Gut microbiota combined with metabolomics reveal the mechanism of curcumol on liver fibrosis in mice

Zheng, Yang; Wang, Jiahui; Wang, Jia-Ru; Jiang, Ruizhu; Zhao, Tiejian

doi:10.1016/j.biopha.2022.113204

Cited by 25 publications

(9 citation statements)

References 42 publications

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“…Researchers have found that ICA is easily metabolized by gut microbiota or enzymes after oral administration [ 38 ]. Additionally, CUR may improve liver inflammation by influencing the gut microbiota [ 39 ]. Therefore, the changes in gut microbiota following treatment with ICA + CUR were further analyzed using 16 S rRNA sequencing.…”

Section: Resultsmentioning

confidence: 99%

Icaritin-curcumol activates CD8+ T cells through regulation of gut microbiota and the DNMT1/IGFBP2 axis to suppress the development of prostate cancer

Xu,

Li,

Liu

et al. 2024

J Exp Clin Cancer Res

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Background Prostate cancer (PCa) incidence and mortality rates are rising. Our previous research has shown that the combination of icariin (ICA) and curcumol (CUR) induced autophagy and ferroptosis in PCa cells, and altered lipid metabolism. We aimed to further explore the effects of the combination of ICA and CUR on gut microbiota, metabolism, and immunity in PCa. Methods A mouse subcutaneous RM-1 cell tumor model was established. 16 S rRNA sequencing was performed to detect changes in fecal gut microbiota. SCFAs in mouse feces, and the effect of ICA-CUR on T-cell immunity, IGFBP2, and DNMT1 were examined. Fecal microbiota transplantation (FMT) was conducted to explore the mechanism of ICA-CUR. Si-IGFBP2 and si/oe-DNMT1 were transfected into RM-1 and DU145 cells, and the cells were treated with ICA-CUR to investigate the mechanism of ICA-CUR on PCa development. Results After treatment with ICA-CUR, there was a decrease in tumor volume and weight, accompanied by changes in gut microbiota. ICA-CUR affected SCFAs and DNMT1/IGFBP2/EGFR/STAT3/PD-L1 pathway. ICA-CUR increased the positive rates of CD3+CD8+IFN-γ, CD3+CD8+Ki67 cells, and the levels of IFN-γ and IFN-α in the serum. After FMT (with donors from the ICA-CUR group), tumor volume and weight were decreased. SCFAs promote tumor development and the expression of IGFBP2. In vitro, DNMT1/IGFBP2 promotes cell migration and proliferation. ICA-CUR inhibits the expression of DNMT1/IGFBP2. Conclusions ICA-CUR mediates the interaction between gut microbiota and the DNMT1/IGFBP2 axis to inhibit the progression of PCa by regulating immune response and metabolism, suggesting a potential therapeutic strategy for PCa.

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Section: Resultsmentioning

confidence: 99%

Icaritin-curcumol activates CD8+ T cells through regulation of gut microbiota and the DNMT1/IGFBP2 axis to suppress the development of prostate cancer

Xu,

Li,

Liu

et al. 2024

J Exp Clin Cancer Res

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“…These genes were related to arachidonic acid metabolism, herpes simplex virus 1 infection, the TNF signaling pathway, the IL-17 signaling pathway, neuroactive ligand-receptor interaction, the PI3K - Akt signaling pathway, protein digestion and absorption, ECM-receptor interaction, rheumatoid arthritis, and focal adhesion. It was reported previously that the anti-hepatic fibrosis effect of curcumol was related to its regulation of arachidonic acid metabolism ( 43 ). However, whether arachidonic acid metabolism is involved in the progression of IPF requires further study.…”

Section: Discussionmentioning

confidence: 97%

Construction of a TFs-miRNA-mRNA network related to idiopathic pulmonary fibrosis

