Angelicae Sinensis Radix (Danggui) and Ligusticum Chuanxiong Rhizoma (Chuan Xiong) herb-pair (DC) have been frequently used in
Traditional Chinese medicine (TCM) prescriptions for hundreds of years to prevent
vascular diseases and alleviate
pain. However, the mechanism of DC herb-pair in the prevention of
liver fibrosis development was still unclear. In the present study, the effects and mechanisms of DC herb-pair on
liver fibrosis were examined using network pharmacology and mouse fibrotic model. Based on the network pharmacological analysis of 13 bioactive ingredients found in DC, a total of 46 targets and 71 pathways related to anti-
fibrosis effects were obtained, which was associated with
mitogen-activated protein kinase (MAPK) signal pathway, hepatic
inflammation and fibrotic response. Furthermore, this hypothesis was verified using
carbon tetrachloride (CCl4)-induced
fibrosis model. Measurement of liver functional
enzyme activities and histopathological examination showed that DC dramatically reduced
bile acid levels, inflammatory cell infiltration and
collagen deposition caused by CCl4. The increased expression of
liver fibrosis markers, such as
collagen 1,
fibronectin, α-smooth muscle actin (α-SMA) and
transforming growth factor-β (TGF-β), and inflammatory factors, such as
chemokine (C-C motif) ligand 2 (MCP-1), interleukin-1β (IL-1β),
tumor necrosis factor-α (TNF-α) and
IL-6 in fibrotic mice were significantly downregulated by DC herb-pair through regulation of
extracellular signal-regulated kinase 1/2 (ERK1/2)-
protein kinase B (AKT) signaling pathways. Collectively, these results suggest that DC prevents the development of
liver fibrosis by inhibiting
collagen deposition, decreasing inflammatory reactions and
bile acid accumulation, which provides insights into the mechanisms of herb-pair in improving
liver fibrosis.