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Clarification is required when the term "carbohydrate" is used interchangeably with "saccharide" and "glycan." Carbohydrate classification based on human digestive enzyme activities brings clarity to the energy supply function of digestible sugars and starch. However, categorizing structurally diverse non-digestible carbohydrates (NDCs) to make dietary intake recommendations for health promotion remains elusive. In this review, we present a summary of the strengths and weaknesses of the traditional dichotomic classifications of carbohydrates, which were introduced by food chemists, nutritionists, and microbiologists. In parallel, we discuss the current consensus on commonly used terms for NDCs such as "dietary fiber," "prebiotics," and "fermentable glycans" and highlight their inherent differences from the perspectives of gut microbiome. Moreover, we provide a historical perspective on the development of novel concepts such as microbiota-accessible carbohydrates, microbiota-directed fiber, targeted prebiotics, and glycobiome. Crucially, these novel concepts proposed by multidisciplinary scholars help to distinguish the interactions between diverse NDCs and the gut microbiome. In summary, the term NDCs created based on the inability of human digestive enzymes fails to denote their interactions with gut microbiome. Considering that the gut microbiome possesses sophisticated enzyme systems to harvest diverse NDCs, the subclassification of NDCs should be realigned to their metabolism by various gut microbes, particularly health-promoting microbes. Such rigorous categorizations facilitate the development of microbiome-targeted therapeutic strategies by incorporating specific types of NDCs.
Assuntos
Microbioma Gastrointestinal , Microbioma Gastrointestinal/fisiologia , Humanos , Prebióticos , Carboidratos da Dieta/metabolismo , Fibras na Dieta/metabolismo , Polissacarídeos/metabolismo , Polissacarídeos/química , Digestão/fisiologiaRESUMO
Pseudo-cereals such as buckwheat (Fagopyrum esculentum) are valid candidates to promote diet biodiversity and nutrition security in an era of global climate change. Buckwheat hulls (BHs) are currently an unexplored source of dietary fibre and bioactive phytochemicals. This study assessed the effects of several bioprocessing treatments (using enzymes, yeast, and combinations of both) on BHs' nutrient and phytochemical content, their digestion and metabolism in vitro (using a gastrointestinal digestion model and mixed microbiota from human faeces). The metabolites were measured using targeted LC-MS/MS and GC analysis and 16S rRNA gene sequencing was used to detect the impact on microbiota composition. BHs are rich in insoluble fibre (31.09 ± 0.22% as non-starch polysaccharides), protocatechuic acid (390.71 ± 31.72 mg/kg), and syringaresinol (125.60 ± 6.76 mg/kg). The bioprocessing treatments significantly increased the extractability of gallic acid, vanillic acid, p-hydroxybenzoic acid, syringic acid, vanillin, syringaldehyde, p-coumaric acid, ferulic acid, caffeic acid, and syringaresinol in the alkaline-labile bound form, suggesting the bioaccessibility of these phytochemicals to the colon. Furthermore, one of the treatments, EC_2 treatment, increased significantly the in vitro upper gastrointestinal release of bioactive phytochemicals, especially for protocatechuic acid (p < 0.01). The BH fibre was fermentable, promoting the formation mainly of propionate and, to a lesser extent, butyrate formation. The EM_1 and EC_2 treatments effectively increased the content of insoluble fibre but had no effect on dietary fibre fermentation (p > 0.05). These findings promote the use of buckwheat hulls as a source of dietary fibre and phytochemicals to help meet dietary recommendations and needs.
