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Naturally Occurring Stilbenoid TSG Reverses Non-Alcoholic Fatty Liver Diseases via Gut-Liver Axis.

Lin P, Lu J, Wang Y, Gu W, Yu J, Zhao R - PLoS ONE (2015)

Bottom Line: TSG regulated gut microbiota balanced and increased the protein expression of ZO-1 and occludin, which could improve the function of the intestinal mucosal barrier and reduce serum LPS content by about 25%.TSG reduced TL4 levels by 56% and NF-κB expression by 23% relative to the NAFLD model group.This suggests that prevention of NAFLD by TSG in HFD-fed rats is mediated by modulation of the gut microbiota and TLR4/NF-κB pathway, which may alleviate chronic low-grade inflammation by reducing the exogenous antigen load on the host.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, Yunnan University of Traditional Chinese Medicine, Kunming, Yunnan Province, China.

ABSTRACT
The gut-liver axis is largely involved in the development of non-alcoholic fatty liver disease (NAFLD). We investigated whether 2, 3, 5, 4'-tetrahydroxy-stilbene-2-O-β-D-glucoside (TSG) could reverse NAFLD induced by a high-fat diet (HFD) and whether it did so via the gut-liver axis. Results showed that TSG could reduce the accumulation of FFA and it did so by reducing the expression of L-FABP and FATP4. TSG regulated gut microbiota balanced and increased the protein expression of ZO-1 and occludin, which could improve the function of the intestinal mucosal barrier and reduce serum LPS content by about 25%. TSG reduced TL4 levels by 56% and NF-κB expression by 23% relative to the NAFLD model group. This suggests that prevention of NAFLD by TSG in HFD-fed rats is mediated by modulation of the gut microbiota and TLR4/NF-κB pathway, which may alleviate chronic low-grade inflammation by reducing the exogenous antigen load on the host.

No MeSH data available.


Related in: MedlinePlus

Rat liver tissue gene and protein expression in TLR4/NF-κB pathway.(A) Gene expression clustering tree and the corresponding standardized signal value of major expressed genes in the TLR4/NF-κB pathway. Total RNA from 3 liver tissues (1 from the control group, 1 from the model group, and 1 from the TSG.M group) were harvested, amplified and labeled using an Agilent Whole Rat Genome Oligo Microarray (4 × 44 K) using Agilent SureHyb hybridization chambers. The processed slides were scanned with an Agilent microarray scanner G2505C after.hybridization and washing. Agilent Feature Extraction software was used to analyze acquired array images. Quantile normalization and subsequent data processing were performed with using the GeneSpring GX v11.5.1 software package. After quantile normalization of the raw data, genes that at least 1 out of 3 samples have flags in Detected (“All Targets Value”) were chosen for further data analysis. Differentially expressed genes between the two samples were identified through Fold Change filtering. Hierarchical Clustering was performed using the R scripts. (B) Concentrations of FetA, TLR4, NF-κB, TNF-α, IL-1α, IL-6, and IL-10 proteins in the liver. Tissue samples from the liver were excised and weighed after washing with 0.9% saline after rats were sacrificed using an intraperitoneal injection of 7% chloral hydrate (0.3 mL/100 g).100 mg tissues were rinsed with PBS and homogenized in 1 mL of PBS and then stored overnight at -20°C. Two freeze-thaw cycles were performed to break all cell membranes, and the homogenates were then centrifuged for 10 minutes at 4000 rpm, 4°C. The supernatant was collected for analysis. Concentrations of FetA, TLR4, NF-κB, TNF-α, IL-1α, IL-6, and IL-10 were tested using ELISA assay kits (mean±SD, n = 7). Statistical significance: * p< 0.05 vs. control;** p< 0.01 vs. control;*** p< 0.001 vs. control; # p< 0.05 vs. model; ## p< 0.01 vs. model; ### p< 0.001 vs. model
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pone.0140346.g005: Rat liver tissue gene and protein expression in TLR4/NF-κB pathway.(A) Gene expression clustering tree and the corresponding standardized signal value of major expressed genes in the TLR4/NF-κB pathway. Total RNA from 3 liver tissues (1 from the control group, 1 from the model group, and 1 from the TSG.M group) were harvested, amplified and labeled using an Agilent Whole Rat Genome Oligo Microarray (4 × 44 K) using Agilent SureHyb hybridization chambers. The processed slides were scanned with an Agilent microarray scanner G2505C after.hybridization and washing. Agilent Feature Extraction software was used to analyze acquired array images. Quantile normalization and subsequent data processing were performed with using the GeneSpring GX v11.5.1 software package. After quantile normalization of the raw data, genes that at least 1 out of 3 samples have flags in Detected (“All Targets Value”) were chosen for further data analysis. Differentially expressed genes between the two samples were identified through Fold Change filtering. Hierarchical Clustering was performed using the R scripts. (B) Concentrations of FetA, TLR4, NF-κB, TNF-α, IL-1α, IL-6, and IL-10 proteins in the liver. Tissue samples from the liver were excised and weighed after washing with 0.9% saline after rats were sacrificed using an intraperitoneal injection of 7% chloral hydrate (0.3 mL/100 g).100 mg tissues were rinsed with PBS and homogenized in 1 mL of PBS and then stored overnight at -20°C. Two freeze-thaw cycles were performed to break all cell membranes, and the homogenates were then centrifuged for 10 minutes at 4000 rpm, 4°C. The supernatant was collected for analysis. Concentrations of FetA, TLR4, NF-κB, TNF-α, IL-1α, IL-6, and IL-10 were tested using ELISA assay kits (mean±SD, n = 7). Statistical significance: * p< 0.05 vs. control;** p< 0.01 vs. control;*** p< 0.001 vs. control; # p< 0.05 vs. model; ## p< 0.01 vs. model; ### p< 0.001 vs. model

