title: Identification of novel mechanisms of silymarin on the carbon tetrachloride-induced liver fibrosis in mice by nuclear factor-κB bioluminescent imaging-guided transcriptomic analysis.
abstract: In this study, we applied bioluminescent imaging-guided transcriptomic analysis to evaluate and identify the therapeutic potentials and novel mechanisms of silymarin on carbon tetrachloride (CCl(4))-induced liver fibrosis. Transgenic mice, carrying the luciferase genes driven by nuclear factor-κB (NF-κB), were given with CCl(4) and/or silymarin. In vivo NF-κB activity was evaluated by bioluminescent imaging, liver fibrosis was judged by Sirius red staining and immunohistochemistry, and gene expression profiles of silymarin-treated livers were analyzed by DNA microarray. CCl(4) enhanced the NF-κB-dependent hepatic luminescence and induced hepatic fibrosis, while silymarin reduced the CCl(4)-induced hepatic luminescence and improved CCl(4)-induced liver fibrosis. Microarray analysis showed that silymarin altered the transforming growth factor-β-mediated pathways, which play pivotal roles in the progression of liver fibrosis. Moreover, we newly identified that silymarin downregulated the expression levels of cytoskeleton organization genes and mitochondrion electron-transfer chain genes, such as cytochrome c oxidase Cox6a2, Cox7a1, and Cox8b genes. In conclusion, the correlation of NF-κB-dependent luminescence and liver fibrosis suggested the feasibility of NF-κB bioluminescent imaging for the evaluation of liver fibrosis progression and therapeutic potentials. Moreover, our findings suggested that silymarin might exhibit anti-fibrotic effects in vivo via altering the expression of genes involved in cytoskeleton organization and mitochondrion electron-transfer chain.
authors.affiliation: Graduate Institute of Chinese Medicine, China Medical University, Taichung 40402, Taiwan.
authors.forename: Chia-Cheng
authors.initials: CC
authors.lastname: Li
authors.forename: Chien-Yun
authors.initials: CY
authors.lastname: Hsiang
authors.forename: Shih-Lu
authors.initials: SL
authors.lastname: Wu
authors.forename: Tin-Yun
authors.initials: TY
authors.lastname: Ho
mesh_terms: D000818:Animals; D001483:Base Sequence; D002251:Carbon Tetrachloride / Q000633:toxicity*; D017931:DNA Primers; D020869:Gene Expression Profiling; D007150:Immunohistochemistry; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D049449:Luminescence; D051379:Mice; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D012838:Silymarin / Q000627:therapeutic use*; D059467:Transcriptome
chemical_list: D017931:DNA Primers; D016328:NF-kappa B; D012838:Silymarin; D002251:Carbon Tetrachloride