto de Sódio , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças
2.
Crit Rev Food Sci Nutr ; 62(27): 7591-7614, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33905288

RESUMO

Cardiovascular diseases (CVDs) have been ranked as the leading cause of death in the world, whose global incidence is increasing year by year. Citrus, one of the most popular fruits in the world, is rich in flavonoids. Citrus flavonoids attract special attention due to a variety of biological activities, especially in the prevention and treatment of CVDs. The research progress of citrus flavonoids on CVDs have been constantly updated, but relatively fragmented, which needed to be systematically summarized. Hence, the recent research about citrus flavonoids and CVDs were reviewed, including the types and in vivo processes of citrus flavonoids, epidemiology study and mechanism on prevention and treatment of CVDs by citrus flavonoids. This review would provide a theoretical basis for the citrus flavonoids research and a new idea in the citrus industry development and application.


Assuntos
Doenças Cardiovasculares , Citrus , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Frutas
3.
Bioorg Chem ; 120: 105619, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35086063

RESUMO

A series of 2-Aryl-4-Bis-amide Imidazoles (ABAI-1 to 30) were designed as anti-inflammatory agents. These compounds were synthesized and evaluated for the in vitro anti-inflammatory activities (inhibition of NO production and release of inflammatory cytokines). Several compounds effectively inhibited NO production in lipopolysaccharide (LPS) induced RAW264.7 cells. Among them, ABAI-30 exhibited the highest NO-inhibitory effect (inhibition rate of 87% at 20 µM). The anti-inflammatory mechanism of ABAI-30 was examined and found to be inhibiting the TLR4-pp65 and NLRP3-caspase-1 signaling pathway, thus leading to the downregulation of IL6, IL-1ß and TNFα at both transcriptional and translational levels. Importantly, ABAI-30 demonstrated high in vivo anti-inflammatory efficacy in a dextran sulfate sodium (DSS)-induced colitis mouse model without causing obvious toxicity. Collectively, our study provides a potent anti-inflammatory agent, which deserves further investigation as a novel therapeutic candidate for treating inflammatory bowel diseases.


Assuntos
Amidas , Doenças Inflamatórias Intestinais , Amidas/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Citocinas/metabolismo , Sulfato de Dextrana/uso terapêutico , Imidazóis/farmacologia , Imidazóis/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Camundongos , Camundongos Endogâmicos C57BL
4.
J Anim Physiol Anim Nutr (Berl) ; 104(2): 735-748, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31900998

RESUMO

The structural characteristics of a novel Flammulina velutipes polysaccharide (FVP2) were explored in this study. Besides, immunomodulatory activities of FVP2 on RAW 264.7 cell and its impact on gut microbiota in rats were investigated. FVP2 has a molecular weight of 18.3 kD, and its main components include galactose (19.96%), glucose (60.66%) and mannose (19.38%). By NMR analysis, the main-chain structure consisted of (1 â†’ 3)-linked-ß-D-Gal, (1 â†’ 6) -linked-ß-D-Gal, (1 â†’ 6)-linked-α-D-Glc and (1 â†’ 3,6)-linked-α-D-Man was identified. Results of the in vitro assays on RAW 264.7 murine macrophage cells showed FVP2 could significantly up-regulate the expression of NO, TNF-α and IL-6. FVP2 was intragastrically administered to rats for 2 weeks. Compared with the control group, two caecal short-chain fatty acids (SCFAs) concentration (isobutyric acid and butyric acid) and the abundance of beneficial microbiota of the FVP2-treated group were significantly increased (p < .05) respectively. The results demonstrated that FVP2 could effectively enhance the level of butyric acid and increase beneficial gut microbiota, which could improve the intestinal barrier function and maintain the intestinal mucosal integrity, suggesting that FVP2 could potentially be an immunomodulators or a functional food to promote intestinal health.


