A scheme to navigate "biomolecule X" from Platycladi Folium against hepatocellular carcinoma via phytoinformatics.

Platycladi Folium (PF) is a natural herbal plant and a significant resource with anti-cancer agents, including hepatocellular carcinoma (HCC). In this study, we applied a phytoinformatics approach to identify potential therapeutic components for HCC treatment. The target(s) of PF-derived molecules detected by gas chromatography-mass spectrometry (GC-MS) were relieved from reliable public bioinformatics databases (Similarity Ensemble Approach; SEA, and Swiss Target Prediction; STP), and HCC-responding targets were identified through human disease databases (DisGeNET, and OMIM databases). Holistically, PF-molecules-targets-mechanisms (PMTM) network was constructed to elucidate their therapeutic relationships. Next, molecular docking test (MDT) was conducted to obtain key molecule(s) on key target(s) in a key mechanism. The chemical reactivity level of the key molecule(s) was determined with density functional theory (DFT). Moreover, the toxicity of key molecule(s) was assessed using in silico platform. Ultimately, the 27 final targets were considered as significant targets, revealing in PPI network, then, ESR1 was a key modulator in the network. MDT revealed that 5A-Androstan-3B,17B-diol, 17A-methyl was bound most stably to ESR1, ESR2, FGF1, and Kaurenoic acid formed the most stable conformers with SHH, RXRA, RARA, and RARB. Then, Humulene had the strongest affinity on GLI1, and GLI2. The three molecules showed effective chemical reactivity in density functional theory (DFT), in parallel, they had no noticeable toxicity to develop as new agents. Overall, our findings indicate that three biomolecules (5A-Androstan-3B,17B-diol, 17A-methyl; Kaurenoic acid; and Humulene) from PF have the potential to exert therapeutic effects on multiple targets in the 'Pathways in Cancer' pathway.