Figure 3.

Proposed mechanisms involved in the anti-fibrotic activity of rhein. Rhein suppresses the activity of PSCs by targeting several signaling pathways and regulating fibrotic and tumorigenic markers. It can inhibit PSCs proliferation and migrations by decreasing the STAT3 pathway-induced signaling, which plays an important role in malignant transformation and tumor progression. Furthermore, rhein suppresses NF-κB signaling pathway by reducing its subunit P65. In additional, rhein can inactivate PSCs by attenuating various fibrotic and tumorigenic markers, such as α-SMA, fibronectin, type I collagen, N-cadherin and MMPs by modulating both SHH and AKT signaling pathways. With these, rhein plays a pivotal role in the process of pancreatic fibrosis, and PSCs cell proliferation and migration.