logo

Oxidative Medicine and Cellular Longevity

PDF
Oxidative Medicine and Cellular Longevity / 2019 / Article
Special Issue

Redox Control of Vascular Biology

View this Special Issue

Review Article | Open Access

Volume 2019 |Article ID 3231424 | https://doi.org/10.1155/2019/3231424

Xinyu Yang, Tianmai He, Songjie Han, Xiaoyu Zhang, Yang Sun, Yanwei Xing, Hongcai Shang, "The Role of Traditional Chinese Medicine in the Regulation of Oxidative Stress in Treating Coronary Heart Disease", Oxidative Medicine and Cellular Longevity, vol. 2019, Article ID 3231424, 13 pages, 2019. https://doi.org/10.1155/2019/3231424

The Role of Traditional Chinese Medicine in the Regulation of Oxidative Stress in Treating Coronary Heart Disease

Xinyu Yang,1,2 Tianmai He,1 Songjie Han,1 Xiaoyu Zhang,1 Yang Sun,1 Yanwei Xing ,2 and Hongcai Shang 1

1Key Laboratory of Chinese Internal Medicine of the Ministry of Education, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, China

2Guang An Men Hospital, Chinese Academy of Chinese Medical Sciences, Beijing, China

Academic Editor: Mithun Sinha
Received24 Nov 2018
Revised19 Jan 2019
Accepted04 Feb 2019
Published24 Feb 2019

Abstract

Oxidative stress has been closely related with coronary artery disease. In coronary heart disease (CHD), an excess of reactive oxygen species (ROS) production generates endothelial cell and smooth muscle functional disorders, leading to a disequilibrium between the antioxidant capacity and prooxidants. ROS also leads to inflammatory signal activation and mitochondria-mediated apoptosis, which can promote and increase the occurrence and development of CHD. There are several kinds of antioxidative and small molecular systems of antioxidants, such as β-carotene, ascorbic acid, α-tocopherol, and reduced glutathione (GSH). Studies have shown that antioxidant treatment was effective and decreased the risk of CHD, but the effect of the treatment varies greatly. Traditional Chinese medicine (TCM) has been utilized for thousands of years in China and is becoming increasingly popular all over the world, especially for the treatments of cardiovascular diseases. This review will concentrate on the evidence of the action mechanism of TCM in preventing CHD by modulating oxidative stress-related signaling pathways.

1. Introduction

Coronary heart disease (CHD) is one of the primary reasons of death in the world, with 7.4 million deaths in 2013, being responsible for one-third of all deaths [1–3]. By 2020, it is forecasted that CHD will continue to be the prime and most prevalent threat to human life [4]. CHD is multifactorial and concerns intricate interactions between physiological, genetic, and lifestyle factors [5]. In past studies, traditional risk factors of CHD like diabetes, hypertension, smoking, and hyperlipidemia are linked with oxidative stress [6–8]. However, a number of studies have also associated oxidative stress with the mechanism of coronary atherosclerosis and have assessed the markers of oxidative stress, indicating that they can predict the occurrence of CHD [9]. Therefore, oxidative stress is one of the risk factors of CHD, which can affect the prognosis and reduce the survival time and quality of life of patients with CHD [10, 11].

Oxidative stress has been closely related with the mechanism of atherosclerosis and coronary artery disease. Oxidative stress may take place when the antioxidant ability is insufficient to decrease reactive oxygen species (ROS) and other free radicals. When oxidative stress occurs, ROS may generate oxidative modification or lipid peroxidation damage at the deoxyribonucleic acid (DNA) level and protein level with harmful consequences for the structure and function of the vascular system [12, 13]. In CHD, microvascular pathology revealed a higher level of ROS. The production of excess ROS generates endothelial cells and smooth muscle functional disorder, leading to a disequilibrium between the antioxidant capacity and prooxidants, thus leading to inflammatory signal activation and mitochondria-mediated apoptosis, which can promote and increase the occurrence and development of CHD [14, 15].

There are several types of vital antioxidative systems, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX). There are also numerous crucial small molecular antioxidants such as β-carotene, ascorbic acid, α-tocopherol, and reduced glutathione (GSH) [16]. Studies have shown that antioxidant treatment was effective and decreased the risk of CHD [17]. Oxidative status records for a particular patient are generally inadequate, and specific antioxidants suitable for that patient are rarely prescribed [18] which influences treatment effectiveness. However, traditional Chinese medicine (TCM) has been utilized for thousands of years in China and is becoming increasingly popular all over the world, especially for the treatment of cardiovascular diseases [19]. Modern pharmacological research has indicated that many Chinese herbal extracts protect the development of cardiovascular diseases through their antioxidating effects [20–22]. A schematic diagram of the mechanisms of ROS is demonstrated in Figure 1. This review will concentrate on the current evidence of the action mechanism of TCM in preventing CHD by modulating oxidative stress-related signaling pathways.


Figure 1 
The mechanism of TCM in preventing CHD by oxidative stress-related signaling pathways. HJT: Hongjingtian injection; mTOR: mammalian target of rapamycin; LC-3B: light chain 3B; NADPH: nicotinamide adenine dinucleotide phosphate; GSSG: glutathione disulfide; GSH: glutathione; SOD: superoxide dismutase; PI3K: phosphoinositide 3-kinase; Akt: serine/threonine kinase; Nrf2: nuclear factor erythroid-2-related factor 2; AMPK: adenosine monophosphate-activated protein kinase; PUN: punicalagin; DSS: Danshensu; OP-D: Ophiopogonin D; TXL: Tongxinluo; TNF-α: tumor necrosis factor-α; IL-6: interleukin-6; NF-κB: nuclear factor-κB; IL-10: interleukin-10; CRP: C-reaction protein; DG: Dunye Guanxinning; TMYX: Tongmai Yangxin pill; DSY: Dan-Shen-Yin; OSR: oxysophoridine; QSYQ: Qi-shen-yi-qi; XO: xanthine oxidase; NOX: NADPH oxidase; eNOS: endothelial nitric oxide synthase; CP: cardiotonic pill; SXSM: Shenxian-shengmai; SMS: Shengmai San; Bcl-2: B-cell lymphoma-2; Bax: Bcl-2-associated protein X; YQFM: YiQiFuMai powder injection; SAL: salvianolic acid; TAN: tanshinone; GXT: Guanxintai; BXT: Bao-Xin-Tang; G. acuta: Gentianella acuta.

2. Protective Effects of Traditional Chinese Medicine (TCM) and Its Constituent Compounds on Coronary Heart Disease

2.1. Myocardial Infarction (MI)

MI is considered as one of the most common forms of ischemic heart disease and is one of the main reasons of death worldwide. A growing body of evidence has indicated that ROS can lead to cell loss following MI and is closely related to the generation of MI [23]. ROS reduction may represent a vital therapeutic target for relieving the damage caused by a MI. Therefore, targeting the production of ROS with all kinds of antioxidants has been shown to decrease oxidative stress-related injury and therefore improve MI status.

2.1.1. The Bioactive Ingredients of Traditional Chinese Medicine

Salvia miltiorrhiza: Salvia miltiorrhiza, a famous Chinese herb medicine, has been widely used in treating cardiovascular diseases [24]. Studies showed that it could relieve small artery circulation, decrease ROS production [25–27], restrain cell apoptosis [27–29], and protect the heart against ischemia-reperfusion injury [30–32]. Salvianolic acid (SAL, C36H30O16; C26H22O10) and tanshinone (TAN, C18H12O3; C19H18O3), hydrophilic and lipophilic compounds, are extracted from Salvia miltiorrhiza [33]. Wang et al. [34] studied the use of the MI models to evaluate the cardioprotective functions of SAL and TAN in rats. Both echocardiographic and infarct sizes were assessed after surgery, while gene activity was detected by microarray analysis and validated by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR). These results depicted that SAL is possibly mediated by the downregulation of factors participating in oxidative stress and apoptosis, while TAN is probably mediated by the suppression of intracellular calcium and cell adhesion pathways in the MI.

Danshensu (DSS, C9H10O5), the main water-soluble ingredient of Salvia miltiorrhiza, has also been studied as a significant compound. In a study [35], DSS was detected in an ischemia-reperfusion (I/R) model to research its cardioprotective function. The results showed that DSS significantly reduced the level of creatine kinase and lactate dehydrogenase and that DSS had ROS scavenging activity and enhanced endogenous antioxidants such as SOD, CAT, malondialdehyde (MDA), GSH-PX, and heme oxygenase-1 (HO-1) activities through stimulation of the nuclear factor erythroid-2-related factor 2 (Nrf2) signaling pathway which was regulated by serine/threonine kinase (Akt) and extracellular signaling-regulated kinase 1/2 (ERK1/2) signaling pathway in a western blot analysis. The mechanism might be associated with the improvement of the antioxidant defense system by stimulating Akt/ERK1/2/Nrf2 signaling pathways [36, 37].

Astragalin: astragalin (C21H20O11) is a flavonoid that is extracted from the leaves of Rosa agrestis, persimmon, or green tea seeds. A large number of studies have indicated that astragalin has wide pharmacological activities, covering anti-inflammatory, antioxidative, and other beneficial activities [38–40]. A study [41] that assessed the cardioprotective functions of astragalin against I/R injury in the rat heart by Langendorff apparatus has been conducted. The results revealed that astragalin pretreatment ameliorated myocardial function. SOD activity and the glutathione/glutathione disulfide (GSH/GSSG) ratio were dramatically enhanced, and the levels of MDA, tumor necrosis factor-α (TNF-α), intracellular ROS, and interleukin-6 (IL-6) were reduced in the astragalin-treated groups. Thus, astragalin displayed cardioprotective functions through its antiapoptotic, antioxidative, and anti-inflammatory activities [41–43].

Ophiopogonin D (OP-D): OP-D (C44H70O16) is a significantly valid monomeric ingredient used in the Shenmai injection (SM-I). It is reported that it has a wide range of biological activities, including antiapoptotic effects, antioxidant, and anti-inflammatory actions [44–47]. The rat model of myocardial ischemia-reperfusion (MI/R) damage was produced by ligation of the left anterior descending coronary artery to study the protective actions and underlying mechanisms of OP-D and SM-I [48]. The study found that OP-D and SM-I act by inducing cardioprotection on MI/R injury by regulating cardiac function, reducing acetate dehydrogenase and creatine kinase (CK) generation, decreasing infarct size, and improving the injured cardiac structures. Cardioprotection by OP-D and SM-I was mediated by activating the phosphoinositide 3-kinase (PI3K)/Akt/endothelial nitric oxide synthase (eNOS) signaling pathway and suppressing the nuclear factor-κB (NF-κB) signaling pathway [49, 50].