Assuntos
Flammulina/química , Microbioma Gastrointestinal/efeitos dos fármacos , Polissacarídeos/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Polissacarídeos/química , Células RAW 264.7 , Ratos , Ratos Sprague-Dawley , Testes de Toxicidade
5.
Vet Res ; 50(1): 3, 2019 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-30642401

RESUMO

Echinococcosis is a zoonotic infection caused by cestode species of the genus Echinococcus, with limited treatment options. It is urgent to develop new anti-hydatid agent. In this paper, we reported anacardic acid (AA), a natural product isolated from the Brazilian cashew-nut shell liquid, which presented a high activity against metacestodes of Echinococcus multilocularis (E. multilocularis) and Echinococcus granulosus sensu stricto (E. granulosus s.s.) in vitro and in vivo. AA exerted a better efficacy on E. granulosus s.s. protoscoleces and E. multilocularis metacestodes than that of albendazole (ABZ) and dihydroartemisinin (DHA) in vitro, and an inhibition on the growth of Echinococcus metacestode as effective as ABZ in vivo. Moreover, we also found that one of the mechanisms of AA against Echinococcus could be the suppression of angiogenesis on/in the metacestode mass through inhibiting vascular endothelial growth factor (VEGF)-induced signalling pathways. This work finds that AA is a new promising potential candidate drug for echinococcosis treatment.


Assuntos
Ácidos Anacárdicos/farmacologia , Anticestoides/farmacologia , Echinococcus granulosus/efeitos dos fármacos , Echinococcus multilocularis/efeitos dos fármacos , Neovascularização Fisiológica/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Anacardium/química , Animais , Echinococcus granulosus/crescimento & desenvolvimento , Echinococcus granulosus/fisiologia , Echinococcus multilocularis/crescimento & desenvolvimento , Echinococcus multilocularis/fisiologia , Feminino , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Larva/fisiologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Distribuição Aleatória
6.
Biometals ; 31(4): 457-476, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29748744

RESUMO

To ensure the safe use of nanoparticles (NPs) in modern society, it is necessary and urgent to assess the potential toxicity of NPs. Cardiovascular system is required for the systemic distribution of NPs entering circulation. Therefore, the adverse cardiovascular effects of NPs have gained extensive research interests. Metal based NPs, such as TiO2, ZnO and Ag NPs, are among the most popular NPs found in commercially available products. They may also have potential applications in biomedicine, which could increase their contact with cardiovascular systems. This review aimed at providing an overview about the adverse cardiovascular effects of TiO2, ZnO and Ag NPs. We discussed about the bio-distribution of NPs following different exposure routes. We also discussed about the cardiovascular toxicity of TiO2, ZnO and Ag NPs as assessed by in vivo and in vitro models. The possible mechanisms and contribution of physicochemical properties of metal based NPs were also discussed.


Assuntos
Sistema Cardiovascular/efeitos dos fármacos , Nanopartículas/toxicidade , Titânio/toxicidade , Óxido de Zinco/toxicidade , Cardiotoxicidade/epidemiologia , Sistema Cardiovascular/fisiopatologia , Humanos , Nanopartículas/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/química , Prata/uso terapêutico , Prata/toxicidade , Titânio/uso terapêutico , Óxido de Zinco/uso terapêutico
7.
Mol Nutr Food Res ; 68(3): e2300529, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38044268

RESUMO

SCOPE: The current researches indicated that the epithelial-mesenchymal transition (EMT) of hepatocytes plays a crucial role in the development of liver fibrosis. To date, there is a paucity of literature regarding the impact of nobiletin (NOB) on liver fibrosis. This study investigates the inhibitory effect of NOB on EMT in hepatocytes during the progression of liver fibrosis and its underlying mechanism. METHODS AND RESULTS: The findings demonstrated that NOB significantly suppresses liver fibrosis in carbon tetrachloride (CCl4 )-induced mice by reducing inflammation and fiber deposition in the liver. Moreover, NOB mitigates EMT in hepatocytes, concurrently alleviating inflammatory status and reducing the production of reactive oxygen species (ROS) generation. The comprehensive investigation reveals that the hepatoprotective effect of NOB in liver fibrosis is attributed to autophagy activation, as evidenced by a significant increase in LC3 II expression and p62 degradation upon NOB treatment. Additionally, NOB activates the Hippo/YAP pathway by downregulating YAP and its downstream targets in liver fibrosis, which is regulated by autophagy based on experiments with chloroquine (CQ), 3-methyladenine (3-MA), and siYAP intervention. CONCLUSION: Therefore, this study provides evidences that NOB can protect hepatocytes from undergoing EMT during liver fibrosis by inducing autophagy and subsequently modulating the Hippo/YAP pathway.


