Table 5.

Summary of animal and cell experiments of Panax notoginseng saponins on CAD.

Species	Experimental model	Effects	Signaling molecules involved	References
PNS	Human granulocytic HL-60, erythrocytic K562, megakaryocytic CHRF-288, and Meg-01 cell line	Promote proliferation and differentiation	Kinase MEK-1↑, MEK-2↑, ERK-1↑, ERK-2↑, AKT-1↑, AKT-2↑, PI3K↑	Fan et al., 2012
PNS	THP-1 macrophage cells	Reduced secretion of inflammatory factors	LXRalpha↑, ABCA1↑, ABCG1↑, NF-κB↓, IL-6↓, MCP-1↓	Dou et al., 2012
PNS	Apo-E-deficient mice	Inhibit the progression of atherosclerotic lesions via antioxidant/anti-inflammatory biological properties	VCAM-1↓, ICAM-1↓, MCP-1↓, RAGE↓, NF-κB↓, JNK, p38(MAPK)↓, ERK1/2↓	Aronoff et al., 2004
PNS	Peritoneal macrophage cells	Enhanced phagocytosis	COX-2, PGE↓, PGD↑	Yuan et al., 2009
PNS	Haemorrhagic shock rats	Protective to rat haemorrhagic shock model by antioxidative stress and anti-inflammation	ICAM-1↓, SOD↑, MDA↓, endotoxin↓, MPO↓, TNF alpha↓, IL-6↓	Liu H. Z. et al., 2014
NG	Rat washed platelets	Inhibit ADP-induced platelet aggregation	Grb2↑, thrombospondin 1↑, tubulin alpha 6↑, thioredoxin↑, Cu–Zn superoxide dismutase, DJ-1↑, peroxiredoxin 3↑, thioredoxin-like protein 2↑, ribonuclease inhibitor↑, potassium channel subfamily V member 2↑, myosin regulatory light chain 9↑, laminin receptor 1↑	Yao et al., 2008a
Ginsenoside-Rd	Basilar artery smooth muscle cells	Inhibit cell proliferation and reversed basilar artery remodeling	Cytochrome C↑, caspase-9/caspase-3↑, MMP↓, Bcl-2/Bax↓, Cyclosporine A↓	Li et al., 2012
NR1	Human endothelial EA. hy926 cells	Suppress oxLDL-induced inflammatory cytokines production	PPARgamma↑, NF-κB↓, MAPK↓	Su et al., 2016
NR1	Human aortic smooth muscle cells	Inhibits TNF-alpha-induced PAI-1 production	ERK↓, PKB↓	Zhang and Wang, 2006
NR1	H9c2 cardiomyocytes	Reduced cardiomyocyte apoptosis and inflammation	ERalpha↑	Zhong et al., 2015
NR1	Endotoxaemic mice	Protection of cardiac function	ERalpha↑, phospho-Akt↑, phospho-GSK3beta↑, I-κB alpha↑	Sun B. et al., 2013
Ginsenoside Rg1	Hypoxia/reoxygenation cardiomyocytes	Antioxidative effect	ROS↓, T-SOD↑, CAT↑, GSH↑	Zhu et al., 2009
PNS	Foam cells	Decrease cholesterol ester	ABCA1↑	Jia et al., 2010
PNS	CAD rats	Improve lipid metabolism	LPL↑, FABP4↓, CPT-1A↓, cytochrome P450↑, PPARalpha↓, PPARgamma↓, RXRA↓, PGC-1alpha↓	Fan et al., 2012
PNS	Atherosclerosis rats	Regulate the blood lipid profile and anti-inflammation	Integrins↓, IL-18↓, IL-1beta↓, MMP-2↓, MMP-9↓, NF-κB/p65↓, IκBalpha↑	Zhang et al., 2008
PNS	Atherosclerosis rabbit	Regulate the blood lipid profile and anti-inflammation	IL-6↓, CRP↓, MCP-1↓, NF-κB/p65↓	Liu et al., 2010
PNS	apoE(−/−) mice	Prevent the development of atherosclerosis	Ca2+ influx↑, SR-A↓	Hall et al., 2005
Ginsenoside-Rd	Macrophage cells	Inhibits ox-LDL-induced foam cell formation	Ca2+ influx↑	Hall et al., 2005