Curcumin: curcumin (C21H20O6), used both as a seasoning and a traditional medicine, is a natural compound derived from the roots of Curcuma longa L. It has various pharmacological activities such as anti-inflammatory, antioxidant, and anticarcinogenic activities in different models [51–53]. In a study [54], the possible protective function of curcumin on cardiac function in MI/R rats was researched. The rats suffered from myocardial injuries through ligation of the left anterior descending coronary artery. Afterwards, lipid peroxidation products and antioxidant enzymes were evaluated in the myocardial tissue. The result showed that curcumin might decrease the venture of coronary heart disease via activating the JAK2/STAT3 signal pathway, reducing oxidative damage and suppressing myocardium apoptosis [55–57].

Punicalagin (PUN): PUN (C48H28O30), a main bioactive constituent in pomegranate juice, has been tested for neuroprotective functions against cerebral ischemia-reperfusion (I/R) injury by antioxidative mechanisms [58, 59]. Another study [60] investigated if PUN offers cardioprotective effects against MI/R damage and the potential mechanisms. MI/R was achieved by ligating the left anterior descending coronary artery. PUN acts by ameliorating cardiac function and infarct size, decreasing serum creatine kinase-MB (CK-MB) and lactate dehydrogenase, and inhibiting myocardial apoptosis against MI/R damage. These results showed that PUN protects against I/R-induced ROS and myocardial damage by activating adenosine monophosphate-activated protein kinase (AMPK) [60, 61].

Barbaloin (BAR): BAR (C21H22O9) is the major medicinal ingredient of Aloe vera belonging to the liliaceous plant group that has good antioxidant properties [62]. Zhang et al. [63] investigated if BAR offers cardioprotection in the MI myocardial damage. BAR was intragastrically administrated to rats before MI operation. The result showed that BAR pretreatment efficiently suppressed I/R-induced ROS and inflammatory effects by activating AMPK signaling in MI/R rat hearts [62–65].

Oxysophoridine (OSR): OSR (C15H24N2O2), a natural alkaloid from the Chinese herbal medicine Sophora alopecuroides L., can play multiple pharmacological roles such as the suppression of oxidative stress and apoptosis [66, 67]. A study [68] assessed the cardioprotective effect of OSR against MI in rats. OSR decreased infarction size and the levels of myocardial enzymes, including the CK-MB, cardiac troponin T, and lactate dehydrogenase. A decreased level of MDA was noticed while increased levels of catalase, SOD, glutathione peroxidase activity, and nonenzymatic scavenger glutathione were also verified in OSR-treated rats. In addition, OSR suppressed the activities of various inflammatory cytokines [69, 70]. The results showed that OSR relieves myocardial damage in the rat model of acute myocardial infarction (AMI) and that the cardioprotective effects may be associated with antiapoptotic, anti-inflammatory, and antioxidative mechanisms.

Gentianella acuta (G. acuta): G. acuta (C13H8O2) is extensively used for the therapy of coronary heart disease in Mongolian medicine. It is commonly known as “Wenxincao” in traditional Chinese medicine [71]. The potential protective effect of G. acuta on myocardial I/R injury by using the Langendorff apparatus in isolated rats was studied [72]. Some hemodynamic parameters were logged during the perfusion. These results showed that the xanthones from G. acuta dramatically ameliorated myocardial function and enhanced the levels of SOD, succinate dehydrogenase (SDH), CAT, malate dehydrogenase (MDH), adenosine triphosphate (ATP), and the proportion of GSH/GSSG while inhibiting the levels of CK, MDA, and LDH. Moreover, xanthones could upregulate the Bcl-2 protein and downregulate the Bax protein. In short, xanthones from G. acuta displayed a cardioprotective effect on myocardial I/R damage via antioxidative and antiapoptosis activities [73–76].

Azafrin: Centranthera grandiflora Benth. is an ethnic drug known as Ye-Can-Dou-Gen (YCDG) and has been extensively used to cure cardiovascular system diseases in China. Azafrin (C27H38O4), a carotene antioxidant, is one of the richest active compounds in YCDG [77]. Yang et al. [78] investigated the cardioprotective capacity of azafrin on the MI and MI/R damage to understand its potential myocardium preservation mechanisms. By experimental procedures, the results indicated that azafrin treatment significantly ameliorated heart function and infarct size in rats; reduced the levels of myocardial enzymes, cardiac troponin l (cTnI), and MDA; and increased SOD activity in vivo. In a word, azafrin displayed cardioprotective effects against myocardial damage through activation of the Nrf2-antioxidant response element (ARE) pathway [79].

2.1.2. Traditional Chinese Medicine Decoction

Bao-Xin-Tang (BXT): BXT is a Chinese herbal compound used to treat coronary heart disease and is made of Codonopsis pilosula, Atractylodes macrocephala, Astragalus, Fructus crataegi, etc. Previous studies have verified that it can ameliorate blood circulation to protect the myocardium of patients with MI [80]. A study [81] designed to explore if BXT offers cardioprotection against MI has been conducted. The rat model of MI was made by the ligation of the left anterior descending coronary artery. The data suggested that BXT could decrease the infarction size, myeloperoxidase, interleukin-6 (IL-6), and levels of C-reactive protein (CRP) and enhance SOD activities and anti-inflammatory media such as interleukin-10 (IL-10). Thus, the functions of BXT may be associated with antioxidant and anti-inflammation properties [82, 83].

Dan-Shen-Yin (DSY): DSY, including sandalwood Fructus amomi and Salvia miltiorrhiza, is a famous Chinese herbal formula which is extensively used for the therapy of CHD [84, 85]. A study [86] explored whether DSY could protect from MI. The left anterior descending branch of the coronary artery was ligated to induce myocardial ischemia in rats, measuring the infarction size, inflammation factor, and antioxidative enzyme activities. DSY decreased the infarction size, IL-6, CRP, TNF-α, and MAD, as well as enhanced SOD activities and glutathione [87, 88]. These results suggested that DSY plays a remarkable role against ischemic myocardial damage in rats, probably through an anti-inflammatory reaction and antioxidative properties.

2.1.3. Patented Drugs from Traditional Chinese Medicine

Dunye Guanxinning (DG): DG, a traditional Chinese herbal medicine formula, is extracted from the rhizomes of Dioscorea zingiberensis and is widely used for the treatment of angina, hyperlipidemia, and coronary heart disease [89, 90]. A study [91] explored that DG ameliorates myocardial I/R damage by suppressing caspase-1 activity and neutrophil infiltration. The result suggested that DG restrained neutrophil infiltration and decreased the interleukin-1 beta (IL-1β). In addition, DG suppressed caspase-1 activity and activatory AMPK phosphorylation in rat hearts. Thus, DG may be able to suppress the inflammatory response by the AMPK pathway [90, 91].

Hongjingtian injection (HJT): HJT is extracted from Rhodiola rosea and could prevent all kinds of vascular diseases like coronary heart disease and angina [92]. A study [93] assessed the cardioprotective effects of HJT. The experiments showed that HJT suppressed H/R-induced apoptosis and adjusted the expression of apoptosis-related proteins caspase 3 and Bcl-2. In addition, HJT obviously regulated the activity of the Akt, ERK/mTOR, and Akt/Beclin-1 pathways in cardiac cell autophagy. HJT prominently reduced the infarct size and ameliorated cardiac function and enhanced the light chain 3B (LC-3B) protein expression in the coronary ligation rat model. As a result, HJT reduced myocardial injury by adjusting the balance of apoptosis and autophagy and by decreasing ROS levels [94, 95].

Guanxintai (GXT): GXT, a Chinese compound formula, is often used in the treatment of cardiovascular diseases and is mainly composed of Ginseng, Astragalus, Rehmannia, Ophiopogon root, etc. Previous studies have verified the cardioprotective effects of GXT on the angina [96–99] and arrhythmia [100], as well as its inhibitory actions on blood lipid levels [101]. Yang et al. [102] studied the protective actions of GXT on ischemic cardiomyocytes and the related antioxidative effects. The research findings showed that GXT decreased the degree of myocardial cell injury and apoptosis and partly ameliorated cardiac function after MI. Furthermore, GXT restrained the ROS level and reduced NADPH oxidase (NOX) and mitogen-activated protein kinase (MAPK) protein expression. Therefore, the cardioprotective effects of GXT are exerted by the activity of the antioxidative NOX suppression [103, 104].

Cardiotonic pill (CP): CP includes Salvia miltiorrhiza, Borneol, and Panax notoginseng and is extensively used for the treatment of ischemic angina pectoris. A study [105] explored the underlying mechanisms of CP antioxidative activity. Male rats had left anterior descending artery ligation, and then, reperfusion was performed. The result suggested that CP decreased myocardial damage, ROS, and microcirculation disturbance. CP prominently suppressed I/R-induced NOX subunit p67phox, gp91phox, and p47phox protein expression. These data indicated that the CP alleviated I/R-induced rat myocardial damage and the disorder of microcirculation by inhibiting NOX activity [105–107].

Shenxian-shengmai (SXSM): SXSM oral liquid, a Chinese compound formula, has been widely used for bradyarrhythmias in clinical practice [108, 109]. MI, especially in right coronary-associated cardiac diseases, can give rise to bradyarrhythmias. A study [110] evaluated the functions of SXSM on bradyarrhythmias and cardiac insufficiency caused by myocardial I/R damage. Results showed that SXSM enhanced heart rate and protected from myocardial I/R damage. The study also discovered that SXSM ameliorated myocardial interstitial dilatation and the structural changes of myocardial cells. At the same time, SXSM protected myocardial cells against ROS induced by H2O2 and I/R damage by decreasing the intracellular levels of ROS. Furthermore, SXSM enhanced the activity of SOD and aggrandized the content of GSH by accelerating the glutamate-cysteine ligase catalytic subunit (GCLC) expression and GSH-Px activity, suggesting the antiarrhythmia and cardioprotective effects [111] (Table 1).

