Research progress of related signal pathways in the prevention and treatment of heart failure with traditional Chinese medicine

LIU Long-yan, LU Jian-qi, CHEN Wen-peng, HE Ye-hui, XIE Yan-ze, LIU Hui-yun

1.Guangxi University of Traditional Chinese Medicine, Nanning 530001, China

2.The First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine, Branch of National Clinical Research Center for Chinese Medicine Cardiology, Nanning 530023, China

Keywords:

ABSTRACT Heart failure ( HF) is a kind of continuous development syndrome of cardiac insufficiency caused by various heart diseases.Not only does the prevalence continue to rise, but the mortality rate and readmission rate remain high.Heart failure is also the end-stage of cardiovascular disease and the main cause of death of patients, which seriously affects the health and quality of life of people all over the world.Ventricular remodeling plays a key role in the occurrence and development of heart failure.Therefore, by improving ventricular remodeling, it is of important research value to explore the intervention of traditional Chinese medicine in the development of heart failure.Studies have shown that the mediation of multiple signaling pathways can lead to progressive aggravation of ventricular remodeling,and experimental studies often confirm the therapeutic effects of traditional Chinese medicine.Traditional Chinese medicine usually achieves the therapeutic effect of heart failure through multiple targets and multiple approaches.In recent years, there have been more and more researches on the role and mechanism of Chinese medicine intervention in heart failure.However, it is concluded that Chinese medicine intervention has less influence on heart failure signal pathways.This article summarizes the understanding of Chinese medicine on heart failure and the five signal pathways related to Chinese medicine intervention in heart failure.The 5 signaling pathways in the world, namely transforming growth factor-β1 ( TGF-β1)/signal transduction protein ( Smads) signaling pathway, Toll-like receptor ( TLR)/nuclear transcription factor-κB (NF-κB) inflammation signaling pathway, Renin-angiotensinaldosterone ( RAAS) system, phosphoinositide 3-kinase ( PI3K)-serine/threonine protein kinase ( AKT) signaling pathway and mitogen-activated protein kinase ( MAPK) dependent signaling pathway.

1.Introduction

Heart failure (Heart failure, HF) is a complex clinical syndrome,which is characterized by multiple causes or diseases that damage the structure or function of the heart, resulting in impaired ventricular contraction or (and) diastolic function.The clinical manifestations are mostly dyspnea, Fatigue and fluid retention.Usually, heart failure has many symptoms.It is the last stage of cardiovascular disease and the main cause of death.It seriously affects the health and quality of life of people all over the world.In recent years, the prevalence rate has continued to increase, and the mortality rate and readmission rate are still high[1,2].Currently,heart failure is considered to be a chronic spontaneous progressive disease.Activation of the neuroendocrine system and myocardial hypertrophy leading to ventricular remodeling are key factors in the development of heart failure.Cardiomyocytes, extracellular matrix, and non-cardiomyocytes (fibroblasts, smooth muscle cells and endothelial cells, etc.) undergo corresponding changes in the compensatory process of impaired cardiac function, cardiac cavity enlargement, and cardiac hypertrophy, that is, ventricular remodeling(also Called ventricular remodeling) is the basic pathological mechanism of the occurrence and development of heart failure.First,it can partially compensate the heart function.However, ventricular remodeling will gradually worsen, and heart function will gradually turn from compensatory to decompensated.In this process,significant heart failure symptoms appear[3,4].If specific or targeted treatment can be taken as soon as possible, it is likely to delay the progression of heart failure.

In recent years, Chinese medicine has made great progress in the occurrence, development and prevention of heart failure.However,the pathological mechanism of the occurrence and development of heart failure is very complicated.Traditional Chinese medicine plays an important role in the clinical treatment of heart failure based on its syndrome differentiation and treatment thinking, as well as the advantages of multiple components, multiple targets, and multiple pathways of traditional Chinese medicine[5,6].The good clinical diagnosis and treatment effect also proves the correctness of the theory of Chinese medicine.In recent years, there have been more and more studies on the role and mechanism of Chinese medicine intervention in heart failure, but it is concluded that Chinese medicine intervention has less influence on heart failure signaling pathways.This article reviews this issue to provide a theoretical basis for clinical diagnosis and treatment of heart failure.

