Baicalin Ameliorates Experimental Liver Cholestasis in Mice by Modulation of Oxidative Stress, Inflammation, and NRF2 Transcription Factor.
Kezhen ShenXiaowen FengHao PanFeng ZhangHaiyang XieShushen ZhenPublished in: Oxidative medicine and cellular longevity (2017)
Experimental cholestatic liver fibrosis was performed by bile duct ligation (BDL) in mice, and significant liver injury was observed in 15 days. Administration of baicalin in mice significantly ameliorates liver fibrosis. Experimental cholestatic liver fibrosis was associated with induced gene expression of fibrotic markers such as collagen I, fibronectin, alpha smooth muscle actin (SMA), and connective tissue growth factor (CTGF); increased inflammatory cytokines (TNFα, MIP1α, IL1β, and MIP2); increased oxidative stress and reactive oxygen species- (ROS-) inducing enzymes (NOX2 and iNOS); dysfunctional mitochondrial electron chain complexes; and apoptotic/necrotic cell death markers (DNA fragmentation, caspase 3 activity, and PARP activity). Baicalin administration on alternate day reduced fibrosis along with profibrotic gene expression, proinflammatory cytokines, oxidative stress, and cell death whereas improving the function of mitochondrial electron transport chain. We observed baicalin enhanced NRF2 activation by nuclear translocation and induced its target genes HO-1 and GCLM, thus enhancing antioxidant defense. Interplay of oxidative stress/inflammation and NRF2 were key players for baicalin-mediated protection. Stellate cell activation is crucial for initiation of fibrosis. Baicalin alleviated stellate cell activation and modulated TIMP1, SMA, collagen 1, and fibronectin in vitro. This study indicates that baicalin might be beneficial for reducing inflammation and fibrosis in liver injury models.
Keyphrases
- oxidative stress
- liver fibrosis
- liver injury
- drug induced
- cell death
- diabetic rats
- gene expression
- dna damage
- induced apoptosis
- reactive oxygen species
- growth factor
- ischemia reperfusion injury
- smooth muscle
- transcription factor
- high fat diet induced
- single cell
- cell cycle arrest
- dna methylation
- rheumatoid arthritis
- dna repair
- high glucose
- cell therapy
- mouse model
- genome wide
- metabolic syndrome
- circulating tumor
- cell free
- mesenchymal stem cells
- insulin resistance
- endothelial cells
- wild type
- signaling pathway
- dna binding
- cell proliferation
- nitric oxide synthase
- systemic sclerosis
- genome wide identification
- anti inflammatory