Type of TCMTCM (molecular formula)Type of studyMechanism of actionReferences
The bioactive ingredients of TCMSAL (C36H30O16; C26H22O10),
TAN (C18H12O3; C19H18O3)		In vivoDownregulation of factors participated in oxidative stress and apoptosis; inhibition of intracellular calcium and cell adhesion pathwaysWang et al. [129]
Danshensu (C9H10O5)In vivoActivation of the Akt/ERK1/2/Nrf2 signaling pathwayYu et al. [35]
Astragalin (C21H20O11)In vivoAntiapoptotic, antioxidative, and anti-inflammatory activitiesQu et al. [41]
OP-D (C44H70O16)   
Curcumin (C21H20O6)In vivoActivating JAK2/STAT3 signal pathway, reducing oxidative damage and suppressing myocardium apoptosisLiu et al. [111]
Punicalagin (C48H28O30)In vivoActivation of AMPKDing et al. [60]
Barbaloin (C21H22O9)In vivoAntioxidative, anti-inflammatoryZhang et al. [93]
OSR (C15H24N2O2)In vivoAntiapoptotic, anti-inflammatory, and antioxidativeMeng et al. [68]
G. acuta (C13H8O2)In vivoActivities of antioxidative and antiapoptosisWang et al. [81]
Azafrin (C27H38O4)In vivo, in vitroActivation of the Nrf2-ARE pathwayYang et al. [158]
Traditional Chinese medicine decoctionBao-Xin-TangIn vivoAntioxidant and anti-inflammation propertiesWang et al. [81]
Dan-Shen-YinIn vivoAnti-inflammatory and antioxidant propertiesYan et al. [86]
Patented drugs from traditional Chinese medicineDunye GuanxinningIn vivoInhibits inflammasome activity through the AMPK pathwayZhang et al. [91]
Hongjingtian injectionIn vivo, in vitroDecreasing myocardial oxidative damageZhang et al. [93]
GuanxintaiIn vivo, in vitroReduced NOX and MAPK proteinsYang et al. [158]
Cardiotonic pillIn vivoInhibiting NOX activityYang et al. [105]
Shenxian-shengmaiIn vivoEnhanced the activity of SOD and aggrandized the content of GSHZhao et al. [110]
TCM: traditional Chinese medicine; SAL: salvianolic acid; TAN: tanshinone; OP-D: Ophiopogonin D; OSR: oxysophoridine; G. acuta: Gentianella acuta; SOD: superoxide dismutase; GSH: glutathione; NOX: NADPH oxidase; MAPK: mitogen-activated protein kinase; AMPK: adenosine monophosphate-activated protein kinase; Nrf2: nuclear factor erythroid-2-related factor 2; Akt: serine/threonine kinase.
Table 1 
The role of traditional Chinese medicine (TCM) in the regulation of reactive oxygen species (ROS) in myocardial infarction (MI).
2.2. Ischemic Heart Failure
2.2.1. Patented Drugs from Traditional Chinese Medicine

Qi-shen-yi-qi (QSYQ): QSYQ, a formula used for the routine treatment of HF in China, includes Radix, Astragali mongolici, Salvia miltiorrhiza Bunge, Flos Lonicerae, Scrophularia, Radix Aconiti Lateralis preparata, and Radix glycyrrhizae and has been proven to ameliorate cardiac function by downregulating the Renin-Angiotensin-Aldosterone System (RAAS) activity [112, 113]. A study [114] surveyed the treatment with QSYQ ischemic heart failure prevention by alleviating oxidative stress and suppressing inflammation. Rats were processed by coronary artery ligation, and then, the indicators of fibrosis such as Masson dyeing, matrix metalloproteinases (MMPs) and collagens, and inflammation factors were detected. The study demonstrated that QSYQ ameliorated cardiac function via reducing the degree of myocardial fibrosis, TNF-a, NF-κB, and IL-6-STAT3 pathways and modulating angiotensin II-NADPH oxidase-ROS-MMP pathways [114, 115].

Tongxinluo (TXL): TXL is a prescription compound of Chinese medicine and has been verified as having anti-inflammatory, lipid-lowering, and antioxidant effects in ameliorating ischemic heart diseases [116]. A study [117] explored if TXL protected against the pressure overload-inducedischemic heart failure in mice. The transverse aortic constriction (TAC) operation was carried in mice to induce ischemic heart failure. TXL ameliorated cardiac function and relieved cardiac hypertrophy and myocardial fibrosis after treatment. Furthermore, TXL also enhanced myocardial capillary density and reduced oxidative stress damage by activating the vascular endothelial growth factor (VEGF)/Akt/eNOS signaling pathway [118].

YiQiFuMai powder injection (YQFM): YQFM, a Chinese medicinal formula rediscovered on the basis of Shengmai San, is extracted from Panax ginseng, Ophiopogon japonicus, and Schisandra chinensis and is widely used to treat angina and ischemic heart failure [119, 120]. Another study [121] noticed the therapeutic effect of YQFM on coronary artery occlusion-induced ischemic heart failure. Ischemic heart failure was induced by coronary artery occlusion in mice. After treatment with YQFM, the result displayed that YQFM can reduce LDH and CK activities and levels of MDA, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and hydroxyproline (HYP). Moreover, YQFM relieves coronary artery occlusion-induced ischemic heart failure by ameliorating the cardiac function and structure damage, oxidative stress, and cell apoptosis and suppressing the MAPK pathways [122–125].

2.3. Angina
2.3.1. Tongmai Yangxin (TMYX) pill

TMYX, a frequently used drug, is a Chinese compound formula used in the treatment of angina [126]. It mainly includes rehmannia, Caulis Spatholobi, Ophiopogon, licorice, Polygonum multiflorum, donkey-hide gelatin, fructus schisandrae, Codonopsis pilosula, tortoise, dates, and cassia. Metabolomics is a vital part of systems biology, which aims to monitor the changes of endogenous metabolites under physiological or pathological conditions. Cai et al. [127] analyzed the serum samples in clinical patients after oral administration of TMYX gathered from seven different clinical units in China. Using performance liquid chromatography, they tested metabolite profile changes in serum samples. Biomarkers, including metabolism, oxidative stress, and inflammation, were measured. The result indicated that after TMYX treatment, 10 biomarkers were reversed to normal conditions. These biomarkers participate mainly in energy metabolism, oxidative stress, and inflammation. As a result, TMYX has a therapeutic action via relieving myocardial energy disturbance, ROS, and inflammatory response [127–129]. The study, which is the first multicenter clinical study to reveal the basis and therapeutic mechanism of molecular biology of TMYX on the stable angina, can provide an objective index for the evaluation of the efficacy of TMYX in the stable angina pectoris, setting the stage for the clinical use of TMYX (Table 2).

Type of diseaseType of TCMTCM (molecular formula)Type of studyMechanism of actionReferences
Ischemic heart failurePatented drugs from traditional Chinese medicineQi-shen-yi-qiIn vivoRecovering angiotensin II-NADPH oxidase-ROS-MMP pathwaysLi et al. [114]
 TongxinluoIn vivoActivation of the VEGF/Akt/eNOS signaling pathwayWang et al. [117]
 YiQiFuMai powder injectionIn vivoAmeliorating cardiac function and structure damage, oxidative stress, and cell apoptosis and inhibiting the MAPK signaling pathwaysPang et al. [121]
Stable angina Tongmai Yangxin pillIn clinicAttenuating oxidative stress and inflammationCai et al. [127]
ROS: reactive oxygen species; MMPs: matrix metalloproteinases; VEGF: vascular endothelial growth factor; Akt: serine/threonine kinase; eNOS: endothelial nitric oxide synthase; MAPK: mitogen-activated protein kinase.
Table 2 
The role of traditional Chinese medicine (TCM) in the regulation of reactive oxygen species (ROS) in ischemic heart failure and angina.
2.4. Coronary Atherosclerotic Heart Disease
2.4.1. Single Chinese Herbal Medicines

Radix notoginseng: Radix notoginseng, a traditional Chinese medicine extracted from the roots of Panax notoginseng, is widely planted and used as an herbal medicine in Southern China. It indicates multiple biological activities, and it is also used as a therapeutic agent for coronary heart disease and peroxidation [130, 131]. A study [132] explored the cardioprotection effect of Radix notoginseng in cardiovascular system diseases related to hyperlipidemia and excess cholesterol. The rat model was established by using a dietary supplement to keep a high fat diet. Radix notoginseng led to a significant reduction in cholesterol and triglycerides, with a rise in the high-density lipoprotein-cholesterol. In addition, Radix notoginseng ameliorated antioxidant status through the SOD and glutathione peroxidase (GPx) activity and decreased the lipid peroxidation [133, 134]. The result showed that Radix notoginseng could ameliorate lipid distributions, suppress peroxidation, and enhance antioxidant enzymes activity, thereby decreasing the occurrence of CHD.

Pomegranate: pomegranate fruit is abundant in polyphenols, has an antioxidant activity, and has been suggested to have advantageous effects in cardiovascular disease [135]. The impacts of pomegranate on ROS and inflammation in the model of coronary heart disease in mice have been studied [136, 137]. Transgenic mice were treated with pomegranate extract [138]. Pomegranate could improve cardiac enlargement and electrocardiogram (ECG) abnormalities by reducing macrophage infiltration, lipid accumulation, ROS, and monocyte chemotactic protein-1 in transgenic mice with coronary atherosclerotic plaque. These results indicated that the protective effect of pomegranate against atherosclerosis may relate to reduce inflammation and ROS.

2.4.2. Patented Drugs from Traditional Chinese Medicine

Shengmai San (SMS): SMS includes Panax ginseng, Schisandra chinensis, and Ophiopogon and is a Chinese patent medicine used to treat CHD with antioxidative effects [139]. There was a study [140] which explored the influence of SMS on lipid peroxides and antioxidant reactions in the heart of cholesterol-raised rats. Antioxidant activities and ROS markers in the heart of rats were assessed. Results suggested that GSH-Px, glutathione-S-transferase (GST), and SOD activities were slightly improved after the SMS treatment [141] (Table 3).

Type of TCMTCM (molecular formula)Type of studyMechanism of actionReferences
Single Chinese herbal medicinesRadix notoginsengIn vivoInhibit peroxidation and increase the activity of antioxidant enzymesXia et al. [132]
PomegranateIn vivoReduced oxidative stress and inflammationAl-Jarallah et al. [138]
Patented drugs from traditional Chinese medicineShengmai SanIn vivoInhibit peroxidation and increase the activity of antioxidant enzymesYao et al. [140]
Table 3 
The role of traditional Chinese medicine (TCM) in the regulation of reactive oxygen species (ROS) in coronary atherosclerotic heart disease.

3. Discussion

Awareness of the importance of ROS in CHD pathogenesis and the development of novel treatments has increased [142]. As a crucial resource of treatment, TCM has multiple bioactivities with antioxidative ability [143, 144]. As a result, we summarized the research progress of TCM on the treatment of CHD by regulating ROS.

