Systems pharmacology dissection of the anti-inflammatory mechanism for the medicinal herb Folium eriobotryae

Abstract

Inflammation is a hallmark of many diseases like diabetes, cancers, atherosclerosis and arthritis. Thus, lots of concerns have been raised toward developing novel anti-inflammatory agents. Many alternative herbal medicines possess excellent anti-inflammatory properties, yet their precise mechanisms of action are yet to be elucidated. Here, a novel systems pharmacology approach based on a large number of chemical, biological and pharmacological data was developed and exemplified by a probe herb Folium Eriobotryae, a widely used clinical anti-inflammatory botanic drug. The results show that 11 ingredients of this herb with favorable pharmacokinetic properties are predicted as active compounds for anti-inflammatory treatment. In addition, via systematic network analyses, their targets are identified to be 43 inflammation-associated proteins including especially COX2, ALOX5, PPARG, TNF and RELA that are mainly involved in the mitogen-activated protein kinase (MAPK) signaling pathway, the rheumatoid arthritis pathway and NF-κB signaling pathway. All these demonstrate that the integrated systems pharmacology method provides not only an effective tool to illustrate the anti-inflammatory mechanisms of herbs, but also a new systems-based approach for drug discovery from, but not limited to, herbs, especially when combined with further experimental validations.

Figure 1

Active ingredients’ screening scheme.

Figure 2

The D–T network where fuchsia circular nodes represent the DrugBank ID of anti-inflammatory drugs and lime diamond nodes represent the therapeutic targets, respectively.

Figure 3

I-T network for Folium Eriobotryae.

Figure 4

T-P network. The orange nodes represent the targets, while the purple ones the pathways. Node size is proportional to its degree.

Figure 5

T-D network. The blue nodes show the representative diseases, while the magenta ones the targets.