RESUMO
BACKGROUND: Tangshen formula (TSF) has an ameliorative effect on hepatic lipid metabolism in non-alcoholic fatty liver disease (NAFLD), but the role played by the gut microbiota in this process is unknown. METHOD: We conducted three batches of experiments to explore the role played by the gut microbiota: TSF administration, antibiotic treatment, and fecal microbial transplantation. NAFLD mice were induced with a high-fat diet to investigate the ameliorative effects of TSF on NAFLD features and intestinal barrier function. 16S rRNA sequencing and serum untargeted metabolomics were performed to further investigate the modulatory effects of TSF on the gut microbiota and metabolic dysregulation in the body. RESULTS: TSF ameliorated insulin resistance, hypercholesterolemia, lipid metabolism disorders, inflammation, and impairment of intestinal barrier function. 16S rRNA sequencing analysis revealed that TSF regulated the composition of the gut microbiota and increased the abundance of beneficial bacteria. Antibiotic treatment and fecal microbiota transplantation confirmed the importance of the gut microbiota in the treatment of NAFLD with TSF. Subsequently, untargeted metabolomics identified 172 differential metabolites due to the treatment of TSF. Functional predictions suggest that metabolisms of choline, glycerophospholipid, linoleic acid, alpha-linolenic acid, and arachidonic acid are the key metabolic pathways by which TSF ameliorates NAFLD and this may be influenced by the gut microbiota. CONCLUSION: TSF treats the NAFLD phenotype by remodeling the gut microbiota and improving metabolic profile, suggesting that TSF is a functional gut microbial and metabolic modulator for the treatment of NAFLD.
Assuntos
Medicamentos de Ervas Chinesas , Microbioma Gastrointestinal , Hepatopatia Gordurosa não Alcoólica , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/metabolismo , Fígado , Dieta Hiperlipídica/efeitos adversos , Antibacterianos/farmacologia , Camundongos Endogâmicos C57BLRESUMO
In this study, purification of polysaccharide ulvan by anion exchange chromatography was prepared, and the major polysaccharide fraction (FU) was collected at 1.0â¯M NaCl elute by anion exchange chromatography, then high sulfate content purified ulvan (HFU) was prepared with sulfur trioxide/N,N-dimethylformamide (SO3-DMF) in formamide. The antioxidant activity and the antihyperlipidemic activity of HFU in mice were determined. The results showed that treatment with HFU could improve the antioxidant and antihyperlipidemic activity. Compared with the hyperlipidemic group, the antihyperlipidemic activity of HFU (125â¯mg/kg) was the strongest, TC concentrations were significantly decreased by 26.7% (Pâ¯<â¯.01), significantly reduced LDL-C (32.6%, Pâ¯<â¯.01), significantly increased HDL-C (19.6%, Pâ¯<â¯.01), and HFU-treated group (250â¯mg/kg) exhibited optimal effects on TG (29.0%, Pâ¯<â¯.01); the HFU groups at the doses of 125â¯mg/kg could significantly decrease the MDA (29.9%, Pâ¯<â¯.01); the HFU groups at the doses of 500â¯mg/kg could increase the activities of GSH-Px obviously (19.9%, Pâ¯<â¯.01).
Assuntos
Antioxidantes/farmacologia , Hipolipemiantes/farmacologia , Extratos Vegetais/farmacologia , Polissacarídeos/química , Sulfatos/química , Ulva/química , Animais , Antioxidantes/química , Peso Corporal/efeitos dos fármacos , Modelos Animais de Doenças , Radical Hidroxila/análise , Hipolipemiantes/química , Masculino , Camundongos , Peso Molecular , Monossacarídeos/isolamento & purificação , Extratos Vegetais/química , Superóxidos/análiseRESUMO
Ulvan was the polysaccharide (U) from a large edible green algae Ulva pertusa. In this study, phosphorylated ulvan (PU) was prepared by the sodium trimetaphosphate -sodium tripolyphosphate method. Antioxidant and antihyperlipidemic effects of U and PU were investigated employing in vivo systems. The PU was confirmed by IR, 31P NMR and 13C NMR spectra. And in addition, we found that the PU3 group at the dose of 500 mg/kg showed stronger antioxidant activity. Compared with hyperlipidemia group, it significantly increased GSH-Px (34.29%; P < 0.01), SOD (20.04%; P < 0.01) and CAT (37.49%; P < 0.01). Treatment of hyperlipidemia mice with PU resulted in a significant decrease in TC, TG and LDL-C, and significant increase in HDL-C. The PU3 significantly increased HDL-C (33.70%; P < 0.01), decreased LDL-C (52.73%; P < 0.01) and TG (33.58%; P < 0.01) compared with hyperlipidemia group. The result showed that phosphorylation could improve hypolipidaemic and antioxidant activities in vivo. PU may be used as a drug for hyperlipidaemia treatment.