During MI, mechanisms of pathogenesis are associated with a number of factors, like the large amount of free radical generation, enhanced inflammation, and apoptosis [145]. When MI/R injury happens, cardiac intracellular calcium overload can increase XO synthesis and NOX, resulting in a rapid increase of ROS generation [146]. OSR cardioprotection, CP, and SXSM against MI in rats were correlated with antioxidant properties, particularly regarding NOX. Meanwhile, inflammatory signaling pathways are related to the occurrence and development of CHD, and I/R injury is closely connected with increased inflammation [147]. Astragalin, Barbaloin, BXT, and DSY can act on various targets such as suppression of NOX and the rise of GSH, which efficiently decreases ROS injury after I/R damage. Moreover, the anti-inflammatory action of TCM is, at least partly, attributed to its antioxidant effects. A number of studies have also indicated that the upregulation of several antiapoptotic factors and proapoptotic genes, such as the Bcl-2 and Bax, plays a vital function in the ischemic tissue [148, 149]. Curcumin, G. acuta, HJT, and GXT offer cardioprotection by ameliorating heart functions, inhibiting the ROS of cardiac cells, enhancing the release of antioxidant enzymes, and restraining mitochondria disorder and cardiomyocyte apoptosis during I/R damage. There is growing evidence that the PI3K/Akt and Nrf2 pathways help in ROS resistance and play a key function in improving myocardial cell survival [150, 151]. Activating antiapoptotic signaling pathways such as Nrf2 and PI3K/Akt could adjust Bcl-2 and suppress caspase c activation. Therefore, a large number of studies have shown that TCM treatment, such as SAL, TAN, DSS, OP-D, and azafrin, could decrease cardiomyocyte ROS and apoptosis through activation of the Nrf2 and PI3K/Akt signaling pathways during I/R damage. AMPK can also upregulate the cell antioxidant enzymes such as SOD and catalase, thereby decreasing oxidative damage [152]. The activation of the AMPK signaling pathway during I/R injury has been thought to be a mechanism of treatment against ROS and myocardial damage [153]. Above all, PUN, Barbaloin, DG, and GXT have been noticed to improve mitochondrial damage and ROS by the AMPK signaling pathway.

In ischemic heart failure, the oxidative stress system is activated, thereby significantly promoting coronary arterial disease and damaging cardiac myocytes [154]. In this pathway, NOX plays an important role in the occurrence and progression of IHF [155, 156]. At the same time, increased oxidative stress combined with the activation of a variety of inflammatory and apoptosis pathways significantly influence the effect on the occurrence and development of ischemic heart failure [157]. TCM has been used to cure ischemic heart failure for thousands of years. A lot of TCMs, such as QSYQ, TXL, and YQFM, showed cardioprotection against HF by alleviation of apoptosis, inflammation, and ROS.

Increased oxidative stress, disturbed lipid metabolism, and increased inflammation are critical factors in the occurrence and development of atherosclerosis and subsequent CHD [158, 159]. Radix notoginseng, pomegranate, and SMS offer tissue damage protection, attributed to ROS, by decreasing lipid peroxidation and enhancing the activity of antioxidant enzymes. In angina, pathogenesis mainly involves energy metabolism, ROS, and inflammation [160]. TMYX may have therapeutic actions by ameliorating myocardial energy supply dysfunction and amino acid disorders and by reducing ROS and inflammation.

4. Conclusions

In conclusion, there is overwhelming evidence that oxidative stress is associated with the pathogenesis of CHD. TCM therapy has unique advantages in CHD. In recent years, Chinese medicine has made great progress in the treatment of CHD, which can effectively ameliorate the symptoms of patients and improve the quality of life of patients. Compared with Western medicine, it has significant therapeutic effects, few side effects, and no obvious drug dependence. The treatment of this disease by TCM has a broad prospect, and it is worthy of further promotion and development.

Conflicts of Interest

All authors claim that there is no conflict of interests about the publication of this review.

Authors’ Contributions

Xinyu Yang, Yanwei Xing, and Hongcai Shang designed the idea for drafting this review. Xinyu Yang and Tianmai He collected the documents and wrote the paper. Songjie Han contributed to Discussion. Xiaoyu Zhang and Yang Sun revised and edited the review. All authors commented on the manuscript.

Acknowledgments

The work was supported by the National Key Research and Development Program of China (Grant No. 2017YFC1700400), the National Natural Science Foundation of China (Grant Nos. 81725024 and 81430098) and National High-Level Talent Special Support Plan (No. W02020052), the clinical base project of the State Administration of Traditional Chinese Medicine of China (JDZX2015007), and the outstanding project of the Beijing University of Chinese Medicine (2015-JYBXJQ001).

