Shujing Sheng1, Jinxu Wang2, Lirong Wang3, Hong Liu4, Peibo Li4, Menghua Liu4, Chaofeng Long5, Chengshi Xie5, Xiangqun Xie6, Weiwei Su7. 1. Guangzhou Quality R & D Center of Traditional Chinese Medicine, Guangdong Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, PR China; Guangdong Zhongsheng Pharmaceutical Co., Ltd., Dongguan 523325, PR China. 2. Guangzhou Quality R & D Center of Traditional Chinese Medicine, Guangdong Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, PR China; Visiting Scholar in Xie's laboratory at University of Pittsburgh, USA. 3. Computational Chemical Genomics Screening Center, Department of Pharmaceutical Sciences, School of Pharmacy, Drug Discovery Institute, University of Pittsburgh, Pittsburgh, PA 15261, USA. 4. Guangzhou Quality R & D Center of Traditional Chinese Medicine, Guangdong Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, PR China. 5. Guangdong Zhongsheng Pharmaceutical Co., Ltd., Dongguan 523325, PR China. 6. Computational Chemical Genomics Screening Center, Department of Pharmaceutical Sciences, School of Pharmacy, Drug Discovery Institute, University of Pittsburgh, Pittsburgh, PA 15261, USA. Electronic address: xix15@pitt.edu. 7. Guangzhou Quality R & D Center of Traditional Chinese Medicine, Guangdong Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, PR China. Electronic address: lssswwhk@gmail.com.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Fufang Xueshuantong (FXST) Capsule is developed on a traditional Chinese medicine remedy, with a four-herb formula of Panax notoginseng, Radix astragali, Salvia miltiorrhizae and Radix scrophulariaceae. It has been used for treatment of the clinic cardiovascular disease for many years. MATERIALS AND METHODS: Due to its complexity of compositions and polypharmacological effects, it often complicates understanding of the mechanisms of action. In the present work, we have constructed an integrated model of system pharmacology to investigate the polypharmacological mechanisms of FXST formulation for treatment of thrombosis disease. RESULTS: The predicted results showed that 22 ingredients in FXST were closely associated with 41 protein targets related to blood coagulation, fibrinolysis and platelet aggregation. Through analysis of the compound-protein target association, significant cross-targets between each herb indicated the multiple active chemical ingredients might interact with the same target simultaneously and thus explained the synergistic mechanisms of the principle of Traditional Chinese medicines (TCMs) as ''Jun (emperor) - Chen (minister) - Zuo (adjuvant) - Shi (courier)''. To validate the polypharmacological effects predicted by our network pharmacology (NetPharm) analysis, we have carried out experimental investigation the effects of FXST on the disorders of the blood coagulation system in a lipopolysaccharide-induced disseminated intravascular coagulation (DIC) rat model. The results showed that FXST could significantly ameliorate the activation of coagulation system, which is congruent with the cross-target prediction by NetPharm approach. CONCLUSIONS: The combined investigations provide more insight into better understanding of the pharmacological mechanisms of FXST, and may also offer an alternative avenue to further explore the chemical and pharmacological basis of TCMs.
ETHNOPHARMACOLOGICAL RELEVANCE: Fufang Xueshuantong (FXST) Capsule is developed on a traditional Chinese medicine remedy, with a four-herb formula of Panax notoginseng, Radix astragali, Salvia miltiorrhizae and Radix scrophulariaceae. It has been used for treatment of the clinic cardiovascular disease for many years. MATERIALS AND METHODS: Due to its complexity of compositions and polypharmacological effects, it often complicates understanding of the mechanisms of action. In the present work, we have constructed an integrated model of system pharmacology to investigate the polypharmacological mechanisms of FXST formulation for treatment of thrombosis disease. RESULTS: The predicted results showed that 22 ingredients in FXST were closely associated with 41 protein targets related to blood coagulation, fibrinolysis and platelet aggregation. Through analysis of the compound-protein target association, significant cross-targets between each herb indicated the multiple active chemical ingredients might interact with the same target simultaneously and thus explained the synergistic mechanisms of the principle of Traditional Chinese medicines (TCMs) as ''Jun (emperor) - Chen (minister) - Zuo (adjuvant) - Shi (courier)''. To validate the polypharmacological effects predicted by our network pharmacology (NetPharm) analysis, we have carried out experimental investigation the effects of FXST on the disorders of the blood coagulation system in a lipopolysaccharide-induced disseminated intravascular coagulation (DIC) rat model. The results showed that FXST could significantly ameliorate the activation of coagulation system, which is congruent with the cross-target prediction by NetPharm approach. CONCLUSIONS: The combined investigations provide more insight into better understanding of the pharmacological mechanisms of FXST, and may also offer an alternative avenue to further explore the chemical and pharmacological basis of TCMs.