RÉSUMÉ
Age-related cognitive decline is primarily attributed to the progressive weakening of synaptic function and loss of synapses, while age-related gut microbial dysbiosis is known to impair synaptic plasticity and cognitive behavior by metabolic alterations. To improve the health of the elderly, the protective mechanisms of Oudemansiella raphanipes polysaccharide (ORP-1) against age-related cognitive decline are investigated. The results demonstrate that ORP-1 and its gut microbiota-derived metabolites SCFAs restore a healthy gut microbial population to handle age-related gut microbiota dysbiosis mainly by increasing the abundance of beneficial bacteria Dubosiella, Clostridiales, and Prevotellaceae and reducing the abundance of harmful bacteria Desulfovibrio, strengthen intestinal barrier integrity by abolishing age-related alterations of tight junction (TJ) and mucin 2 (MUC2) proteins expression, diminish age-dependent increase in circulating inflammatory factors, ameliorate cognitive decline by reversing memory- and synaptic plasticity-related proteins levels, and restrain hyperactivation of microglia-mediated synapse engulfment and neuroinflammation. These findings expand the understanding of prebiotic-microbiota-host interactions.
Sujet(s)
Agaricales , Axe cerveau-intestin , Dysfonctionnement cognitif , Humains , Sujet âgé , Dysbiose/métabolisme , Prébiotiques , Dysfonctionnement cognitif/traitement médicamenteux , Dysfonctionnement cognitif/prévention et contrôle , Dysfonctionnement cognitif/métabolismeRÉSUMÉ
Age-associated increase in intestinal permeability is known to relate with gut microbiota dysbiosis and loss of epithelial tissue integrity. To improve healthy aging and prevent age-associated chronic disabilities, the protective potential of polysaccharides from Oudemansiella raphanipes (ORP-1) against age-associated intestinal epithelial barrier dysfunction in d-galactose-induced Caco-2 cells monolayer was investigated. In-vitro results demonstrated that ORP-1 can restore a healthy gut microbial population to handle age-related gut microbiota dysbiosis mainly by facilitating the proliferation and adhesion of probiotics Lactobacillus acidophilus (L. acidophilus) and Bifidobacterium bifidum (B. bifidum) to compete with intestinal pathogenic Escherichia coli (E. coli) for ecological niches and nutrition. Meanwhile, ORP-1 strengthened the intestinal structural integrity primarily by abolishing the aggravation of apoptosis and the age-associated alterations of tight junction (TJ) proteins expression in intestine. These findings highlighted that ORP-1 could be a potential functional food component with preventive utility against age-associated intestinal barrier injury.
Sujet(s)
Dysbiose , Maladies gastro-intestinales , Humains , Cellules Caco-2 , Escherichia coli , Hydrates de carbone alimentaires , Polyosides/pharmacologie , Lactobacillus acidophilusRÉSUMÉ
The objectives of this study were (1) to prepare Armillariella tabescens mycelia polysaccharides (PAT) with remarkably growth inhibitory effect on typical food-borne pathogenic bacteria using a green and efficient polyamide method and (2) to explore the antibacterial mechanism of PAT for use as a natural antibacterial agent. The sugar and uronic acid contents of PAT were 93.41% and 12.24%, respectively. PAT could inhibit the growth of Escherichia coli, Proteus vulgaris, Bacillus subtilis, and Staphylococcus aureus cells, with minimum inhibitory concentrations of 0.5, 1.0, 4.0, and 4.0 mg/mL, respectively. Ultra-high-resolution field emission scanning electron microscopy and high-resolution transmission electron microscopy analysis revealed cell wall and membrane rupture of E. coli treated with PAT. Further, 0.5-4.0 mg/mL PAT was found to significantly (P < 0.01) and concentration-dependently increase the conductivity of the broth, exudation of the intracellular protein, and alkaline phosphatase and ß-galactosidase activities. Confocal laser scanning microscopy revealed morphological changes in E. coli DNA after PAT treatment and intracellular reactive oxygen species accumulation; flow cytometry revealed E. coli cell apoptosis. Our findings provide a theoretical basis and technical support for the development of PAT as a natural antibacterial product.
