Yin-Dan-Ping-Gan Capsule Mitigates CCL4-Induced Liver Fibrosis via Regulating PPAR γ/GPX4 Signaling and Suppressing Ferroptosis

Background: Liver fibrosis is a major global public health issue that is only getting worse. The underlying molecular mechanisms of Yindanpinggan Capsule (YDPG), a traditional Chinese medication, are still unknown, although it has shown notable effectiveness in treating fibrosis and Other forms of liver injury. Methods: To evaluate the impact of YDPG on liver fibrosis, a mouse model of liver damage caused by carbon tetrachloride (CCL₄) was used. Proteomics, deep learning, network pharmacology, and later biological process validation using Western blot were used to elucidate the possible mechanism of YDPG in reducing liver damage. Results: Following YDPG treatment, we observed a decrease in the fibrosis index and an improvement in liver function. Network pharmacology, deep learning, and proteomics collectively identified the Ferroptosis and Peroxisome Proliferator-activated Receptor (PPAR) signaling pathways as pivotal in the anti-fibrosis effects of YDPG on the liver. Further experimental results showed that YDPG inhibited Malondialdehyde (MDA) and Fe²⁺ content and increased Glutathione (GSH) activity in fibrotic liver. Mechanistically, both SLC7A11/GSH pathway-mediated Ferroptosis and oxidative stress up-regulated by the PPAR γ/GPx4 pathway were alleviated following YDPG treatment. Conclusions: Our present study corroborates that YDPG limits the progression of liver fibrosis by regulating the PPARγ-GPX4-ferroptosis pathway. These results indicate that YDPG could be a potential medication for hepatic fibrosis.

PPAR γ; Yindanpinggan Capsule; ferroptosis; liver fibrosis; network pharmacology; proteomics.