Synergistic mechanisms of Sanghuang–Danshen phytochemicals on postprandial vascular dysfunction in healthy subjects: A network biology approach based on a clinical trial

Yeni Lim, Woochang Hwang, Ji Yeon Kim, Choong Hwan Lee, Yong Jae Kim, Doheon Lee, Oran Kwon

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

With the increased risk of cardiovascular disease, the use of botanicals for vascular endothelial dysfunction has intensified. Here, we explored the synergistic mechanisms of Sanghuang–Danshen (SD) phytochemicals on the homeostatic protection against high-fat-induced vascular dysfunction in healthy subjects, using a network biology approach, based on a randomised crossover clinical trial. Seventeen differential markers identified in blood samples taken at 0, 3 and 6 h post-treatment, together with 12SD phytochemicals, were mapped onto the network platform, termed the context-oriented directed associations. The resulting vascular sub-networks illustrated associations between 10 phytochemicals with 32 targets implicated in 143 metabolic/signalling pathways. The three key events included adhesion molecule production (ellagic acid, fumaric acid and cryptotanshinone; VCAM-1, ICAM-1 and PLA2G2A; fatty acid metabolism), platelet activation (ellagic acid, protocatechuic acid and tanshinone IIA; VEGFA, APAF1 and ATF3; mTOR, p53, Rap1 and VEGF signalling pathways) and endothelial inflammation (all phytochemicals, except cryptotanshinone; 29 targets, including TP53 and CASP3; MAPK and PI3K-Akt signalling pathways, among others). Our collective findings demonstrate a potential of SD to protect unintended risks of vascular dysfunction in healthy subjects, providing a deeper understanding of the complicated synergistic mechanisms of signature phytochemicals in SD.

Original languageEnglish
Article number9746
JournalScientific Reports
Volume9
Issue number1
DOIs
StatePublished - 1 Dec 2019

Bibliographical note

Funding Information:
This study was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science & ICT (NRF-2012M3A9C4048761 and NRF-2012M3A9C4048758). We thank the subjects for their involvement.

Publisher Copyright:
© 2019, The Author(s).

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