Mentions: Rat liver tissue gene spectrum scanning of three groups was performed using 4 × 44 k gene expression in rats with Agilent production chips. The gene expression clustering tree and the corresponding standardized signal value of major expressed genes in TLR4 inherent immune response system are shown in Fig 5A.


Naturally Occurring Stilbenoid TSG Reverses Non-Alcoholic Fatty Liver Diseases via Gut-Liver Axis.

Lin P, Lu J, Wang Y, Gu W, Yu J, Zhao R - PLoS ONE (2015)

Rat liver tissue gene and protein expression in TLR4/NF-κB pathway.(A) Gene expression clustering tree and the corresponding standardized signal value of major expressed genes in the TLR4/NF-κB pathway. Total RNA from 3 liver tissues (1 from the control group, 1 from the model group, and 1 from the TSG.M group) were harvested, amplified and labeled using an Agilent Whole Rat Genome Oligo Microarray (4 × 44 K) using Agilent SureHyb hybridization chambers. The processed slides were scanned with an Agilent microarray scanner G2505C after.hybridization and washing. Agilent Feature Extraction software was used to analyze acquired array images. Quantile normalization and subsequent data processing were performed with using the GeneSpring GX v11.5.1 software package. After quantile normalization of the raw data, genes that at least 1 out of 3 samples have flags in Detected (“All Targets Value”) were chosen for further data analysis. Differentially expressed genes between the two samples were identified through Fold Change filtering. Hierarchical Clustering was performed using the R scripts. (B) Concentrations of FetA, TLR4, NF-κB, TNF-α, IL-1α, IL-6, and IL-10 proteins in the liver. Tissue samples from the liver were excised and weighed after washing with 0.9% saline after rats were sacrificed using an intraperitoneal injection of 7% chloral hydrate (0.3 mL/100 g).100 mg tissues were rinsed with PBS and homogenized in 1 mL of PBS and then stored overnight at -20°C. Two freeze-thaw cycles were performed to break all cell membranes, and the homogenates were then centrifuged for 10 minutes at 4000 rpm, 4°C. The supernatant was collected for analysis. Concentrations of FetA, TLR4, NF-κB, TNF-α, IL-1α, IL-6, and IL-10 were tested using ELISA assay kits (mean±SD, n = 7). Statistical significance: * p< 0.05 vs. control;** p< 0.01 vs. control;*** p< 0.001 vs. control; # p< 0.05 vs. model; ## p< 0.01 vs. model; ### p< 0.001 vs. model
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4608713&req=5

