Understanding the polypharmacological anticancer effects of Xiao Chai Hu Tang via a computational pharmacological model

Abstract

Xiao Chai Hu Tang (XCHT), a traditional herbal formula, is widely administered as a cancer treatment. However, the underlying molecular mechanisms of its anticancer effects are not fully understood. In the present study, a computational pharmacological model that combined chemical space mapping, molecular docking and network analysis was employed to predict which chemical compounds in XCHT are potential inhibitors of cancer-associated targets, and to establish a compound-target (C-T) network and compound-compound (C-C) association network. The identified compounds from XCHT demonstrated diversity in chemical space. Furthermore, they occupied regions of chemical space that were the same, or close to, those occupied by drug or drug-like compounds that are associated with cancer, according to the Therapeutic Targets Database. The analysis of the molecular docking and the C-T network demonstrated that the potential inhibitors possessed the properties of promiscuous drugs and combination therapies. The C-C network was classified into four clusters and the different clusters contained various multi-compound combinations that acted on different targets. The study indicated that XCHT has a polypharmacological role in treating cancer and the potential inhibitory components of XCHT require further investigation as potential therapeutic strategies for cancer patients.

Keywords: Xiao Chai Hu Tang; cancer; computational pharmacology; polypharmacology.

Figure 1

Map demonstrating the chemical space of the compounds in Xiao Chai Hu Tang (black circles) and the known inhibitors (white circles) that are associated with cancer targets, obtained from the Therapeutic Targets Database. PC1, first principal component; PC2, second principal component; PC3, third principal component.

Figure 2

XCHT compound-target network. The rectangles and circles represent the target proteins that are associated with cancer and the XCHT compounds, respectively. The numbers indicate the index numbers of the compounds. XCHT, Xiao Chai Hu Tang.

Figure 3

Xiao Chai Hu Tang compound-compound association network. The numbers indicate the index numbers of the compounds.

Figure 4

Subnetworks made up of highly interconnected regions. The circles represent compounds present in Xiao Chai Hu Tang. (A) cluster 1, (B) cluster 2, (C) cluster 3 and (D) cluster 4.