References

  1. L. Anderson, N. Oldridge, D. R. Thompson et al., “Exercise-based cardiac rehabilitation for coronary heart disease: Cochrane systematic review and meta-analysis,” Journal of the American College of Cardiology, vol. 67, no. 1, pp. 1–12, 2016. View at: Publisher Site | Google Scholar
  2. X. Yang, Y. Li, X. Ren et al., “Effects of exercise-based cardiac rehabilitation in patients after percutaneous coronary intervention: a meta-analysis of randomized controlled trials,” Scientific Reports, vol. 7, no. 1, article 44789, 2017. View at: Publisher Site | Google Scholar
  3. B. B. Kelly, J. Narula, and V. Fuster, “Recognizing global burden of cardiovascular disease and related chronic diseases,” Mount Sinai Journal of Medicine: A Journal of Translational and Personalized Medicine, vol. 79, no. 6, pp. 632–640, 2012. View at: Publisher Site | Google Scholar
  4. K. Kaur, G. Bedi, M. Kaur, A. Vij, and I. Kaur, “Lipid peroxidation and the levels of antioxidant enzymes in coronary artery disease,” Indian Journal of Clinical Biochemistry, vol. 23, no. 1, pp. 33–37, 2008. View at: Publisher Site | Google Scholar
  5. N. Ahmad and R. Bhopal, “Is coronary heart disease rising in India? A systematic review based on ECG defined coronary heart disease,” Heart, vol. 91, no. 6, pp. 719–725, 2005. View at: Publisher Site | Google Scholar
  6. F. Cosentino, J. C. Sill, and Z. S. Katusic, “Role of superoxide anions in the mediation of endothelium-dependent contractions,” Hypertension, vol. 23, no. 2, pp. 229–235, 1994. View at: Publisher Site | Google Scholar
  7. D. G. Harrison, “Cellular and molecular mechanisms of endothelial cell dysfunction,” The Journal of Clinical Investigation, vol. 100, no. 9, pp. 2153–2157, 1997. View at: Publisher Site | Google Scholar
  8. S. Kerr, M. J. Brosnan, M. McIntyre, J. L. Reid, A. F. Dominiczak, and C. A. Hamilton, “Superoxide anion production is increased in a model of genetic hypertension: role of the endothelium,” Hypertension, vol. 33, no. 6, pp. 1353–1358, 1999. View at: Publisher Site | Google Scholar
  9. S. Tsimikas, “In vivo markers of oxidative stress and therapeutic interventions,” The American Journal of Cardiology, vol. 101, no. 10A, pp. 34D–42D, 2008. View at: Publisher Site | Google Scholar
  10. R. P. Juni, H. J. Duckers, P. M. Vanhoutte, R. Virmani, and A. L. Moens, “Oxidative stress and pathological changes after coronary artery interventions,” Journal of the American College of Cardiology, vol. 61, no. 14, pp. 1471–1481, 2013. View at: Publisher Site | Google Scholar
  11. B. Q. Li, D. M. Liu, and W. Cui, “Advances in the study of sudden cardiac death after revascularization in patients with coronary heart disease,” Chinese Circulation Journal, vol. 33, no. 11, pp. 1134–1137, 2018. View at: Google Scholar
  12. J. A. Leopold and J. Loscalzo, “Oxidative risk for atherothrombotic cardiovascular disease,” Free Radical Biology and Medicine, vol. 47, no. 12, pp. 1673–1706, 2009. View at: Publisher Site | Google Scholar
  13. E. Lubos, J. Loscalzo, and D. E. Handy, “Glutathione peroxidase-1 in health and disease: from molecular mechanisms to therapeutic opportunities,” Antioxidants & Redox Signaling, vol. 15, no. 7, pp. 1957–1997, 2011. View at: Publisher Site | Google Scholar
  14. F. Tullio, C. Angotti, M.-G. Perrelli, C. Penna, and P. Pagliaro, “Redox balance and cardioprotection,” Basic Research in Cardiology, vol. 108, no. 6, p. 392, 2013. View at: Publisher Site | Google Scholar
  15. C. Zhang, H. Yu, Y. Shen, X. Ni, S. Shen, and U. N. Das, “Polyunsaturated fatty acids trigger apoptosis of colon cancer cells through a mitochondrial pathway,” Archives of Medical Science, vol. 11, no. 5, pp. 1081–1094, 2015. View at: Google Scholar
  16. J. A. Leopold, “Antioxidants and coronary artery disease: from pathophysiology to preventive therapy,” Coronary Artery Disease, vol. 26, no. 2, pp. 176–183, 2015. View at: Publisher Site | Google Scholar
  17. B. J. Willcox, J. D. Curb, and B. L. Rodriguez, “Antioxidants in cardiovascular health and disease: key lessons from epidemiologic studies,” The American Journal of Cardiology, vol. 101, no. 10, pp. S75–S86, 2008. View at: Publisher Site | Google Scholar
  18. M. J. Kendall and S. L. Nuttall, “Anti-oxidant therapy for the treatment of coronary artery disease,” Expert Opinion on Investigational Drugs, vol. 8, no. 11, pp. 1763–1784, 1999. View at: Publisher Site | Google Scholar
  19. D. Wang, E. J. Calabrese, B. Lian, Z. Lin, and V. Calabrese, “Hormesis as a mechanistic approach to understanding herbal treatments in traditional Chinese medicine,” Pharmacology & Therapeutics, vol. 184, pp. 42–50, 2018. View at: Publisher Site | Google Scholar
  20. M. Rajadurai and P. Stanely Mainzen Prince, “Preventive effect of naringin on lipid peroxides and antioxidants in isoproterenol-induced cardiotoxicity in Wistar rats: biochemical and histopathological evidences,” Toxicology, vol. 228, no. 2-3, pp. 259–268, 2006. View at: Publisher Site | Google Scholar
  21. L. Wu, H. Qiao, Y. Li, and L. Li, “Protective roles of puerarin and Danshensu on acute ischemic myocardial injury in rats,” Phytomedicine, vol. 14, no. 10, pp. 652–658, 2007. View at: Publisher Site | Google Scholar
  22. C.-s. Li, Z.-q. Qu, S.-s. Wang et al., “Effects of Suxiao Jiuxin pill (速效救心丸) on oxidative stress and inflammatory response in rats with experimental atherosclerosis,” Journal of Traditional Chinese Medicine, vol. 31, no. 2, pp. 107–111, 2011. View at: Publisher Site | Google Scholar
  23. F. Bagheri, V. Khori, A. M. Alizadeh, S. Khalighfard, S. Khodayari, and H. Khodayari, “Reactive oxygen species-mediated cardiac-reperfusion injury: mechanisms and therapies,” Life Sciences, vol. 165, pp. 43–55, 2016. View at: Publisher Site | Google Scholar
  24. S. Y. Jiang, J. C. Tong, R. Y. Sun, and H. T. Xie, “Meta-analysis of compound Danshen dropping pills(DSP) in treating coronary heart disease angina,” Practical Pharmacy and Clinical Remedies, vol. 10, no. 6, pp. 334–337, 2007. View at: Google Scholar
  25. X. Zhou, S. W. Chan, H. L. Tseng et al., “Danshensu is the major marker for the antioxidant and vasorelaxation effects of Danshen (Salvia miltiorrhiza) water-extracts produced by different heat water-extractions,” Phytomedicine, vol. 19, no. 14, pp. 1263–1269, 2012. View at: Publisher Site | Google Scholar
  26. G. R. Zhao, H. M. Zhang, T. X. Ye et al., “Characterization of the radical scavenging and antioxidant activities of Danshensu and salvianolic acid B,” Food and Chemical Toxicology, vol. 46, no. 1, pp. 73–81, 2008. View at: Publisher Site | Google Scholar
  27. Q. T. Zhao, Q. M. Guo, P. Wang, and Q. Wang, “Salvianic acid A inhibits lipopolysaccharide-induced apoptosis through regulating glutathione peroxidase activity and malondialdehyde level in vascular endothelial cells,” Chinese Journal of Natural Medicines, vol. 10, no. 1, pp. 53–57, 2012. View at: Publisher Site | Google Scholar
  28. G.-D. Yang, H. Zhang, R. Lin et al., “Down-regulation of CD40 gene expression and inhibition of apoptosis with Danshensu in endothelial cells,” Basic & Clinical Pharmacology & Toxicology, vol. 104, no. 2, pp. 87–92, 2009. View at: Publisher Site | Google Scholar
  29. Y. Guan, Y. Yin, Y.-R. Zhu et al., “Dissection of mechanisms of a Chinese medicinal formula: Danhong injection therapy for myocardial ischemia/reperfusion injury in vivo and in vitro,” Evidence-Based Complementary and Alternative Medicine, vol. 2013, Article ID 972370, 12 pages, 2013. View at: Publisher Site | Google Scholar
  30. B. L. Zhao, W. Jiang, Y. Zhao, J. W. Hou, and W. J. Xin, “Scavenging effects of salvia miltiorrhiza on free radicals and its protection for myocardial mitochondrial membranes from ischemia-reperfusion injury,” Biochemistry and Molecular Biology International, vol. 38, no. 6, pp. 1171–1182, 1996. View at: Google Scholar
  31. X.-Y. Le, C.-L. Chen, L. Ma, N. Zhao, Y.-Q. Tang, and X.-Q. Liu, “Effects of Danshensu on the incidence of ischemia-reperfusion induced arrhythmia in hypertrophy rat heart,” Chinese Journal of Natural Medicines, vol. 6, no. 6, pp. 461–465, 2008. View at: Publisher Site | Google Scholar
  32. Y. Yin, Y. Guan, J. Duan et al., “Cardioprotective effect of Danshensu against myocardial ischemia/reperfusion injury and inhibits apoptosis of H9c2 cardiomyocytes via Akt and ERK1/2 phosphorylation,” European Journal of Pharmacology, vol. 699, no. 1-3, pp. 219–226, 2013. View at: Publisher Site | Google Scholar
  33. M. Li, C. Zhao, R. N. Wong, S. Goto, Z. Wang, and F. Liao, “Inhibition of shear-induced platelet aggregation in rat by tetramethylpyrazine and salvianolic acid B,” Clinical Hemorheology and Microcirculation, vol. 31, no. 2, pp. 97–103, 2004. View at: Google Scholar
  34. X. Wang, Y. Wang, M. Jiang et al., “Differential cardioprotective effects of salvianolic acid and tanshinone on acute myocardial infarction are mediated by unique signaling pathways,” Journal of Ethnopharmacology, vol. 135, no. 3, pp. 662–671, 2011. View at: Publisher Site | Google Scholar
  35. J. Yu, L. Wang, M. Akinyi et al., “Danshensu protects isolated heart against ischemia reperfusion injury through activation of Akt/ERK1/2/Nrf2 signaling,” International Journal of Clinical and Experimental Medicine, vol. 8, no. 9, pp. 14793–14804, 2015. View at: Google Scholar
  36. Y. Tang, M. Wang, X. le et al., “Antioxidant and cardioprotective effects of Danshensu (3-(3, 4-dihydroxyphenyl)-2-hydroxy-propanoic acid from Salvia miltiorrhiza) on isoproterenol-induced myocardial hypertrophy in rats,” Phytomedicine, vol. 18, no. 12, pp. 1024–1030, 2011. View at: Publisher Site | Google Scholar
  37. J. Liu, H. M. Shen, and C. N. Ong, “Role of intracellular thiol depletion, mitochondrial dysfunction and reactive oxygen species in Salvia miltiorrhiza-induced apoptosis in human hepatoma HepG2 cells,” Life Sciences, vol. 69, no. 16, pp. 1833–1850, 2001. View at: Publisher Site | Google Scholar
  38. M.-S. Kim and S.-H. Kim, “Inhibitory effect of astragalin on expression of lipopolysaccharide-induced inflammatory mediators through NF-κB in macrophages,” Archives of Pharmacal Research, vol. 34, no. 12, pp. 2101–2107, 2011. View at: Publisher Site | Google Scholar
  39. O. Burmistrova, J. Quintana, J. G. Díaz, and F. Estévez, “Astragalin heptaacetate-induced cell death in human leukemia cells is dependent on caspases and activates the MAPK pathway,” Cancer Letters, vol. 309, no. 1, pp. 71–77, 2011. View at: Publisher Site | Google Scholar
  40. I. H. Cho, J. H. Gong, M. K. Kang et al., “Astragalin inhibits airway eotaxin-1 induction and epithelial apoptosis through modulating oxidative stress-responsive MAPK signaling,” BMC Pulmonary Medicine, vol. 14, no. 1, 2014. View at: Publisher Site | Google Scholar
