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

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.

SUBMITTER: Lim Y

PROVIDER: S-EPMC6611899 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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

Lim Yeni Y Hwang Woochang W Kim Ji Yeon JY Lee Choong Hwan CH Kim Yong-Jae YJ Lee Doheon D Kwon Oran O

Scientific reports 20190705 1

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 wi ...[more]

PMID: 31278329

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Project description:BackgoundTheobromine, a component of cocoa, may favorably affect conventional lipid-related cardiovascular risk markers, but effects on flow-mediated dilation (FMD) and other vascular function markers are not known.ObjectiveTo evaluate the effects of 4-week theobromine consumption (500 mg/day) on fasting and postprandial vascular function markers.DesignIn a randomized, double-blind crossover study, 44 apparently healthy overweight (N = 30) and obese (N = 14) men and women with low HDL-C concentrations, consumed daily 500 mg theobromine or placebo for 4 weeks. After 4 weeks, FMD, peripheral arterial tonometry (PAT), augmentation index (AIx), pulse wave velocity (PWV), blood pressure (BP) and retinal microvasculature measurements were performed. These measurements were carried out under fasting conditions and 2.5 h after a high-fat mixed meal challenge.Results4-week theobromine consumption did not change fasting vascular function markers, except for a decrease in central AIx (cAIx, - 1.7 pp, P = 0.037) and a trend towards smaller venular calibers (- 2 µm, P = 0.074). Consuming a high-fat mixed meal decreased FMD (0.89 pp, P = 0.002), reactive hyperemia index (RHI, - 0.30, P < 0.001), peripheral systolic BP (SBP, - 3 mmHg, P ≤ 0.001), peripheral diastolic BP (DBP, - 2 mmHg, P ≤ 0.001), central SBP (- 6 mmHg, P ≤ 0.001) and central DBP (- 2 mmHg, P ≤ 0.001), but increased heart rate (HR, 2 bpm, P < 0.001). Theobromine did not modify these postprandial effects, but increased postprandially the brachial artery diameter (0.03 cm, P = 0.015), and decreased the cAIx corrected for a HR of 75 (cAIx75, - 5.0 pp, P = 0.004) and peripheral AIx (pAIx, - 6.3 pp, P = 0.017).ConclusionTheobromine consumption did not improve fasting and postprandial endothelial function, but increased postprandial peripheral arterial diameters and decreased the AIx. These findings do not suggest that theobromine alone contributes to the proposed cardioprotective effects of cocoa. This trial was registered on clinicaltrials.gov under study number NCT02209025.

Project description:BackgroundCloperastine is a pivotal antibechic widely prescribed to treat cough caused by respiratory diseases. The present trial evaluated the pharmacokinetics (PK), bioequivalence (BE) and safety effects of the generic test (T) tablet of cloperastine after single-dose administration of cloperastine, compared with the original reference (R) tablet of cloperastine.ObjectiveThe purpose of this trial was to compare the PK, BE and safety of a test 10 mg versus the reference 10 mg formulation of cloperastine under fasting and postprandial conditions in healthy Chinese volunteers.MethodsA single-centre, randomised, open, double-cycle, self-crossover, single oral administration Phase I trial was performed in healthy Chinese volunteers. A total of 60 subjects were enrolled in either the fasting (28 subjects) or the postprandial condition (32 subjects). Subjects randomly received a single dose of the T or R preparation (10 mg dose). Plasma concentrations of cloperastine were analysed by a validated LC-MS/MS method. The primary endpoints of the PK parameters were the area under the plasma concentration-time curve from zero to 72 h (AUC0-72h), under the plasma concentration-time curve from zero to infinity (AUC0-∞) and the maximal plasma concentration (Cmax). The equivalence standard range (80.0-125.0%) was used to evaluate the BE of the two preparations. The safety parameter as secondary endpoint was mainly evaluated by the occurrence of adverse events (AEs).ResultsA total of 25 and 30 subjects in the fasting and postprandial conditions completed this clinical trial, respectively. The geometric mean ratio (GMR) of the T/R for the Cmax, AUC0-72h and AUC0-∞ were 102.1%, 103.8% and 104.0% in the fasting condition, respectively. In the postprandial condition, the GMR of the T/R for the Cmax, AUC0-72h and AUC0-∞ were 94.2%, 98.8% and 99.0%, respectively. All the values fell within the range (80.0-125.0%). The Cmax and AUC0-72h values of the T and R preparations in fasting and postprandial conditions were not statistically significant (P > 0.05). Furthermore, no serious adverse events (SAEs) occurred during the whole trial.ConclusionsThe T and R preparations were bioequivalent under both conditions. Food has no significant effect on the absorption of cloperastine. Moreover, T and R preparations were well tolerated. The trial registration number (TRN) and date of registrations were CTR20212515, 13 October 2021.

Dataset Information

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

Publications

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

Similar Datasets

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