2.Understanding of Heart Failure in Traditional Chinese Medicine

The term “heart failure” first appeared in the book “Pulse Meridian Spleen and Stomach Diseases” written by Wang Quanhe in the Western Jin Dynasty.The above performance is “the liver is weak and sinks,” and “heart failure” is a description of the pathogenesis.Heart failure is also called lack of heart yang or deficiency of heart qi.In mild clinical manifestations, fatigue and shortness of breath can be seen, and wheezing when moving, shortness of breath and palpitations; Limb syncope, faint and delirium.The name of heart failure does not appear in the “Huangdi Neijing”, but there are related symptoms and pathogenesis discussed.The book “Su Wen Ni Tiao Lun” records that “the husband can’t lie down, and those who lie down and breathe are the guests of water and gas.” It points out the symptoms of heart failure by drinking water and lingering on the heart.“Lingshu Benzang Pian” says that “the heart is small and the heart is safe, the evil spirit can hurt, and it is easy to be hurt.” The etiology and pathogenesis of heart failure are pointed out, that is, chronic heart palpitations, heart palsy, chest numbness,true heartache and other diseases.Causes qi and blood yin and yang deficiency, visceral dysfunction, heart failure, and heartache.Deficiency of yin and yang in the heart, blood flow, and blood stasis are the basic pathogenesis of heart failure.

Existing studies have shown that myocardial fibrosis is an important factor in cardiac remodeling, leading to the worsening and progression of heart failure, while ventricular remodeling is the basic pathological basis of heart failure, which runs through the course of heart failure.Myocardial fibrosis is mostly manifested as lack of righteousness and heart stasis.The initial stage is mainly due to deficiency of qi, and the method of strengthening the body and eliminating evil is the main method.Studies have shown that immune inflammatory response and inflammatory cell infiltration are involved in the development of heart failure, which is very similar to the traditional Chinese medicine “blood stagnation,water drinking phlegm and dampness”.Therefore, the use of traditional Chinese medicine to intervene in the progress of heart failure requires intervention in signal pathways related to heart failure.“Lingshu Tiannian”: “The heart qi begins to decline, if you are sad, and the blood qi is lazy, so you can lie down.” That is, its pathological basis is the deficiency of yang qi in the heart, and the central link is blood stasis.Heart failure belongs to the deficiency of the essence, the deficiency of qi and blood, the deficiency of yin and yang, the deficiency of blood, blood stasis, turbid phlegm, drinking water, and stagnation of qi are the signs of deficiency.Therefore,after weighing the urgency and debating the deficiency of the specimen, the prescription medication can be used to promote blood circulation and remove blood stasis throughout the treatment of heart failure, and can also be combined with the treatment of warming yang or warming yang to drink or replenishing yin.

3.Chinese medicine intervention in heart failurerelated signal pathways

3.1 TGFβ1/Smads signaling pathway

Transforming growth factor-β1 (TGF-β1) is an important cytokine involved in the fibrosis of lung, kidney, heart and other organs, guiding fibroblasts to differentiate into myofibroblasts.After TGF-β1 binds to its receptor, it phosphorylates and activates the Smads protein.After the signal is transmitted to the nucleus,it regulates the gene expression of related cytokines, increases the synthesis and deposition of collagen, and enhances the viability of fibroblasts, leading to tissue fibrosis or tissue remodeling.Smads protein is a downstream regulator of the TGF-β1 signaling pathway,and Smad2 and Smad3 play a key role in the process of myocardial remodeling.Myocardial fibrosis is one of the important pathological changes of heart failure, and the TGF-β/Smads signaling pathway is the main path of fibrosis[7-8].Studies have shown that through the TGF-β1/Smad pathway, cardiac fibrosis can be reduced, thereby delaying the progression of heart failure[9].