Assuntos
Flavonas , Hepatócitos , Transdução de Sinais , Camundongos , Animais , Cirrose Hepática/tratamento farmacológico , Fígado/metabolismo , Transição Epitelial-Mesenquimal/fisiologia , Autofagia
8.
Food Res Int ; 177: 113900, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38225143

RESUMO

This work aims to explore an available avenue to design an equilibrium modified atmosphere packaging (EMAP) by the modification of gas permeability of material. In this work, the introduction of available active sites endowed materials with adjustable gas permeability properties. With varying concentrations of the resulting materials with various gas permeability, the CO2 and O2 gas permeability of the blending films were modified at the range of 3.92 âˆ¼ 17.84 barrier and 0.65 âˆ¼ 3.46 barrier, respectively. On this basis, the films were used as EMAP to preserve postharvest cabbages. The results indicated that each EMAP achieved an equilibrium atmosphere containing 6.8 % ∼ 3.8 % CO2 and 2.1 % ∼ 5.2 % O2 within 15 h and maintained it continuously. In these atmosphere, the respiratory rate of the preserved cabbages was significantly inhibited, thereby delaying the deterioration of their storage quality. As the results, sensory scores of the preserved samples were maximally maintained. Declines of color indexes and texture indexes were obviously inhibited. Chemical variations in chlorophyll content, total phenolics content, total flavonoids content, ascorbic acid and nitrite content were significantly suppressed. The overall findings revealed that this method is suitable and promising to develop EMAP for the postharvest vegetables.


Assuntos
Brassica , Embalagem de Alimentos , Embalagem de Alimentos/métodos , Conservação de Alimentos/métodos , Dióxido de Carbono , Oxigênio/química , Domínio Catalítico , Atmosfera
9.
Food Chem ; 454: 139834, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38815322

RESUMO

Modern science often overlooks to reveal the scientific essence of traditional crafts to promote their inheritance and development. In this work, five different types of tea products were prepared using the same variety of tea leaves referring to traditional methods. The analysis of their components and activities indicated that the processing reduced total catechin contents (from 172.8 mg/g to 48.2 mg/g) and promoted the synthesis of theaflavins (from 17.9 mg/g to 43.4 mg/g), reducing antioxidant and antimicrobial abilities of the resulting tea products. On this basis, the tea products were applied to "tea flavored beef" to reveal long-term effects. Within 15 days of storage, tea treatment showed remarkable antimicrobial and antioxidant activities on the beef. Also, the declines of sensory scores and texture of the treated beef were significantly suppressed. Meanwhile, protein degradation in the beef was inhibited, limiting the contents of various biogenic amines within relatively low levels.


Assuntos
Antioxidantes , Camellia sinensis , Aromatizantes , Chá , Animais , Bovinos , Camellia sinensis/química , Aromatizantes/química , Antioxidantes/química , Antioxidantes/farmacologia , Chá/química , Paladar , Catequina/química , Catequina/análise , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Humanos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , China , Biflavonoides/química , Biflavonoides/análise , Biflavonoides/farmacologia
10.
Int J Biol Macromol ; 275(Pt 1): 133426, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38936574

