Journal: International Journal of Molecular Sciences

Article Title: Ellagic Acid: A Green Multi-Target Weapon That Reduces Oxidative Stress and Inflammation to Prevent and Improve the Condition of Alzheimer’s Disease

doi: 10.3390/ijms26020844

Figure Lengend Snippet: Biological activities of UROs in different animal models.

Article Snippet: Sprague Dawley rats , Uro-A (50 mg kg −1 d −1 p.o.) for 5 days in a cisplatin-induced nephrotoxicity model , ↓ Cisplatin-induced inflammation Inhibition of the proapoptotic pathway Prevention of renal impairments and histopathological damage , [ ] .

Techniques: Activity Assay, Preserving, Antioxidant Activity Assay, Clinical Proteomics, Inhibition, Permeability, Activation Assay, Expressing, Infection, Histopathology, Knock-Out, Transgenic Assay, Phospho-proteomics, Quantitative Proteomics, Biomarker Discovery

Journal: Cellular and Molecular Gastroenterology and Hepatology

Article Title: Microbial-derived Urolithin A Targets GLS1 to Inhibit Glutaminolysis and Attenuate Cirrhotic Portal Hypertension

doi: 10.1016/j.jcmgh.2024.101379

Figure Lengend Snippet: The gut microbiota metabolite UroA was deficient in patients and mice with CPH. ( A ) The chemical structure of UroA. ( B ) The levles of UroA in the humans feces and plasma were determined by LC-MS/MS (n = 20 healthy subjects; n = 30 patients with CPH). ( C ) The statistical correlation between UroA levels and portal pressure (Spearman rank-order correlation test) (n = 30 patients with CPH). ( D ) The UroA levels in different patients with CPH. Child-Pugh score (A/B+C, n = 13/17 patients with CPH), ascites (no/yes, n = 12/18 patients with CPH). Mice were administered 14 weeks CCl 4 to induce liver fibrosis and CPH. ( E ) The concentration of UroA in the feces and plasma of mice was determined by LC-MS/MS (n = 10). ( F ) Mice were pre-administered with antibiotics by oral gavage. The total bacterial load in mice cecum and the levels of UroA in mice (n = 6). ( G ) Alpha diversity (observed species) in mice was calculated using the Chao1 index, Shannon index, and observed ASVs index (n = 10). ( H ) Beta diversity of mice feces (microbial community structures) was calculated using a PCoA score based on the weighted UniFrac distance matrixes (n = 10). ( I ) The relative abundance of bacteria at the phyla and class levels in mice feces (n = 10). ( J ) Heatmap of bacterial genus with significant difference in control and CPH mice. Red represents high relative expression and blue represents low relative expression (n = 10). ( K ) The relative abundance of Lactobacillus at the genus level in mice feces (n = 10) and the statistical correlation between UroA levels and the relative abundance of genus Lactobacillus in mice (n = 20, Spearman rank-order correlation test). ( L ) The relative abundance of Roseburia at the genus level in mice feces (n = 10) and the statistical correlation between UroA levels and the relative abundance of genus Roseburia in mice (n = 20, Spearman rank-order correlation test). ( M ) The relative abundance of Streptococcus at the genus level in mice feces (n = 10) and the statistical correlation between UroA levels and the relative abundance of genus Streptococcus in mice (n = 20, Spearman rank-order correlation test). Data were expressed as mean ± SEM; ∗ P < .05.

Article Snippet: For prophylactic administration of UroA, CCl 4 -induced mice were treated with UroA (10 mg/kg; Macklin) or its vehicle (1% DMSO in phosphate buffered saline [PBS]) by oral gavage daily from the first day of CCl 4 injection.

Techniques: Clinical Proteomics, Liquid Chromatography with Mass Spectroscopy, Concentration Assay, Bacteria, Control, Expressing

Journal: Cellular and Molecular Gastroenterology and Hepatology

Article Title: Microbial-derived Urolithin A Targets GLS1 to Inhibit Glutaminolysis and Attenuate Cirrhotic Portal Hypertension

doi: 10.1016/j.jcmgh.2024.101379

Figure Lengend Snippet: UroA attenuated liver fibrosis in CCl 4 -induced mice. Mice were administered with CCl 4 for 14 weeks and treated with 10 mg/kg UroA once a day from the first day of CCl 4 . ( A ) The plasma level of UroA in each group was detect by LC-MS/MS. (n = 8). Mice were administered with CCl 4 for 6 weeks to induce liver fibrosis, and treated with 10 mg/kg UroA once a day from the first day of CCl 4 treatment. ( B ) Representative photographs of mice livers, HE, and ( C ) quantification of Sirius Red, α-SMA, and F4/80 in mice liver (n = 6). ( D ) Hepatic hydroxyproline (n = 6). ( E ) The mRNA levels of hepatic α-SMA, Col1α1, TGF-β, PDGF, TIMP-1, F4/80, TNF-α, and IL-1β (n = 6). Representative results from 3 independent experiments with similar results. Scale bar: 100 μm. Data were expressed as mean ± SEM; ∗ P < .05; n.s. indicates nonsignificant.

