Edited by: Aiping Lu, Hong Kong Baptist University, Hong Kong
Reviewed by: Zhenhua Dai, Guangdong Provincial Academy of Chinese Medical Sciences, China; Thomas Heinbockel, Howard University, United States
*Correspondence: Jie Wang
This article was submitted to Ethnopharmacology, a section of the journal Frontiers in Pharmacology
†These authors have contributed equally to this work.
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Coronary artery disease (CAD) is a major public health problem and the chief cause of morbidity and mortality worldwide.
Coronary artery disease (CAD) is a major public health problem and a chief cause of morbidity and mortality worldwide. The number of deaths due to CAD was 56 million people globally during a decade from 2000 (WHO,
In recent years, Traditional Chinese Medicine (TCM) has gained widespread popularity. Furthermore, an increasing number of studies have confirmed the efficacy of TCM for treating CAD. In 2007, nearly 4 out of 10 adults had used TCM therapy in the past 12 months, with natural products as the most commonly used therapies (Barnes et al.,
The terms “
The important person and classic medical books in which
Radix
The chemical structure of the main active ingredients of PNS.
Many plant species are named Sanqi (
We conducted a systematic search of oral PNS for over 4 weeks against CAD on four English databases and four Chinese databases: MEDLINE, the Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE Database, WHO Clinical Trials Registration Platform, Chinese National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), WANFANG, and SinoMed. The search time frame ranged from the databases' inception until 20 Feb 2017. We also searched reference lists for further publications. The search expression used in MEDLINE was ((“coronary heart disease” [MeSH Terms] OR (“coronary artery disease” [MeSH Terms] AND (“
Seventeen randomized clinical trials with 1,747 participants was collected which randomly assigned to a conventional treatment vs. a PN preparation evaluated cardiovascular outcomes (Table
The basic information of the 17 RCTs of PNS on CAD.
Du, 2009 | 56/56 | 58.8 ± 9.2 | 58.8 ± 9.2 | Unclear | Unclear | XST + conventional drugs | 4 | Conventional drugs | FAA, DAA, DN | Du and Chen, |
Feng, 2016 | 36/35 | 69.3 ± 4.8 | 69.4 ± 5.2 | 21/15 | 20/15 | PNS | 12 | Atorvastatin | lipid, PEP | Feng et al., |
Han, 2008 | 30/30 | 64.1 ± 10.8 | 63.7 ± 11.7 | 23/7 | 21/9 | XST + conventional drugs | 12 | Conventional drugs | FAA, DAA | Han, |
Hou, 2016 | 42/42 | 62.3 ± 2.31 | 62.4 ± 2.32 | 23/19 | 22/20 | XST + conventional drugs | 4 | Conventional drugs | FAA, DAA, ECG | Hou, |
Kong, 2006 | 52/52 | 61.2 ± 5.73 | 60.77 ± 5.61 | 31/21 | 32/20 | XST + conventional drugs | 4 | Conventional drugs | FAA, ECG | Kong and Zhang, |
Kuang, 2011 | 90/90 | 56.3 ± 6.9 | 57.1 ± 7.2 | 47/43 | 46/44 | XST + conventional drugs | 4 | Conventional drugs | FAA, DAA | Kuang et al., |
Liu, 2008 | 30/30 | 64.6 ± 5.4 | 63.6 ± 4.5 | Unclear | Unclear | XST + conventional drugs | 4 | Conventional drugs | ECG, lipid | Liu et al., |
Meng, 2013 | 600/600 | 68 ± 11 | 69 ± 9 | 421/179 | 368/232 | PNS tablet + conventional drugs | 52 | Conventional drugs | PEP | Meng et al., |
Song, 2005 | 50/50 | 61.2 ± 5.73 | 60.8 ± 5.61 | 31/19 | 33/17 | XST + conventional drugs | 4 | Conventional drugs | FAA, DN, ECG | Song et al., |
Teng, 2014 | 40/40 | 70.7 ± 6.87 | 71.7 ± 4.32 | 17/23 | 21/19 | XST + conventional drugs | 4 | Conventional drugs+XST capsule placebo | FAA, lipid | Teng, |
Wan, 2011 | 26/26 | 65.7 | Unclear | 15/11 | 13/13 | XST + conventional drugs | 4 | Conventional drugs | ECG | Wan, |
Wei, 2010 | 90/90 | 60.4 ± 3.5 | 60.4 ± 3.5 | Unclear | Unclear | XST +conventional drugs | 4 | Conventional drugs | FAA, DAA | Wei, |
Yan, 2015 | 28/27 | 76.3 ± 9.04 | 76.32 ± 9.04 | Unclear | Unclear | Sanqi Tongshu capsule +aspirin | 24 | Aspirin | PEP | Yan et al., |
Yu, 2010 | 50/50 | 64.2 ± 12.13 | 62.8 ± 10.8 | 29/21 | 28/22 | XST + conventional drugs | 4 | Conventional drugs | ECG | Yu, |
Zhang, 2014 | 30/30 | 60 ± 3.4 | 61 ± 4.0 | 16/14 | 15/15 | XST + trimetazidine | 4 | Trimetazidine | FAA, DAA | Zhang, |
Zheng, 2014 | 56/56 | Unclear | Unclear | Unclear | Unclear | XST + conventional drugs | 4 | Conventional drugs | ECG | Zheng, |
Zhou, 2009 | 43/43 | 65 ± 6 | 65 ± 6 | 32/11 | 34/9 | XST + conventional drugs | 4 | Conventional drugs | ECG | Zhou and Bai, |
Risk of bias in the 17 RCTs of PNS on CAD.