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Fagopyrum , Humanos , Fagopyrum/metabolismo , Cromatografia Líquida , RNA Ribossômico 16S/metabolismo , Espectrometria de Massas em Tandem , Fibras na Dieta/metabolismo , Compostos Fitoquímicos/metabolismoRESUMO
Circular RNAs (circRNAs) play vital roles in human diseases, including acute kidney injury (AKI). In this paper, we focused on the effect of circRNA zinc finger protein 644 (circZNF644) on AKI cell model progression. qRT-PCR was conducted for the levels of circZNF644, ZNF644, miR-140-5p and mixed lineage kinase domain like pseudokinase (MLKL). RNase R assay, actinomycin D assay and subcellular fraction analysis were conducted to analyze the features of circZNF644. CCK-8 assay and EdU assay were used to explore cell proliferation. Flow cytometry analysis was conducted to analyze cell cycle and cell apoptosis. Western blot assay was executed for protein levels. ELISA was performed for the levels of inflammatory cytokines. The relationships among circZNF644, miR-140-5p and MLKL were analyzed by dual-luciferase reporter assay and RIP assay. CircZNF644 was upregulated in LPS-stimulated HK-2 cells. LPS-mediated inhibitory effects on cell proliferation and cell cycle and promotional effects on apoptosis and inflammation were reversed by circZNF644 knockdown. CircZNF644 directly interacted with miR-140-5p and MLKL was the target gene of miR-140-5p. The impact of circZNF644 knockdown on HK-2 cell injury was relieved by miR-140-5p inhibition. Moreover, miR-140-5p enhancement alleviated LPS-triggered HK-2 cell damage, while MLKL elevation reversed the effect. CircZNF644 knockdown protected HK-2 cells from LPS-induced injury by altering miR-140-5p/MLKL pathway, suggesting that circZNF644 may be a hopeful therapeutic target for AKI.
Assuntos
Injúria Renal Aguda , MicroRNAs , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/genética , Injúria Renal Aguda/metabolismo , Apoptose/fisiologia , Proliferação de Células , Citocinas , Dactinomicina , Humanos , Lipopolissacarídeos , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas Quinases , RNA Circular/genéticaRESUMO
Diabetes mellitus (DM) and its complications are major public health concerns which strongly influence the quality of humans' life. Modification of gut microbiota has been widely used for the management of diabetes. In this review, the relationship between diabetes and gut microbiota, as well as the effects of different dietary components and traditional Chinese medicine (TCM) on gut microflora are summarized. Dietary compounds and TCM possessing bioactive components (fiber and phytochemicals) first change the composition of gut microbiota (inhibiting pathogens and promoting the beneficial bacteria growth) and then influence the production of their metabolites, which would further modify the intestinal environment through inhibiting the production of detrimental compounds (such as lipopolysaccharide, hydrogen sulfide, indol, etc.). Importantly, metabolites (short chain fatty acids and other bioactive components) fermented/degraded by gut microbiota can target multiple pathways in intestine, liver, pancreas, etc., resulting in the improvement of gut health, glycemic control, lipids profile, insulin resistance and inflammation. Furthermore, understanding the interaction between different dietary components and gut microbiota, as well as underlying mechanisms would help design different diet formula for the management of diabetes. Further researches could focus on the combination of different dietary components for preventing and treating diabetes, based on the principle of "multiple components against multiple targets" from the perspective of gut microbiota.
Assuntos
Diabetes Mellitus Tipo 2/terapia , Dieta , Microbioma Gastrointestinal , Medicina Tradicional Chinesa , Glicemia/metabolismo , Fibras na Dieta/administração & dosagem , Humanos , Intestinos/microbiologia , Melatonina/administração & dosagem , Polifenóis/administração & dosagem , Verrucomicrobia/metabolismoRESUMO
We demonstrate an optical frequency comb in which an Er:fiber-based femtosecond laser employs nonlinear amplifier loop mirror (NALM) and nonlinear polarization evolution (NPE) mode-locking mechanisms. The laser combines advantages of good robustness of NALM and low noise feature of NPE. Our experimental results show that the hybrid mode-locked laser has high power, low relative intensity noise and self-started property, enabling the construction of a robust optical frequency comb system. In-loop relative instabilities of both stabilized repetition rate and carrier-envelope-offset frequency are well below 1 × 10-17 at 1 second integration time.
