Betulinic acid attenuates liver fibrosis by inducing autophagy via the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway.
Yuan LiuYanmeng BiChan MoTing ZengSha HuangLei GaoXuegang SunZhi-Ping LvPublished in: Journal of natural medicines (2018)
The present study was designed to investigate the effects of betulinic acid on human hepatic stellate cells in vitro and C57BL/6 mice in vivo, as well as the signaling pathways involved. In this study, we explored the effects of betulinic acid on expression of alpha smooth muscle actin and autophagy-related proteins. Betulinic acid reduced pathological damage associated with liver fibrosis, as well as serum platelet-derived growth factor and serum hydroxyproline levels. Furthermore, betulinic acid downregulated the expression of alpha smooth muscle actin and type I collagen in mouse liver and upregulated the expression of microtubule-associated protein light chain 3B and autophagy-related gene 7 at the gene and protein levels. LC3II expression was increased and alpha smooth muscle actin expression was decreased in betulinic acid-treated hepatic stellate cells. Interventions with bafilomycin A1 and mCherry-GFP-LC3 adenoviruses promoted the formation of autophagosomes in hepatic stellate cells and the development of autophagic flow. Our study found that mitogen-activated protein kinase/extracellular signal-regulated kinase may be involved in the effects of betulinic acid on liver fibrosis. The present study suggests that betulinic acid has anti-hepatic fibrosis activity by inducing autophagy and could serve as a promising new agent for treating hepatic fibrosis.
Keyphrases
- liver fibrosis
- smooth muscle
- poor prognosis
- induced apoptosis
- cell death
- signaling pathway
- endoplasmic reticulum stress
- oxidative stress
- growth factor
- cell cycle arrest
- endothelial cells
- tyrosine kinase
- type diabetes
- gene expression
- physical activity
- metabolic syndrome
- mass spectrometry
- protein kinase
- copy number
- dna methylation
- cell migration