Du and Chen, |
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Feng et al., |
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Han, |
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Hou, |
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Kong and Zhang, |
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Kuang et al., |
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Meng et al., |
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Song et al., |
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The primary outcome of CAD is the primary end point which was defined as the composite of all-cause mortality, myocardial infarction (MI), revascularization, and rehospitalization for unstable angina. PNS has been observed to have several beneficial effects in patients with different stages of CAD. Several RCTs reported oral PNS could reduce the primary outcome. In 2008, a team underwent a RCT of 60 patients with CAD after PCI. The patients who had PNS (120 mg every time, three times every day) or a placebo was prescribed daily in combination with their conventional therapy for 3 months. The end point, rehospitalization, was focused on. The rehospitalization rate of patients with PNS was better than in the control group (1/30 and 3/30; Han,
The end point with PNS+conventional drugs and conventional drugs alone.
Cardiac death | 52 w | 1/600 | 1/600 | >0.05 |
12 w | 0/30 | 0/30 | >0.05 | |
Myocardial infarction | 52 w | 2/600 | 4/600 | < 0.05 |
12 w | 0/30 | 0/30 | >0.05 | |
Revascularization | 52 w | 16/600 | 37/600 | <0.05 |
12 w | 0/30 | 0/30 | >0.05 | |
Stent thrombosis | 52 w | 1/600 | 5/600 | <0.05 |
Rehospitalization for unstable angina | 12 w | 1/30 | 3/30 | >0.05 |
Secondary outcomes include electrocardiogram (ECG), attack of angina pectoris, such as frequency of angina pectoris, duration of angina pectoris and dosage of nitroglycerin, quality of life. Two systematic reviews estimated current evidence for the benefit of secondary outcomes and adverse events of PNS for CAD. One systematic review included 17 randomized clinical trials. Oral PN could alleviate angina pectoris (Shang et al.,
Angina pectoris is the symptoms for chest pain or discomfort due to CAD (Xiong et al.,
In this overview, nine RCTs reviewed the therapeutic effects of PNS on angina pectoris compared PNS + conventional drugs with conventional drugs. It's demonstrated PNS is one effective agents to decrease frequency and duration of angina pectoris. PNS could decrease significantly frequency and duration of angina pectoris. 180 patients of unstable angina were randomly divided into treatment group and control group of, respectively 90 patients. The treatment group added PNS (2 times/d for 4 weeks) on the basis of conventional treatment of angina pectoris. The control group administered conventional treatment of angina pectoris. The results showed that the frequency of unstable angina pectoris, pain intensity and duration were significantly reduced (Kuang et al.,
ECG is the other important secondary outcome on evaluating the clinical efficacy against angina pectoris. A total of eight RCTs observed ECG changes with PNS on CAD patients. Positive correlations of PNS and improvements of ECG were reported that ischaemic changes on ECG were attenuated significantly. A RCT divided 100 patients randomly into treatment group and control group. The two groups were given conventional drugs, treatment group plus PNS for 4 weeks. It's elucidated that ECG in the treatment group were better than those in the control group, in company with the curative effect of angina pectoris, FAA, the rate of stopping and the dosage of nitroglycerin (Song et al.,
Lipid disorder is one of the main risk factors for CAD. A 20% reduction in major coronary events within 5 years was caused by a decrease of 1 mmol/L in LDL level (Baigent et al.,
In this overview, 15 RCTs observe the effect of PNS as alternative and complementary medicine on secondary outcomes, such as frequency of angina attack, duration of angina attack, ECG and lipid metabolism. And the results illustrated PNS combined with conventional drugs had also significant effects on changing the secondary outcomes.