PNS	Endothelial cells	Inhibit platelet activation	COX-2, 6-keto-PGF1alpha↑, COX-1↓, TXB2↓	Wang M. M. et al., 2016
PNS	Rats	Inhibit ADP-induced platelet aggregation of platelet rich plasma		Yao et al., 2008b
PNS	Rabbit and human platelet	Anti-platelet aggregation	ERK2↓, p38↓	Qi et al., 2016
PNS, ginsenosides (Rg1, Re, and NR1)	Human plasma	Anticoagulation activity		Li et al., 2013
Ginsenosides, Rg1, Rg2	Rat washed platelets	Enhanced platelet aggregation	Ca2+↑, P2Y12 receptors↑	Gao et al., 2014
notoginsenoside Ft1	HEK293 cells	None	Ca2+↑, P2Y12 receptors↑, cAMP, phosphorylation of PI3K↑, Akt↑	Gao et al., 2014
NR1	Cultured HUVECs	Activate tissue-type plasminogen	TPA↑, TPA-PAI-1 complexes↑	Zhang et al., 1994
PNS	H9c2 cells	Anti-apoptosis	PI3K↑, p-Akt↑	Li et al., 2014
PNS	Myocardial ischaemia injury rats	Improved cardiac function in rats	p-Akt↑	Wang et al., 2015
PNS	Rat aorta after balloon angioplasty	Inhibit intima hyperplasia by inhibiting VSMCs proliferation	PCNA↓	Wang et al., 2009
PNS	VSMCs	Inhibit VSMCs proliferation and induce VSMCs apoptosis	p53↑, Bax↑, caspase-3↑, Bcl-2↓	Xu et al., 2011
PNS	VSMCs	inhibit VSMCs proliferation	cyclinD1↓, CDK4↓, p21↓, P-ERK1/2↓, MKP-1↑	Zhang et al., 2012
PNS	Human umbilical vein endothelial cells(HUVECs)	Stimulate the proliferation of HUVECs	PI3K↑, Akt↑, eNOS↑	Hong et al., 2009
PNS	Zebrafish	Promote changes in the subintestinal vessels	VEGF-KDR/Flk-1↑	Hong et al., 2009
Notoginsen-oside F1	HUVECs	Pro-angiogenesis, stimulate the proliferation of HUVECs	VEGF-KDR/Flk-1↑, PI3K↑, eNOS↑, Akt↑	Yang et al., 2016
Notoginsen-oside F1	Rat mesenteric arteries	Induce endothelium-dependent relaxation	eNOS↑, ER beta↑, Akt↑, ERK1/2↓	Shen et al., 2014
PNS	Apolipoprotein E-knockout mice	Lower serum lipid levels	CD40↓, MMP-9↓	Liu et al., 2009
PNS	Apolipoprotein E-knockout mice	Reduce the size of atherosclerotic plaque	SDF-1 alpha↑, SCF↑, MMP-9↑, CXCR4↑	Liu et al., 2013
PNS	Zymosan A induced atherosclerosis rats	Inhibit atherogenesis	p-FAK↓, NF-κB↓	Zhang et al., 1994
PNS	Acute myocardial ischaemia in anesthetic dogs	Attenuate the damage of myocardial ischaemia and infarction	ET↓, TXA2↓, MBF↑	Yuan et al., 2011
PNS	Post-myocardial infarction-ventricular rats	Reduce pathological injury of cardiac myocytes in myocardial ischaemia and cardiac muscle	ACE2↑, TNF-alpha↓	Guo et al., 2010
PNS	Rabbits after balloon endothelial denudation (BED)	Promote endothelial, regeneration and reduce extracellular matrix thickening	VEGF↓, MMP-2↓	Liu et al., 2009
PNS	Cardiomyocytes with hypoxia-reoxygenation	Inhibit apoptosis and improve energy metabolism		Gong et al., 2013
NG	Rats of ischaemia-reperfusion (IR)	Cardioprotective effect		Yue et al., 2012
Ginsenoside Rg1, Rb1	Myocardial infarction rats	Improved heart contractility		Deng et al., 2015