Assuntos
Antioxidantes/química , Hipolipemiantes/química , Extratos Vegetais/química , Polissacarídeos/química , Ulva/química , Animais , Antioxidantes/farmacologia , Peso Corporal , China , Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/farmacologia , Masculino , Camundongos , Peso Molecular , Fosforilação , Extratos Vegetais/farmacocinéticaRESUMO
OBJECTIVE: To explore the effects of cluster needling at the scalp points on the expression of choline acetyl transferase (ChAT) and choline cholinesterase (AchE). METHODS: A total of 60 Wistar rats were randomized into a sham-operation group, a model group, a medication group and a cluster needling group, 15 rats in each one. In the model group, the medication group and the cluster needling group, the models of Alzheimer's disease (AD) were established by the orienteering injection with Aß1-42 in the bilateral hippocampal CA1 in the rats. In the sham-operation group, the distilled water was injected in bilateral hippocampus of rats. In the medication group, the lavage with aricept was adopted for the basic treatment, once a day, for 4 weeks consecutively. In the cluster needling group, on the base of the treatment as the medication group, the cluster needling at the scalp points was adopted, once a day, 6 times a week, for 4 weeks totally. In the sham-operation group and the model group, the normal feeding was provided. After intervention, the learning and memory ability was measured with Morris water maze in the rats of each group. The changes in the hippocampal gross structure were observed with HE staining. The changes in the positive expressions of hippocampal ChAT and AchE were determined with the immunohistochemical method. RESULTS: Compared with the sham-operation group, the escape latency was prolonged and the percentage of the second quadrant and the frequency of platform leaping were reduced in the rats of the model group (all P<0.01). Compared with the model group, the escape latency was shortened and the percentage of the second quadrant and the frequency of platform leaping were increased in the rats of the cluster needling group and the medication group (P<0.05, P<0.01). Compared with the medication group, the escape latency was shortened and the percentage of the second quadrant and the frequency of platform leaping were increased in the rats of the cluster needling group (all P<0.05). Compared with the sham-operation group, the expression of ChAT was decreased and that of AchE increased in the model group (both P<0.01). Compared with the model group, the difference was not significant in ChAT expression (P>0.05) and the expression of AchE was reduced (P<0.05) in the medication group; the expression of ChAT was increased (P<0.05) and that of AchE decreased (P<0.01) in the cluster needling group. Compared with the medication group, the expression of ChAT was increased and that of AchE decreased in the cluster needling group (both P<0.05). CONCLUSION: The effect mechanism of cluster needling at the scalp points on AD could be related to the up-regulation of ChAT expression and down-regulation of AchE expression in the hippocampus. The combined treatment with the cluster needling and aricept achieves the better therapeutic effect on AD.
Assuntos
Doença de Alzheimer , Animais , Colina O-Acetiltransferase , Hipocampo , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Couro CabeludoRESUMO
The hypolipidemic and antioxidant effects of porphyran from the red algae Porphyra haitanensis as a dietary supplement were evaluated in mice. The levels of serum TC, TG and LDL-C in MP group increased significantly (p<0.05 or p<0.01) by 28.5%, 29.4% and 33.5% compared with the model group. These significant rises were accompanied by significant declines of plasma HDL-C by 21.6% compared with the model group. In addition, the liver content of malondialdehyde significantly decreased, while the superoxide dismutase, catalase, glutathione peroxidase activities significantly increased. The levels of serum SOD and GSH-Px in MP group increased significantly by 51.2% and 99.6% compared with the model group. The results suggested that porphyran could be used as functional foods and natural drugs in preventing the hyperlipidemia and this activity might be attributed to its antioxidant potential.
Assuntos
Antioxidantes/farmacologia , Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/farmacologia , Sefarose/análogos & derivados , Animais , Catalase/metabolismo , Glutationa Peroxidase/metabolismo , Masculino , Malondialdeído/metabolismo , Camundongos , Porphyra/química , Sefarose/farmacologia , Superóxido Dismutase/metabolismoRESUMO
Numerous studies have suggested that hyperlipidemia is closely linked to cardiovascular disease. The aim of this study was to investigate the possible antihyperlipidemia mechanism of HU (high sulfate content of ulvan) in high-cholesterol fed rats. Wistar rats were made hyperlipidemic by feeding with a high-cholesterol diet. HU was administered to these hyperlipidemia rats for 30 days. Lipid levels and the mRNA expressions of FXR, LXR and PPARγ in liver were measured after 30 days of treatment. In the HU-treated groups, the middle dosage group of male rats (total cholesterol (TC): p < 0.01) and the low-dosage group of female rats (TC, LDL-C: p < 0.01) showed stronger activity with respect to antihyperlipidemia. Moreover, some HU groups could upregulate the mRNA expression of FXR and PPARγ and downregulate the expression of LXR. For the male rats, compared with the hyperlipidemia group, the middle dosage HU had the most pronounced effect on increasing the mRNA levels of FXR (p < 0.01); low- and high-dosage HU showed a significant inhibition of the mRNA levels of LXR (p < 0.01). All HU female groups could upregulate the mRNA expression of PPARγ in a concentration-dependent manner. In summary, HU could improve lipid profiles through upregulation of FXR and PPARγ and downregulation of LXR.