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In underwater range-gated imaging (URGI), enhancement of low-brightness and low-contrast images is critical for human observation. Traditional histogram equalizations over-enhance images, with the result of details being lost. To compress over-enhancement, a lower-upper-threshold correlation method is proposed for underwater range-gated imaging self-adaptive enhancement based on double-plateau histogram equalization. The lower threshold determines image details and compresses over-enhancement. It is correlated with the upper threshold. First, the upper threshold is updated by searching for the local maximum in real time, and then the lower threshold is calculated by the upper threshold and the number of nonzero units selected from a filtered histogram. With this method, the backgrounds of underwater images are constrained with enhanced details. Finally, the proof experiments are performed. Peak signal-to-noise-ratio, variance, contrast, and human visual properties are used to evaluate the objective quality of the global and regions of interest images. The evaluation results demonstrate that the proposed method adaptively selects the proper upper and lower thresholds under different conditions. The proposed method contributes to URGI with effective image enhancement for human eyes.
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Fermentation is an effective method for improving the nutritional quality and functional characteristics of grains. This study investigated changes in the structural, physicochemical, and functional properties of fermented barley dietary fiber (FBDF) exerted by Lactiplantibacillus plantarum dy-1 (Lp. plantarum dy-1) as well as its in vitro fecal fermentation characteristics. Lp. plantarum dy-1 fermentation remarkably changed the structure of FBDF, including the microstructure and monosaccharide components, correlating with improved water or oil retaining and cholesterol adsorption capacities. Additionally, Lp. plantarum dy-1 fermentation significantly (p < 0.05) promoted the release of bound phenolics from 6.24 mg g-1 to 6.93 mg g-1 during in vitro digestion, contributing to the higher antioxidant capacity and inhibitory activity of α-amylase and pancreatic lipase compared with those of raw barley dietary fiber (RBDF). A total of 14 phenolic compounds were detected in the supernatants of digestion and fermentation samples. During colonic fermentation, FBDF significantly increased the production of acetate, propionate, and butyrate (p < 0.05), inhibited the growth of Escherichia-Shigella, and promoted the abundance of SCFA-producing microbiota such as Faecalibacterium and Prevotella_9. In conclusion, Lp. plantarum dy-1 fermentation enhanced the physicochemical properties and in vitro fermentation characteristics of barley dietary fiber, representing a promising bioprocessing technology for modifying barley bran.
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Fibras na Dieta , Fezes , Fermentação , Hordeum , Fibras na Dieta/metabolismo , Fibras na Dieta/análise , Hordeum/química , Fezes/microbiologia , Humanos , Microbioma Gastrointestinal , Digestão , Antioxidantes/metabolismo , Ácidos Graxos Voláteis/metabolismo , Lactobacillus plantarum/metabolismo , Fenóis/metabolismoRESUMO
Barley, rich in bioactive components including dietary fiber, polyphenolic compounds and functional proteins, exhibits health benefits such as regulating glucose and lipid metabolism. Previous studies have found that the content and composition of free phenolic acids in barley may be significantly changed by fermentation with the laboratory patented strain Lactobacillus plantarum dy-1 (L. p dy-1), but the mechanism of enzymatic release of phenolic acid remains to be elucidated. Based on this, this study aimed to identify the key enzyme in L. p dy-1 responsible for releasing the bound phenolic acid and to further analyze its enzymatic properties. The Carbohydrate-Active enZYmes database revealed that L. p dy-1 encodes 7 types of auxiliary enzymes, among which we have identified a membrane sulfatase. The enzyme gene LPMS05445 was heterologous to that expressed in E. coli, and a recombinant strain was induced to produce the target protein and purified. The molecular weight of the purified enzyme was about 59.9 kDa, with 578.21 U mg-1 enzyme activity. The optimal temperature and pH for LPMS05445 expression were 40 °C and 7.0, respectively. Furthermore, enzymatic hydrolysis by LPMS05445 can obviously change the surface microstructure of dietary fiber from barley bran and enhance the release of bound phenolic acid, thereby increasing the free phenolic acid content and improving its physiological function. In conclusion, sulfatase produced by Lactobacillus plantarum dy-1 plays a key role in releasing bound phenolic acids during the fermentation of barley.