The results of Shi Binhao et al.[10] showed that Qidanlixin Pills can reduce the expression of CollagenⅠ and Ⅲ mRNA in the serum of rats with heart failure, and the expression of TGF-β1 and Smad3 proteins significantly decrease (P<0.05), the level of inhibitory protein Smad7 is significantly increased.It is suggested that Qidan Lixin Pill may regulate the expression of TGF-β1 and its downstream signal Smad3, increase the level of Smad7 protein,reduce the synthesis of pathological collagen, delay the progression of myocardial fibrosis, and interfere with chronic heart failure.The results of Gao Pengrong[11] and other studies showed that Qishen Granules can reduce the expression of TGF-β and Smad3 proteins,and HE staining shows that the morphology of cardiomyocytes is uniform and there are fewer inflammatory cells.Masson staining shows the myocardium The cells are arranged regularly, with a small amount of collagen fibers.It is suggested that Qishen granules can improve myocardial fibrosis in rats with heart failure after myocardial infarction, and the TGF-β/Smads signaling pathway plays a key role.Jiao Mei et al.[12] found that quercetin can reduce the expression levels of TGF-β1, Smad3, p-smad3, collagen I, and collagen III in the heart tissue of rats with heart failure,suggesting that quercetin It can reduce myocardial cell damage.The mechanism of action may be achieved by down-regulating the expression of TGF-β1, Smad3, and p-Smad3, and mediating the TGFβ1/Smad3 signaling pathway.The experimental results of Cheng Yanling et al.[13] showed that after administration of Shenfu Yixin Granules, the expression of TGF-β1 and Smad 3 proteins in myocardial tissues were reduced, the expression of miR-21 mRNA was low, and TGF- The mRNA expression of βR Ⅲ increased.The above results suggest that Shenfu Yixin Granules can reduce myocardial fibrosis in rats with heart failure, possibly by regulating Mir-21 to over-activate the TGF-β1/Smads signaling pathway.The experimental results of Qi Jing et al[14] showed that the expression of collagen I and collagen Ⅲ in the heart failure model group rats were significantly increased, and the expression of TGF-β1 protein in the tissues was significantly increased, and the phosphorylation of Smad3 was promoted (P<0.05); In the Shengmaisan group, the expression of collagen Ⅰ and collagen Ⅲ was low, the expression of TGF-β1 protein decreased, and the phosphorylation of Smad3 was inhibited.It suggests that Shengmai San can reduce down-regulation of TGF-β1 protein expression, reduce Smad3 levels, interfere with myocardial fibrosis in rats with heart failure, and improve heart function.

The TGF-β/Smads signaling pathway is a very important approach in the research process of intervening myocardial fibrosis in heart failure.The main research directions are Smad 2 and Smad 3, and other Smads family members are rarely involved.On the other hand, most of the initial studies are animal experiments, and clinical trials can be added on this basis.Traditional Chinese medicine has a significant effect in the treatment of myocardial fibrosis, providing a new direction for the diagnosis and treatment of heart failure.

3.2 Toll-like receptor (TLR)/nuclear transcription factor-κB(NF-κB) inflammation signaling pathway

The TLR/NF-κB signaling pathway includes TLR, myeloid differentiation factor 88 (MyD 88) and NF-κB.The overexpression of TLR is related to the occurrence and development of heart failure.TLR stimulates the innate immune response, specifically recognizes the specific structure shared by pathogens or their products, induces signal transduction into cells, triggers the Myd88 pathway, activates NF-κB, and promotes inflammation Cytokines (such as TNF-α,IL-1β, IL-6) are released.Under the negative inotropic action of inflammatory cytokines, cardiomyocyte apoptosis and myocardial fibroblast proliferation levels increase, which ultimately leads to myocardial remodeling and cardiac function damage.According to research, the TLR4 /NF-κB inflammatory signal pathway plays an important role in the occurrence and development of heart failure,which can reduce inflammation, significantly improve the heart function of rats with heart failure and delay the process of ventricular remodeling[15-18].It may be a new target for heart failure treatment.Feng Qingtao et al[19] selected a total of 124 patients with chronic heart failure as the research objects, used Shengui Yixin Decoction to treat patients with chronic heart failure (74 cases), and set up a control group (50 cases).Results:After taking Shengui Yixin Decoction for 4 weeks, compared with the control group, the total effective rate of the treatment group increased significantly, and the expression levels of TLR4, NF-κB, TNF-α, IL-6, IL-1β mRNA and protein decreased significantly (P<0.05); the rehospitalization rate and mortality of the treatment group decreased significantly.Shengui Yixin Decoction may reduce the inflammatory response of patients with heart failure by regulating the expression of TLR4 and NF-κB protein, improve heart function, and reduce the patient’s rehospitalization rate, fatality rate and number of rehospitalizations.Zhao Lulu et al[20] found after experiments that the serum levels of TNF-α and IL-6 in the model group increased, while IL-10 decreased, while the inflammatory factors TNF-α and IL-6 in the Lingguizhugan decoction group Low expression, high IL-10 expression, and the expression levels of TLR4, Myd88, and NFκB in heart tissue decreased significantly (P<0.05).It is suggested that Linggui Zhugan Decoction can reduce the expression levels of TLR4, Myd88 and NF-κB in heart tissues, reduce inflammatory reactions, and significantly improve heart function and ventricular remodeling in rats with heart failure.Tang Yanping[21] and other studies have shown that after the intervention of Wenyang Zhenshuai Granules, the TLR2 and NF-κB protein levels of the low, medium,and high dose experimental groups decreased significantly, and the high dose group was the most obvious.It is suggested that the cardiac insufficiency caused by adriamycin can be improved after the intervention of Wenyang Zhenshuai Granules, which may be related to the regulation of the expression of TLR2 and NF-κB protein.Huang Zheng[22] and other studies have shown that Qili Qiangxin Capsule can significantly reduce the expression levels of inflammatory factors TNF-α, IL-1β, IL-6, TLR4 and NF-κBp65 in heart failure rats.It can be seen that Qiliqiangxin Capsule can intervene in the process of heart failure, which may be related to the regulation of the expression of TLR4 and NF-κBp65.