Assuntos
Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/farmacologia , Polissacarídeos/farmacologia , Animais , Colesterol/sangue , Colesterol/metabolismo , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Feminino , Hipolipemiantes/administração & dosagem , Hipolipemiantes/química , Lipídeos/sangue , Fígado/metabolismo , Receptores X do Fígado , Masculino , Receptores Nucleares Órfãos/genética , PPAR gama/genética , Polissacarídeos/administração & dosagem , Polissacarídeos/química , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Receptores Citoplasmáticos e Nucleares/genética , Fatores Sexuais , Sulfatos/química , Regulação para Cima/efeitos dos fármacosRESUMO
Sulfated polysaccharides exerted potent biological property which was relative to degree of sulfation, molecular weight, substitution position and chain conformation. In present study, the polysaccharide with low molecular weight (LEP) from Enteromorpha linza was sulfated with chlorosulfuric acid in formamide. The obtained polysaccharide sulfate was selected to evaluate their antioxidant activities and the anticoagulant activity in the coagulation assays, activated partial thromboplastin time (APTT), thrombin time (TT) and prothrombin time (PT). The data obtained in vitro models indicated that high DS and moderate Mw showed the best anticoagulant and antioxidant activities.
Assuntos
Anticoagulantes/química , Extratos Vegetais/química , Polissacarídeos/química , Ulva/química , Animais , Anticoagulantes/farmacologia , Galinhas , Sequestradores de Radicais Livres , Metilação , Tempo de Tromboplastina Parcial , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Tempo de Protrombina , Espectroscopia de Infravermelho com Transformada de Fourier , Sulfatos , Superóxidos/química , Tempo de TrombinaRESUMO
Crude polysaccharides were extracted from Athyrium multidentatum (Doll.) Ching (AMC) rhizome and fractionated by DEAE-Cellulose 52 ion-exchange column chromatography. Two polysaccharide fractions (F1 and F2) were obtained and had their antioxidant activities investigated employing various established in vitro systems. All fractions possessed considerable antioxidant activity. Chemical analysis suggested that F1 and F2 were neutral heteropolysaccharide in which glucose was the major component. Available data suggested that the molecular weight and sulfate content played very important roles on antioxidant activity. Our results indicated that the polysaccharides may contribute to the medicinal functions of AMC.
Assuntos
Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Gleiquênias/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Polissacarídeos/isolamento & purificação , Polissacarídeos/farmacologia , Antioxidantes/química , Cromatografia Líquida de Alta Pressão , Sequestradores de Radicais Livres/farmacologia , Radical Hidroxila/metabolismo , Íons , Ferro/metabolismo , Quelantes de Ferro/farmacologia , Extratos Vegetais/química , Polissacarídeos/química , Superóxidos/metabolismoRESUMO
In this study, acetylated ulvan (AU) was prepared with acetic anhydride in N,N-dimethylacetamide, and the antihyperlipidemic activity of natural ulvan and its acetylated ulvan derivative (AU) in mice was determined. Obvious differences in antihyperlipidemic activity between natural ulvan and its derivative were observed, moreover, AU showed stronger antihyperlipidemic activity on triglyceride (TG) and low density lipoprotein cholesterol (LDL-C).
Assuntos
LDL-Colesterol/química , Hiperlipidemias/tratamento farmacológico , Polissacarídeos/metabolismo , Triglicerídeos/química , Ulva/metabolismo , Acetilação , Animais , Colesterol/química , Feminino , Masculino , Camundongos , Modelos Estatísticos , Ácidos Nicotínicos/química , Extratos Vegetais/farmacologia , Polissacarídeos/química , Polissacarídeos/farmacologia , TemperaturaRESUMO
Fucoidan, the sulphated polysaccharide extracted from brown seaweed, has various biological activities. The effect of fucoidan on the formation of proteinuria and renal functions in active Heymann nephritis was investigated in this study. Active Heymann nephritis was induced by administering brush border protein of rat proximal uriniferous tubules (FX1A). Fucoidan was administered by oral intubation to Heymann nephritis rats at three doses (50, 100 and 200 mg/kg) once daily for 4 weeks. The elevated urinary protein excretion and plasma creatinine due to the induction of Heymann nephritis were significantly reduced by fucoidan at doses of 100 and 200 mg/kg. The results indicated that fucoidan has a renoprotective effect on active Heymann nephritis and is a promising therapeutic agent for nephritis.