A systematic review evaluated the safety of PNS for UA, including six RCTs with 716 participants. Four of the included trials (66.7%) reported adverse effects related to treatment with PNS combined with conventional drugs. The only reported adverse effect was rash at 0.27% (1/363). No severe adverse events were reported (Yang et al.,
Focusing on PNS for CAD, nine RCTs reported adverse events in all 17 RCTs. No observable toxicity in liver or kidney function was measured by serum markers. Several RCTs described adverse events that indicated that oral PNS for CAD is not related to adverse reactions (Table
The incidence of adverse reactions with PNS for CAD.
Elevated transaminase | 0/36 | 2/35 | Feng et al., |
Gastrointestinal discomfort | 0/36 | 1/35 | Feng et al., |
Muscle pain | 0/36 | 1/35 | Feng et al., |
Subcutaneous hemorrhage | 1/28 | 0/27 | Yan et al., |
Fecal occult blood positive | 1/28 | 1/27 | Yan et al., |
Nausea | 0/28 | 1/27 | Yan et al., |
Rash | 1/50 | 0/50 | Yu, |
Total | 3/214 | 6/208 |
CAD occurs when atherosclerotic lesions impede blood flow in the coronary artery. The plaque activation causes ischaemia and infarction. Ruptures tend to happen near the thin and easy destroyed fibrous cap where activated immune cells, inflammatory molecules, and proteolytic enzymes are abundant (Santos-Gallego et al.,
Saponins are a group of natural compounds in plants and foods. PNS is the most important compound among
Summary of animal and cell experiments of
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., |
PNS | THP-1 macrophage cells | Reduced secretion of inflammatory factors | LXRalpha↑, ABCA1↑, ABCG1↑, NF-κB↓, IL-6↓, MCP-1↓ | Dou et al., |
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., |
PNS | Peritoneal macrophage cells | Enhanced phagocytosis | COX-2, PGE↓, PGD↑ | Yuan et al., |
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., |
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., |
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., |
NR1 | Human endothelial EA. hy926 cells | Suppress oxLDL-induced inflammatory cytokines production | PPARgamma↑, NF-κB↓, MAPK↓ | Su et al., |
NR1 | Human aortic smooth muscle cells | Inhibits TNF-alpha-induced PAI-1 production | ERK↓, PKB↓ | Zhang and Wang, |
NR1 | H9c2 cardiomyocytes | Reduced cardiomyocyte apoptosis and inflammation | ERalpha↑ | Zhong et al., |
NR1 | Endotoxaemic mice | Protection of cardiac function | ERalpha↑, phospho-Akt↑, phospho-GSK3beta↑, I-κB alpha↑ | Sun B. et al., |
Ginsenoside Rg1 | Hypoxia/reoxygenation cardiomyocytes | Antioxidative effect | ROS↓, T-SOD↑, CAT↑, GSH↑ | Zhu et al., |
PNS | Foam cells | Decrease cholesterol ester | ABCA1↑ | Jia et al., |
PNS | CAD rats | Improve lipid metabolism | LPL↑, FABP4↓, CPT-1A↓, cytochrome P450↑, PPARalpha↓, PPARgamma↓, RXRA↓, PGC-1alpha↓ | Fan et al., |
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., |
PNS | Atherosclerosis rabbit | Regulate the blood lipid profile and anti-inflammation | IL-6↓, CRP↓, MCP-1↓, NF-κB/p65↓ | Liu et al., |
PNS | apoE(−/−) mice | Prevent the development of atherosclerosis | Ca2+ influx↑, SR-A↓ | Hall et al., |
