Coronary
heart disease (CHD) is the UK's biggest killer. Although western medicine has
achieved a lot progress in treating CHD, it is still causing around 82,000
deaths each year. About one in five men and one in eight women die
from the disease. In traditional Chinese medicine many herbal remedies have
showed a good effect on treating angina. Many laboratory studies have been done
to investigate the mechanism of treating myocardial ischemia (MI). I published
a research review on this topic many years ago (Tang, T. 2003). Many progressive
new reports have been published in the last 5 years. For a clinical
practitioner these research updates will provide a helpful reference in
treatment of CHD. For researchers and students it can provide a useful reference
for future research projects. As for the general public, it has displayed some scientific
evidence for Chinese herbs in treating ischemic heart disease.
1. Research on
individual herb and plant monomer
Danshen (Salvia miltiorrhiza) is
a very commonly used traditional Chinese herb in treating heart disease. It
contains many sub fractions, which are mainly TanshinoneⅠ, ⅡA, ⅡB, Salvianolic
acid A (SAA), and Salvianolic acid B (SAB). In an in vivo study, rat MI model was induced by
permanent left anterior descending coronary artery ligation. The results showed
Tanshinone IIA attenuates the MI pathological changes and improves heart
function, and reduces expression of MCP-1, TGF-β1 and macrophage infiltration. It could
also decrease the expression of TNF-α and activation of nuclear transcription
factor-kappa B (Z.H.Ren, 2010). Researchers applied a myocardial infarct rats model. The rats were given different concentrations of SAA. Immunohistological analysis was performed
to measure vascular endothelial growth factor and vascular endothelial growth
factor receptor-2 expressions. The secretion of matrix metalloproteinase type X
was evaluated in serum of post-ischemic rats. The result showed SAA potentiated
the ischemia induced neovascularization. These findings show that SAA has potent
proangiogenic properties by promoting the expression of proangiogenic factors (Yujuan
Li, 2014). Another study shows SAB also can
markedly and dose-dependently reduce fibrinogen and malonaldehyde levels,
increase the HDL level, improve blood viscosity and plasma viscosity in MI
rabbits (Qian Yang, 2010). A study applied an RT-PCR and Western blot method to detect p38 MAPK gene expression. The result suggests that Tanshinone
IIA play a role in protection cardiomyocytes from ischemic and hypoxic injury.
The effect is based on inhibiting miR-1 expression through p38 MAPK signal
pathway (Zhang, Y. 2010).
Asperosaponin VI is a saponin from Chinese herb Xuduan (Dipsacus asper). A study investigated the anti-MI
effects of Asperosaponin VI both in vivo and in vitro. The
results suggested that it could provide significant cardioprotective effects
against acute MI in rats. These mechanisms might be attributed to scavenging
lipid peroxidation products and reactive oxygen species, increasing antioxidant
defence enzymes and preventing mitochondrial damage (Chunmei Li, 2010).
Angelica sinensis polysaccharides are an active ingredient extracted
from Danggui (Angelica sinensis). The cardioprotective
effects were evaluated by using MI/reperfusion rats. A.sinensis polysaccharides
treatment significantly reduced myocardial infarction size, enhanced CT-1 and
antioxidant enzymes activity, down regulated caspase-12 mRNA expression in rats
(Song Zhang, 2010).
Juemingzi
(Semen Cassiae) was proved to
reduce blood lipid levels. A study investigated
whether it can reduce MI and
reperfusion injury. The results showed
Juemingzi extract can not only significantly reduce the plasma lipid level, but it can
also improve
the instantaneous first derivation of left ventricle pressure and reduce
infarct size (Feng Fu, 2014).
Gegen (Lobed Kudzuvine Root) has been widely used in the treatment of myocardial and
cerebral ischemia. Puerarin is a major active ingredient extracted from Gegen.
A study was designed to observe the effects of puerarin on the signalling
transmission mediated by P2X3 receptor in stellate ganglia and cervical
dorsal root ganglia after MI damage. The results suggested that Puerarin could
reduce systolic blood pressure and heart rate, relieved pain and decreased
up-regulated expression of P2X3 mRNA and protein after MI. Puerarin
was shown to inhibit the up-regulated ATP-activated currents after MI. This suggested
that puerarin can relieve MI through blocking the P2X3 signalling
transmission (Shuangmei Liu, 2014).
