Wei-Hong Cong
Beijing University of Chinese Medicine, China
Title: Synergistic effects of chuanxiong-chishao herb-pair on promoting angiogenesis at network pharmacological and pharmacodynamic levels
Biography
Biography: Wei-Hong Cong
Abstract
Objective: The objective of the study is to investigate the synergistic effects of Chuanxiong-Chishao herb-pair (CCHP) on promoting
angiogenesis in silico and in vivo.
Methods: The mechanisms of action of a herb-pair, Chuanxiong-Chishao, were investigated using the network pharmacological and
pharmacodynamic strategies involving computational drug target prediction and network analysis, and experimental validation.
A set of network pharmacology methods were created to study the herbs in the context of targets and diseases networks, including
prediction of target profiles and pharmacological actions of main active compounds in Chuanxiong and Chishao. Furthermore, the
therapeutic effects and putative molecular mechanisms of Chuanxiong-Chishao actions were experimentally validated in a chemicalinduced
vascular insufficiency model of transgenic zebrafish in vivo. The mRNA expression of the predicted targets was further
analyzed by real-time polymerase chain reaction (RT-PCR).
Results: The computational prediction results found that the compounds in Chuanxiong have antithrombotic, antihypertensive,
antiarrhythmic, and antiatherosclerotic activities, for hypoxic-ischemic encephalopathy, ischemic stroke, myocardial infarction and
heart failure.In addition, compounds in Chishao were found to participate in anti-inflammatory effect and analgesics. Particularly,
estrogen receptor α (ESRα) and hypoxia-inducible factor 1-α (HIF-1α) were the most important potential protein targets in the
predicted results. In vivo experimental validation showed that post-treatment of tetramethylpyrazine hydrochloride (TMP•HCl) and
paeoniflorin (PF) promoted the regeneration of new blood vessels in zebrafish involving up-regulating ESRα mRNA expression. Cotreatment
of TMP•HCl and PF could enhance the vessel sprouting in chemical-induced vascular insufficiency zebrafish at the optimal
compatibility proportion of PF 10 μmol/L with TMP•HCl 1 μmol/L.
Conclusions: The network pharmacological strategies combining drug target prediction and network analysis identified some
putative targets of CCHP. Moreover, the transgenic zebrafish experiments demonstrated that the Chuanxiong-Chishao combination
synergistically promoted angiogenic activity, probably involving ESRα signaling pathway.