Sujet(s)
Infections à Escherichia coli , Escherichia coli , Antibactériens/pharmacologie , Armillaria , Bacillus subtilis , Humains , Tests de sensibilité microbienne , Polyosides/pharmacologieRÉSUMÉ
In our continuous exploration for bioactive polysaccharides, a novel polysaccharide FMP-2 was isolated and purified from the fruiting bodies of Morchella esculenta by alkali-assisted extraction. FMP-2 had an average molecular weight of 1.09 × 106 Da and contained mannose, glucuronic acid, glucose, galactose, and arabinose in a molar ratio of 4.10:0.22:1.00:5.75:0.44. The backbone of FMP-2 mainly consisted of 1,2-α-D-Galp, 1,6-α-D-Galp, and 1,4-α-D-Manp, with branches of 1,4,6-α-D-Manp and 1,2,6-α-D-Galp. FMP-2 can stimulate phagocytosis and promote the secretion of NO, ROS, and cytokines like IL-6, IL-1ß, and TNF-α in RAW264.7 cells ranging from 25 to 400 µg/mL. FMP-2 had great repairing effect on the immune injury of zebrafish induced by chloramphenicol. The phagocytosis ability of zebrafish macrophages and the proliferation of neutrophils can be greatly enhanced by polysaccharide FMP-2 with concentrations from 50 to 200 µg/mL. These findings suggest that FMP-2 might be used as a potential immunomodulator in the food and pharmaceutical industries.
Sujet(s)
Alcalis/composition chimique , Ascomycota/composition chimique , Corps fructifères de champignon/composition chimique , Polysaccharides fongiques/pharmacologie , Galactose/analogues et dérivés , Facteurs immunologiques/pharmacologie , Mannanes/pharmacologie , Animaux , Prolifération cellulaire/effets des médicaments et des substances chimiques , Survie cellulaire/effets des médicaments et des substances chimiques , Cellules cultivées , Polysaccharides fongiques/composition chimique , Polysaccharides fongiques/isolement et purification , Galactose/composition chimique , Galactose/isolement et purification , Galactose/pharmacologie , Facteurs immunologiques/composition chimique , Facteurs immunologiques/isolement et purification , Lipopolysaccharides/antagonistes et inhibiteurs , Lipopolysaccharides/pharmacologie , Macrophages/effets des médicaments et des substances chimiques , Mannanes/composition chimique , Mannanes/isolement et purification , Souris , Granulocytes neutrophiles/effets des médicaments et des substances chimiques , Monoxyde d'azote/antagonistes et inhibiteurs , Monoxyde d'azote/biosynthèse , Cellules RAW 264.7 , Danio zébréRÉSUMÉ
The pharmaceutical application of fungal polysaccharides has been extensively studied based on their multiple biological activities. However, the effect of Morchella esculenta polysaccharides on the development of atherosclerosis remains unknown. This study aims to investigate the anti-atherosclerotic effect of a novel polysaccharide (MCP) extracted from Morchella esculenta. The average molecular weight of MCP is 1.69 × 105 Da, and it is composed of glucose, mannose and galactose in the molar ratio of 1 : 1.9 : 0.51. LDLR-deficient (LDLR-/-) mice were fed high-fat diet (HFD) and administered intragastrically (i.g.) with saline or MCP dissolved in saline for 15 weeks. We found that MCP inhibited en face and sinus lesions. Moreover, serum levels of total and low-density lipoprotein cholesterol and triglyceride were decreased by MCP. The HFD-induced hepatic lipid accumulation was also attenuated by MCP. The underlying molecular mechanisms of anti-atherogenic and lipogenic effects of MCP might be attributed to reduced cholesterol synthesis by activating AMPKα signaling pathway and inhibiting SREBP2 expression. In addition, MCP-decreased serum triglyceride level is related to inhibiting LXRα expression. Taken together, these results indicate that MCP markedly alleviates atherosclerosis and M. esculenta can be used as a functional food additive to benefit patients with atherosclerosis.