Ginsenoside-Rd | Macrophage cells | Inhibits ox-LDL-induced foam cell formation | Ca2+ influx↑ | Hall et al., |
PNS | Endothelial cells | Inhibit platelet activation | COX-2, 6-keto-PGF1alpha↑, COX-1↓, TXB2↓ | Wang M. M. et al., |
PNS | Rats | Inhibit ADP-induced platelet aggregation of platelet rich plasma | Yao et al., |
|
PNS | Rabbit and human platelet | Anti-platelet aggregation | ERK2↓, p38↓ | Qi et al., |
PNS, ginsenosides (Rg1, Re, and NR1) | Human plasma | Anticoagulation activity | Li et al., |
|
Ginsenosides, Rg1, Rg2 | Rat washed platelets | Enhanced platelet aggregation | Ca2+↑, P2Y12 receptors↑ | Gao et al., |
notoginsenoside Ft1 | HEK293 cells | None | Ca2+↑, P2Y12 receptors↑, cAMP, phosphorylation of PI3K↑, Akt↑ | Gao et al., |
NR1 | Cultured HUVECs | Activate tissue-type plasminogen | TPA↑, TPA-PAI-1 complexes↑ | Zhang et al., |
PNS | H9c2 cells | Anti-apoptosis | PI3K↑, p-Akt↑ | Li et al., |
PNS | Myocardial ischaemia injury rats | Improved cardiac function in rats | p-Akt↑ | Wang et al., |
PNS | Rat aorta after balloon angioplasty | Inhibit intima hyperplasia by inhibiting VSMCs proliferation | PCNA↓ | Wang et al., |
PNS | VSMCs | Inhibit VSMCs proliferation and induce VSMCs apoptosis | p53↑, Bax↑, caspase-3↑, Bcl-2↓ | Xu et al., |
PNS | VSMCs | inhibit VSMCs proliferation | cyclinD1↓, CDK4↓, p21↓, P-ERK1/2↓, MKP-1↑ | Zhang et al., |
PNS | Human umbilical vein endothelial cells(HUVECs) | Stimulate the proliferation of HUVECs | PI3K↑, Akt↑, eNOS↑ | Hong et al., |
PNS | Zebrafish | Promote changes in the subintestinal vessels | VEGF-KDR/Flk-1↑ | Hong et al., |
Notoginsen-oside F1 | HUVECs | Pro-angiogenesis, stimulate the proliferation of HUVECs | VEGF-KDR/Flk-1↑, PI3K↑, eNOS↑, Akt↑ | Yang et al., |
Notoginsen-oside F1 | Rat mesenteric arteries | Induce endothelium-dependent relaxation | eNOS↑, ER beta↑, Akt↑, ERK1/2↓ | Shen et al., |
PNS | Apolipoprotein E-knockout mice | Lower serum lipid levels | CD40↓, MMP-9↓ | Liu et al., |
PNS | Apolipoprotein E-knockout mice | Reduce the size of atherosclerotic plaque | SDF-1 alpha↑, SCF↑, MMP-9↑, CXCR4↑ | Liu et al., |
PNS | Zymosan A induced atherosclerosis rats | Inhibit atherogenesis | p-FAK↓, NF-κB↓ | Zhang et al., |
PNS | Acute myocardial ischaemia in anesthetic dogs | Attenuate the damage of myocardial ischaemia and infarction | ET↓, TXA2↓, MBF↑ | Yuan et al., |
PNS | Post-myocardial infarction-ventricular rats | Reduce pathological injury of cardiac myocytes in myocardial ischaemia and cardiac muscle | ACE2↑, TNF-alpha↓ | Guo et al., |
PNS | Rabbits after balloon endothelial denudation (BED) | Promote endothelial, regeneration and reduce extracellular matrix thickening | VEGF↓, MMP-2↓ | Liu et al., |
PNS | Cardiomyocytes with hypoxia-reoxygenation | Inhibit apoptosis and improve energy metabolism | Gong et al., |
|
NG | Rats of ischaemia-reperfusion (IR) | Cardioprotective effect | Yue et al., |
|
Ginsenoside Rg1, Rb1 | Myocardial infarction rats | Improved heart contractility | Deng et al., |
Summary of seven main functions of PNS in CAD.