Assuntos
Lactobacillus plantarum , Sulfatases , Lactobacillus plantarum/enzimologia , Lactobacillus plantarum/metabolismo , Lactobacillus plantarum/genética , Sulfatases/metabolismo , Sulfatases/genética , Sulfatases/química , Hordeum , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/química , Fermentação , Hidroxibenzoatos/metabolismo , Concentração de Íons de Hidrogênio , Escherichia coli/genética , Temperatura , Fibras na Dieta/metabolismoRESUMO
Previous studies have shown that fermented barley has a lower digestion rate. However, it remains unclear whether the antidigestibility of starch in fermented barley is affected by other nonstarch components. In this paper, the removal of protein, lipid, and ß-glucan improved the hydrolysis rate of starch and the protein showed the greatest effect. Subsequently, the inhibitory mechanism of protein on starch digestion was elucidated from the perspective of starch physicochemical properties and structural changes. The removal of protein increased the swelling power of starch from 10.09 to 11.14%. The short-range molecular ordered structure and the helical structure content decreased. The removal of protein reduced the coating and particle size of the starch particles, making the Maltese cross more dispersed. In summary, protein in fermented barley enhanced the ordered structure of starch by forming a physical barrier around starch and prevented the expansion of starch, which inhibited the hydrolysis of starch.
Assuntos
Digestão , Fermentação , Hordeum , Proteínas de Plantas , Amido , Hordeum/química , Hordeum/metabolismo , Amido/química , Amido/metabolismo , Hidrólise , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Tamanho da PartículaRESUMO
The effect of barley ß-glucan on soybean oil digestion characteristics before and after fermentation was studied in an in vitro-simulated gastrointestinal digestion model. The addition of barley ß-glucan made the system more unstable, the particle size increased significantly, and confocal laser imaging showed that it was easier to form agglomerates. The addition of barley ß-glucan increased the proportion of unsaturated fatty acids in digestion products, and reduced digestibility of soybean oil. In a co-culture model of Caco-2/HT29 and HepG2 cells, the effects of digestive products of soybean oil and barley ß-glucan before and after fermentation on lipid metabolism in HepG2 cells were investigated. The results showed that adding only soybean oil digestion products significantly increased triglycerides (TG) content and lipid accumulation in basolateral HepG2 cells. When fermented barley ß-glucan was added, lipid deposition was significantly decreased, and the lipid-lowering activity was better than that of unfermented barley ß-glucan.
Assuntos
Hordeum , Hipercolesterolemia , beta-Glucanas , Humanos , Óleo de Soja/metabolismo , Técnicas de Cocultura , Células CACO-2 , beta-Glucanas/farmacologia , DigestãoRESUMO
Barley bran has potential bioactivities due to its high content of polyphenols and dietary fiber, etc. Fermentation has been considered as an effective way to promote the functional activity of food raw materials. In this study, polysaccharides from barley bran extract fermented by Lactiplantibacillus plantarum dy-1 (FBBE-PS) were analyzed, and its effects on lipid accumulation and oxidative stress in high-fat HepG2 cells induced by sodium oleate were evaluated. The results showed that the molecular weight decreased and monosaccharide composition of polysaccharides changed significantly after fermentation. In addition, 50 µg/mL FBBE-PS could reduce the triglyceride (TG) content and reaction oxygen species (ROS) level in high-fat HepG2 cells by 21.62% and 30.01%, respectively, while increasing the activities of superoxide dismutase (SOD) and catalase (CAT) represented by 64.87% and 22.93%, respectively. RT-qPCR analysis revealed that FBBE-PS could up-regulate the lipid metabolism-related genes such as ppar-α, acox-1 and cpt-1α, and oxidation-related genes such as nrf2, ho-1, nqo-1, sod1, cat, etc. The metabolomics analysis indicated that FBBE-PS could alleviate lipid deposition by inhibiting the biosynthesis of unsaturated fatty acids, which is consistent with the downregulation of scd-1 expression. It is demonstrated that fermentation can alter the properties and physiological activities of polysaccharides in barley bran, and FBBE-PS exhibited an alleviating effect on lipid deposition and oxidative stress in high-fat cells.
