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Nutrients 2019, 11(1), 108; https://doi.org/10.3390/nu11010108

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

1
Department of Nutritional Science and Food Management, Ewha Womans University, Seoul 03760, Korea
2
Department of Neurology, Ewha Womans University School of Medicine, Seoul 07985, Korea
3
Department of Bio and Brain Engineering, KAIST, Daejeon 34141, Korea
4
Department of Food Science and Technology, Seoul National University of Science and Technology, Seoul 01811, Korea
5
Department of Neurology, Eunpyeong St. Mary’s Hospital, The Catholic University of Korea, Seoul 06591, Korea
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Received: 18 December 2018 / Revised: 31 December 2018 / Accepted: 2 January 2019 / Published: 7 January 2019
(This article belongs to the Special Issue Dietary Bioactive Compounds and Human Health and Disease)
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Abstract

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 1H 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. View Full-Text
Keywords: Sanghuang mushroom; Danshen; arterial stiffness; endothelium-dependent vasodilation; randomized clinical trial; in silico network analysis; integrative approach Sanghuang mushroom; Danshen; arterial stiffness; endothelium-dependent vasodilation; randomized clinical trial; in silico network analysis; integrative approach
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Lim, Y.; Song, T.-J.; Hwang, W.; Kim, J.Y.; Lee, D.; Kim, Y.-J.; Kwon, O. 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. Nutrients 2019, 11, 108.

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