Sujet(s)
Ascomycota/composition chimique , Athérosclérose/traitement médicamenteux , Polysaccharides fongiques/pharmacologie , AMP-Activated Protein Kinases/métabolisme , Animaux , Aorte/effets des médicaments et des substances chimiques , Athérosclérose/métabolisme , Cholestérol LDL/sang , Alimentation riche en graisse , Femelle , Additifs alimentaires , Polysaccharides fongiques/composition chimique , Foie/métabolisme , Souris , Souris de lignée C57BL , Souris knockout , Plaque d'athérosclérose/traitement médicamenteux , Plaque d'athérosclérose/métabolisme , Transduction du signal/effets des médicaments et des substances chimiques , Protéine-2 de liaison à l'élément de régulation des stérols/métabolisme , Triglycéride/sangRÉSUMÉ
The hydrolyzation of raffinose into melibiose by using invertases under mild conditions improves the nutritional value of soybean products. However, this strategy has received little attention because a suitable invertase remains lacking. In this study, a novel invertase named InvDz13 was screened and purified from Microbacterium trichothecenolyticum and characterized. InvDz13 was one of the invertases with the highest specific activity toward raffinose. Specifically, it had a specific activity of 229 U/mg toward raffinose at pH 6.5 and 35°C. InvDz13 retained more than 80% of its maximum activity at pH 5.5-7.5 and 25-40°C and was resistant to or stimulated by most cations that presented in soymilk. In soymilk treated with InvDz13 under mild conditions, melibiose concentration increased from 3.1 ± 0.2 to 6.1 ± 0.1 mM due to raffinose hydrolyzation by InvDz13. Furthermore, the prebiotic property of InvDz13-treated soymilk was investigated via in vitro fermentation by human gut microbiota. Results showed that InvDz13 treatment increased the proportion of the beneficial bacteria Bifidobacterium and Lactobacillus by 1.6- and 3.7-fold, respectively. By contrast, the populations of Escherichia and Collinsella decreased by 1.8- and 11.7-fold, respectively. Thus, our results proved that the enzymatic hydrolysis of raffinose in soymilk with InvDz13 was practicable and might be an alternative approach to improving the nutritional value of soymilk.
RÉSUMÉ
The Gram-negative pathogen Pseudomonas aeruginosa adopts several elaborate strategies to colonize a wide range of natural or clinical niches and to overcome the neighboring bacterial competitors in polymicrobial communities. However, the relationship and interaction mechanism of P. aeruginosa with other bacterial pathogens remains largely unexplored. Here we explore the interaction dynamics of P. aeruginosa and Escherichia coli, which frequently coinfect the lungs of immunocompromised hosts, by using a series of on-plate proximity assays and RNA-sequencing. We show that the extracellular products of P. aeruginosa can inhibit the growth of neighboring E. coli and induce a large-scale of transcriptional reprogramming of E. coli, especially in terms of cellular respiration-related primary metabolisms and membrane components. In contrast, the presence of E. coli has no significant effect on the growth of P. aeruginosa in short-term culture, but causes a dysregulated expression of genes positively controlled by the quorum-sensing (QS) system of P. aeruginosa during subsequent pairwise culture. We further demonstrate that the divergent QS-regulation of P. aeruginosa may be related to the function of the transcriptional regulator PqsR, which can be enhanced by E. coli culture supernatant to increase the pyocyanin production by P. aeruginosa in the absence of the central las-QS system. Moreover, the extracellular products of E. coli promote the proliferation and lethality of P. aeruginosa in infecting the Caenorhabditis elegans model. The current study provides a general characterization of the extracellular products-mediated interactions between P. aeruginosa and E. coli, and may facilitate the understanding of polymicrobial infections.
Sujet(s)
Escherichia coli/physiologie , Espace extracellulaire/métabolisme , Pseudomonas aeruginosa/physiologie , Protéines bactériennes/génétique , Protéines bactériennes/métabolisme , Escherichia coli/génétique , Régulation de l'expression des gènes bactériens , Pseudomonas aeruginosa/génétique , Pseudomonas aeruginosa/croissance et développement , Détection du quorumRÉSUMÉ
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by hyperglycemia mainly due to insulin resistance. The objective of this study was to investigate the effects of polysaccharides from Armillariella tabescens mycelia (AT) on insulin resistance in mice fed a high-fat diet in combination with streptozotocin to induce T2DM. Following treatment with different doses of AT, hyperglycemia and lipid metabolism dysfunction, insulin resistance, and hepatic function-related indices were markedly ameliorated; the histopathological alterations, oxidative stress, and inflammatory reaction in hepatic tissue were also alleviated; most importantly, AT inhibited the expression of hepatic thioredoxin-interacting protein (TXNIP) to repress the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation and activated the 5'AMP-activated protein kinase (AMPK) pathway in a dose-dependent manner in T2DM mice. In conclusion, these findings revealed that the hypoglycemic and hypolipidemic activities of AT were associated with the alleviation of insulin resistance through repression of the TXNIP/NLRP3 inflammasome pathway and activation of the AMPK pathway.