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The structure and function of ß-glucan in barley have been reported to change significantly after fermentation with Lactobacillus plantarum dy-1, but little information is available to explain this phenomenon. The Carbohydrate-Active enZYmes database revealed that L. plantarum dy-1 encodes 158 types of glycosidic hydrolases, among which we have identified an endoglucanase. Therefore, we conducted a heterologous expression of this endoglucanase gene, namely Lpeg14265. The pH of 6.0 and the temperature of 60 °C were optimal for LPEG14265. The physiological activities of ß-glucan, such as the capacity to adsorb cholesterol or to block α-amylase and α-glucosidase, increased as a result of enzymatic hydrolysis of LPEG14265, which also caused a significant change in the microstructure of barley bran. Based on these findings, it was concluded that barley bran, a by-product of agriculture, may be processed with LPEG14265 to reveal its potential value, which could have applications in the brewing and feed industries, among others.
Assuntos
Celulase , Lactobacillus plantarum , beta-Glucanas , Lactobacillus plantarum/metabolismo , Celulase/genética , beta-Glucanas/química , Fermentação , alfa-Glucosidases/metabolismoRESUMO
Bioactive polysaccharides known as the biological response modifiers, can directly interact with intestinal epithelium cells (IEC) and regulate key metabolic processes such as lipid metabolism. Here, the coculture of Caco-2/HT29 monolayer (>400 Ω × cm2) and HepG2 cells was developed to mimic the gut-liver interactions. This system was used to investigate the effects of raw and fermented barley ß-glucans (RBG and FBG) on lipid metabolism by directly interacting with IEC. Both RBG and FBG significantly and consistently reduced the lipid droplets and triacylglycerol levels in monoculture and coculture of HepG2 overloaded with oleic acid. Notably, FBG significantly and distinctly elevated PPARα (p < 0.05) and PPARα-responsive ACOX-1 (p < 0.01) gene expressions, promoting lipid degradation in cocultured HepG2. Moreover, the metabolomics analyses revealed that FBG had a unique impact on extracellular metabolites, among them, the differential metabolite thiomorpholine 3-carboxylate was significantly and strongly correlated with PPARα (r = -0.68, p < 0.01) and ACOX-1 (r = -0.76, p < 0.01) expression levels. Taken together, our findings suggest that FBG-mediated gut-liver interactions play a key role in its lipid-lowering effects that are superior to those of RBG. These results support the application of Lactiplantibacillus fermentation for improving hypolipidemic outcomes.
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Hordeum , beta-Glucanas , Humanos , Hordeum/metabolismo , PPAR alfa/metabolismo , Fermentação , beta-Glucanas/farmacologia , beta-Glucanas/metabolismo , Células CACO-2 , Fígado/metabolismo , Triglicerídeos/metabolismoRESUMO
Fermentation is one of the most economical and safe methods to improve the nutritional value, sensory quality and functional characteristics of raw materials, and it is also an important method for cereal processing. This paper reviews the effects of microbial fermentation on cereals, focusing on their nutritional value and health benefits, including the effects of fermentation on the protein, starch, phenolic compounds contents, and other nutrient components of cereals. The bioactive compounds produced by fermented cereals have positive effects on health regulation. Finally, the future market development of fermented cereal products is summarized and prospected.
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We present a depth fingerprint map to obtain three-dimensional (3D) spatial information from objects in a large deterministic background by active range-gated imaging, for night remote surveillance. This method first gives the depth fingerprint map of the region of interest in the background by gate viewing in the form of contour bands in range. The map is then embedded in the range-gated laser surveillance system. Finally, 3D spatial information such as target scale and location can be estimated by segmenting the target from the background and matching them with the depth fingerprint map. The measurement is performed by computer background processing. Therefore, the method has no influence on the frame rate of surveillance systems and can realize real-time surveillance. In this paper, the approach to acquisition of the depth fingerprint map is also demonstrated without an echo-broadening effect.