  41. D. Qu, J. Han, H. Ren et al., “Cardioprotective effects of astragalin against myocardial ischemia/reperfusion injury in isolated rat heart,” Oxidative Medicine and Cellular Longevity, vol. 2016, Article ID 8194690, 11 pages, 2016. View at: Publisher Site | Google Scholar
  42. J. Han, D. Wang, B. Yu et al., “Cardioprotection against ischemia/reperfusion by licochalcone B in isolated rat hearts,” Oxidative Medicine and Cellular Longevity, vol. 2014, Article ID 134862, 11 pages, 2014. View at: Publisher Site | Google Scholar
  43. M. Zhou, L. Liu, W. Wang et al., “Role of licochalcone C in cardioprotection against ischemia/reperfusion injury of isolated rat heart via antioxidant, anti-inflammatory, and anti-apoptotic activities,” Life Sciences, vol. 132, pp. 27–33, 2015. View at: Publisher Site | Google Scholar
  44. J. Qian, F. Jiang, B. Wang et al., “Ophiopogonin D prevents H2O2-induced injury in primary human umbilical vein endothelial cells,” Journal of Ethnopharmacology, vol. 128, no. 2, pp. 438–445, 2010. View at: Publisher Site | Google Scholar
  45. M. Jiang, L. Kang, Y. Wang et al., “A metabonomic study of cardioprotection of ginsenosides, schizandrin, and ophiopogonin D against acute myocardial infarction in rats,” BMC Complementary and Alternative Medicine, vol. 14, no. 1, p. 350, 2014. View at: Publisher Site | Google Scholar
  46. Q. Huang, B. Gao, L. Wang et al., “Ophiopogonin D: a new herbal agent against osteoporosis,” Bone, vol. 74, pp. 18–28, 2015. View at: Publisher Site | Google Scholar
  47. W. You, T. Zhou, Z. Ma et al., “Ophiopogonin D maintains Ca2+ homeostasis in rat cardiomyocytes in vitro by upregulating CYP2J3/EETs and suppressing ER stress,” Acta Pharmacologica Sinica, vol. 37, no. 3, pp. 368–381, 2016. View at: Publisher Site | Google Scholar
  48. X. Huang, Y. Wang, Y. Wang, L. Yang, J. Wang, and Y. Gao, “Ophiopogonin D reduces myocardial ischemia-reperfusion injury via upregulating CYP2J3/EETs in rats,” Cellular Physiology and Biochemistry, vol. 49, no. 4, pp. 1646–1658, 2018. View at: Publisher Site | Google Scholar
  49. X. Y. Huang, Y. G. Wang, Z. Y. Zhang et al., “Ophiopogonin D and EETs ameliorate Ang IIinduced inflammatory responses via activating PPARalpha in HUVECs,” Biochemical and Biophysical Research Communications, vol. 490, no. 2, pp. 123–133, 2017. View at: Publisher Site | Google Scholar
  50. J. Seubert, B. Yang, J. A. Bradbury et al., “Enhanced postischemic functional recovery in CYP2J2 transgenic hearts involves mitochondrial ATP-sensitive K+ channels and p42/p44 MAPK pathway,” Circulation Research, vol. 95, no. 5, pp. 506–514, 2004. View at: Publisher Site | Google Scholar
  51. T. Morimoto, Y. Sunagawa, T. Kawamura et al., “The dietary compound curcumin inhibits p300 histone acetyltransferase activity and prevents heart failure in rats,” The Journal of Clinical Investigation, vol. 118, no. 3, pp. 868–878, 2008. View at: Publisher Site | Google Scholar
  52. S. Ahuja, S. Kohli, S. Krishnan, D. Dogra, D. Sharma, and V. Rani, “Curcumin: a potential therapeutic polyphenol, prevents noradrenaline-induced hypertrophy in rat cardiac myocytes,” The Journal of Pharmacy and Pharmacology, vol. 63, no. 12, pp. 1604–1612, 2011. View at: Publisher Site | Google Scholar
  53. S. Kumphune, S. Surinkaew, S. C. Chattipakorn, and N. Chattipakorn, “Inhibition of p38 MAPK activation protects cardiac mitochondria from ischemia/reperfusion injury,” Pharmaceutical Biology, vol. 53, no. 12, pp. 1831–1841, 2015. View at: Publisher Site | Google Scholar
  54. H. J. Liu, C. H. Wang, Z. Qiao, and Y. Xu, “Protective effect of curcumin against myocardium injury in ischemia reperfusion rats,” Pharmaceutical Biology, vol. 55, no. 1, pp. 1144–1148, 2017. View at: Publisher Site | Google Scholar
  55. O. S. Kim, E. J. Park, E. Joe, and I. Jou, “JAK-STAT signaling mediates gangliosides-induced inflammatory responses in brain microglial cells,” Journal of Biological Chemistry, vol. 277, no. 43, pp. 40594–40601, 2002. View at: Publisher Site | Google Scholar
  56. S. O. Cho, J. W. Lim, and H. Kim, “Red ginseng extract inhibits the expression of MCP-1 and iNOS in Helicobacter pylori-infected gastric epithelial cells by suppressing the activation of NADPH oxidase and Jak2/Stat3,” Journal of Ethnopharmacology, vol. 150, no. 2, pp. 761–764, 2013. View at: Publisher Site | Google Scholar
  57. D. Guo, J. Li, Y. Wang, L. Lei, C. Yu, and N. Chen, “Cyclovirobuxinum D suppresses lipopolysaccharide-induced inflammatory responses in murine macrophages in vitro by blocking JAK-STAT signaling pathway,” Acta Pharmacologica Sinica, vol. 35, no. 6, pp. 770–778, 2014. View at: Publisher Site | Google Scholar
  58. B. Chen, M. S. Longtine, and D. M. Nelson, “Punicalagin, a polyphenol in pomegranate juice, downregulates p53 and attenuates hypoxia-induced apoptosis in cultured human placental syncytiotrophoblasts,” American Journal of Physiology-Endocrinology and Metabolism, vol. 305, no. 10, pp. E1274–E1280, 2013. View at: Publisher Site | Google Scholar
  59. L. Yaidikar, B. Byna, and S. R. Thakur, “Neuroprotective effect of punicalagin against cerebral ischemia reperfusion-induced oxidative brain injury in rats,” Journal of Stroke and Cerebrovascular Diseases, vol. 23, no. 10, pp. 2869–2878, 2014. View at: Publisher Site | Google Scholar
  60. M. Ding, Y. Wang, D. Sun et al., “Punicalagin pretreatment attenuates myocardial ischemia-reperfusion injury via activation of AMPK,” The American Journal of Chinese Medicine, vol. 45, no. 01, pp. 53–66, 2017. View at: Publisher Site | Google Scholar
  61. K. Cao, J. Xu, W. Pu et al., “Punicalagin, an active component in pomegranate, ameliorates cardiac mitochondrial impairment in obese rats via AMPK activation,” Scientific Reports, vol. 5, no. 1, article 14014, 2015. View at: Publisher Site | Google Scholar
  62. R. Y. Y. Lam, A. Y. H. Woo, P. S. Leung, and C. H. K. Cheng, “Antioxidant actions of phenolic compounds found in dietary plants on low-density lipoprotein and erythrocytes in vitro,” Journal of the American College of Nutrition, vol. 26, no. 3, pp. 233–242, 2007. View at: Publisher Site | Google Scholar
  63. P. Zhang, X. Liu, G. Huang, C. Bai, Z. Zhang, and H. Li, “Barbaloin pretreatment attenuates myocardial ischemia-reperfusion injury via activation of AMPK,” Biochemical and Biophysical Research Communications, vol. 490, no. 4, pp. 1215–1220, 2017. View at: Publisher Site | Google Scholar
  64. X. Ren, X. Wang, M. Yuan et al., “Mechanisms and treatments of oxidative stress in atrial fibrillation,” Current Pharmaceutical Design, vol. 24, no. 26, pp. 3062–3071, 2018. View at: Publisher Site | Google Scholar
  65. D. K. Patel, K. Patel, and V. Tahilyani, “Barbaloin: a concise report of its pharmacological and analytical aspects,” Asian Pacific Journal of Tropical Biomedicine, vol. 2, no. 10, pp. 835–838, 2012. View at: Publisher Site | Google Scholar
  66. R. Wang and X. C. Tang, “Neuroprotective effects of huperzine A. A natural cholinesterase inhibitor for the treatment of Alzheimer’s disease,” Neurosignals, vol. 14, no. 1-2, pp. 71–82, 2005. View at: Publisher Site | Google Scholar
  67. W. Yu, Q. Liu, and S. Zhu, “Carvacrol protects against acute myocardial infarction of rats via anti-oxidative and anti-apoptotic pathways,” Biological & Pharmaceutical Bulletin, vol. 36, no. 4, pp. 579–584, 2013. View at: Publisher Site | Google Scholar
  68. C. Meng, C. Liu, Y. Liu, and F. Wu, “Oxysophoridine attenuates the injury caused by acute myocardial infarction in rats through anti‑oxidative, anti‑inflammatory and anti‑apoptotic pathways,” Molecular Medicine Reports, vol. 11, no. 1, pp. 527–532, 2015. View at: Publisher Site | Google Scholar
  69. D. N. Müller, E. M. A. Mervaala, R. Dechend et al., “Angiotensin II (AT1) receptor blockade reduces vascular tissue factor in angiotensin II-induced cardiac vasculopathy,” The American Journal of Pathology, vol. 157, no. 1, pp. 111–122, 2000. View at: Publisher Site | Google Scholar
  70. E. Speir, “Cytomegalovirus gene regulation by reactive oxygen species. Agents in atherosclerosis,” Annals of the New York Academy of Sciences, vol. 899, pp. 363–374, 2000. View at: Google Scholar
  71. N. R. Wu, L. Chun, and B. G. Khas, “Ewenki folk medicinal plants and its comparison with Mongolian medicine,” Chinese Journal of Ethnomedicine and Ethnopharmacy, vol. 17, pp. 156–158, 2009. View at: Google Scholar
  72. H. X. Kuang, G. S. Wu, H. Liu et al., “Isolation and identification of xanthones from Gentianella acuta,” Zhongguo Zhong Yao Za Zhi, vol. 41, no. 12, pp. 2280–2283, 2016. View at: Publisher Site | Google Scholar
  73. H. Marona, T. Librowski, M. Cegła, C. Erdogan, and N. O. Sahin, “Antiarrhythmic and antihypertensive activity of some xanthone derivatives,” Acta Poloniae Pharmaceutica, vol. 65, no. 3, pp. 383–390, 2008. View at: Google Scholar
  74. G. Mahendran, M. Manoj, E. Murugesh et al., “In vivo anti-diabetic, antioxidant and molecular docking studies of 1, 2, 8-trihydroxy-6-methoxy xanthone and 1, 2-dihydroxy-6-methoxyxanthone-8-O-β-d-xylopyranosyl isolated from Swertia corymbosa,” Phytomedicine, vol. 21, no. 11, pp. 1237–1248, 2014. View at: Publisher Site | Google Scholar
  75. C. Tantapakul, W. Maneerat, T. Sripisut et al., “New benzophenones and xanthones from Cratoxylum sumatranum ssp. neriifolium and their antibacterial and antioxidant activities,” Journal of Agricultural and Food Chemistry, vol. 64, no. 46, pp. 8755–8762, 2016. View at: Publisher Site | Google Scholar
  76. M. Kavitha, J. Nataraj, M. M. Essa, M. A. Memon, and T. Manivasagam, “Mangiferin attenuates MPTP induced dopaminergic neurodegeneration and improves motor impairment, redox balance and Bcl-2/Bax expression in experimental Parkinson’s disease mice,” Chemico-Biological Interactions, vol. 206, no. 2, pp. 239–247, 2013. View at: Publisher Site | Google Scholar
  77. X. Yang, N. Liu, X. Li et al., “A review on the effect of traditional Chinese medicine against anthracycline-induced cardiac toxicity,” Frontiers in Pharmacology, vol. 9, p. 444, 2018. View at: Publisher Site | Google Scholar
  78. S. Yang, G. Chou, and Q. Li, “Cardioprotective role of azafrin in against myocardial injury in rats via activation of the Nrf2-ARE pathway,” Phytomedicine, vol. 47, pp. 12–22, 2018. View at: Publisher Site | Google Scholar
  79. T. W. Kensler, N. Wakabayashi, and S. Biswal, “Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway,” Annual Review of Pharmacology and Toxicology, vol. 47, no. 1, pp. 89–116, 2007. View at: Publisher Site | Google Scholar
