Network pharmacology analyses of the antithrombotic pharmacological mechanism of Fufang Xueshuantong Capsule with experimental support using disseminated intravascular coagulation rats.
BACKGROUND
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.


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.
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.
Shujing
S
Sheng
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.
Jinxu
J
Wang
Computational Chemical Genomics Screening Center, Department of Pharmaceutical Sciences, School of Pharmacy, Drug Discovery Institute, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Lirong
L
Wang
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.
Hong
H
Liu
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.
Peibo
P
Li
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.
Menghua
M
Liu
Guangdong Zhongsheng Pharmaceutical Co., Ltd., Dongguan 523325, PR China.
Chaofeng
C
Long
Guangdong Zhongsheng Pharmaceutical Co., Ltd., Dongguan 523325, PR China.
Chengshi
C
Xie
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.
Xiangqun
X
Xie
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.
Weiwei
W
Su
D000818:Animals; D004195:Disease Models, Animal; D004211:Disseminated Intravascular Coagulation / Q000188:drug therapy*; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D005343:Fibrinolytic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D058990:Molecular Targeted Therapy; D051381:Rats; D017207:Rats, Sprague-Dawley
D004365:Drugs, Chinese Herbal; D005343:Fibrinolytic Agents; D008070:Lipopolysaccharides; C530083:fufang xiaojingtong
Angoroside C (PubChem CID: 6444153); Astragaloside IV (PubChem CID: 158694); Calycosin-7-O-β-d-glucopyranoside (PubChem CID: 5318267); Disseminated intravascular coagulation; Fufang Xueshuantong Capsule; Ginsenoside Rb1 (PubChem CID: 9898279); Harpagoside (PubChem CID: 5281542); Network pharmacology; Panaxytriol (PubChem CID: 93484); Salvianolic acid A (PubChem CID: 5281793); Salvianolic acid B (PubChem CID: 11629084); Tanshinone I (PubChem CID: 114917); Tanshinone IIA (PubChem CID: 164676); Thrombosis disease