Bohui Li1, Weiyang Tao1, Chunli Zheng1, Piar Ali Shar2, Chao Huang1, Yingxue Fu1, Yonghua Wang3. 1. College of Life Sciences, Northwest A&F University, Yangling 712100, Shaanxi, China; Lab of Systems Pharmacology, Bioinformatics Center, Northwest A&F University, China. 2. Lab of Systems Pharmacology, Bioinformatics Center, Northwest A&F University, China; College of International, Northwest A&F University, Yangling, Shaanxi, China. 3. College of Life Sciences, Northwest A&F University, Yangling 712100, Shaanxi, China; Lab of Systems Pharmacology, Bioinformatics Center, Northwest A&F University, China. Electronic address: yh_wang@nwsuaf.edu.cn.
Abstract
BACKGROUND: Addition and subtraction theory (AST), a basic theory of herb combination in traditional Chinese medicine (TCM), is often used to add or subtract the "fundamental formulae" to generate more targeted prescriptions. This theory plays a core role in individualized medicine and compound compatibility of TCM. However, the mechanisms underlying AST have largely remained elusive. METHODS: An integrated platform of systems pharmacology was proposed for revealing how the oral administration, drug half-life, and target interactions affect the pharmacological functions of herbal medicines. This platform was further applied on two classical prescriptions, i.e., Xiao Chaihu decoction (XCHD) and Da Chaihu decoction (DCHD) to dissect the addition and subtraction theory (AST). RESULTS: We uncovered the candidate compounds, key molecular targets and interaction network involved in XCHD and DCHD, and summarized its pharmacological characters and therapeutic indications. The results show that the "fundamental formula" is responsible for the major therapeutic effects, whereas the "additive herbs" synergistically enhance the treatment outcomes by targeting the same or complementary proteins between the foundational and additive herbs. CONCLUSION: This work has established a novel method to comprehensively understand the mechanism of AST, which would be beneficial for the TCM recipe optimization as well as the production of new herbal formula with desirable therapeutic effects.
BACKGROUND: Addition and subtraction theory (AST), a basic theory of herb combination in traditional Chinese medicine (TCM), is often used to add or subtract the "fundamental formulae" to generate more targeted prescriptions. This theory plays a core role in individualized medicine and compound compatibility of TCM. However, the mechanisms underlying AST have largely remained elusive. METHODS: An integrated platform of systems pharmacology was proposed for revealing how the oral administration, drug half-life, and target interactions affect the pharmacological functions of herbal medicines. This platform was further applied on two classical prescriptions, i.e., Xiao Chaihu decoction (XCHD) and Da Chaihu decoction (DCHD) to dissect the addition and subtraction theory (AST). RESULTS: We uncovered the candidate compounds, key molecular targets and interaction network involved in XCHD and DCHD, and summarized its pharmacological characters and therapeutic indications. The results show that the "fundamental formula" is responsible for the major therapeutic effects, whereas the "additive herbs" synergistically enhance the treatment outcomes by targeting the same or complementary proteins between the foundational and additive herbs. CONCLUSION: This work has established a novel method to comprehensively understand the mechanism of AST, which would be beneficial for the TCM recipe optimization as well as the production of new herbal formula with desirable therapeutic effects.