A systems-pharmacology analysis of herbal medicines used in health improvement treatment: predicting potential new drugs and targets

Abstract

For thousands of years, tonic herbs have been successfully used all around the world to improve health, energy, and vitality. However, their underlying mechanisms of action in molecular/systems levels are still a mystery. In this work, two sets of tonic herbs, so called Qi-enriching herbs (QEH) and Blood-tonifying herbs (BTH) in TCM, were selected to elucidate why they can restore proper balance and harmony inside body, organ and energy system. Firstly, a pattern recognition model based on artificial neural network and discriminant analysis for assessing the molecular difference between QEH and BTH was developed. It is indicated that QEH compounds have high lipophilicity while BTH compounds possess high chemical reactivity. Secondly, a systematic investigation integrating ADME (absorption, distribution, metabolism, and excretion) prediction, target fishing and network analysis was performed and validated on these herbs to obtain the compound-target associations for reconstructing the biologically-meaningful networks. The results suggest QEH enhance physical strength, immune system and normal well-being, acting as adjuvant therapy for chronic disorders while BTH stimulate hematopoiesis function in body. As an emerging approach, the systems pharmacology model might facilitate to understand the mechanisms of action of the tonic herbs, which brings about new development for complementary and alternative medicine.

Figure 1

Flowchart of the model building.

Figure 2

Visualization of the  10 × 10  SOM of qi versus blood compounds using  U-matrix. Every square corresponds to a map neuron in the same position. The green and red colors represent qi, blood compounds, respectively.

Figure 3

Target network and functional enrichment of the QEH. A target network of each herb was uniquely identified by mapping the possible targets of each herb into QEH-specific molecular network. The functions for the target networks were divided into 5 classifications. These enriched biological functions are associated with qi-enriching. Diagram frame labeled in pink color denote QEH, diagram frame labeled in green color denote the active compounds of the each QEH, diagram frame labeled in purple color represent targets of active compounds, and diagram frame labeled in blue color represent functions for the target networks. The effective molecules of Codonopsis pilosula and Radix pseudostellariae are contained in atractylodes and Ginseng, so target analysis no longer mentions Codonopsis pilosula and Radix pseudostellariae.

Figure 4

Target network and functional enrichment of the BTH. The functions for the target networks were divided into 3 classifications. Diagram frame labeled in color pink, green, purple and blue denote BTH, active compounds of the each BTH, targets of active compound and functions for the target networks, respectively.

Figure 5

Flowchart shows the process of QEH and BTH application in a simplified sequence. The flowchart suggests QEH enhances physical strength, immune system and normal well-being while BTH stimulates hematopoiesis function in body. As a result, both qi-enriching herbs and blood-tonifying herbs could enhance human normal well-being and increase the overall quality of life.