Systems pharmacology reveals the unique mechanism features of Shenzhu Capsule for treatment of ulcerative colitis in comparison with synthetic drugs

Abstract

In clinic, both synthetic drugs and Shenzhu Capsule (SZC), one kind of traditional Chinese medicines (TCMs), are used to treat ulcerative colitis (UC). In our study, a systems pharmacology approach was employed to elucidate the chemical and mechanism differences between SZC and synthetic drugs in treating UC. First, the compound databases were constructed for SZC and synthetic drugs. Then, the targets of SZC were predicted with on-line tools and validated using molecular docking method. Finally, chemical space, targets, and pathways of SZC and synthetic drugs were compared. Results showed that atractylenolide I, atractylone, kaempferol, etc., were bioactive compounds of SZC. Comparison of SZC and synthetic drugs showed that (1) in chemical space, the area of SZC encompasses the area of synthetic drugs; (2) SZC can act on more targets and pathways than synthetic drugs; (3) SZC can not only regulate immune and inflammatory reactions but also act on ulcerative colitis complications (bloody diarrhea) and prevent UC to develop into colorectal cancer whereas synthetic drugs mainly regulate immune and inflammatory reactions. Our study could help us to understand the compound and mechanism differences between TCM and synthetic drugs.

Figure 1

Schematic diagram of the systems pharmacology-based strategy for unraveling the bioactive compounds and mechanism features of Shenzhu Capsule (SZC).

Figure 2

Comparison of the chemical space between ShenZhu Capsule and synthetic drugs. The cyan and blue balls represent compounds in Renshen and Baizhu, respectively. The red balls stand for synthetic drugs. The green ball (M10, nearly over shadowed by cyan balls) delineate common compounds in Renshen and Baizhu.

Figure 3

Docking modes of kaempferol and four target proteins. (A) peroxisome proliferator activated receptor gamma (PPARG), (B) prostaglandin-endoperoxide synthase 2 (PTGS2), (C) thrombin (F2), (D) tumor necrosis factor (TNF). Kaempferol and residues are shown in stick format, hydrogen bonds are shown as yellow dashed lines. Pink and green: carbon; red: oxygen; gray: hydrogen; blue: nitrogen.

Figure 4

Comparison of the targets and pathways of synthetic drugs and Shenzhu Capsule (SZC). (A) Comparison of the number of targets for synthetic drugs and SZC (blue represents synthetic drugs, cyan delineates shared targets, light red stands for SZC). (B) Comparison of the number of pathways for synthetic drugs and SZC. (C) Number of targets for synthetic drugs and SZC in each pathway.

Figure 5

Compound-Target (C-T) network of Shenzhu Capsule. Nodes represent compounds and targets, and the node size is related to the degree of nodes.

Figure 6

Non-disease associated Target-Pathway (T-P) network of Shenzhu Capsule. Nodes represent targets and non-disease associated pathways. The node size is related to the degree of nodes.

Figure 7

Distribution of the targets of Shenzhu Capsule on the compressed TNF signaling pathway. The red nodes are potential targets of SZC, and the light blue nodes are relevant targets in the pathway. The compressed signaling pathway was obtained from KEGG.