RESUMO

The structure and bioactivities of a novel polysaccharide from Lonicera caerulea L. var. edulis Turcz. ex Herd. fruit (THP-3) were investigated. The crude polysaccharides of Turcz. ex Herd. (THP) were extracted by hot water extraction. After purification, the chemical structure of polysaccharides was identified. Then, a mouse model of acute drug-induced liver injury was constructed using 4-acetamidophenol (APAP) and pretreated with THP. The number-average molecular weight of THP-3 was 48.89 kDa and the mass average molar mass was 97.87 kDa. THP-3 was mainly composed of arabinose (42.54 %), glucose (27.62 %), galacturonic acid and galactose (29.84 %). The main linkage types of THP-3 were 1-linked Araf, 1,4-linked Glcp, and 1,3,6-linked Galp. In addition, after THP treatment, serum Alanine aminotransferase (ALT), Aspartate aminotransferase (AST) and γ-glutamyl transpeptidase (γGT) in AILI mice were successfully down-regulated. The results showed that THP could prevent the characteristic morphological changes of hepatic lobular injury and lipid depletion caused by APAP, reduced the level of oxidative damage in mice, increased the expression of APAP-induced hypolipidemia and related inflammatory indicators, and improved the detoxification function of liver. In general, the newly extracted THP polysaccharide has a good liver protection effect and is an ideal natural medicine for the treatment of liver diseases.

11.
Food Funct ; 15(13): 7124-7135, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38881239

RESUMO

Alcoholic liver injury has become a leading threat to human health, with complicated pathogenesis and limited therapeutic options. Our previous study showed that Musculus senhousei peptides (MSPs) exhibit protective potential against early-stage alcoholic liver injury, although the underlying mechanism is not yet clear. In this study, histopathological analysis, mRNA abundance of injury-associated biomarkers, the gut microbiota, and faecal metabolome were evaluated using a mouse model subjected to acute alcohol exposure, aiming to identify the mechanism by which MSP can alleviate alcoholic hepatotoxicity. The results showed that MSP intervention significantly ameliorated symptoms of liver injury (suppressed serum ALT increment, hepatic lipid accumulation, and neutrophil infiltration in liver tissue), and reversed the abnormal mRNA abundance of biomarkers associated with oxidative stress (iNOS), inflammation (TNF-α, IL-1ß, MCP-1, TNF-R1, and TLR4), and apoptosis (Bax and Casp. 3) in the liver. Moreover, MSP improved intestinal barrier function by increasing the expression of tight junction proteins (Claudin-1 and Claudin-3). Further analysis of faecal microbiota and metabolome revealed that MSP promoted the growth of tryptophan-metabolizing bacteria (Clostridiales, Alistipes, and Odoribacter), leading to increased production of indole derivatives (indole-3-lactic acid and N-acetyltryptophan). These results suggested that MSPs may alleviate alcohol-induced liver injury targeting the gut-liver axis, and could be an effective option for the prevention of alcoholic liver injury.


Assuntos
Microbioma Gastrointestinal , Hepatopatias Alcoólicas , Fígado , Camundongos Endogâmicos C57BL , Animais , Camundongos , Microbioma Gastrointestinal/efeitos dos fármacos , Masculino , Hepatopatias Alcoólicas/tratamento farmacológico , Hepatopatias Alcoólicas/metabolismo , Fígado/metabolismo , Fígado/efeitos dos fármacos , Peptídeos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Modelos Animais de Doenças
12.
Int J Biol Macromol ; 272(Pt 1): 132697, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38843607

RESUMO

As a translucent functional gel with biodegradability, non-toxicity and acid resistance, gellan gum has been widely used in probiotic packaging, drug delivery, wound dressing, metal ion adsorption and other fields in recent years. Because of its remarkable gelation characteristics, gellan gum is suitable as the shell material of microcapsules to encapsulate functional substances, by which the functional components can improve stability and achieve delayed release. In recent years, many academically or commercially reliable products have rapidly emerged, but there is still a lack of relevant reports on in-depth research and systematic summaries regarding the process of microcapsule formation and its corresponding mechanisms. To address this challenge, this review focuses on the formation process and applications of gellan gum-based microcapsules, and details the commonly used preparation methods in microcapsule production. Additionally, it explores the impact of factors such as ion types, ion strength, temperature, pH, and others present in the solution on the performance of the microcapsules. On this basis, it summarizes and analyzes the prospects of gellan gum-based microcapsule products. The comprehensive insights from this review are expected to provide inspiration and design ideas for researchers.