Sujet(s)
Armillaria , Diabète expérimental/induit chimiquement , Diabète expérimental/prévention et contrôle , Aliment fonctionnel , Polyosides/pharmacologie , Animaux , Diabète de type 2/induit chimiquement , Diabète de type 2/prévention et contrôle , Modèles animaux de maladie humaine , Insulinorésistance , Mâle , Souris , Souris de lignée C57BL , StreptozocineRÉSUMÉ
Diabetic kidney disease (DKD), accompanied by chronic low-grade inflammation, is one of the most common complications of diabetes. Armillariella tabescens has potent anti-inflammatory and immunomodulatory properties. The purpose of the present study was to investigate the effects of polysaccharides from Armillariella tabescens mycelia (AT) on the kidney in type 2 diabetic mice and explore the underlying mechanism. The mice were randomized into 4 groups: normal control (NC), diabetic control (DC), DC + 200 mg/kg AT (LAT), and DC + 400 mg/kg AT (HAT). The results showed that compared with the NC group, the levels of fasting blood glucose, renal function-related indices, and serum pro-inflammatory mediators including lipopolysaccharide (LPS), interleukin (IL)-1ß, and IL-18 were elevated; the renal morphopathological alterations, oxidative stress, and nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome-mediated inflammation and renal fibrosis were aggravated; the intestinal microbiota dysbiosis and colonic inflammation and barrier dysfunction were deteriorated in the DC group. After supplementation with AT, the aforementioned indices were ameliorated in the AT treatment groups, especially in the HAT group. In conclusion, these results demonstrated that modulating the intestinal microbiota and inflammatory reaction was implicated in the effects of AT against DKD in mice.
Sujet(s)
Armillaria/composition chimique , Diabète expérimental/traitement médicamenteux , Néphropathies diabétiques/traitement médicamenteux , Microbiome gastro-intestinal/effets des médicaments et des substances chimiques , Rein/effets des médicaments et des substances chimiques , Extraits de plantes/usage thérapeutique , Polyosides/usage thérapeutique , Animaux , Anti-inflammatoires/usage thérapeutique , Facteurs immunologiques/usage thérapeutique , Inflammation/traitement médicamenteux , Rein/anatomopathologie , Mâle , Souris , Souris de lignée C57BL , Stress oxydatif/effets des médicaments et des substances chimiquesRÉSUMÉ
5-Fluorouracil (5-Fu) is an effective anticarcinogenic agent, however, continuous use of 5-Fu may cause severe side effects. The goal of this study was to investigate the effectiveness of Sarcodon aspratus polysaccharides (SATP) in alleviating 5-Fu-induced toxicity in Lewis tumor-bearing mice. Lewis tumor-bearing mice were treated with saline, SATP, 5-Fu or 5-Fu + SATP. The results indicated that compared to the 5-Fu group, the 5-Fu + SATP group showed effective amelioration of the liver, kidney and small intestine injury caused by 5-Fu and decreases in the levels of related biochemical indicators, such as aspartate aminotransferase (AST), alanine aminotransferase (ALT) and urea nitrogen (BUN). Additionally, the combination therapy enhanced the quality of life and immune organ indexes of mice. Further mechanistic studies indicated that the 5-Fu + SATP group showed a decrease in hepatotoxicity caused by 5-Fu via a reduction in the levels of interleukin-1ß (IL-1ß), an increase in the expression of Bcl-2 and decreases in the expression of p-p38, p-JNK and Bax. Collectively, the results indicated that SATP could significantly alleviate the toxicity of 5-Fu in Lewis tumor-bearing mice and showed the hepatoprotective capability of SATP via its effect on the expression levels of inflammatory factors and components of the MAPK/P38/JNK pathway, which shows that it may be a potential adjuvant for the chemotherapeutic drug 5-Fu in cancer treatment.