Rougui (Cinnamomum cassia) is widely used for the
treatment of ischemic heart disease. The active components, cinnamic aldehyde and
cinnamic acid, can be isolated from Rougui. A study has investigated the effects of anti MI of
Cinnamic aldehyde and cinnamic acid. The results showed these two extracts can
decrease the ST elevation induced by acute MI, decreased serum levels of CK-MB,
LDH, TNF-α and IL-6, and increased serum NO activity, increased SOD activity
and decreased MDA content in myocardial tissue (Fan Song,2013).
Shanzha
(hawthorn)
is commonly used Chinese medicine. A study was designed to investigate the
effects and mechanisms of hawthorn leaf flavonoids on acute MI/reperfusion in
anesthetized dogs. The results indicated that this flavonoid
can significantly decrease the degree and scope of MI, markedly inhibit
the increase of myeloperoxidase activity, and IL-1 and TNF-α content induced by
MI/infarction. It can also increase G protein-coupled receptor
kinase 2 expression and inhibited NF-κB expression (Jianhua Fu, 2013).
Tetramethylpyrazine,
sodium ferulate and puerarin are extracts from Chinese herbs Chuangxiong, Danggui and Gegen respectively.
Some research has shown that these three extracts can antagonize the
nociceptive or pain transmission mediated by P2X3 and/or P2X2/3 receptors
in primary afferent neurons. They could therefore be considered as new methods
for treating MI injury and cardiac arrhythmia (Shangdong
Liang, 2010).
Dracocephalum
moldavica L is an extract from Chinese herb
Xiang Qing Lan. A study evaluates
antioxidative and cardioprotective effects of total flavonoids extracted from Xiang Qing Lan. It
showed remarkable scavenging effects against 1, 1-diphenyl-2-picrylhydrazyl,
hydroxyl and superoxide anion radicals in vitro. It can improve the heart rate and coronary flow, raise left
ventricular developed pressure and decrease creatine kinase, lactate
dehydrogenase levels in coronary flow. It can also reduce the infarct size in
ischemic area of heart. (Jiangtao Jian, 2014).
2.
Research on compound formulas
Apart from individual
herb and plant monomers, some studies have focused on compound formulas. Many traditional and modern formulas have been
shown to be effective in treating MI.
Compound
Danshen Tablets (CDT) are formulated from a compound remedy. The
ingredients are Danshen, Sanqi,
and Borneol. A study investigated therapeutic mechanisms of CDT
by using a metabolomic approach. Plasma extracts from sham, MI model, CDT and
western medicines were used in treating rats. Plasma was analyzed by
ultra-performance liquid chromatography/quadruple. The orthogonal partial least
square model was built, and found that metabolites were expressed in
significantly different amounts between MI and sham groups of rats. The results
showed that CDT presented protective effects on MI by reversing potential
biomarkers to sham levels, especially for the four metabolites in the pathway
of purine metabolism. (Yonghai Lv,
2010).
Tanshinone IIA, SAB and ginsenoside Rb1 are the three major
active ingredients of CDT. A report has found that the combination of these
three ingredients brings nearly equal therapeutic effects on MI as CDT and it
plays more stable regulated action on those 22 identified metabolites than
single compound (Yonghai Lu, 2011). Another report uses an in vivo myocardial infarction model mice; endothelial nitric
oxide syntheses (eNOS)/nitric oxide (NO) pathway were detected. The results
showed that both Tanshinone IIA and
salvianolic acid B have cardio protective function in certain levels through
multiple targets related with NO production, such as eNOS phosphorylation,
L-arginine uptake (Chunshui Pan, 2011).
Another study applied an ischemia-reperfusion injury
rat model to examine coronary blood flow, vascular diameter, velocity of red
blood cells, and albumin leakage in vivo after reperfusion. The result showed
pre-treatment with CPT significantly attenuated myocardial microcirculatory
disturbance, including decreased coronary blood flow and red blood cell
velocity in arterioles, increased expression of CD18 on neutrophils and
intercellular adhesion molecule 1 on endothelial cells, and albumin leakage
from venules. It was also shown that it could significantly ameliorate the
myocardial damage and apoptosis, inhibitor-κBα degradation, and expression of
Bcl-2, Bax, and caspase-3 in myocardial tissues (Na Zhao,
2010). A metabonomic study was conducted to
assess the effect of Danshen, Sanqi and their compound formula for myocardial infarction in
rats. As a result, the compound was
shown to exert synergistic therapeutic efficacies to exhibit a better effect on
MI when compared to singular herbs (Xiaoping Liang, 2011).
