Unveiling the Anti-Cancer Potential of Yu Gan San Jie Fang: A Network Pharmacology Exploration of its Mechanisms in Liver Cancer Treatment

Unveiling the Anti-Cancer Potential of Yu Gan San Jie Fang: A Network Pharmacology Exploration of its Mechanisms in Liver Cancer Treatment

Abstract:

Purpose: This study delves into the intricate mechanisms of Yu Gan San Jie Fang, a traditional Chinese herbal formula, in the treatment of liver cancer. By employing network pharmacology techniques, we aim to identify the key target points, active ingredients, and signaling pathways involved in its therapeutic action.

Methods: We harnessed the power of multiple databases, including TCMSP, Pubchem, SEA, and Swiss Target Prediction, to meticulously screen and identify the potential target points and active ingredients of Yu Gan San Jie Fang. Leveraging OMIM and Gene Cards databases, we pinpointed disease target points specifically associated with 'liver cancer.' The intricate relationships between 'drug-target-disease' were visualized using Cytoscape 3.9.1 software, providing a comprehensive network perspective. Further insights into the functional roles of potential therapeutic target points were gained through Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis using a sophisticated bioinformatics platform.

Results: Our network pharmacological analysis unveiled a compelling narrative: quercetin and β-sitosterol emerged as the core ingredients within Yu Gan San Jie Fang. GO enrichment analysis illuminated the formula's primary focus on liver disease-related targets, particularly hepatitis B, hepatitis C, alcoholic liver disease, and non-alcoholic fatty liver disease. Metabolic pathways, especially those related to steroid hormone biosynthesis and tryptophan metabolism, also emerged as key players. The intricate dance of cellular processes, including cell aging, the P13K-Akt signaling pathway, and the p53 signaling pathway, were also implicated. Furthermore, the study highlighted the involvement of the IL7 signaling pathway and the TNF-α signaling pathway in inflammation and immune responses. Intriguingly, KEGG pathway enrichment analysis suggested that Yu Gan San Jie Fang exerts its therapeutic effects through the modulation of signaling pathways such as PI3K-AKT, MAPK, IL7, and TNF-α, effectively targeting hepatitis B and liver cirrhosis in the fight against liver cancer. Key target points such as protein kinase 1 (AKT1), AP-1 transcription factor subunit (JUN), and estrogen receptor 1 (ESR1) were identified as crucial players in this intricate biological network.

Conclusion: Our findings strongly suggest that Yu Gan San Jie Fang holds immense promise as a potential therapeutic agent for liver cancer. Its mechanism of action appears to involve the inhibition of AKT1 and MAPK protein expression, coupled with the upregulation of TNF-α protein expression. These modulatory effects on tumor cell proliferation and apoptosis are likely mediated through the intricate interplay of the P13K-Akt signaling pathway and other crucial pathways. Further research is warranted to fully elucidate the clinical significance of these findings and to pave the way for the development of novel therapeutic strategies against this devastating disease.