Assuntos
Cápsulas , Emulsões , Polissacarídeos Bacterianos , Polissacarídeos Bacterianos/química , Cápsulas/química , Emulsões/química , Concentração de Íons de Hidrogênio , Temperatura
13.
J Nutr Biochem ; 118: 109353, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37116815

RESUMO

Hepatic lipidome has been given emphasis for years since hepatic steatosis is the most remarkable character of nonalcoholic fatty liver diseases, an increasingly serious health issue worldwide. Nobiletin (NOB), one of the citrus flavonoids, exerted outstanding effect on lipid metabolism disorder. However, the underlying mechanism of NOB exerting effect on hepatic lipid alternation remains unclear. In this study, the animal model was built by feeding APOE-/- mice with high fat diet (HFD). The results of Oil Red O-stained liver section and the biochemical assay of lipid parameters confirmed the protective effect of NOB on hepatic steatosis and global lipid metabolism disorder in APOE-/- mice. The hepatic lipidomic study revealed a total of 958 lipids significantly altered by HFD and a total of 86, 116, 212 lipid metabolites changed by L-NOB (50 mg/kg/d NOB), M-NOB (100 mg/kg/d NOB) and H-NOB (200 mg/kg/d NOB) respectively. In the further screening analysis, an amount of 60 lipids were identified as the potential lipid markers of NOB treatment, most of which belonged to glycerophospholipids lipid categories and exhibited obvious correlation with each other and the lipid parameters related to hepatic steatosis. Taken together, our data demonstrated that glycerophospholipids metabolism played an indispensable role in the progression of hepatic steatosis and the protective effect of NOB. Besides, the modulation towards genes involved in lipid synthesis was observed after NOB administration in this study. These finding illustrated the antihepatic steatosis effect of NOB based on altering hepatic lipidome, particularly the glycerophospholipids metabolism, and provided a new insight in the pathogenesis of hepatic steatosis.


Assuntos
Lipidômica , Hepatopatia Gordurosa não Alcoólica , Camundongos , Animais , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Metabolismo dos Lipídeos , Dieta Hiperlipídica/efeitos adversos , Lipídeos/farmacologia , Apolipoproteínas E/metabolismo , Camundongos Endogâmicos C57BL
14.
Int J Biol Macromol ; 253(Pt 1): 126614, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37652331

RESUMO

The structure and bioactivity of a novel polysaccharide from Dendrobium Chrysotoxum Lindl (DCP-1) were investigated. The crude polysaccharides of Dendrobium Chrysotoxum Lindl (DCP) were extracted by hot water extraction, and the protein was removed by enzymatic hydrolysis and Sevage. After purification, the chemical structure of polysaccharides was identified by infrared spectroscopy, methylation analysis and nuclear magnetic resonance spectroscopy. Then, a mouse model of acute kidney injury (AKI) was constructed using lipopolysaccharide (LPS), and pretreated with DCP. Structure characterization demonstrated that the number-average molecular weight and mass average molar mass of DCP-1 were 28.43 kDa and 15.00 kDa, respectively. DCP-1 mainly consisted of mannose (37.8 %) and glucose (55.6 %). The main linkage types of DCP-1 were contained 1,4-Linked Manp and 1,4-Linked Glcp. And DCP-1 was demonstrated to be an O-acetylglucomannan with ß-ᴅ-configuration in pyranoid form. Besides, the bioactivity of DCP was further investigated. The results showed that DCP exhibited notable anti-inflammatory activity in LPS-induced AKI mice. After treated with DCP, the creatinine (CREA) and urea nitrogen (BUN) in serum were successfully down-regulated in AKI mice. DCP treatment prevented the characteristic morphological changes of LPS-induced renal tubular injury. The results showed that DCP treatment significantly reduced the concentration of oxidative damage indicators (MDA, SOD) and the expression of inflammatory indices (TNF-α, IL-6, MCP-1, COX-2). In general, the newly extracted polysaccharide DCP showed excellent nephroprotective effect, which enabled it to be an ideal natural medicine for kidney diseases therapy.