Inflammation dominates in CAD and atherosclerosis. Immune cells gather in the early atherosclerotic lesions, where effector molecules promote the progress of inflammation which can induce acute coronary syndrome (ACS; Han,
Illustration of the mechanism of PNS on
First, NF-κB is critical for the trigger and development of atherosclerosis (Hopkins,
Second, oxidation is generally considered as a facilitator or a modulator of inflammatory signaling (Oliveira-Marques et al.,
PNS also are considered as free radical-scavengers with antioxidant properties. PNS could impede the development of atherosclerotic lesions through the antioxidant and anti-inflammatory effects (Aronoff et al.,
Treatment with Notoginsengnosides (NG) could decrease the ROS level in platelets (Shang et al.,
Lipoprotein disorder is one of the main risk factors of CAD. A meta-analysis of 14 randomized trials showed that a decrease of 1 mmol/L in plasma LDL levels generates a 20% reduction in major coronary events including coronary revascularization and stroke within 5 years (Baigent et al.,
PNS could markedly reduce TC, TG, and LDL-C (Zhang et al.,
Lipid metabolic disorder can be caused by inflammation and can exasperate the inflammation (Hotamisligil,
In conclusion, CAD is closely related to lipid metabolic disorders, specifically including increased TG, LDL-C, ox-LDL, and TC. PNS could depress the level of TC by elevating LXR alpha, ABCA1, and ABCG1 and reducing NF-κB. In addition, PNS can regulate lipid metabolism by inhibiting LPL and increasing FABP4 and CPT-1A. Furthermore, lipidosis is closely related to inflammation, which PNS have diverse effects on.
In CAD, antiplatelet therapy has become an important treatment according to several important guidelines (Chew et al.,
PNS inhibited platelet activation by multiple ingredients and pathways. PNS could decrease platelet activation, inhibit adhesion and aggregation of platelet, prevent thrombosis, and improve microcirculation (Wang et al.,
However, in PNS, notoginsenoside Ft1 as the potent procoagulant component induced platelet aggregation dose-dependently. The P2Y12 receptor serves as a crucial regulator of haemostasis and thrombosis on the platelet. When conditioned by ADP, the P2Y12 receptor activated a series of downstream events that result in platelet aggregation, shape change, dense granule secretion (Dorsam and Kunapuli,
Fibrinolysis is part of the coagulation cascade, which is adjusted by plasminogen activator (PA) and PA inhibitor (PAI-1). Abnormal fibrinolysis and high plasma concentrations of PAI-1 are related to an increased risk of CAD (McBane et al.,
Myocardial ischaemia can lead to widespread cell apoptosis (Ohno et al.,
PNS could protect myocardial cells from apoptosis induced by ischaemia both
The pathological proliferation of VSMCs is a crucial factor involved in the pathogenesis of atherosclerosis, associated with inflammation, apoptosis, and matrix alterations (Zakar and Ken,
Angiogenesis is the stimulation of the endothelium to shape new blood vessels, which is implicated in the pathophysiology of CAD (Tello-Montoliu et al.,
PNS could enhance angiogenesis and the proangiogenic effects including the VEGF-KDR/Flk-1 and PI3K-Akt-eNOS signaling pathways
Ft1 can stimulate angiogenesis. Ft1 led to proliferation, migration and tube formation in HUVECs by activation of the PI3K/Akt and ERK1/2 pathways in rat mesenteric arteries. This leads to the phosphorylation of eNOS and release of NO, which triggers soluble guanylyl cyclase in the VSMCs (Shen et al.,
Atherosclerosis is the pathological basis of CAD. Furthermore, the development of chronic atherosclerosis to form thrombosis is the pathogenesis of ACS (Mann et al.,
A high-fat diet together with Zymosan (Zym) induces atherogenesis in rats. PNS reduced the levels of TC, TG, LDL-C, IL-6, and C-reactive protein and increased the HDL-C level significantly in serum of atherosclerosis rabbits by inhibiting FAK phosphorylation, integrins expression and NF-κB translocation (Yuan et al.,
Ginsenoside Rd, isolated from PNS, is a voltage dependent Ca2+ channel blocker. Ginsenoside Rd decreased remarkably the size of atherosclerotic plaque and ox-LDL of macrophage in the apoE(−/−) rats.
PNS exerted a certain degree of improvement on myocardial ischaemia (Tang et al.,
The PPAR family, a series of transcription factors, regulates cardiac energy metabolism and impacts metabolism of cardiac fatty acid and glucose (Madrazo and Kelly,
In addition, salvianolic acids' compatibility with PNS could protect cardiomyocytes (Figure
In the past two decades, a breakthrough has been achieved in the pharmacology of PNS. The knowledge of PNS functions offers a new opportunity for the prevention and treatment of CAD. PNS has been observed to have multiple positive effects in the key processes of CAD, including anti-inflammation, the regulation of lipid metabolism and the coagulation system, anti-apoptosis, pro-angiogenesis, anti-atherosclerosis, and anti-myocardial ischaemia (Figure
PNS on the evolution of atherosclerotic plaque. In the evolution of atherosclerosis plaque, PNS has effects on the oxidation of LDL, the accumulation of lipoprotein, chemoattractant cytokines related to macrophages, modified lipoprotein particles, platelet aggregation, the migration of smooth muscle cells (SMCs), apoptosis of SMCs and the development of foam cells.