Article Snippet: For prophylactic administration of UroA, CCl 4 -induced mice were treated with UroA (10 mg/kg; Macklin) or its vehicle (1% DMSO in phosphate buffered saline [PBS]) by oral gavage daily from the first day of CCl 4 injection.

Techniques: Clinical Proteomics, Liquid Chromatography with Mass Spectroscopy

Journal: Cellular and Molecular Gastroenterology and Hepatology

Article Title: Microbial-derived Urolithin A Targets GLS1 to Inhibit Glutaminolysis and Attenuate Cirrhotic Portal Hypertension

doi: 10.1016/j.jcmgh.2024.101379

Figure Lengend Snippet: The prophylactic administration of UroA attenuated liver injury and CPH in CCl 4 -induced and BDL-induced mice. Liver injury and CPH was induced by CCl 4 administration in mice. Ten mg/kg UroA was administered to mice by oral gavage once a day. ( A ) Representative photographs of mice livers, HE, and ( B ) quantification of Sirius Red, α-SMA, p-MLC2, and F4/80 in mice liver (n = 8). ( C ) Hepatic hydroxyproline (n = 8) and ascites of mice (n = 8). ( D ) The mRNA levels of hepatic α-SMA, Col1α1, TGF-β, PDGF, TIMP-1, F4/80, TNF-α, and IL-1β (n = 8). ( E ) Spleen enlargement, spleen coefficient, and portal pressure (n = 8). In BDL-induced mice, 10 mg/kg UroA was administered to mice by oral gavage once a day. ( F ) Representative photographs of mice livers, HE, and ( G ) quantification of Sirius Red, α-SMA, F4/80, and p-MLC2 in mice liver (n = 8). ( H ) Hepatic hydroxyproline (n = 8) and ascites of mice (n = 8). ( I ) The mRNA levels of hepatic α-SMA, Col1α1, TGF-β, PDGF, TIMP-1, F4/80, TNF-α, and IL-1β (n = 8). ( J ) Spleen enlargement, spleen coefficient and portal pressure (n = 8). Representative results from 3 (A–J) independent experiments with similar results. Scale bar: 100 μm. Data were expressed as mean ± SEM; ∗ P < .05.

Article Snippet: For prophylactic administration of UroA, CCl 4 -induced mice were treated with UroA (10 mg/kg; Macklin) or its vehicle (1% DMSO in phosphate buffered saline [PBS]) by oral gavage daily from the first day of CCl 4 injection.

Techniques:

Journal: Cellular and Molecular Gastroenterology and Hepatology

Article Title: Microbial-derived Urolithin A Targets GLS1 to Inhibit Glutaminolysis and Attenuate Cirrhotic Portal Hypertension

doi: 10.1016/j.jcmgh.2024.101379

Figure Lengend Snippet: The interventional administration of UroA attenuated liver injury and CPH in CCl 4 -induced and BDL-induced mice. Liver injury and CPH was induced by CCl 4 administration in mice. Ten mg/kg UroA was administered beginning in the 8th week of CCl 4 treatment. ( A ) Representative photographs of mice livers, HE, and ( B ) quantification of Sirius Red, α-SMA, and p-MLC2 in mice liver (n = 8). ( C ) Hepatic hydroxyproline (n = 8) and ascites of CPH mice (n = 8). ( D ) The mRNA levels of hepatic α-SMA, Col1α1, TGF-β, PDGF, and TIMP-1 (n = 8). ( E ) Spleen enlargement, spleen coefficient, and portal pressure (n = 8). In BDL-induced mice, 10 mg/kg UroA was administered from the 14th day after BDL surgery. ( F ) Representative photographs of mice livers, HE, and ( G ) quantification of Sirius Red, α-SMA, p-MLC2 in mice liver (n = 8). ( H ) Hepatic hydroxyproline (n = 8) and ascites of CPH mice (n = 8). ( I ) The mRNA levels of hepatic α-SMA, Col1α1, TGF-β, PDGF, and TIMP-1 (n = 8). ( J ) Spleen enlargement, spleen coefficient, and portal pressure (n = 8). Scale bar: 100 μm. Data were expressed as mean ± SEM; ∗ P < .05; n.s. indicates nonsignificant.