Assuntos
Injúria Renal Aguda , Dendrobium , Camundongos , Animais , Lipopolissacarídeos , Dendrobium/química , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Polissacarídeos/química , Espectroscopia de Ressonância Magnética , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/tratamento farmacológico
15.
Mol Nutr Food Res ; 67(12): e2200289, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36906890

RESUMO

SCOPE: Prediabetes and diabetes are major public health problems worldwide without specific cure currently. Gut microbes have been recognized as one of the vital therapeutic targets for diabetes. The exploration that nobiletin (NOB) whether affects gut microbes provides a scientific basis for its application. METHODS AND RESULTS: A hyperglycemia animal model is established using high-fat-fed ApoE-/- mice. After 24 weeks of NOB intervention, the level of fasting blood glucose (FBG), glucose tolerance, insulin resistance, and glycosylated serum protein (GSP) are measured. Pancreas integrity is observed by hematoxylin-eosin (HE) staining and transmission electron microscopy. 16s RNA sequencing and untargeted metabolomics are to determine the changes of intestinal microbial composition and metabolic pathways. The levels of FBG and GSP in hyperglycemic mice are effectively reduced. The secretory function of pancreas is improved. Meanwhile, NOB treatment restored the gut microbial composition and affected metabolic function. Furthermore, NOB treatment regulates the metabolic disorder mainly through lipid metabolism, amino acid metabolism, and Secondary bile acid metabolism, etc. In addition, it is possibly existed mutual promotion between microbe and metabolites. CONCLUSION: NOB probably plays a vital role in the hypoglycemic effect and pancreatic islets protection by improving microbiota composition and gut metabolism.


Assuntos
Microbioma Gastrointestinal , Hipoglicemiantes , Camundongos , Animais , Hipoglicemiantes/farmacologia , Camundongos Obesos , Dieta Hiperlipídica
17.
J Agric Food Chem ; 71(3): 1713-1726, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36634352

RESUMO

The widespread use of titanium dioxide nanoparticles (TiO2 NPs) in the food industry has brought about human safety risks related to nanotoxicity. In this study, food-related TiO2 NPs (anatase, 40 nm) were given to rats by oral gavage for 90 days at doses of 10, 100, and 1000 mg/kg bw. An additional two satellite groups underwent the same protocol for 45 days and for 90 days followed by a 28 day recovery. TiO2 NPs tended to agglomerate together in H2O, AGJ, and AIJ. No systemic toxicity was observed after 90 day agglomerated TiO2 NP exposure with no Ti distribution in major tissues/organs. Furthermore, TiO2 NP consumption for 90 days had no impact on microbiota diversity; the community structure of the gut microbiota is shifted to some extent at the genus level. Collectively, the NOAEL of agglomerated TiO2 NPs for 90 days of oral administration was 1000 mg/kg bw, the highest dose tested in male and female rats.


Assuntos
Microbioma Gastrointestinal , Nanopartículas Metálicas , Nanopartículas , Humanos , Ratos , Masculino , Feminino , Animais , Titânio/toxicidade , Titânio/química , Distribuição Tecidual , Nanopartículas/toxicidade , Administração Oral , Nanopartículas Metálicas/toxicidade , Nanopartículas Metálicas/química
18.
Food Funct ; 13(19): 10186-10199, 2022 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-36111578

RESUMO

Nonalcoholic fatty liver disease (NAFLD), an increasingly serious health issue around the world, is characterized as a lipid metabolic disorder without any satisfactory treatment. Nobiletin (NOB), a citrus flavonoid, is considered a promising candidate for NAFLD prevention although there is limited research towards its exact mechanism. In this study, the preventative effect of NOB on NAFLD was investigated using high fat diet-fed ApoE-/- mice and free fatty acid-treated HepG2 cells. The results of hematoxylin and eosin staining of liver sections revealed that L-NOB (50 mg kg-1 d-1 NOB), M-NOB (100 mg kg-1 d-1 NOB) and H-NOB (200 mg kg-1 d-1 NOB) could significantly ameliorate NAFLD. Further exploration illustrated that NOB alleviated hepatic steatosis mainly via TFEB-mediated lysosomal biogenesis and lipophagy. Besides, NOB could mitigate NLRP3 inflammasome assembly and modulate M1/M2 macrophage polarization in vivo and in vitro. The mechanisms above allowed NOB to attenuate NAFLD, but their close association needed further investigation. Our research not only illustrated NOB as a potential candidate for NAFLD prevention, but also provided new insight into the pathogenic mechanisms of NAFLD development.