  80. Z. Q. Zhang, Z. H. Xing, T. Tang, W. P. Liu, and L. Yi, “Influence of baoxin decoction on serum VEGF in patients with myocardial infarction after PTCA,” Journal of Beijing University of Traditional Chinese Medicine, vol. 29, no. 4, pp. 277-278, 2006. View at: Google Scholar
  81. Y. Wang, W. Wang, W. Peng et al., “Cardioprotective roles of the Chinese medicinal formula Bao-Xin-Tang on acute myocardial infarction in rats,” African Journal of Traditional, Complementary, and Alternative Medicines, vol. 14, no. 2, pp. 65–74, 2017. View at: Publisher Site | Google Scholar
  82. Q. Shang, H. Wang, S. Li, and H. Xu, “The effect of sodium Tanshinone IIA sulfate and simvastatin on elevated serum levels of inflammatory markers in patients with coronary heart disease: a study protocol for a randomized controlled trial,” Evidence-based Complementary and Alternative Medicine, vol. 2013, Article ID 756519, 8 pages, 2013. View at: Publisher Site | Google Scholar
  83. P. V. Kiruthiga, R. B. Shafreen, S. K. Pandian, S. Arun, S. Govindu, and K. P. Devi, “Protective effect of silymarin on erythrocyte haemolysate against benzo(a)pyrene and exogenous reactive oxygen species (H2O2) induced oxidative stress,” Chemosphere, vol. 68, no. 8, pp. 1511–1518, 2007. View at: Publisher Site | Google Scholar
  84. M. Xie, “Sheng-Mai-San and Dan-Shen-Yin treat coronary heart disease 60 cases,” Chinese Medicine Modern Distance Education of China, vol. 6, no. 11, p. 1357, 2008. View at: Google Scholar
  85. R. S. Liu, “Jia-Wei-Dan-Shen-Yin treat coronary heart disease 68 cases,” Chinese Journal of Integrative Medicine on Cardio/Cerebrovascular Disease, vol. 8, no. 5, p. 604, 2010. View at: Google Scholar
  86. K.-P. Yan, Y. Guo, Z. Xing et al., “Dan-Shen-Yin protects the heart against inflammation and oxidative stress induced by acute ischemic myocardial injury in rats,” Experimental and Therapeutic Medicine, vol. 3, no. 2, pp. 314–318, 2012. View at: Publisher Site | Google Scholar
  87. P. Krishnamurthy, E. Lambers, S. Verma et al., “Myocardial knockdown of mRNA-stabilizing protein HuR attenuates post-MI inflammatory response and left ventricular dysfunction in IL-10-null mice,” The FASEB Journal, vol. 24, no. 7, pp. 2484–2494, 2010. View at: Publisher Site | Google Scholar
  88. X. Li, X. Yang, Y. Li et al., “Mitochondria and the pathophysiological mechanism of atrial fibrillation,” Current Pharmaceutical Design, vol. 24, no. 26, pp. 3055–3061, 2018. View at: Publisher Site | Google Scholar
  89. M. Yuan, N. Liu, X. Wang et al., “The mechanism of exosomes function in neurological diseases: a progressive review,” Current Pharmaceutical Design, vol. 24, no. 24, pp. 2855–2861, 2018. View at: Publisher Site | Google Scholar
  90. L. A. Zhen, Z. X. Ying, D. Tao, W. H. Qing, G. J. Yan, and W. Liang, “Therapeutic effect of Danhong injection combined with Dunye Guanxinning tablet on acute myocardial infarction and its effect on platelet activation biomarkers,” Modern Journal of Integrated Traditional Chinese and Western Medicine, vol. 25, no. 6, pp. 615–617, 2016. View at: Google Scholar
  91. Q. G. Zhang, S. R. Wang, X. M. Chen, H. N. Guo, S. Ling, and J. W. Xu, “Dunye Guanxinning improves acute myocardial ischemia-reperfusion injury by inhibiting neutrophil infiltration and caspase-1 activity,” Mediators of Inflammation, vol. 2018, Article ID 4608017, 13 pages, 2018. View at: Publisher Site | Google Scholar
  92. M. Qi, M. Y. Tang, H. Q. Zhou, and Y. Zhou, “Clinical observation of sofren injection in the treatment of angina pectoris,” China Modern Doctor, vol. 54, no. 21, pp. 139–144, 2016. View at: Google Scholar
  93. S. Zhang, L. Zhang, H. Zhang et al., “Hongjingtian injection attenuates myocardial oxidative damage via promoting autophagy and inhibiting apoptosis,” Oxidative Medicine and Cellular Longevity, vol. 2017, Article ID 6965739, 11 pages, 2017. View at: Publisher Site | Google Scholar
  94. T. Wu, H. Zhou, Z. Jin et al., “Cardioprotection of salidroside from ischemia/reperfusion injury by increasing N-acetylglucosamine linkage to cellular proteins,” European Journal of Pharmacology, vol. 613, no. 1–3, pp. 93–99, 2009. View at: Publisher Site | Google Scholar
  95. K. Shi, X. Wang, J. Zhu, G. Cao, K. Zhang, and Z. Su, “Salidroside protects retinal endothelial cells against hydrogen peroxide-induced injury via modulating oxidative status and apoptosis,” Bioscience, Biotechnology, and Biochemistry, vol. 79, no. 9, pp. 1406–1413, 2015. View at: Publisher Site | Google Scholar
  96. Y. Wang and D. L. Cai, “Clinical observation on the treatment of unstable angina pectoris with Guanxintai pills,” Heilongjiang Medicine and Pharmacy, vol. 34, no. 3, p. 104, 2011. View at: Google Scholar
  97. Y. Z. Zhang, “Observation of curative effect of Guanxintai pills on angina pectoris,” Clinical Rational Drug Use, vol. 5, no. 2C, pp. 74-75, 2012. View at: Google Scholar
  98. X. P. Bai, “Clinical observation on the treatment of unstable angina pectoris with Guanxintai,” Modern Journal of Integrated Traditional Chinese and Western Medicine, vol. 20, no. 22, pp. 2763–2766, 2011. View at: Google Scholar
  99. L. Q. Song, X. D. Zhang, L. P. Zhao, M. L. Zhang, X. H. Han, and D. Sun, “Observation of curative effect of Guanxintai on angina pectoris,” Practical Journal of Cardiac Cerebral Pneumal and Vascular Disease, vol. 20, no. 3, p. 464, 2012. View at: Google Scholar
  100. Y. H. Qi, M. L. Zhang, and L. Yin, “The 34 cases of the patients with ventricular premature beats treated with Guanxintai and amiodarone hydrochloride tablets,” Guide of China Medicine, vol. 10, no. 10, pp. 301-302, 2012. View at: Google Scholar
  101. C. Y. Sun and R. Y. Wang, “Clinical efficacy of Guanxintai pills combined with Western medicine on the treatment of angina pectoris combined with hyperlipidemia,” China Medical Engineering, vol. 19, no. 2, pp. 49–51, 2011. View at: Google Scholar
  102. J. Yang, W. Sun, J. Sun et al., “Guanxintai exerts protective effects on ischemic cardiomyocytes by mitigating oxidative stress,” Evidence-Based Complementary and Alternative Medicine, vol. 2017, Article ID 4534387, 10 pages, 2017. View at: Publisher Site | Google Scholar
  103. F. Y. Guan, H. Li, X. X. Yu, and S. J. Yang, “Effects of astragalus injection on myocardial cell damages due to oxidative stress,” Chinese Journal of Rehabilitation Theory and Practice, vol. 16, no. 9, pp. 830–832, 2010. View at: Google Scholar
  104. D. F. Zhang, M. W. Wang, L. S. Wang et al., “Effect of salvianolate on oxidative stress and brain natriuretic peptide in acute myocardial infarction,” Chinese Journal of Integrative Medicine on Cardio/Cerebrovascular Disease, vol. 6, no. 11, pp. 1304–1306, 2008. View at: Google Scholar
  105. X. Y. Yang, N. Zhao, Y. Y. Liu et al., “Inhibition of NADPH oxidase mediates protective effect of cardiotonic pills against rat heart ischemia/reperfusion injury,” Evidence-Based Complementary and Alternative Medicine, vol. 2013, Article ID 728020, 15 pages, 2013. View at: Publisher Site | Google Scholar
  106. N. Zhao, Y. Y. Liu, F. Wang et al., “Cardiotonic pills, a compound Chinese medicine, protects ischemia-reperfusion-induced microcirculatory disturbance and myocardial damage in rats,” American Journal of Physiology-Heart and Circulatory Physiology, vol. 298, no. 4, pp. H1166–H1176, 2010. View at: Publisher Site | Google Scholar
  107. H. Y. Son, H. S. Han, H. W. Jung, and Y.-K. Park, “Panax notoginseng attenuates the infarct volume in rat ischemic brain and the inflammatory response of microglia,” Journal of Pharmacological Sciences, vol. 109, no. 3, pp. 368–379, 2009. View at: Publisher Site | Google Scholar
  108. J. H. Hu, S. J. Chen, and X. L. Hua, “Clinical research of Shenxianshengmai oral liquid in the treatment of sick sinus syndrome and sinus bradycardia,” Chinese Traditional Patent Medicine, vol. 34, no. 1, pp. 7–9, 2012. View at: Google Scholar
  109. P. Li and L. Zeng, “Clinical observation of Shenxian-shengmaioral liquid in the treatment of bradycardia,” Chinese Journal of Integrative Medicine on Cardio, vol. 9, no. 9, pp. 1121-1122, 2011. View at: Google Scholar
  110. Y. Zhao, X. Zhang, J. Luan et al., “Shenxian-Shengmai oral liquid reduces myocardial oxidative stress and protects myocardium from ischemia-reperfusion injury,” Cellular Physiology and Biochemistry, vol. 48, no. 6, pp. 2503–2516, 2018. View at: Publisher Site | Google Scholar
  111. Z. Y. Liu, J. Huang, N. N. Liu et al., “Molecular mechanisms of increased heart rate in Shenxianshengmai-treated bradycardia rabbits,” Chinese Medical Journal, vol. 130, no. 2, pp. 179–186, 2017. View at: Google Scholar
  112. C. Hong, Y. Wang, J. Lou, Q. Liu, H. Qu, and Y. Cheng, “Analysis of myocardial proteomic alteration after QiShenYiQi formula treatment in acute infarcted rat hearts,” Zhongguo Zhong Yao Za Zhi, vol. 34, no. 8, pp. 1018–1021, 2009. View at: Google Scholar
  113. G. H. Dai, B. L. Zhang, and Z. X. Guo, “Application of central randomized system in project of clinical trial for secondary prevention of myocardial infarction by Qishen Yiqi drop pill,” Zhongguo Zhong Xi Yi Jie He Za Zhi, vol. 27, no. 7, pp. 653–656, 2007. View at: Google Scholar
  114. C. Li, Y. Wang, Q. Qiu et al., “QiShenYiQi protects ligation-induced left ventricular remodeling by attenuating inflammation and fibrosis via STAT3 and NF-κB signaling pathway,” PLoS One, vol. 9, no. 8, article e104255, 2014. View at: Publisher Site | Google Scholar
  115. Y. Wang, C. Li, Y. Ouyang et al., “Cardioprotective effects of QiShenYiQi mediated by angiotensin II type 1 receptor blockade and enhancing angiotensin-converting enzyme 2,” Evidence-Based Complementary and Alternative Medicine, vol. 2012, Article ID 978127, 9 pages, 2012. View at: Publisher Site | Google Scholar
  116. L. Zhang, Y. Liu, X. T. Lu et al., “Traditional Chinese medication Tongxinluo dose-dependently enhances stability of vulnerable plaques: a comparison with a high-dose simvastatin therapy,” American Journal of Physiology-Heart and Circulatory Physiology, vol. 297, no. 6, pp. H2004–H2014, 2009. View at: Publisher Site | Google Scholar
  117. B. Wang, Q. Yang, W. W. Bai et al., “Tongxinluo protects against pressure overload–induced heart failure in mice involving VEGF/Akt/eNOS pathway activation,” PLoS One, vol. 9, no. 6, article e98047, 2014. View at: Publisher Site | Google Scholar
  118. W. W. Bai, Y. F. Xing, B. Wang et al., “Tongxinluo improves cardiac function and ameliorates ventricular remodeling in mice model of myocardial infarction through enhancing angiogenesis,” Evidence-based Complementary and Alternative Medicine, vol. 2013, Article ID 813247, 9 pages, 2013. View at: Publisher Site | Google Scholar