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Fructans such as fructo-oligosaccharides (FOS) and inulin have been reported to directly regulate ileal inflammatory responses in lipopolysaccharide (LPS)-induced endotoxemic mice, without alterations in the colonic microbiota. Firstly, we replicated this model and found that a single gavage of 10 mg g-1 of fructans directly promoted caecal acetate and propionate production. Thus, the previous understanding of microbiota-independent effects of prebiotic fructans in endotoxemic mice has been challenged. In parallel, we performed a daily gavage of 160 mg kg-1 of inulin, xylan, or Dendrobium officinale polysaccharides (DOP) for two weeks prior to LPS injection. The long-term intake of prebiotic fibres reduced the bacterial load in the spleen and mesenteric lymph nodes (MLNs), and in comparison, a single gavage of fructans increased that. However, the long-term intake was unable to improve the short-chain fatty acid (SCFA) synthesis and epithelial barrier function that were impaired by LPS. Notably, the three fibre types consistently reduced the expression of mucin 2 (MUC2) and variously modulated critical mediators (IL-18, IL-22, and HIF-1α) to regulate the host-commensal microbiota interactions in the ileum. In addition, the three fibre types consistently inhibited the inflammatory T helper (Th) cell response in the ileum, while they diversely modulated the peripheral and systemic Th cell responses. Overall, the prebiotic fibres displayed microbiota-related changes in endotoxemic mice, and the potential associations with the in vivo anti-inflammatory effects of prebiotic fibres need further investigation.
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Endotoxemia/metabolismo , Ácidos Graxos Voláteis/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Íleo/metabolismo , Prebióticos/administração & dosagem , Translocação Genética/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Lipopolissacarídeos , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Lactic acid bacteria strain (LAB) NCU116 fermented Asparagus officinalis polysaccharides (FAOP) have been proven to cause substantial changes in physicochemical properties such as monosaccharide composition and molecular weight, accounting for their enhanced immune activity than unprocessed Asparagus officinalis polysaccharides (AOP). In the current study, the hepatoprotective effects of FAOP in mice with cyclophosphamide (CTX)-induced hepatotoxicity were investigated. FAOP were more effective than AOP in alleviating CTX-induced hepatic damage, including inhibition of hepatic biochemical markers (ALT, AST, AKP and LDH) and pro-inflammatory cytokines (TNF-α and IL-1ß) as well as reinforcement of antioxidant systems (T-AOC, SOD, CAT, and MDA). In particular, compared with AOP, FAOP showed superior performance by promoting GSH biosynthesis, and normalizing the expression level of bile acid receptors (FXR and SHP) and key enzymes in bile acid synthesis (CYP7A1, CYP8B1 and CYP27A1). Modulation of disordered homeostasis of bile acids by FAOP can be attributed to the upregulation of hepatic short chain fatty acid (SCFA) receptors GPR41 and GPR109A as well as intestinal SCFA production. Furthermore, serum metabolomics study validated the hepatoprotective superiority of FAOP than AOP with evidence from variations in bile acid compositions and the construction of related metabolic pathways. Therefore, LAB NCU116 fermentation of Asparagus officinalis was practical and effective to obtain promising hepatoprotective polysaccharides, which might arise from enhanced SCFA production than unprocessed AOP.
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Asparagus/química , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Alimentos Fermentados , Lactobacillus plantarum/metabolismo , Fígado/metabolismo , Polissacarídeos Bacterianos/administração & dosagem , Animais , Ácidos e Sais Biliares/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Ciclofosfamida , Citocinas/metabolismo , Ácidos Graxos Voláteis/metabolismo , Feminino , Fermentação , Regulação da Expressão Gênica , Glutationa/metabolismo , Homeostase , Fígado/patologia , Metaboloma , Camundongos , Camundongos Endogâmicos BALB C , Distribuição AleatóriaRESUMO
Acute kidney injury (AKI) is one of the most common complications of sepsis, which largely contributes to the high mortality rate of sepsis. Honokiol, a natural polyphenol from the traditional Chinese herb Magnolia officinalis, is known to possess anti-inflammatory and antioxidant activity. Here, the underlying mechanism of honokiol-induced amelioration of sepsis-associated AKI was analyzed. The expression patterns of oxidative stress moleculars and TLRs-mediated inflammation pathway were examined to identify the response of NRK-52E cells incubated with septic rats' serum to honokiol. The levels of iNOS, NO, and myeloperoxidase in NRK-52E cells were increased during sepsis, which could be reversed by honokiol. The production of GSH and SOD as in vivo antioxidant was increased after honokiol treatment. The administration of honokiol significantly inhibited TLR2/4/MyD88 signaling pathway in AKI-induced NRK-52E cells. Furthermore, ZnPPIX, the HO-1 inhibitor, weakened honokiol-mediated morphological amelioration, and the reduced level of TNF-α, IL-1ß, and IL-6 in kidneys of rats subjected to CLP. Finally, Honokiol was shown to connect with the Nrf2-Keap1 dimensionally. These findings suggest that honokiol plays its protective role on sepsis-associated AKI against oxidative stress and inflammatory signals.