pone.0140346.g005: Rat liver tissue gene and protein expression in TLR4/NF-κB pathway.(A) Gene expression clustering tree and the corresponding standardized signal value of major expressed genes in the TLR4/NF-κB pathway. Total RNA from 3 liver tissues (1 from the control group, 1 from the model group, and 1 from the TSG.M group) were harvested, amplified and labeled using an Agilent Whole Rat Genome Oligo Microarray (4 × 44 K) using Agilent SureHyb hybridization chambers. The processed slides were scanned with an Agilent microarray scanner G2505C after.hybridization and washing. Agilent Feature Extraction software was used to analyze acquired array images. Quantile normalization and subsequent data processing were performed with using the GeneSpring GX v11.5.1 software package. After quantile normalization of the raw data, genes that at least 1 out of 3 samples have flags in Detected (“All Targets Value”) were chosen for further data analysis. Differentially expressed genes between the two samples were identified through Fold Change filtering. Hierarchical Clustering was performed using the R scripts. (B) Concentrations of FetA, TLR4, NF-κB, TNF-α, IL-1α, IL-6, and IL-10 proteins in the liver. Tissue samples from the liver were excised and weighed after washing with 0.9% saline after rats were sacrificed using an intraperitoneal injection of 7% chloral hydrate (0.3 mL/100 g).100 mg tissues were rinsed with PBS and homogenized in 1 mL of PBS and then stored overnight at -20°C. Two freeze-thaw cycles were performed to break all cell membranes, and the homogenates were then centrifuged for 10 minutes at 4000 rpm, 4°C. The supernatant was collected for analysis. Concentrations of FetA, TLR4, NF-κB, TNF-α, IL-1α, IL-6, and IL-10 were tested using ELISA assay kits (mean±SD, n = 7). Statistical significance: * p< 0.05 vs. control;** p< 0.01 vs. control;*** p< 0.001 vs. control; # p< 0.05 vs. model; ## p< 0.01 vs. model; ### p< 0.001 vs. model
Mentions: Rat liver tissue gene spectrum scanning of three groups was performed using 4 × 44 k gene expression in rats with Agilent production chips. The gene expression clustering tree and the corresponding standardized signal value of major expressed genes in TLR4 inherent immune response system are shown in Fig 5A.

Bottom Line: TSG regulated gut microbiota balanced and increased the protein expression of ZO-1 and occludin, which could improve the function of the intestinal mucosal barrier and reduce serum LPS content by about 25%.TSG reduced TL4 levels by 56% and NF-κB expression by 23% relative to the NAFLD model group.This suggests that prevention of NAFLD by TSG in HFD-fed rats is mediated by modulation of the gut microbiota and TLR4/NF-κB pathway, which may alleviate chronic low-grade inflammation by reducing the exogenous antigen load on the host.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, Yunnan University of Traditional Chinese Medicine, Kunming, Yunnan Province, China.

ABSTRACT
The gut-liver axis is largely involved in the development of non-alcoholic fatty liver disease (NAFLD). We investigated whether 2, 3, 5, 4'-tetrahydroxy-stilbene-2-O-β-D-glucoside (TSG) could reverse NAFLD induced by a high-fat diet (HFD) and whether it did so via the gut-liver axis. Results showed that TSG could reduce the accumulation of FFA and it did so by reducing the expression of L-FABP and FATP4. TSG regulated gut microbiota balanced and increased the protein expression of ZO-1 and occludin, which could improve the function of the intestinal mucosal barrier and reduce serum LPS content by about 25%. TSG reduced TL4 levels by 56% and NF-κB expression by 23% relative to the NAFLD model group. This suggests that prevention of NAFLD by TSG in HFD-fed rats is mediated by modulation of the gut microbiota and TLR4/NF-κB pathway, which may alleviate chronic low-grade inflammation by reducing the exogenous antigen load on the host.

No MeSH data available.


Related in: MedlinePlus