Target Network Features Exist In Synergistically Inducing Apoptosis By Herbal Ingredient Pairs

Synergism caused by combinations of multi-herbal ingredients has been reported in a lot of research articles and scientific reviews, and it has been found that synergism tends to require the interactions among multi-targets. However, there is no publication which discusses whether synergy has some characteristics, and what these characteristics are based on target interaction networks. Here, based on the targets of herbal ingredients, we are the first to explore the target network features existing potentially in synergistically inducing apoptosis.Known herbal ingredient pairs that could synergistically trigger apoptosis (positive group) was collected, and corresponding negative group was constructed as well. The statistical differences were further computed between positive and negative group in the network by the usage of some parameters. According to our analysis, compared to the negative group, herbal ingredient pairs that could induce apoptosis synergistically (positive group) have some statistical significance in some features:(1) The targets of synergistic pairs have some overlapping ratio, and most of the same targets focus on the target core network (Apoptosis Pathway).(2) Even though the targets of the pairs can be enriched into different pathways, synergistic pairs tend to enrich into those that are highly related to the function goals.(3) Except for the same targets, different targets interact closely in the network (For instance, there are only1to2steps among most of them).(4) In the Apoptosis Pathway, the action modes of the same targets of synergistic combinations are cis-acted (i.e. the pairs tend to be both either up-or down-regulated) on the same targets and pro-apoptotic. Different targets in this core network, though are in different positions and show different regulation effects (either up-regulation or down-regulation), the two effects are serving for the functional goal (such as pro-apoptotic). Thus, the different targets are complementary for inducing apoptosis.