3.3 Renin-Angiotensin-Aldosterone (RAAS) System

The renin-angiotensin-aldosterone (RAAS) system is the main component of cardiac neurohormonal signals and the basis of adaptive steady-state myocardial response.The RAAS system is an important neurohumoral mechanism that can regulate the metabolism of water and sodium, contract and dilate blood vessels,and stabilize blood pressure.When heart failure occurs, the RAAS system is over-activated, and cardiotoxic reactions occur.The heart produces fibrosis and aggravates ventricular remodeling[23-25].Existing studies have shown that inhibiting the activation of the RAAS system can improve heart function and ventricular remodeling, and this signaling pathway has become the mechanism of action for the treatment of heart failure[26-27].

The results of Li Qing et al.[28] showed that after the intervention of Fuzi Decoction, the PRA, AngⅡ, and ALD of the experimental group decreased.It is suggested that Fuzi Decoction can downregulate the activity of RAAS system and improve ventricular remodeling and cardiac function.Li Yan et al.[29] found that Qiliqiangxin Capsule can reduce the levels of PRA, AngⅡ and ALD in rats with heart failure, and down-regulate the expression levels of cardiac ACE and AT1R mRNA and protein (P<0.05).It is suggested that Qiliqiangxin Capsule can reduce the oxidative stress level of rats with heart failure, reduce the activity of cardiac RAAS,and significantly improve the heart function of rats with chronic heart failure.The results of Wu Jie et al.[30] showed that salidroside can significantly reduce PRA, AngⅡ and ALD in rats with heart failure (P<0.05), suggesting that salidroside can make the heart of rats with heart failure Function and ventricular remodeling have been improved, which may be related to the reduction of RAAS activation.Feng Jingyuan et al.[31] found that compared with the model group, the levels of PRA, AngⅡ and ALD in the serum of rats in the curcumin group were significantly reduced, and the expression of ACE and AT1R mRNA and protein in the myocardial tissue was low.It is suggested that in the RAAS system of rats with chronic heart failure, curcumin can improve the heart function of rats with chronic heart failure.Liu Jing et al.[32] found that after giving Liuwei Tongxin Granules, the levels of PRA, AngⅡ, and ALD in rats with heart failure increased significantly.This indicates that the RASS system is continuously activated in rats with heart failure,and Liuwei Tongxin Granules may delay ventricular remodeling by inhibiting the RAAS system.Hong Lili[33] and other studies have found that Zhenwu Decoction can increase serum Ang Ⅱ, ALD, NFκB, N-terminal brain natriuretic peptide (NT-proBNP), TNF-α,IL-6 levels and myocardial NF The decrease in the expression level of -κB protein inhibits the activation of the NF-κB pathway in the state of chronic heart failure, resulting in the activation of NTproBNP gene in an inactive state, improving ventricular remodeling,and slowing the further development of chronic heart failure.The results of Meng Tuo et al[34] showed that the serum NT-proBNP,PRA, AngⅡ, and ALD levels in the Yangxin Decoction group decreased, suggesting that Yangxin Decoction inhibits the activation of the RAAS system and can reduce heart failure in rats.

As one of the classic signaling pathways of heart failure, the RAAS system plays a key role in the occurrence and development of heart failure.There are many ways for Chinese medicine to intervene in heart failure, and the RAAS system is still worthy of in-depth study.

