TY - JOUR
T1 - Synergistic effects of sanghuang–danshen bioactives on arterial stiffness in a randomized clinical trial of healthy smokers
T2 - An integrative approach to in silico network analysis
AU - Lim, Yeni
AU - Song, Tae Jin
AU - Hwang, Woochang
AU - Kim, Ji Yeon
AU - Lee, Doheon
AU - Kim, Yong Jae
AU - Kwon, Oran
N1 - Funding Information:
Funding: This research was funded by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science & ICT (NRF-2012M3A9C4048761).
Funding Information:
This research was funded by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science & ICT (NRF-2012M3A9C4048761).
Publisher Copyright:
© 2019, MDPI AG. All rights reserved.
PY - 2019/1
Y1 - 2019/1
N2 - 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, and1 H 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.
AB - 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, and1 H 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.
KW - Arterial stiffness
KW - Danshen
KW - Endothelium-dependent vasodilation
KW - In silico network analysis
KW - Integrative approach
KW - Randomized clinical trial
KW - Sanghuang mushroom
UR - http://www.scopus.com/inward/record.url?scp=85059794957&partnerID=8YFLogxK
U2 - 10.3390/nu11010108
DO - 10.3390/nu11010108
M3 - Article
C2 - 30621047
AN - SCOPUS:85059794957
SN - 2072-6643
VL - 11
JO - Nutrients
JF - Nutrients
IS - 1
M1 - 108
ER -