Sujet(s)
Basidiomycota/composition chimique , Fluorouracil/pharmacologie , Polysaccharides fongiques/composition chimique , Polysaccharides fongiques/pharmacologie , Animaux , Carcinome pulmonaire de Lewis , Lignée cellulaire tumorale , Modèles animaux de maladie humaine , Antagonisme des médicaments , Immunohistochimie , Interleukine-1 bêta/sang , Mâle , Souris , Charge tumorale , Tests d'activité antitumorale sur modèle de xénogreffeRÉSUMÉ
Sarcodon aspratus is a popular edible fungus that has commonly been used as a functional food in China and other Asian countries. This study is conducted to examine the potential health benefits of Sarcodon aspratus polysaccharides (SATPs), on obesity and related metabolism disorders. C57BL/6J mice were fed with a high-fat diet (HFD) and supplemented with SATPs (100-400 mg kg-1) for 14 weeks. The results indicated that SATP treatment markedly reduced HFD-induced body weight gain and fat accumulation in a dose-dependent manner. SATPs could improve lipid homeostasis and glucose tolerance in HFD-fed mice. Furthermore, SATP intervention significantly attenuated hepatic steatosis, liver oxidative stress and inflammation. Additionally, we detected the macrophage and mRNA levels of lipogenesis markers in epididymal adipose tissues, and the results revealed that SATPs exerted inhibitory effects on the activation of immune cells and adipocyte differentiation in adipose tissues. High-throughput pyrosequencing of 16S rRNA suggested that SATP intervention was able to down-regulate the Firmicutes-to-Bacteroidetes ratio, and also increase the relative abundance of Lactobacillus, Bacteroides and Akkermansia in mice with HFD challenge. Taken together, SATPs showed ameliorative effects on hepatic steatosis, inflammation and adipocyte differentiation in HFD-fed mice. Notably, SATPs could modulate HFD-induced dysbiosis of gut microbiota. Thus, they might be a potential health supplement or prebiotic in the prevention of obesity and related metabolic disorders.
Sujet(s)
Basidiomycota/composition chimique , Alimentation riche en graisse/effets indésirables , Maladies métaboliques/prévention et contrôle , Obésité/induit chimiquement , Polyosides/composition chimique , Polyosides/pharmacologie , Tissu adipeux/effets des médicaments et des substances chimiques , Animaux , Compléments alimentaires , Microbiome gastro-intestinal/effets des médicaments et des substances chimiques , Intolérance au glucose , Hypolipémiants/pharmacologie , Inflammation/induit chimiquement , Inflammation/traitement médicamenteux , Métabolisme lipidique/effets des médicaments et des substances chimiques , Foie/effets des médicaments et des substances chimiques , Maladies métaboliques/complications , Souris , Obésité/complications , Stress oxydatif/effets des médicaments et des substances chimiques , Simvastatine/pharmacologie , Prise de poids/effets des médicaments et des substances chimiquesRÉSUMÉ
Pseudomonas aeruginosa is an important opportunistic pathogen normally associated with increasing morbidity and mortality of immunocompromised hosts with respiratory infections. The phenotypic and genetic features of P. aeruginosa from patients with chronic obstructive pulmonary disease (COPD) remain poorly understood. By using the sputum samples of 25 hospitalized COPD patients from the affiliated hospital of Southwest Medical University (China), we identified a P. aeruginosa isolate, COP2, which showed multiple antibiotic resistance and enhanced Pseudomonas quinolone signal (PQS) production but decreased motility, biofilm formation and virulence compared with the model strain PAO1. Importantly, COP2 harbored a substantial amount of mutations that might influence the functions of 1771 genes in the genome and the evolutionary status of this isolate was clearly distinct from the PAO1 lineage. Accordingly, COP2 had a discrepant transcriptional pattern relating to flagellar assembly, antibiotic resistance, biofilm and PQS production, and can increase the capacities of compound degradation in response to resource/space stresses. Therefore, the identification of COP2 in this study provides preliminary information regarding the genetic features and survival strategy of P. aeruginosa in colonizing COPD lungs and lays the foundations for further understanding of the pathogenic mechanisms of pseudomonal infections.
Sujet(s)
Poumon/microbiologie , Infections à Pseudomonas/microbiologie , Pseudomonas aeruginosa/génétique , Pseudomonas aeruginosa/physiologie , Broncho-pneumopathie chronique obstructive/complications , Biofilms/croissance et développement , Chine , Résistance bactérienne aux médicaments , Humains , Locomotion , Mutation , Pseudomonas aeruginosa/isolement et purification , Quinolinone , Expectoration , Transcriptome , Virulence , Séquençage du génome entierRÉSUMÉ
In this research, a polysaccharide fraction (EFSP-1) was obtained from the seeds of Euryale ferox Salisb. by DEAE sepharose FF and Superdex™ 75 gel chromatography. The average molecular weight (Mw) of EFSP-1 was 8.75 kDa. Monosaccharides composition analysis indicated that EFSP-1 was a glucan. The structure of EFSP-1 was characterized by analysis of FT-IR, GC-MS and NMR, which indicated that the backbone of EFSP-1 was mainly composed of (1â4)-α-D-Glcp with branches substituted at O-6 and terminated with T-α-D-Glcp. Moreover, the hypoglycemic effect of EFSP-1 was investigated by establishing insulin resistance HepG2 and 3T3-L1 cells. The results showed that EFSP-1 could increase glucose consumption by up-regulating the expression of GLUT-4 via activating PI3K/Akt signal pathway in IR cells. Hence, EFSP-1 could be a potential functional food to ameliorate insulin resistance for diabetes therapy.