Assuntos
Flavonas , Hepatopatia Gordurosa não Alcoólica , Animais , Apolipoproteínas E , Autofagia , Dieta Hiperlipídica , Amarelo de Eosina-(YS)/metabolismo , Amarelo de Eosina-(YS)/farmacologia , Ácidos Graxos não Esterificados/metabolismo , Flavonas/metabolismo , Flavonas/farmacologia , Hematoxilina/metabolismo , Hematoxilina/farmacologia , Inflamassomos/metabolismo , Inflamação/metabolismo , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo
19.
J Agric Food Chem ; 70(19): 5805-5818, 2022 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-35522926

RESUMO

Nobiletin is a natural nutrient (or polymethoxyflavonoid) in orange peels exerting a preventive effect against metabolic diseases. However, there are very few reports on the hypoglycemic effect of nobiletin. In the present study, the hypoglycemic effect of nobiletin was investigated using NIT-1 cells and streptozocin (STZ)-challenged mouse models. Our results indicated that nobiletin could significantly suppress the high blood glucose in STZ-challenged mice. In addition, nobiletin could effectively activate the mitophagy and inhibit the inflammatory pathways in NIT-1 cells. The mitochondria membrane potential dysbiosis induced by glucotoxicity in NIT-1 cells was restored after treatment by nobiletin. Further investigation revealed that the hypoglycemic effect of nobiletin was mainly through regulation of gut microbiota dysbiosis, activation of mitophagy flux, inhibition of inflammasome expression, and restoration of islet morphological destruction in the pancreas of STZ-challenged mice. Our study revealed that nobiletin could be used as a functional food or drug candidate for the treatment of diabetes.


Assuntos
Microbioma Gastrointestinal , Hipoglicemiantes , Animais , Disbiose , Flavonas , Homeostase , Hipoglicemiantes/farmacologia , Camundongos , Mitofagia , Estreptozocina
20.
J Pharm Anal ; 12(2): 339-349, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35582406

RESUMO

GB7 acetate is a galbulimima alkaloid obtained from Galbulimima belgraveana. However, information regarding its structure, biological activities, and related mechanisms is not entirely available. A series of spectroscopic analyses, structural degradation, interconversion, and crystallography were performed to identify the structure of GB7 acetate. The MTT assay was applied to measure cell proliferation on human colorectal cancer HCT 116 cells. The expressions of the related proteins were measured by Western blotting. Transmission electron microscopy (TEM), acridine orange (AO) and monodansylcadaverine (MDC) staining were used to detect the presence of autophagic vesicles and autolysosomes. A transwell assay was performed to demonstrate metastatic capabilities. Oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) assays were performed to determine the mitochondrial oxidative phosphorylation (OXPHOS) and glycolysis activity of HCT 116 cells. The data showed that GB7 acetate suppressed the proliferation and colony-forming ability of HCT 116 cells. Pretreatment with GB7 acetate significantly induced the formation of autophagic vesicles and autolysosomes. GB7 acetate upregulated the expressions of LC3 and Thr172 phosphorylated adenosine 5'-monophosphate (AMP)-activated protein kinase α (p-AMPKα), which are key elements of autophagy. In addition, GB7 acetate suppressed the metastatic capabilities of HCT 116 cells. Additionally, the production of matrix metallo-proteinase-2 (MMP-2) and MMP-9 was reduced, whereas the expression of E-cadherin (E-cad) was upregulated. Furthermore, GB7 acetate significantly reduced mitochondrial OXPHOS and glycolysis. In conclusion, the structure of the novel Galbulimima alkaloid GB7 acetate was identified. GB7 acetate was shown to have anti-proliferative, pro-autophagic, anti-metastatic, and anti-metabolite capabilities in HCT 116 cells. This study might provide new insights into cancer treatment efficacy and cancer chemoprevention.

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