Article Snippet: For prophylactic administration of UroA, CCl 4 -induced mice were treated with UroA (10 mg/kg; Macklin) or its vehicle (1% DMSO in phosphate buffered saline [PBS]) by oral gavage daily from the first day of CCl 4 injection.

Techniques:

Journal: Cellular and Molecular Gastroenterology and Hepatology

Article Title: Microbial-derived Urolithin A Targets GLS1 to Inhibit Glutaminolysis and Attenuate Cirrhotic Portal Hypertension

doi: 10.1016/j.jcmgh.2024.101379

Figure Lengend Snippet: UroA exerted the therapeutic effect by acting on HSCs. Liver injury and CPH was induced by CCl 4 administration in mice. Ten mg/kg UroA was administered to mice by oral gavage once a day for 14 weeks. ( A ) The differences of hepatic transcriptional levels between 2 groups were analyzed by transcriptome. The heatmap was performed to display the transcriptional level of gene expression with significant difference in mice livers. Red represents high relative expression and blue represents low relative expression (n = 5). ( B ) KEGG signaling pathway analysis revealed HSCs-related functional terms enriched in CPH mice. ( C ) The volcano plots of genes expression in UroA-treated group and CCl 4 group. ( D ) Cellular component, molecular function, and biological process were used to reveal metabolism-related functional terms enriched by the DEGs based on Cytoscape software combined with ClueGO App. ( E ) LX-2 cells were treated with or without UroA for 24 hours. LX-2 cells apoptosis (n = 3). ( F ) The mRNA levels of α-SMA and Col1α1 with different doses of UroA in primary mice aHSCs (n = 4). Data were expressed as mean ± SEM; ∗ P < .05; n.s. indicates nonsignificant.

Article Snippet: For prophylactic administration of UroA, CCl 4 -induced mice were treated with UroA (10 mg/kg; Macklin) or its vehicle (1% DMSO in phosphate buffered saline [PBS]) by oral gavage daily from the first day of CCl 4 injection.

Techniques: Gene Expression, Expressing, Functional Assay, Software

Journal: Cellular and Molecular Gastroenterology and Hepatology

Article Title: Microbial-derived Urolithin A Targets GLS1 to Inhibit Glutaminolysis and Attenuate Cirrhotic Portal Hypertension

doi: 10.1016/j.jcmgh.2024.101379

Figure Lengend Snippet: UroA suppressed the glutamine metabolism to regulate the fibrogenic and contraction phenotype of HSCs. LX-2 cells were treated with or without 10 μmol/L UroA. ( A ) Glutamic acid and α-Ketoglutaric acid levels in LX-2 cells (n = 3). LX-2 cells were cultured in medium deprived of glutamine and treated with or without UroA, control cells were cultured in complete medium. ( B ) The mRNA levels of α-SMA, Col1α1, TGF-β, PDGF, and TIMP-1 (n = 6). ( C ) Cell growth (n = 5) and ( D ) EdU staining. ( E ) p-MLC2 fluorescent staining. ( F ) The protein expression of α-SMA and Col1α1. ( G ) Collagen gel contraction. Primary HSCs from healthy mice were isolated. Quiescent HSCs were cultured for 0 days, and activated HSCs were cultured for 7 days and treated with or without 10 μmol/L UroA. ( H ) The relative ATP content (n = 5). Liver injury and CPH was induced by CCl 4 administration in mice. Ten mg/kg UroA was administered to mice by oral gavage once a day for 14 weeks. ( I ) The mRNA levels of TNF-α and IL-1β in liver macrophage of CPH mice (n = 8). Liver injury and CPH was induced by 14 weeks CCl 4 administration in mice. Ten mg/kg UroA was administered to mice by oral gavage once a day. ( J ) Plasma ALT level (n = 8) and the relative ATP content in primary hepatocytes (n = 5). Representative results from 3 independent experiments with similar results. Scale bar: 50 μm. Data were expressed as mean ± SEM; ∗ P < .05; n.s. indicates nonsignificant.

Article Snippet: For prophylactic administration of UroA, CCl 4 -induced mice were treated with UroA (10 mg/kg; Macklin) or its vehicle (1% DMSO in phosphate buffered saline [PBS]) by oral gavage daily from the first day of CCl 4 injection.