Sujet(s)
Glucanes/composition chimique , Glucanes/pharmacologie , Hypoglycémiants/composition chimique , Hypoglycémiants/pharmacologie , Nymphaeaceae/composition chimique , Cellules 3T3-L1 , Animaux , Glucose/métabolisme , Cellules HepG2 , Humains , Insulinorésistance , Souris , Oses/analyse , Phosphatidylinositol 3-kinases/métabolisme , Protéines proto-oncogènes c-akt/métabolisme , Graines/composition chimiqueRÉSUMÉ
Our previous report showed that the novel polysaccharide SAP isolated from the fruiting bodies of Sarcodon aspratus induced Hela cells apoptosis via mitochondrial dysfunction. In this study we found that SAP enhanced immunostimulatory activities of RAW264.7 cells, which was characterized by increased the production of nitric oxide (NO), reactive oxygen species (ROS), cytokines and phagocytic. However, SAP-induced macrophage activation was abolished when Toll-like receptor 4 (TLR4) signaling was blocked by anti-TLR4 antibodies. Moreover, according to the Western blot analysis and use of specific inhibitors against the MAPKs (mitogen-activated protein kinases) and NF-κB (nuclear factor-κB), we speculated that SAP activated RAW264.7 cells through TLR4-mediated activation of NF-κB and MAPKs pathways. Thus, Sarcodon aspratus is a potential immunomodulator that can be used as healthcare food.
Sujet(s)
Basidiomycota/composition chimique , Polyosides/pharmacologie , Transduction du signal/génétique , Animaux , Régulation de l'expression des gènes/effets des médicaments et des substances chimiques , MAP Kinase Kinase 1/génétique , Souris , Facteur de transcription NF-kappa B/génétique , Polyosides/composition chimique , Polyosides/isolement et purification , Cellules RAW 264.7/effets des médicaments et des substances chimiques , Récepteur de type Toll-4/génétiqueRÉSUMÉ
Oxidative stress is considered to involve cell death in severe pulmonary diseases like idiopathic pulmonary fibrosis (IPF). Polysaccharide FMP-1 from Morchella esculenta can exert significant antioxidant activity. However, its effects on alveolar epithelial cells remain unperceived. Herein, the effects of FMP-1 against H2O2-induced oxidative damage in human alveolar epithelial A549 cells were investigated. FMP-1 could inhibit H2O2-induced cytochrome C and Caspase-3 release to prevent cell apoptosis via attenuation of MDA and ROS levels, and enhancement the enzymatic activities of SOD and T-AOC. Furthermore, the underlying molecular mechanisms were clarified. The phosphorylation of AKT and the nuclear translocation of Nrf2 were observed to be promoted by FMP-1 as well as the level of HO-1. These findings suggested that FMP-1 attenuate cellular oxidative stress through PI3K/AKT pathway, and FMP-1 could be explored as natural potential antioxidants to lower oxidative stress relevant to the progression of IPF.
Sujet(s)
Ascomycota/composition chimique , Tumeurs du poumon/traitement médicamenteux , Stress oxydatif/effets des médicaments et des substances chimiques , Polyosides/pharmacologie , Cellules A549 , Pneumocytes/effets des médicaments et des substances chimiques , Heme oxygenase-1/génétique , Humains , Tumeurs du poumon/génétique , Tumeurs du poumon/anatomopathologie , Facteur-2 apparenté à NF-E2/génétique , Stress oxydatif/génétique , Phosphatidylinositol 3-kinases/génétique , Polyosides/composition chimique , Protéines proto-oncogènes c-akt/génétique , Transduction du signal/effets des médicaments et des substances chimiquesRÉSUMÉ
Polysaccharides from Morchella esculenta are known to exhibit diverse bioactivities, while an anti-melanogenesis effect has been barely addressed. Herein, the anti-melanogenesis activity of a heteropolysaccharide from M. esculenta (FMP-1) was investigated in vitro and in vivo. FMP-1 had no significant cytotoxic effect on B16F10 melanoma cells as well as zebrafish larvae, but did reduce melanin contents and tyrosinase activities in both of them. Treatment with FMP-1 also effectively suppressed the expression of melanogenesis-related proteins, including MC1R, MITF, TRP-1 and TRP-2, through decreasing the phosphorylation of cyclic adenosine monophosphate response element-binding protein (CREB). Moreover, the mitogen-activated protein kinase (MAPK) pathway was observed mediating FMP-1's inhibitory effect against melanin production. Specifically, FMP-1 treatment markedly inhibited the activation of phosphorylation of p38 mitogen-activated protein kinase. These results suggested that FMP-1's inhibitory effect against melanogenesis is mediated by the inhibition of CREB and p38 signaling pathways, thereby resulting in the downstream repression of melanogenesis-related proteins and the subsequent melanin production. These data provide insight into FMP-1's potential anti-melanogenesis effect in food and cosmetic industries.
