Metabolomics and network pharmacology-based identification of phenolic acids in Polygonatum kingianum var. grandifolium rhizomes as anti-cancer/Tumor active ingredients

Abstract

Broadly targeted metabolomics techniques were used to identify phenolic acid compounds in Polygonatum kingianum var. grandifolium (PKVG) rhizomes and retrieve anti-cancer/tumor active substance bases from them. We identified potential drug targets by constructing Venn diagrams of compound and disease targets. Further, KEGG pathway analysis was performed to reveal the relevant pathways for anti-cancer/tumor activity of PKVG. Finally, we performed molecular docking to determine whether the identified proteins were targets of phenolic acid compounds from PKVG rhizome parts. The study's results revealed 71 phenolic acid compounds in PKVG rhizomes. Among them, three active ingredients and 42 corresponding targets were closely related to the anticancer/tumor activities of PKVG rhizome site phenolic acids. We identified two essential compounds and eight important targets by constructing the compound-target pathway network. 2 essential compounds were androsin and chlorogenic acid; 8 key targets were MAPK1, EGFR, PRKCA, MAPK10, GSK3B, CASP3, CASP8, and MMP9. The analysis of the KEGG pathway identified 42 anti-cancer/tumor-related pathways. In order of degree, we performed molecular docking on two essential compounds and the top 4 targets, MAPK1, EGFR, PRKCA, and MAPK10, to further validate the network pharmacology screening results. The molecular docking results were consistent with the network pharmacology results. Therefore, we suggest that the phenolic acids in PKVG rhizomes may exert anti-cancer/tumor activity through a multi-component, multi-target, and multi-channel mechanism of action.

Fig 1. Venn diagram of antitumor activity of PKVG rhizome phenolic acid analogs.

Fig 2. Results of GO pathway enrichment analysis for anti-cancer/tumor activity of phenolic acids from PKVG rhizomes.

Fig 3. Results of KEGG pathway enrichment analysis for anti-cancer/tumor activity of phenolic acids from PKVG rhizomes.

Bubble color and size correspond to the p-value and gene number enriched in the pathway.

Fig 4. Compound-target-pathway network for anti-cancer/tumor activity of PKVG rhizome phenolic acid analogs.

Blue squares represent active components in the PKVG rhizome, purple circles represent predicted targets, and red triangles represent associated pathways.

Fig 5. Interaction graphics between the compounds and targets.

(A) Androsin-MAPK1, (B) Androsin-EGFR, (C) Androsin-MAPK10, (D) Chlorogenic acid-PRKCA.