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

• Published in: Scientific reports Vol. 9; no. 1; pp. 9746 - 9
• Main Authors: Lim, Yeni, Hwang, Woochang, Kim, Ji Yeon, Lee, Choong Hwan, Kim, Yong-Jae, Lee, Doheon, Kwon, Oran
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05.07.2019; Nature Publishing Group
• Subjects: 1-Phosphatidylinositol 3-kinase; 38; 38/77; 45/41; 631/553/1833; 692/699/75/593/2100; Activating transcription factor 3; Adult; AKT protein; Biomarkers; Blood Vessels - drug effects; Blood Vessels - metabolism; Blood Vessels - physiopathology; Cardiovascular diseases; Clinical trials; Computational Biology - methods; Cryptotanshinone; Ellagic acid; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Female; Fumaric acid; Gene Expression Profiling; Health risks; Humanities and Social Sciences; Humans; Intercellular adhesion molecule 1; Male; MAP kinase; Metabolomics - methods; Middle Aged; multidisciplinary; p53 Protein; Phytochemicals; Phytochemicals - chemistry; Phytochemicals - pharmacology; Plant Extracts - chemistry; Plant Extracts - pharmacology; Postprandial Period; Protocatechuic acid; Rap1 protein; Salvia miltiorrhiza - chemistry; Science; Science (multidisciplinary); Signal Transduction; TOR protein; Vascular cell adhesion molecule 1; Vascular endothelial growth factor
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-46289-3

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.