Sujet(s)
Ascomycota/composition chimique , Corps fructifères de champignon/composition chimique , Polysaccharides fongiques/pharmacologie , Système de signalisation des MAP kinases/effets des médicaments et des substances chimiques , Mélanines/antagonistes et inhibiteurs , Mélanome/traitement médicamenteux , Pigmentation de la peau/effets des médicaments et des substances chimiques , Animaux , Antinéoplasiques/effets indésirables , Antinéoplasiques/pharmacologie , Lignée cellulaire tumorale , Survie cellulaire/effets des médicaments et des substances chimiques , Protéine de liaison à l'élément de réponse à l'AMP cyclique/métabolisme , Embryon non mammalien/effets des médicaments et des substances chimiques , Embryon non mammalien/enzymologie , Embryon non mammalien/métabolisme , Développement embryonnaire/effets des médicaments et des substances chimiques , Antienzymes/effets indésirables , Antienzymes/pharmacologie , Polysaccharides fongiques/effets indésirables , Larve/effets des médicaments et des substances chimiques , Larve/croissance et développement , Larve/métabolisme , Mélanines/métabolisme , Mélanome/enzymologie , Mélanome/métabolisme , Souris , Monophenol monooxygenase/antagonistes et inhibiteurs , Monophenol monooxygenase/métabolisme , Protéines tumorales/antagonistes et inhibiteurs , Protéines tumorales/métabolisme , Phosphorylation/effets des médicaments et des substances chimiques , Maturation post-traductionnelle des protéines/effets des médicaments et des substances chimiques , Danio zébré , Protéines de poisson-zèbre/antagonistes et inhibiteurs , Protéines de poisson-zèbre/métabolisme , p38 Mitogen-Activated Protein Kinases/antagonistes et inhibiteurs , p38 Mitogen-Activated Protein Kinases/métabolismeRÉSUMÉ
A new polysaccharide fraction (CCPP-1) was obtained from Craterellus cornucopioides. CCPP-1 had an average molecular weight of 9.2â¯×â¯105â¯Da, which was mainly composed of mannose, glucose, xylose, arabinose, fructose in molar ratio of 0.7:0.05:0.18:1:0.05. Results of structural characterization revealed that the dominant linkage types of CCPP-1 were â3, 6)-Manp(1â, T-Araf, â4, 6)-Manp (1â, â5)-Araf (1â and â3)-Araf (1â. Interesting, in vitro antioxidant activities assays showed that CCPP-1 possessed strong scavenging abilities on DPPH and ABTS radicals. The oxidative hemolysis induced by AAPH in mice erythrocytes was effectively reversed by incubation with CCPP-1. CCPP-1 significantly prevented AAPH-induced intracellular reactive oxygen species (ROS) generation. Moreover, CCPP-1 could significantly restore AAPH-induced increase of intracellular antioxidant enzyme glutathione peroxidase (GPx) and catalase (CAT) activities to normal level, as well as inhibit intracellular malondialdehyde (MDA) formation. Therefore, CCPP-1 could protect against AAPH-induced oxidative-stress in erythrocytes, which would be explored as naturally potential antioxidant agent applied in food and cosmetic fields.