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Injúria Renal Aguda/tratamento farmacológico , Compostos de Bifenilo/farmacologia , Inflamação/tratamento farmacológico , Lignanas/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Sepse/tratamento farmacológico , Injúria Renal Aguda/complicações , Animais , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Compostos de Bifenilo/uso terapêutico , Linhagem Celular , Lignanas/uso terapêutico , Ratos , Sepse/complicaçõesRESUMO
This study investigated the possible protective effect of combined fungal polysaccharides (CFP), consisting of Cordyceps sinensis polysaccharides (CSP) and Ganoderma atrum polysaccharides (PSG) with well-defined structural characteristics, against cyclophosphamide (CTX)-induced hepatotoxicity in mice. Our results indicated CFP effectively prevented the liver injury by decreasing toxicity markers (aspartate transaminase, alanine aminotransferase and alkaline phosphatase). Further biochemical and molecular analysis indicated CSP particularly inhibited the activation of Toll-like receptor 9 (TLR9) and its related inflammatory signals, including pro-inflammatory cytokines, inducible nitric oxide synthase, and cyclooxygenase-2 to modulate hepatic inflammation response. Relatively, through activation of peroxisome proliferator-activated receptor α (PPARα), PSG increased hepatic glutathione peroxidase and glutathione content depleted by CTX, as well as prevented mitochondria-dependent apoptosis with regulation on Bcl-2 family proteins (Bad, Bax and Bcl-2). In addition, protective effect of CFP was associated with enhanced modulations on cellular oxidant/antioxidant imbalance, mitochondrial apoptotic pathway and pro-inflammatory factors via PPARα upregulation and TLR9 downregulation. Taking together, the combinatorial approach based on CSP and PSG presented a practical option for the management of drug-induced liver injury.
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Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Cordyceps/química , Ciclofosfamida/toxicidade , Polissacarídeos Fúngicos/farmacologia , Ganoderma/química , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Biomarcadores , Feminino , Polissacarídeos Fúngicos/química , Regulação da Expressão Gênica/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , PPAR alfa/genética , PPAR alfa/metabolismo , Organismos Livres de Patógenos Específicos , Receptor Toll-Like 9/genética , Receptor Toll-Like 9/metabolismoRESUMO
In vivo an ecological network of polysaccharides utilization by gut microbiota is not only an intense competition but also an impressive cooperation pattern. The present study evaluated the in vivo protective effect of combined fungal polysaccharides (CFP) from Cordyceps sinensis and Ganoderma atrum on colon immune dysfunction, induced by 150mg/kg cyclophosphamide (CP). The results showed that C. sinensis polysaccharides (CSP) significantly promoted microbial-derived butyrate to improve histone h3 acetylation mediating regulatory T (Treg) cell specific Foxp3, as well as significantly restored CP-induced elevation of interleukin (IL)-17 and IL-21. Additionally, G. atrum polysaccharides (PSG) significantly down-regulated MyD88, as well as significantly increased IL-10 and TGF-ß3. Furthermore, CFP balanced the disequilibrium of cytokines secretion and Foxp3/RORγt ratio related Treg/T helper 17 (Th17) balance, as well as down-regulated the TLR-mediated inflammatory signaling pathway and promoted secretory immunoglobulin A (sIgA) secretion to suppress colonic inflammation. Therefore, our results typically contribute to understand the in vivo immunoregulatory function of fungal polysaccharides compounds, involving microbial-associated inflammatory signals and specific metabolic products.