3.4 PI3K-Akt signal path

PI3K (phosphoinositide 3-kinase) is a lipid kinase with many important biological activities.It promotes its downstream serine/threonine protein kinase (AKT) and mammalian target of rapamycin(mTOR) by activating Cell proliferation and survival.AKT is the target of downstream phosphatidylinositol 3 kinase (PI3K)[35,36].After PI3K binds to AKT, AKT is transferred from the cytoplasm to the cell membrane to activate AKT.Activated AKT sequentially regulates various downstream targets to promote nutrient absorption,metabolism, cell growth and proliferation.Studies have found that in the process of inhibiting cardiomyocyte apoptosis and ventricular remodeling, the PI3K-Akt signaling pathway plays a vital role in protecting the heart function[37,38].

The experimental results of Xue Yitao et al.[39] showed that compared with the model group, the positive expression of p-PI3K and p-Akt in the cardiomyocytes of the Fuxin Decoction group was significantly reduced, and the expression of GSK-3β increased.It is suggested that Fuxin Decoction can regulate the expression of PI3KAKT-GSK3β pathway protein in rat cardiomyocytes and delay myocardial remodeling.Zheng Wei[40] and other experiments found that after the intervention of salidroside, the levels of ColI, Profilin-1 protein and mRNA in rat myocardial tissue were significantly reduced, and p-PI3K /PI3K, p-AKT The contents of /AKT and p-GSK3β/AKT were significantly lower than those of the model group.Salidroside reduces the protein levels of ColI and Profilin-1 in the myocardial tissue of rats with heart failure after AMI,reduces the phosphorylation of proteins in the PI3K/AKT/GSK3β pathway, and reduces myocardial fibrosis.The experimental results of Qi Yuehan et al.[41] showed that the relative expression of BAX gene mRNA in the myocardial tissue of the control group was significantly increased, and BCL2 was down-regulated, consistent with protein expression, and significantly increased the levels of PI3K and p-AKT.In the high-dose Guanxinning group, the protein expression of PI3K and p-AKT and the mRNA expression of BAX were significantly reduced in myocardial tissue.It is suggested that Guanxinning tablets can improve the heart function of mice with chronic heart failure and increase the survival rate of mice with chronic heart failure.Its mechanism of action is related to downregulation of PI3K expression level and AKT phosphorylation level, which reduces the apoptosis of cardiomyocytes.The results of Feng Qingtao et al.[42] showed that the expression of Bax and caspase-3 mRNA and protein in the myocardial tissue of the Buyiqiangxin tablet group was significantly down-regulated, and the expression of Bcl-2 mRNA and protein, p-PI3K/PI3K, and p-Akt/Akt were significantly down-regulated.Increase (P<0.05, P<0.01).Buyiqiangxin tablets increase the ratios of p-PI3K/PI3K and p-Akt/Akt, suggesting that after PI3K-Akt signaling pathway is activated,it reduces cardiomyocyte apoptosis and the expression of Bax and caspase-3, and increases the expression of Bcl-2, Play a role in protecting the myocardium.Yang Jiahao et al.[43] found that after the intervention of Wenyang Xiaoyin Recipe, the expression of p-PI3K,p-Akt, Bcl-2 protein and Bcl-2/Bax value in the experimental group of rats’ myocardial tissues were all Increased, the protein expression of Bax and Caspase-8 decreased (P<0.05, P<0.01).It is suggested that the PI3K-Akt signaling pathway regulates its downstream related apoptosis factors, and Wenyang Xiaoyin Prescription may up-regulate the PI3K-Akt signaling pathway, regulate the expression of the PI3K-Akt signaling pathway, affect the expression of related apoptotic proteins, and reduce cell apoptosis, Improve heart function,prevent and regulate myocardial damage.

