Abstract
BackgroundPanax notoginseng is commonly used for the treatment of cardiovascular diseases in China. The present study investigates the effects of three different saponin fractions (ie total saponins, PNS; protopanaxadiol-type saponin, PDS; and protopanaxatriol-type saponin, PTS) and two major individual ingredients (ie ginsenoside Rg1 and Rb1) from P. notoginseng on the endothelial inflammatory response in vitro and in vivo.MethodsRecombinant human tumor necrosis factor-α (TNF-α) was added to the culture medium of human coronary artery endothelial cells (HCAECs) to induce an inflammatory response. A cell adhesion assay was used to determine the effect of the P. notoginseng saponin fractions on endothelial-monocyte interaction. The cell adhesion molecule (CAMs) expression, including ICAM-1 and VCAM-1, in the protein level on the surface of endothelial cells were measured by cellular ELISA. CAMs expression in mRNA level was also assayed by qRT-PCR in the HCAECs and the aorta of rat fed with high cholesterol diet (HCD). Western blotting was used to detect effect of the saponin fractions on CAMs protein expression in HCAECs. In addition, nuclear translocation of p65, a surrogate marker for NF-κB activation, was measured by immunostaining.ResultsThree saponin fractions and two individual ginsenosides exhibited the inhibitory effects on monocyte adhesion on TNF-α-activated HCAECs and expression of ICAM-1 and VCAM-1 at both mRNA and protein levels in vitro. The saponin fractions exhibited a similar trend of the inhibitory effects on the mRNA expression of CAMs in the aorta of HCD-fed rat in vivo. These inhibitory effect of saponin fractions maybe attribute partially to the suppression of the TNF-α-induced NF-κB activation.ConclusionOur data demonstrate that saponin fractions (ie PNS, PDS and PTS) and major individual ginsenosides (ie Rg1 and Rb1) have potential anti-atherogenic effects. Among the tested saponin fractions, PDS is the most potent saponin fraction against TNF-α-induced monocyte adhesion as well as the expression of adhesion molecules in vitro and in vivo.
Highlights
Panax notoginseng is commonly used for the treatment of cardiovascular diseases in Control of Pharmaceutical and Biological Products (China)
We recently showed that the total saponins from P. notoginseng (PNS) dramatically reduced the extent of atherosclerotic lesion in apolipoprotein E (Apo E)-deficient mice and that effect was associated with an anti-vascular inflammatory activity [6]
PNS is a chemical mixture containing more than 50 different saponins [5] and are classified into two main groups, namely the 20(S)-protopanaxatriol saponins (PTS), such as ginsenoside Rg1, and the 20(S)-protopanaxadiol saponins (PDS), such as ginsenoside Rb1 [5,7]
Summary
Panax notoginseng is commonly used for the treatment of cardiovascular diseases in China. The present study investigates the effects of three different saponin fractions (ie total saponins, PNS; protopanaxadioltype saponin, PDS; and protopanaxatriol-type saponin, PTS) and two major individual ingredients (ie ginsenoside Rg1 and Rb1) from P. notoginseng on the endothelial inflammatory response in vitro and in vivo. The extract of Panax notoginseng has long been prescribed for the treatment of coronary heart diseases in China [5]. PDS and PTS showed diverse or even antagonistic pharmacological activities [8,9,10,11]; the active chemical component(s) in the PNS fraction responsible for the anti-vascular inflammation and the underlying molecular mechanism are largely unknown. This study examines the anti-vascular inflammatory effects of three saponin fractions and two individual ginsenosides on the TNF-a-activated human coronary artery endothelial cells (HCAECs). The anti-vascular inflammatory action of the three saponin fractions is further evaluated by determining the mRNA expression of cell adhesion molecules (CAMs) in the aorta of highcholesterol diet (HCD)-fed rats in vivo
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