Synergistic Effects of Sanghuang-Danshen Bioactives on Arterial Stiffness in a Randomized Clinical Trial of Healthy Smokers: An Integrative Approach to in silico Network Analysis

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The vascular endothelium is a favorite early target of cardiovascular risk factors, including cigarette smoking. Here, we investigated the synergistic effects of Sanghuang-Danshen (SD) bioactives on vascular stiffness in a controlled clinical trial of healthy chronic smokers (n = 72). Relative to placebo, 4-week SD consumption at 900 mg/day improves pulse wave velocity (p = 0.0497), reduces systolic blood pressure (peripheral, p = 0.0008; brachial, p = 0.0046; and ankle, p = 0.0066), and increases endothelial nitric oxide synthase activation (p < 0.0001). We then mapped all differential markers obtained from the clinical data, Affymetrix microarray, and H-1 NMR metabolomics, together with 12 SD bioactives, onto the network platform termed the context-oriented directed associations. The resulting vascular subnetwork demonstrates that ellagic acid, caffeic acid, protocatechuic acid, cryptotanshinone, tanshinone I, and tanshinone IIA are linked to NOS3, ARG2, and EDN1 for vascular dilation, implicated with arginine/proline metabolism. They are also linked to SUCLG1, CYP1A1, and succinate related to the mitochondrial metabolism and detoxification, implicated with various metabolic pathways. These results could explain the synergistic action mechanisms of SD bioactives in the regulation of vascular endothelial dilation and metabolism, confirming the potential of SD in improving vascular stiffness and blood pressure in healthy smokers.
Publisher
MDPI
Issue Date
2019-01
Language
English
Article Type
Article
Citation

NUTRIENTS, v.11, no.1

ISSN
2072-6643
DOI
10.3390/nu11010108
URI
http://hdl.handle.net/10203/251521
Appears in Collection
BiS-Journal Papers(저널논문)
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