Mechanism of action of protopanaxadiol ginsenosides on hepatocellular carcinoma and network pharmacological analysis

Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies globally, posing a major challenge to global health care. Protopanaxadiol ginsenosides (PDs) have been believed to significantly improve liver diseases. PDs, such as Rg₃, have been developed as a new class of anti-cancer drugs. Ginsenosides Rb₁, Rd, Rg₃, and Rh₂ exhibit effective anti-inflammatory and anti-tumor activities. Studies have confirmed that PDs could be used to treat HCC. However, the mechanism of action of PDs on HCC remains unclear. In the study, we reviewed the anti-HCC effects and mechanisms of PDs including Rb₁, Rd, Rg₃, Rg₅, Rh₂, Rk₁, and Compound K (CK). Then, we searched for relevant targets of PDs and HCC from databases and enriched them for analysis. Subsequently, molecular docking was simulated to reveal molecular mechanisms. We found that PDs may treat HCC through multiple signaling pathways and related targets. PDs could inhibit the proliferation, invasion, and metastasis of HCC while promoting apoptosis and inducing differentiation. In conclusion, this review and network pharmacological analysis might offer a direction for in-depth research on related mechanisms. These insights will aid in the direction of further pharmacological studies and the development of safe and effective clinical drugs.