Gualou Xiebai Tang is composed of Gualou (fructus
trichosanthis)
and Xiebai (macrostem onion). It was first recorded
in JinGui YaoLue, and is one of the main formulae to treat chest pain, used
since the Han Dynasty (A.D 206). A study aimed to investigate the effect of Gualou Xiebai Tang ethanol extract on
myocardial fibrosis.
The
mRNA levels of Collagen I and Collagen III were detected by real-time PCR. The results showed that Gualou Xiebai Tang could significantly reduce
the heart weight/body weight ratio as well as the left ventricle weight/body
weight ratio. It also significantly alleviated the degree of inflammation,
decreased myocardial collagen volume fraction, and markedly prevented the up-regulations
of Collagen I and Collagen III, down
regulated
expressions of TGF-β1, TGFβRI, TGFβRII in the rats with myocardial fibrosis (Yongfang
Ding, 2013).
Buyang
Huanwu Tang is a commonly used formula to treat ischemic heart disease. A study
investigated the potential mechanism of this formula in alleviating MI in rats.
The expression of the cluster of differentiation 40 (CD40) in the mononuclear
cells was measured using flow cytometry, and the expressions of CD40 and its
ligand (CD40L) in myocardial tissues were determined by western blotting. The
results showed that Buyang Huanwu Tang could decrease the expression of CD40 in
the mononuclear cells and the CD40 and CD40L expressions in myocardial tissues
(Yu Liu, 2011).
Sini Tang
is has been used to treat MI for many years. A lot of research has been done in
the past two decades. A recent study applied a urinary metabonomic method based
on nuclear magnetic resonance and ultra high-performance liquid chromatography
coupled to mass spectrometry in order to characterize MI related metabolic
profiles and delineate the effect of Sini
Tang on MI. Nineteen potential biomarkers in rat urine were
screened out, primarily related to myocardial energy metabolism, including the
glycolysis, citrate cycle, amino acid metabolism, purine metabolism and
pyrimidine metabolism. The results demonstrated that Sini Tang could provide satisfactory effect on
MI through partially regulating the perturbed myocardial energy metabolism (Guangguo Tan, 2012).
Guanxin II is a relatively new formula, currently used
to treat coronary heart disease. It contains 5 traditional herbs. Akt is a key
protein kinase in the processes of inhibition of apoptosis in cardiomyocytes. The
results of a study found that Guanxin II can significantly activate Akt kinase,
increase the Bcl-2/Bax ratio, inhibit cytochrome c release, reduced caspase-9
activation, and attenuated subsequent caspase-3 activation. These results therefore
suggest that Guanxin II ensures the survival of myocardium by enhancing the
Akt-mediated antiapoptosis pathway (Xi Huang, 2010).
Shen-fu injection is a modern formulation composed by Renshen (Ginseng) and Fuzi (Aconite). A study found that this formula can significantly decrease infarct size, apoptosis, caspase-3 protein expression in myocardial tissues, and increase p-Akt, p-eNOS, bcl-2 protein expression, compared to the control group (Yang Wu, 2011).
In this field a large number of reports have been published within the past 5 years. I have included some of the major ones here. From this review we can sum up a number of points. Firstly, research methods have been updated. A large number of studies have applied the latest biomedical techniques, such as metabolomics, apoptosis, cellular signal transduction etc. These new molecular biology techniques have been widely applied in the research of Chinese herbs. Secondly, Danshen and its sub fractions have become a hot point in this field. There have been approximately 4000-5000 reports conducted annually within the past 3 years. Thirdly, most reports are conducted as laboratory research, and relatively few are clinical reports. Finally, although all the papers are published on formal academic journals, there is still an unfortunate lack of papers from the core journals. As there is a lot of research in Chinese medicine still to be done, I believe there will be much progress in the future of this field.
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