The function of PNS on platelet aggregation resembles aspirin. For the patients with aspirin resistance (Arachidonic acid inhibitory rate <50%) and clopidogrel resistance (Adenosine diphosphate inhibition rate <30%), Ticagreloran, an oral reversibly binding P2Y12 inhibitor, is commonly used alternative drug (Nylander and Schulz,
Statins as a main drug by many guidelines have shown good effects in the primary and secondary prevention of CAD (Harris et al.,
In addition, nitroglycerin is one of the oldest of cardiovascular drugs in clinics. Nitroglycerin exerts anti-ischemic effect mainly by expanding capacity vein, reducing preload and releasing coronary artery spasm. PNS could reduce myocardial ischemia and relieve angina pectoris. In clinic PNS has similar effects and different mechanisms with nitroglycerin. PNS was recommended when patients can't tolerate the side effects of nitroglycerin such as headache, dizziness, tachycardia. Patients with nitrate resistance were also recommended to administrate PNS.
Inflammation runs through the initiation, formation and onset of CAD. The widespread presence of inflammation generates the major feature of vulnerable plaques (Crea and Liuzzo,
Different with western medicines, TCM acts on several targets to play a variety of roles on the mechanisms of the disease. PNS has effects simultaneously on anti-inflammation, the regulation of lipid metabolism and the coagulation system, anti-apoptosis, pro-angiogenesis, anti-atherosclerosis, and anti-myocardial ischaemia. In the entire pathological process of CAD, at different pathological stages, PNS can effectively reduce the occurrence and the development of CAD. In several RCTs, PNS effectively reduce the end-point of CAD, greatly regulate the lipids, improve performance on the ECG and reduce the frequency and the duration of angina attacks. Thus, PNS is a potential agent against CAD.
Recently, the medical community has gradually assigned importance to the primary prevention of CAD with PNS due to their unique advantages. In primary prevention, PNS can regulate lipid metabolism and hypertension (Pan et al.,
Currently, increasing research is focusing on individual PNS. However, these studies are still rare compared to those on total PNS. Individual PNS could have contradictory functions, especially on platelets. Four main ginsenosides (Rg1, Re, NR1, and Rg2) that exist in PNS also showed anti-platelet and anticoagulation activity. Both Rg1 and Rg2 could significantly extend blood clotting time. However, notoginsenoside Ft1 was procoagulant and induced dose-dependent platelet aggregation. Therefore, PNS could be further separated in order to thoroughly investigate the function of
In addition, we need to further improve the drug purity and screen concentrations to reveal and enhance the medicinal value of PNS as an individual lipid-lowering drug or an antiplatelet agglutination drug. We have found some research that focuses on comparing PNS and aspirin or PNS and statins. The inhibitory effect of PNS on platelet activation was similar to aspirin, but the inhibitory effect of PNS on platelet adhesion to ECs was superior to aspirin (Wang M. M. et al.,
However, the medical technology and the related animal experiments and RCTs are limited. Moreover, only one 1-year RCT has reported the effect of PNS on the end-point of CAD. However, we hope that some multi-center, large-sample RCTs will provide high-level evidence for the effectiveness of PNS in CAD.
PNS have multiple positive effects in the key processes of CAD, including anti-inflammation, the regulation of lipid metabolism and the coagulation system, anti-apoptosis, pro-angiogenesis, anti-atherosclerosis, and anti-myocardial ischaemia. Long-term use of PNS can effectively reduce the end point of CAD and improve angina pectoris, ECG and lipid metabolism which illustrates that PNS is potential agent on CAD. However, more high-level RCTs are expected to provide evidence for the efficacy of PNS in CAD.
JW and LD designed the work of review; LD, XX, and JH reviewed the literature available on this topic and wrote the paper; XX, YL, and JL contributed in the scientific writing of the manuscript; JW and XX revised the manuscript.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
The authors apologize to colleagues whose work was not cited due to space limitations or our oversight.
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