Abstract
BackgroundThis study investigated the protective effects of the Danshen (DS) and Sanqi (SQ) herb pair on cell survival in the human cardiovascular endothelial (EA.hy926) cell line exposed to injury.MethodsNine combination ratios of Danshen-Sanqi extracts (DS-SQ) were screened for their protective effects in the EA.hy926 cell line against two different cellular impairments induced by DL-homocysteine (Hcy) – adenosine (Ado) – tumour necrosis factors (TNF) and oxidative stress (H2O2), respectively. The type of interaction (synergistic, antagonistic, additive) between DS and SQ was analysed using a combination index (CI) model. The effects of key bioactive compounds from DS and SQ were tested using the same models. The compound from each herb that demonstrated the most potent activity in cell viability was combined to evaluate their synergistic/antagonistic interaction using CI.ResultsDS-SQ ratios of 6:4 (50–300 μg/mL) produced synergistic effects (CI < 1) in restoring cell viability, reducing lactate dehydrogenase (LDH) leakage and caspase-3 expressions against Hcy-Ado-TNF. Additionally, DS-SQ 6:4 (50–150 μg/mL) was found to synergistically protect endothelial cells from impaired cellular injury induced by oxidative damage (H2O2) by restoring reduced cell viability and inhibiting excessive expression of reactive oxygen species (ROS). In particular, the combination of salvianolic acid A (SA) and ginsenoside Rb1 (Rb1) at 4:6 (1–150 μM) showed synergistic effects in preventing cytotoxic effects caused by Hcy-Ado-TNF (CI < 1). This simplified combination also demonstrated synergistic effects on H2O2-induced oxidative damage on EA.hy926 cells.ConclusionsThis study provides scientific evidence to support the traditional use of the DS-SQ combination on protecting endothelial cells through their synergistic interactions.
Highlights
This study investigated the protective effects of the Danshen (DS) and Sanqi (SQ) herb pair on cell survival in the human cardiovascular endothelial (EA.hy926) cell line exposed to injury
Synergistic effects of DS, SQ and Danshen-Sanqi extracts (DS-SQ) and their bioactive compounds on Hcy-ado-tumour necrosis factor (TNF) impaired cell survival in EA.hy926 cells Synergistic effects of DS, SQ and DS-SQ on impaired cell viability The cytotoxic effects of TNF associated with Hcy and Ado were demonstrated in a concentration-dependent manner in EA.hy926 cells
Significant cell viability was reduced by over 40% in comparison to blank control when the concentration of TNF was greater than 0.5 ng/mL (P < 0.01) (Additional file 3)
Summary
This study investigated the protective effects of the Danshen (DS) and Sanqi (SQ) herb pair on cell survival in the human cardiovascular endothelial (EA.hy926) cell line exposed to injury. Synergy can be understood as augmented bioactivity of compounds on the same target/receptor, and/or multi-target behaviour, and/or enhanced bioavailability. This produces an effect which is greater than the sum of the effect from the individual agents [1]. Endothelial dysfunction is an early marker of vascular dysfunction prior to the development of vascular structural changes and clinical symptoms. This contributes to the progression of atherosclerotic plaques and leads to various types of vascular diseases [2,3,4]. Several in vitro studies reported that Hcy and TNF with Ado significantly impaired endothelial cell survival and induced cell apoptosis [3, 13]
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