Techniques: Cell Culture, Control, Staining, Expressing, Isolation, Clinical Proteomics

Journal: Cellular and Molecular Gastroenterology and Hepatology

Article Title: Microbial-derived Urolithin A Targets GLS1 to Inhibit Glutaminolysis and Attenuate Cirrhotic Portal Hypertension

doi: 10.1016/j.jcmgh.2024.101379

Figure Lengend Snippet: The protective effect of UroA was partly dependent on GLS1 inhibition. LX-2 cells were treated with 10 μmol/L BPTES and/or 10 μmol/L UroA for 24 hours. ( A ) GLS activity (n = 5) and the mRNA levels of α-SMA, Col1α1, TGF-β, PDGF, and TIMP-1 (n = 6). ( B ) EdU staining and p-MLC2 fluorescent staining, scale bar: 50 μm. ( C ) Cell growth (n = 5). ( D ) The protein expression and quantification of α-SMA and Col1α1 (n = 3). ( E ) Collagen gel contraction. Representative results from 3 ( A–E ) independent experiments with similar results. Liver injury and CPH was induced by CCl 4 administration in mice. Then mice were treated with 10 mg/kg BPTES and/or 10 mg/kg UroA. ( F ) Representative photographs of mice livers, HE, Sirius Red, and ( G ) quantification of Sirius Red, α-SMA, p-MLC2 in mice liver (n = 8), scale bar: 100 μm. ( H ) Hepatic hydroxyproline and ascites of CPH mice (n = 8). ( I ) The mRNA levels of hepatic α-SMA, Col1α1, TGF-β, PDGF, and TIMP-1 (n = 8). ( J–K ) Spleen enlargement, spleen coefficient, and portal pressure (n = 8). Representative results from 2 ( F–K ) independent experiments with similar results. Data were expressed as mean ± SEM; ∗ P < .05; n.s. indicates nonsignificant.

Article Snippet: For prophylactic administration of UroA, CCl 4 -induced mice were treated with UroA (10 mg/kg; Macklin) or its vehicle (1% DMSO in phosphate buffered saline [PBS]) by oral gavage daily from the first day of CCl 4 injection.

Techniques: Inhibition, Activity Assay, Staining, Expressing

Journal: Cellular and Molecular Gastroenterology and Hepatology

Article Title: Microbial-derived Urolithin A Targets GLS1 to Inhibit Glutaminolysis and Attenuate Cirrhotic Portal Hypertension

doi: 10.1016/j.jcmgh.2024.101379

Figure Lengend Snippet: Gut bacterium L. murinus protected against CPH in CCl 4 -induced mice by producing metabolite UroA. ( A ) The relative abundance of L. murinus at the species level in mice feces (n = 10), the statistical correlation between the UroA levels and the relative abundance of L. murinus (n = 20, Spearman rank-order correlation test). CPH mice were treated with L. murinus (5×10ˆ 7 CFU) by oral gavage once a day for 14 weeks. ( B ) The UroA levels in mice feces (n = 8). Liver injury and CPH was induced by CCl 4 administration in mice. CPH mice were treated with L. murinus (5×10 ˆ7 CFU) and/or BPTES once a day for 14 weeks. ( C ) Representative photographs of mice livers, HE, Sirius Red, and ( D ) quantification of Sirius Red, α-SMA, and p-MLC2 in mice liver (n = 8). ( E ) Hepatic hydroxyproline and ascites of mice (n = 8). ( F ) The mRNA levels of hepatic α-SMA, Col1α1, TGF-β, PDGF, and TIMP-1 (n = 8). ( G ) Spleen enlargement, spleen coefficient, and portal pressure (n = 8). CPH mice were treated with 10 mg/kg UroA and/or L. murinus (5×10 ˆ7 CFU) for 14 weeks. ( H ) Representative photographs of mice livers, HE, Sirius Red. ( I ) The UroA levels in mice feces and plasma (n = 8). ( J ) Quantification of Sirius Red, α-SMA, and p-MLC2 in mice liver (n = 8). ( K ) Hepatic hydroxyproline and ascites of CPH mice (n = 8). ( L ) The mRNA levels of hepatic α-SMA, Col1α1, TGF-β, PDGF, and TIMP-1 (n = 8). ( M ) Spleen enlargement, spleen coefficient, and portal pressure (n = 8). Representative results from 2 independent experiments with similar results. Scale bar: 100 μm. Data were expressed as mean ± SEM; ∗ P < .05; n.s. indicates nonsignificant.

Article Snippet: For prophylactic administration of UroA, CCl 4 -induced mice were treated with UroA (10 mg/kg; Macklin) or its vehicle (1% DMSO in phosphate buffered saline [PBS]) by oral gavage daily from the first day of CCl 4 injection.

Techniques: Clinical Proteomics