The Strategy of Studying the Herb-Pair Inter-Reinforcement Mechanism Mapping on Chemical Space Between Sparganii Rhizoma and Curcumae Rhizoma
Authors: Chen Zhao , Sun Shiqi , Ren Xingde , Chen Yankun 
Published: January 2021

Abstract
BackgroundWith the ever-increasing acceptance of combination therapy and the use of traditional Chinese medicine (TCM) has become an emerging trend. The multi-herb formulae therapy is one of the most important characteristics of TCM, but the modernization drive of this conventional wisdom has faced many obstacles due to its unimaginable complexity. Herb pairs, the most fundamental and the simplest form of multi-herb formulae, are a centralized representative of Chinese herbal compatibility. A systematic search of herb pair related research was carried out using multiple online literature databases, books and monographs published in the past 20 years. The herb-pair has an important characteristics---inter-reinforcement (Xiangxu in TCM terms) in TCM basic theory. The inter-reinforcement mechanisms of herb pairs are extremely complicated and their exact molecular mechanisms are also still not well elucidated. MethodsThis research integrated the cheminformatics’ and network pharmacology approach to elucidate the inter-reinforcement mechanisms in treating cardiovascular diseases (CVDs) with the herb-pair (Sparganii Rhizoma and Curcumae Rhizoma) at the scale of chemical space. Chemical space is a term often used for ‘multi-dimensional descriptor space’, geographical map to illustrate the distribution of molecules and their properties. It also encompasses all possible small organic molecules in Chinese herbal medicine (CHM). The concept of chemical space was proposed for the first time to study the herb-pair inter-reinforcement mechanism. ResultsThose compounds from Sparganii Rhizoma and Curcumae Rhizoma with the HIA<=2 were as candidate compounds. The herb-pair shared 2 common compounds with 6 common targets and they have 24 targets from four public databases. The compound-target-pathway-disease networks were constructed to obtain a global perspective of the interactions between Sparganii Rhizoma and Curcumae Rhizoma in chemical space. On this basis, a series of pathway guided compound combinations were found. Screen with HIA<2 (Human intestinal Absorption), which were derived from Sparganii Rhizoma and Curcumae Rhizoma (Chinese herb pair). The CTPAs network embodied 327 nodes (100 compounds, 104 targets, and 128 pathways). After setting compounds similarity to 0.7 in each compound combinations, 497 pairs of compound combinations associated 128 pathways were obtained in Target-Pathway Association Interactions (TPAs). Five, three and thirty-six compound combinations were screened which their targets were in platelet activation pathway, vascular smooth muscle contraction and calcium signaling pathway.ConclusionsMapping the chemical compounds of Chinese herbal medicine into chemical space is helpful to explain herb-pair inter-reinforcement mechanism at molecular level. Several combination compounds were mapped into cardiovascular diseases pathways, and the results showed that the strategy of studying the herb-pair inter-reinforcement mechanism mapping on chemical space is a certain scientific and rational method to illustrate material basis of Chinese herbal medicine at multi-dimension.