Sujet(s)
Agaricales/composition chimique , Antioxydants/composition chimique , Antioxydants/pharmacologie , Corps fructifères de champignon/composition chimique , Polyosides/composition chimique , Polyosides/pharmacologie , Amidines/pharmacologie , Animaux , Apoptose/effets des médicaments et des substances chimiques , Benzothiazoles/composition chimique , Dérivés du biphényle/composition chimique , Spectroscopie par résonance magnétique du carbone-13 , Catalase/métabolisme , Érythrocytes/cytologie , Érythrocytes/effets des médicaments et des substances chimiques , Érythrocytes/enzymologie , Érythrocytes/métabolisme , Piégeurs de radicaux libres/pharmacologie , Glutathione peroxidase/métabolisme , Mâle , Malonaldéhyde/métabolisme , Méthylation , Souris , Masse moléculaire , Oses/analyse , Picrates/composition chimique , Polyosides/ultrastructure , Agents protecteurs/pharmacologie , Spectroscopie par résonance magnétique du proton , Espèces réactives de l'oxygène/métabolisme , Spectroscopie infrarouge à transformée de Fourier , Acides sulfoniques/composition chimiqueRÉSUMÉ
This study aimed to investigate the structural features, in vitro and in vivo antioxidant activities of a heteropolysaccharide from the fruiting bodies of Morchella esculenta (FMP-1). FMP-1 had an average molecular weight of 4.7â¯×â¯103â¯Da and consisted of mannose, glucose and galactose. By methylation and NMR analysis, the backbone of FMP-1 was deduced to be made up of 1,4-linked Glcp and 1,6-linked Galp. Hydroxyl, DPPH and superoxide radicals could be efficiently scavenged by FMP-1, with IC50 values of 74.26, 119.32 and 161.49⯵g/mL, respectively. Furthermore, FMP-1 could significantly protect zebrafish embryos against AAPH-induced oxidative damage. Decrease in malformations and mortalities was observed along with the reduction of ROS production, NO production and cell death. The protective effects were by decreasing MDA content and increasing SOD, CAT and GSH-Px levels. The current work provided a good suggestion of the potential utilization of FMP-1 as an attractive natural antioxidant.
Sujet(s)
Antioxydants/composition chimique , Ascomycota/composition chimique , Corps fructifères de champignon/composition chimique , Polysaccharides fongiques/composition chimique , Animaux , Antioxydants/pharmacologie , Catalase/métabolisme , Embryon non mammalien/effets des médicaments et des substances chimiques , Embryon non mammalien/métabolisme , Polysaccharides fongiques/pharmacologie , Galactose/analyse , Glucose/analyse , Glutathione peroxidase/métabolisme , Mannose/analyse , Monoxyde d'azote/métabolisme , Danio zébréRÉSUMÉ
BACKGROUND: Polysaccharides extracted from fungus that have been used widely in the food and drugs industries due to biological activities. OBJECTIVE: The objective of the present study was to investigate the tumor-suppressive activity and mechanism of a novel polysaccharide (SAP) extracted from Sarcodon aspratus. METHODS: The SAP was extracted and purified using Sepharose CL-4B gel from S. aspratus. The cytotoxicity of SAP on cell lines was determined by MTT method. Cellular migration assays were implemented by using transwell plates. The apoptosis and mitochondrial membrane potential (Δψm) of Hela cells were analyzed by flow cytometry. The western blot was used to determine the protein expression of Hela cells. RESULTS: The results showed that SAP with a molecular weight of 9.01×105 Da could significantly inhibit the growth of Hela cells in vitro. Three-dimensional cell culture (3D) and transwell assays showed that SAP restrained the multi-cellular spheroids growth and cell migration. Flow cytometry analysis revealed that SAP induced a loss of mitochondrial membrane potential (Δψm). Western blot assays indicated that SAP promoted the release of cytochrome c, increased Bax expression, down-regulated of Bcl-2 expression and activated of caspase-3 expression. CONCLUSION: This study suggested that SAP induced Hela cells apoptosis via mitochondrial dysfunction that are critical in events of caspase apoptotic pathways. The anti-tumor (Hela cells) activity of SAP recommended that S. aspratus could be used as a powerful medicinal mushroom against cancer.
RÉSUMÉ
Polysaccharides from edible fungi usually exhibit many bioactivities. Our previous studies found that polysaccharide TLH-3 extracted from Tricholoma lobayense possessed noticeable antioxidant activity. To further explore its biological activities, the antioxidant and anti-aging activities of TLH-3 were evaluated in vitro and in vivo. The results of antioxidant activity in vitro showed that TLH-3 could enhance the cell viability, reduce the production of reactive oxygen species (ROS) and inhibit oxidative damage induced by tert-butylhydroperoxide (t-BHP) in human embryonic lung fibroblasts (HELF) cells. The anti-aging capability was measured in d-galactose (d-gal)-induced aged mice model, and the experimental data showed that TLH-3 significantly inhibited the formation of malondialdehyde (MDA) and raised the activities of superoxide dismutase (SOD) and catalase (CAT) in mice liver and serum (p<0.05). This study suggested that TLH-3 possessed apparent antioxidant and anti-aging activities and could be exploited as a potent dietary supplement to attenuate aging and prevent age-related diseases in humans.