posted on 2021-05-25, 20:15authored byMengqi Zhang, Peihai Li, Shanshan Zhang, Xuanming Zhang, Lizhen Wang, Yun Zhang, Xiaobin Li, Kechun Liu
Danggui–Chuanxiong
(DC) is a commonly used nourishing and
activating blood medicine pair in many gynecological prescriptions
and modern Chinese medicine. However, its activating blood mechanism
has not been clearly elucidated. Our research aimed at investigating
the activating blood mechanisms of DC using network pharmacology and
zebrafish experiments. Network pharmacology was used to excavate the
potential targets and mechanisms of DC in treating thrombus. The antithrombotic,
anti-inflammatory, antioxidant, and vasculogenesis activities of DC
and the main components of DC, ferulic acid (DC2), ligustilide (DC7),
and levistilide A (DC17), were evaluated by zebrafish models in vivo.
A total of 24 compounds were selected as the active ingredients with
favorable pharmacological parameters for this herb pair. A total of
89 targets and 18 pathways related to the thrombus process were gathered
for active compounds. The genes, TNF, CXCR4, IL2, ESR1, FGF2, HIF1A,
CXCL8, AR, FOS, MMP2, MMP9, STAT3, and RHOA, might be the main targets
for this herb pair to exert cardiovascular activity from the analysis
of protein–protein interaction and KEGG pathway results, which
were mainly related to inflammation, vasculogenesis, immunity, hormones,
and so forth. The zebrafish experiment results showed that DC had
antithrombotic, anti-inflammatory, antioxidant, and vasculogenesis
activities. The main compounds had different effects of zebrafish
activities. Especially, the antithrombotic activity of the DC17H group,
anti-inflammatory activities of DCH and DC2H groups, antioxidant activities
of DCM, DCH, DC2, DC7, and DC17 groups, and vasculogenesis activities
of DCM, DCH, and DC2 groups were stronger than those of the positive
group. The integrated method coupled zebrafish models with network
pharmacology provided the insights into the mechanisms of DC in treating
thrombus.