Yiqi Liangxue Jiedu Prescription Inhibited the Canonical Wnt Pathway to Prevent Hepatocellular Precancerous Lesions.

Purpose: Yiqi Liangxue Jiedu prescription (YLJP), a Chinese medicine that is commonly used to prevent liver cancer and is authorized by a national patent (patent No. ZL202110889980.5) has a therapeutic effect on precancerous lesions; however, the underlying mechanism remains unclear. This study is aimed at determining the clinical therapeutic efficacy of YLJP in patients with precancerous liver lesions and to explore and validate its possible effector mechanism.

Patients and methods: The 1-year incidence of hepatocellular carcinoma (HCC) was retrospectively analyzed in 241 patients with cirrhosis complicated by abnormal alpha-fetoprotein precancer. Network pharmacological analysis, molecular docking, and molecular dynamics simulation were used to explore the key targets and compounds of YLJP in treating HCC. Immunohistochemical methods were used to detect the expression of key proteins in tumor and cirrhotic tissues. Finally, the mechanism underlying the effects of YLJP was verified in rats with precancerous lesions.

Results: The 1-year incidence of HCC was lower in the YLJP group than in the Western medicine group. The Wnt pathway protein, CTNNB1, is a key target of YLJP in preventing and treating HCC, and the canonical Wnt pathway is the key signaling pathway and is overexpressed in human liver tumors. In vivo experiments showed that YLJP significantly inhibited the canonical Wnt pathway and reduced the abnormal differentiation of hepatic oval cells. The binding of CTNNB1 to oleanolic acid, stigmasterol, and beta-sitosterol was found to be stable, indicating the action of these compounds in treating HCC.

Conclusion: YLJP reduces the 1-year incidence of HCC, with its mechanism likely due to oleanolic acid, beta-sitosterol, and stigmasterol inhibition of the CTNNB1 activation of the β-catenin protein, which in turn regulates the Wnt signaling pathway and prevents the abnormal differentiation of hepatic oval cells into cancer cells, thus delaying the occurrence and progression of the disease.