Su¹,

Liu²,

Wu³

et al. 2023

Ann Transl Med

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Background The transcription factors (TFs)-microRNA (miRNA)-messenger RNA (mRNA) network plays an important role in a variety of diseases. However, the relationship between the TFs-miRNA-mRNA network and idiopathic pulmonary fibrosis (IPF) remains unclear. Methods The GSE110147 and GSE53845 datasets from the Gene Expression Omnibus (GEO) database were used to process differentially expressed genes (DEGs) analysis, gene set enrichment analysis (GSEA), weighted gene co-expression network analysis (WGCNA), as well as Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The GSE13316 dataset was used to perform differentially expressed miRNAs (DEMs) analysis and TFs prediction. Finally, a TFs-miRNA-mRNA network related to IPF was constructed, and its function was evaluated by Gene Ontology (GO) and KEGG analyses. Also, 19 TFs in the network were verified by quantitative real time polymerase chain reaction (qRT-PCR). Results Through our analysis, 53 DEMs and 2,630 DEGs were screened. The GSEA results suggested these genes were mainly related to protein digestion and absorption. The WGCNA results showed that these DEGs were divided into eight modules, and the GO and KEGG analyses results of blue module genes showed that these 86 blue module genes were mainly enriched in cilium assembly and cilium organization. Moreover, a TFs-miRNA-mRNA network comprising 25 TFs, 11 miRNAs, and 60 mRNAs was constructed. Ultimately, the functional enrichment analysis showed that the TFs-miRNA-mRNA network was mainly related to the cell cycle and the phosphatidylinositol 3 kinase-protein kinase B ( PI3K-Akt ) signaling pathway. Furthermore, experimental verification of the TFs showed that ARNTL , TRIM28 , EZH2 , BCOR , and ASXL1 were sufficiently up-regulated in the transforming growth factor (TGF)-β1 treatment groups, while BCL6 , BHLHE40 , FOXA1 , and EGR1 were significantly down-regulated. Conclusions The novel TFs-miRNA-mRNA network that we constructed could provide new insights into the underlying molecular mechanisms of IPF. ARNTL , TRIM28 , EZH2 , BCOR , ASXL1 , BCL6 , BHLHE40 , FOXA1 , and EGR1 may play important roles in IPF and become effective biomarkers for diagnosis and treatment.

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“…Studies on alterations in gut microbes and metabolites in HF have also been reported previously ( Wei et al, 2016 ; Caussy et al, 2018 ; Bajaj et al, 2020 ; Lee et al, 2020 ; Cox et al, 2022 ). Numerous studies have demonstrated that botanical drugs and their extracts are capable of suppressing HF by restoring enteric barriers and modulating intestinal dysbacteriosis and metabolites ( Zhao J. et al, 2021 ; Hu et al, 2021 ; Fu et al, 2022 ; Liu et al, 2022 ; Yue et al, 2022 ; Zheng et al, 2022 ; Chang et al, 2023 ; Guo et al, 2023 ; Hu et al, 2023 ). Studies have suggested that probiotics such as Lactobacillus GG ( Bajaj et al, 2014 ), Bacteroides dorei ( Park et al, 2023 ), Clostridium butyricum and Bifidobacterium longum infantis ( Lu et al, 2023 ), as well as gut microbial metabolites such as indole-3-propionic acid ( Sehgal et al, 2021 ; Yuan et al, 2023 ) and Trimethylamine N-oxide ( Zhou D. et al, 2022 ; Nian et al, 2023 ), are beneficial in HF.…”

Section: Introductionmentioning

confidence: 99%

Gut microbes combined with metabolomics reveal the protective effects of Qijia Rougan decoction against CCl4-induced hepatic fibrosis

Li,

Xu,

Tao

et al. 2024

Front. Pharmacol.

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Background: The occurrence and development of Hepatic fibrosis (HF) are closely related to the gut microbial composition and alterations in host metabolism. Qijia Rougan decoction (QJ) is a traditional Chinese medicine compound utilized clinically for the treatment of HF with remarkable clinical efficacy. However, its effect on the gut microbiota and metabolite alterations is unknown. Therefore, our objective was to examine the impact of QJ on the gut microbiota and metabolism in Carbon tetrachloride (CCl4)-induced HF.Methods: 40% CCl4 was used to induce HF, followed by QJ administration for 6 weeks. Serum biochemical analyses, histopathology, immunohistochemistry, RT-PCR, 16S rRNA gene sequencing, and non-targeted metabolomics techniques were employed in this study to investigate the interventional effects of QJ on a CCl4-induced HF model in rats.Results: This study demonstrated that QJ could effectively ameliorate CCl4-induced hepatic inflammation and fibrosis. Moreover, QJ upregulated the expression of intestinal tight junction proteins (TJPs) and notably altered the abundance of some gut microbes, for example, 10 genera closely associated with HF-related indicators and TJPs. In addition, metabolomics found 37 key metabolites responded to QJ treatment and strongly associated with HF-related indices and TJPs. Furthermore, a tight relation between 10 genera and 37 metabolites was found post correlation analysis. Among them, Turicibacter, Faecalibaculum, Prevotellaceae UCG 001, and unclassified Peptococcaceae may serve as the core gut microbes of QJ that inhibit HF.Conclusion: These results suggest that QJ ameliorates hepatic inflammation and fibrosis, which may be achieved by improving intestinal tight junctions and modulating gut microbiota composition as well as modulating host metabolism.

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Gut microbiota combined with metabolomics reveal the mechanism of curcumol on liver fibrosis in mice

Cited by 25 publications

References 42 publications

Icaritin-curcumol activates CD8+ T cells through regulation of gut microbiota and the DNMT1/IGFBP2 axis to suppress the development of prostate cancer

Icaritin-curcumol activates CD8+ T cells through regulation of gut microbiota and the DNMT1/IGFBP2 axis to suppress the development of prostate cancer

Construction of a TFs-miRNA-mRNA network related to idiopathic pulmonary fibrosis

Gut microbes combined with metabolomics reveal the protective effects of Qijia Rougan decoction against CCl4-induced hepatic fibrosis

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