3.5 Mitogen-activated protein kinase (MAPK) dependent signaling pathway

Mitogen-activated protein kinases (MAPKs) are serine/threonine protein kinases, which are involved in a variety of pathological processes in most cells, such as cell proliferation, apoptosis,inflammation and immune response.The MAPK signal transduction pathway mainly includes three subfamilies: P38 kinase, c-Jun amino-terminal kinase (c-JunNH2-terminaiprotrinkinase, JNK) and extracellular signal-regulated kinase (extracellular signal-regulated enzyme ERR).When cells are stimulated or destroyed by external,these three signal pathways can work independently, or they can be cross-linked with each other[44-46].Studies have shown that the MAPK signaling pathway is involved in the process of myocardial remodeling, and is also the final pathway for cardiomyocyte hypertrophy and the transition from contractile to synthetic [47-48].The results of Meng Hui et al.[49] showed that Baoyuan Decoctionreduced serum ANP, BNP and AngⅡ levels, and down-regulated the expression levels of ACE1 and AT1 in ischemic myocardial tissue.At the same time, the expression levels of phosphorylated P38 mitogen-activated protein kinase (P38 MAPK), TGF-β and Smad3 downstream of the AT1 receptor decreased, while the expression level of ACE2 increased.Cell experiment results showed that Baoyuan Decoction could inhibit the activation of AT1 and its downstream P38 MAPK in cardiomyocytes induced by AngⅡ, and the expression levels of TGF-β and Smad3 proteins were significantly reduced.Baoyuan Decoction can effectively inhibit the degree of fibrosis in the ischemic area after myocardial infarction and delay the progression of heart failure.This may be related to the regulation of AT1/P38 MAPK/TGF-β pathway by Baoyuan Decoction.The experimental results of Chai Songbo et al.[50] showed that the cardiomyocyte apoptosis rate, LC3-II positive rate, p-ERK, p-p38 MAPK, LC3-Ⅱ / LC3-I and beclin-1 protein levels in the Xinshuaikang group Decreased, and the expression of p62 protein increased (P<0.05).It shows that Xinshuaikang can reduce the expression of MAPK/ERK1/2 protein, reduce the level of myocardial autophagy, reduce the damage of myocardial tissue, and protect the myocardium.The results of Sun Tao et al.[51]showed that compared with the model group, the Yixintai group had a higher expression of β-arrestin protein and a lower level of p-p38MAPK protein.It is suggested that Yixintai interferes with the process of ventricular remodeling to a certain extent, possibly by regulating the expression of β-arrestin and p-p38MAPK protein in cardiomyocytes.Gao Ruimin et al.[52] showed that after the intervention of panax notoginseng saponins, compared with the model group, the experimental group had more complete myocardial tissue structure, reduced myocardial cell hypertrophy,and loosened myocardial fiber arrangement.The apoptotic rate of cardiomyocytes decreased significantly, the expression levels of p-ERK, p-JNK and p-p38 proteins in myocardial tissue were significantly decreased (P<0.05), and the levels of serum TNF-α and IL-6 were significantly decreased (P<0.05).It is suggested that panax notoginseng saponins can reduce the expression levels of p-ERK, p-JNK and p-p38 proteins in myocardial tissue, reduce the secretion of serum inflammatory factors, and improve heart function.A summary of the relevant signal pathways and detection indicators for the prevention and treatment of heart failure by Chinese medicine is shown in Table 1.

Tab 1 Relevant signal pathways and detection indicators for the prevention and treatment of heart failure by Chinese medicine

4.Summary and outlook

In summary, Chinese medicine can effectively regulate many aspects related to heart failure and involve multiple signal transduction pathways, such as TGFβ1/Smads, TLR, RAAS,MAPK, PI3K-Akt, etc., thereby inhibiting ventricular remodeling and protecting the myocardium.Cells, delay the progression of heart failure.In recent years, the clinical treatment of heart failure has made some positive progress.Traditional Chinese medicine has unique advantages in the prevention and treatment of heart failure.Its diagnosis and treatment uses a variety of classics and proven prescriptions, taking into account the specimens, and improving heart function, symptom relief, and disease progression.It has outstanding advantages in terms of delay and improvement of prognosis.

At present, most of the researches on the prevention and treatment of heart failure with traditional Chinese medicine are carried out in China.The scale of clinical trials is small and longterm clinical monitoring is lacking.Most clinical studies mainly describe the effectiveness of traditional Chinese medicines, and have not yet compared with the drugs commonly used in clinical practice.Therefore, further research on the mechanism of action of traditional Chinese medicine in the treatment of heart failure is of great significance to provide a reliable basis for the application of traditional Chinese medicine, and to better expand the scope of the dominant diseases of traditional Chinese medicine.

Author’s contribution:

Liu Longyan: Literature collation and analysis, article writing; Lu Jianqi: Project (National Natural Science Foundation of China),responsible for reviewing articles; Chen Wenpeng: Participate in literature collation and analysis; He Yehui, Xie Yanze, Liu Huiyun:Participate in literature Collect and organize.

All Authors Declare no conflict of interest.