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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.

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.

SUBMITTER: Lim Y

PROVIDER: S-EPMC6357070 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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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.

Lim Yeni Y Song Tae-Jin TJ Hwang Woochang W Kim Ji Yeon JY Lee Doheon D Kim Yong-Jae YJ Kwon Oran O

Nutrients 20190107 1

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 ank ...[more]

PMID: 30621047

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Project description:BackgroundIncreased arterial stiffness and low handgrip strength (HGS) are associated with poor health outcomes and are a severe health risk for older adults. However, there is limited evidence and mixed results on whether there is an association between them. Therefore, this study focused on the association between arterial stiffness and HGS in relatively healthy older adults in Beijing, China.MethodsIn 2016, 2,217 adult volunteers were recruited in Beijing. Brachial-ankle pulse wave velocity (baPWV) and the ankle-brachial index were measured using an automatic vascular profiling system. Carotid artery intima-media thickness and common carotid artery-internal diameter (CCAID) were evaluated using Doppler ultrasound, and HGS was measured with a dynamometer. Low HGS was determined using the Asian Sarcopenia Working Group 2019 criteria. Multivariate linear and logistic regressions evaluated the relationship between arterial stiffness and HGS.ResultsUltimately, 776 relatively healthy older adults (mean age 69.05 ± 6.46 years) were included. Based on the AWGS2019 criteria, 137 participants were defined as having low HGS. Compared to the normal HGS group, the low HGS group was older and had higher baPWV (p < 0.001) but lower CCAID, body mass index (BMI) and hemoglobin (Hb) (p < 0.05). The multiple linear regression analysis revealed that baPWV was negatively correlated with HGS (β = -0.173, t = -2.587, p = 0.01). Multivariate logistic regression analysis showed that baPWV and CCAID were associated with an increased risk of low HGS (odds ratio (OR) per SD increase: 1.318, p = 0.007; OR per SD increase: 0.541, p < 0.001).ConclusionArterial stiffness and HGS were significantly negatively correlated in relatively healthy Chinese older adults. Low HGS is associated with increased arterial stiffness. Encouraging exercise training to improve HGS, thereby reducing arterial stiffness and the risk of cardiovascular events, may be a simple and effective intervention.

Project description:BackgroundDevelopment of instruments capable of detecting early stage vascular disease has increased interest in employing arterial stiffness (e.g. pulse wave velocity (PWV), augmentation index (AIx)) and endothelial dysfunction (e.g. reactive hyperemia index (RHI)) to diagnose atherosclerotic disease before occurrence of a cardiovascular event. However, amongst the equipment designed for this purpose, there is insufficient information regarding each of these parameters to establish appropriate cutoffs to distinguish between healthy and unhealthy blood vessels. To address these limitations, the study was designed to establish the upper arterial stiffness and endothelial function thresholds in a healthy population, by comparing the outputs from different instruments capable of measuring PWV, AIx and RHI.MethodsA systematic comparison of PWV, AIx and RHI was conducted to determine the inter-relationships between these parameters of vascular functionality. Outputs were obtained non-invasively using three instruments, the VP-1000 (VP), SphygmoCor (SC), and EndoPAT (EP), in 40 apparently healthy males and females.ResultsCorrelations were found between the brachial-ankle PWV and radial-ankle PWV (by VP and SC), and PWV (VP) with AIx (SC). The interchangeability of these outputs was demonstrated by the Bland Altman test, making it feasible to extrapolate cut-offs for radial-ankle PWV and AIx equivalent to brachial-ankle PWV that signify healthy vessels. In contrast, RHI showed no association with AIx, suggesting these endothelial and arterial parameters are functionally distinct.ConclusionsIt was concluded that it is possible to compare the vascular function outputs of different instruments and identify healthy from unhealthy vessels, even though the approaches for quantifying the underlying physiological processes may differ. In this way, non-invasive determination of arterial function could be a new paradigm for detecting existing early stage asymptomatic atherosclerotic disease in individuals using techniques that are amenable to the clinical setting.

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Dataset Information

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.

Publications

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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