A Network Pharmacology Approach to Understanding the Mechanisms of Action of Traditional Medicine: Bushenhuoxue Formula for Treatment of Chronic Kidney Disease

Abstract

Traditional Chinese medicine (TCM) has unique therapeutic effects for complex chronic diseases. However, for the lack of an effective systematic approach, the research progress on the effective substances and pharmacological mechanism of action has been very slow. In this paper, by incorporating network biology, bioinformatics and chemoinformatics methods, an integrated approach was proposed to systematically investigate and explain the pharmacological mechanism of action and effective substances of TCM. This approach includes the following main steps: First, based on the known drug targets, network biology was used to screen out putative drug targets; Second, the molecular docking method was used to calculate whether the molecules from TCM and drug targets related to chronic kidney diseases (CKD) interact or not; Third, according to the result of molecular docking, natural product-target network, main component-target network and compound-target network were constructed; Finally, through analysis of network characteristics and literature mining, potential effective multi-components and their synergistic mechanism were putatively identified and uncovered. Bu-shen-Huo-xue formula (BSHX) which was frequently used for treating CKD, was used as the case to demonstrate reliability of our proposed approach. The results show that BSHX has the therapeutic effect by using multi-channel network regulation, such as regulating the coagulation and fibrinolytic balance, and the expression of inflammatory factors, inhibiting abnormal ECM accumulation. Tanshinone IIA, rhein, curcumin, calycosin and quercetin may be potential effective ingredients of BSHX. This research shows that the integration approach can be an effective means for discovering active substances and revealing their pharmacological mechanisms of TCM.

Network pharmacology applications to map the unexplored target space and therapeutic potential of natural products

“…Some of the approaches reviewed below do not go as far as suggesting a direct MoA, although it may for example be unrealistic to expect to be able to de-convolute the mechanism of action of a mix of many compounds, as is the case in Shi et al, 48 where individual components themselves are polypharmacologic. Some of the approaches reviewed below do not go as far as suggesting a direct MoA, although it may for example be unrealistic to expect to be able to de-convolute the mechanism of action of a mix of many compounds, as is the case in Shi et al, 48 where individual components themselves are polypharmacologic.…”

Herb-target interaction network analysis helps to disclose molecular mechanism of traditional Chinese medicine

“…Many studies have been reported to elucidate the molecular mechanism of TCM formulae in systematic view23456789. Compound-target networks were constructed and analyzed in these studies, and the effectiveness of TCM formulae was evaluated at compound level.…”

“…Systematic docking and drug-target network analysis is widely applied in these studies23456789, however, the therapeutic effectiveness of TCM formulae is still ascribed to a few number of interactions between individual compounds and key target proteins. As TCMs are prescribed as herbs, compounds from one herb should be considered as a whole and mode of action at herb-level should be noticed.…”

Network pharmacology: An emerging tool for natural product drug discovery and evidence-based Ayurveda

“…A concept of 'network target' has been proposed to help design and predict the best possible treatments (Li, 2007;Li et al, 2011). The constructed network system can predict the main active components, and their corresponding targets, which can be helpful for the therapeutic applications of complex formulations of traditional medicine (Shi et al, 2014).…”