  119. G. S. Cao, H. L. Chen, Y. Y. Zhang et al., “YiQiFuMai powder injection ameliorates the oxygen-glucose deprivation-induced brain microvascular endothelial barrier dysfunction associated with the NF-κB and ROCK1/MLC signaling pathways,” Journal of Ethnopharmacology, vol. 183, pp. 18–28, 2016. View at: Publisher Site | Google Scholar
  120. Y. Q. Wang, C. H. Liu, J. Q. Zhang, D. N. Zhu, and B. Y. Yu, “Protective effects and active ingredients of Yi-Qi-Fu-Mai sterile powder against myocardial oxidative damage in mice,” Journal of Pharmacological Sciences, vol. 122, no. 1, pp. 17–27, 2013. View at: Publisher Site | Google Scholar
  121. L. Z. Pang, A. C. Ju, X. J. Zheng et al., “YiQiFuMai powder injection attenuates coronary artery ligation-induced myocardial remodeling and heart failure through modulating MAPKs signaling pathway,” Journal of Ethnopharmacology, vol. 202, pp. 67–77, 2017. View at: Publisher Site | Google Scholar
  122. L. Xing, M. Jiang, L. Dong et al., “Cardioprotective effects of the YiQiFuMai injection and isolated compounds on attenuating chronic heart failure via NF-κB inactivation and cytokine suppression,” Journal of Ethnopharmacology, vol. 148, no. 1, pp. 239–245, 2013. View at: Publisher Site | Google Scholar
  123. E. P. Daskalopoulos, C. Dufeys, L. Bertrand, C. Beauloye, and S. Horman, “AMPK in cardiac fibrosis and repair: actions beyond metabolic regulation,” Journal of Molecular and Cellular Cardiology, vol. 91, pp. 188–200, 2016. View at: Publisher Site | Google Scholar
  124. Y.-Q. Feng, A.-C. Ju, C.-H. Liu, T. Wang, B.-Y. Yu, and J. Qi, “Protective effect of the extract of Yi-Qi-Fu-Mai preparation on hypoxia-induced heart injury in mice,” Chinese Journal of Natural Medicines, vol. 14, no. 6, pp. 401–406, 2016. View at: Publisher Site | Google Scholar
  125. F. Li, X. Zheng, X. Fan et al., “YiQiFuMai powder injection attenuates ischemia/reperfusion-induced myocardial apoptosis through AMPK activation,” Rejuvenation Research, vol. 19, no. 6, pp. 495–508, 2016. View at: Publisher Site | Google Scholar
  126. National Pharmacopoeia Committee, Pharmacopoeia of the People’s Republic of China, China Medical Science and Technology Press, Bejing, China, 2015.
  127. X. Cai, J. du, L. Li et al., “Clinical metabolomics analysis of therapeutic mechanism of Tongmai Yangxin pill on stable angina,” Journal of Chromatography B, vol. 1100-1101, pp. 106–112, 2018. View at: Publisher Site | Google Scholar
  128. S. Tao, X. Y. Liang, Y. Wang, and Y. Wang, “Screening of active compounds with myocardial protective effects from Tongmai Yangxin pill,” Zhejiang Da Xue Xue Bao Yi Xue Ban, vol. 44, no. 2, pp. 145–153, 2015. View at: Google Scholar
  129. Y. Wang, L. Zhang, Y. Xiao, L. Zhang, and Y. Xing, “Effect of Tongmai Yangxin pills on inflammatory factors and oxidative stress of cardiomyocyte injury induced by hypoxia,” Journal of Traditional Chinese Medicine, vol. 52, no. 4, pp. 326–328, 2011. View at: Google Scholar
  130. K. Kumari and K. T. Augusti, “Lipid lowering effect of S-methyl cysteine sulfoxide from Allium cepa Linn in high cholesterol diet fed rats,” Journal of Ethnopharmacology, vol. 109, no. 3, pp. 367–371, 2007. View at: Publisher Site | Google Scholar
  131. I. S. Son, J. H. Kim, H. Y. Sohn, K. H. Son, J.-S. Kim, and C.-S. Kwon, “Antioxidative and hypolipidemic effects of diosgenin, a steroidal saponin of yam (Dioscorea spp.), on high-cholesterol fed rats,” Bioscience, Biotechnology, and Biochemistry, vol. 71, no. 12, pp. 3063–3071, 2007. View at: Publisher Site | Google Scholar
  132. W. Xia, C. Sun, Y. Zhao, and L. Wu, “Hypolipidemic and antioxidant activities of Sanchi (Radix Notoginseng) in rats fed with a high fat diet,” Phytomedicine, vol. 18, no. 6, pp. 516–520, 2011. View at: Publisher Site | Google Scholar
  133. Q. Li, Y. H. Ye, and Q. Y. Xing, “Progress on the water-soluble constituents and its pharmacology of Panax notoginseng,” Chemical Research in Chinese Universities, vol. 17, no. 12, pp. 1886–1892, 1996. View at: Google Scholar
  134. X. J. Wang and P. Feng, “Antioxidant activity of qizhu tang,” Acta Pharmacologica Sinica, vol. 21, no. 12, pp. 1141–1144, 2000. View at: Google Scholar
  135. A. Basu and K. Penugonda, “Pomegranate juice: a heart-healthy fruit juice,” Nutrition Reviews, vol. 67, no. 1, pp. 49–56, 2009. View at: Publisher Site | Google Scholar
  136. M. Hassanpour Fard, A. E. Ghule, S. L. Bodhankar, and M. Dikshit, “Cardioprotective effect of whole fruit extract of pomegranate on doxorubicin-induced toxicity in rat,” Pharmaceutical Biology, vol. 49, no. 4, pp. 377–382, 2011. View at: Publisher Site | Google Scholar
  137. M. Aviram, M. Rosenblat, D. Gaitini et al., “Pomegranate juice consumption for 3 years by patients with carotid artery stenosis reduces common carotid intima-media thickness, blood pressure and LDL oxidation,” Clinical Nutrition, vol. 23, no. 3, pp. 423–433, 2004. View at: Publisher Site | Google Scholar
  138. A. Al-Jarallah, F. Igdoura, Y. Zhang et al., “The effect of pomegranate extract on coronary artery atherosclerosis in SR-BI/APOE double knockout mice,” Atherosclerosis, vol. 228, no. 1, pp. 80–89, 2013. View at: Publisher Site | Google Scholar
  139. L. Wang, H. Nishida, Y. Ogawa, and T. Konishi, “Prevention of oxidative injury in PC12 cells by a traditional Chinese medicine, Shengmai San, as a model of an antioxidant-basedcomposite formula,” Biological & Pharmaceutical Bulletin, vol. 26, no. 7, pp. 1000–1004, 2003. View at: Publisher Site | Google Scholar
  140. H. T. Yao, Y. W. Chang, C. T. Chen, M. T. Chiang, L. Chang, and T. K. Yeh, “Shengmai San reduces hepatic lipids and lipid peroxidation in rats fed on a high-cholesterol diet,” Journal of Ethnopharmacology, vol. 116, no. 1, pp. 49–57, 2008. View at: Publisher Site | Google Scholar
  141. J. S. You, H. F. Huang, Y. L. Chang, and Y. S. Lee, “Sheng-Mai-San reduces adriamycin-induced cardiomyopathy in rats,” The American Journal of Chinese Medicine, vol. 34, no. 02, pp. 295–305, 2006. View at: Publisher Site | Google Scholar
  142. U. Forstermann, “Oxidative stress in vascular disease: causes, defense mechanisms and potential therapies,” Nature Clinical Practice. Cardiovascular Medicine, vol. 5, no. 6, pp. 338–349, 2008. View at: Publisher Site | Google Scholar
  143. M. F. El-Refaei, S. H. Abduljawad, and A. H. Alghamdi, “Alternative medicine in diabetes - role of angiogenesis, oxidative stress, and chronic inflammation,” The Review of Diabetic Studies, vol. 11, no. 3-4, pp. 231–244, 2014. View at: Publisher Site | Google Scholar
  144. C. Lopez-Alarcon and A. Denicola, “Evaluating the antioxidant capacity of natural products: a review on chemical and cellular-based assays,” Analytica Chimica Acta, vol. 763, pp. 1–10, 2013. View at: Publisher Site | Google Scholar
  145. Y.-M. Lee, P.-Y. Cheng, S.-Y. Chen, M.-T. Chung, and J.-R. Sheu, “Wogonin suppresses arrhythmias, inflammatory responses, and apoptosis induced by myocardial ischemia/reperfusion in rats,” Journal of Cardiovascular Pharmacology, vol. 58, no. 2, pp. 133–142, 2011. View at: Publisher Site | Google Scholar
  146. S. Sanada, I. Komuro, and M. Kitakaze, “Pathophysiology of myocardial reperfusion injury: preconditioning, postconditioning, and translational aspects of protective measures,” American Journal of Physiology-Heart and Circulatory Physiology, vol. 301, no. 5, pp. H1723–H1741, 2011. View at: Publisher Site | Google Scholar
  147. L. Timmers, G. Pasterkamp, V. C. de Hoog, F. Arslan, Y. Appelman, and D. P. V. de Kleijn, “The innate immune response in reperfused myocardium,” Cardiovascular Research, vol. 94, no. 2, pp. 276–283, 2012. View at: Publisher Site | Google Scholar
  148. L.-N. Yu, J. Yu, F.-J. Zhang et al., “Sevoflurane postconditioning reduces myocardial reperfusion injury in rat isolated hearts via activation of PI3K/Akt signaling and modulation of Bcl-2 family proteins,” Journal of Zhejiang University Science B, vol. 11, no. 9, pp. 661–672, 2010. View at: Publisher Site | Google Scholar
  149. H.-F. Luan, Z.-B. Zhao, Q.-H. Zhao, P. Zhu, M.-Y. Xiu, and Y. Ji, “Hydrogen sulfide postconditioning protects isolated rat hearts against ischemia and reperfusion injury mediated by the JAK2/STAT3 survival pathway,” Brazilian Journal of Medical and Biological Research, vol. 45, no. 10, pp. 898–905, 2012. View at: Publisher Site | Google Scholar
  150. A. Dhanasekaran, S. K. Gruenloh, J. N. Buonaccorsi et al., “Multiple antiapoptotic targets of the PI3K/Akt survival pathway are activated by epoxyeicosatrienoic acids to protect cardiomyocytes from hypoxia/anoxia,” American Journal of Physiology-Heart and Circulatory Physiology, vol. 294, no. 2, pp. H724–H735, 2008. View at: Publisher Site | Google Scholar
  151. H. Zhu, Z. Jia, B. R. Misra et al., “Nuclear factor E2-related factor 2-dependent myocardiac cytoprotection against oxidative and electrophilic stress,” Cardiovascular Toxicology, vol. 8, no. 2, pp. 71–85, 2008. View at: Publisher Site | Google Scholar
  152. V. G. Zaha, D. Qi, K. N. Su et al., “AMPK is critical for mitochondrial function during reperfusion after myocardial ischemia,” Journal of Molecular and Cellular Cardiology, vol. 91, pp. 104–113, 2016. View at: Publisher Site | Google Scholar
  153. A. S. Kim, E. J. Miller, T. M. Wright et al., “A small molecule AMPK activator protects the heart against ischemia–reperfusion injury,” Journal of Molecular and Cellular Cardiology, vol. 51, no. 1, pp. 24–32, 2011. View at: Publisher Site | Google Scholar
  154. R. Khatib, P. Joseph, M. Briel, S. Yusuf, and J. Healey, “Blockade of the renin–angiotensin–aldosterone system (RAAS) for primary prevention of non-valvular atrial fibrillation: a systematic review and meta analysis of randomized controlled trials,” International Journal of Cardiology, vol. 165, no. 1, pp. 17–24, 2013. View at: Publisher Site | Google Scholar
  155. M. Zhang, A. Perino, A. Ghigo, E. Hirsch, and A. M. Shah, “NADPH oxidases in heart failure: poachers or gamekeepers?” Antioxidants & Redox Signaling, vol. 18, no. 9, pp. 1024–1041, 2013. View at: Publisher Site | Google Scholar
  156. K. Schröder, M. Zhang, S. Benkhoff et al., “Nox4 is a protective reactive oxygen species generating vascular NADPH oxidase,” Circulation Research, vol. 110, no. 9, pp. 1217–1225, 2012. View at: Publisher Site | Google Scholar
  157. L. Gullestad, T. Ueland, L. E. Vinge, A. Finsen, A. Yndestad, and P. Aukrust, “Inflammatory cytokines in heart failure: mediators and markers,” Cardiology, vol. 122, no. 1, pp. 23–35, 2012. View at: Publisher Site | Google Scholar
  158. X. Yang, Y. Li, Y. Li et al., “Oxidative stress-mediated atherosclerosis: mechanisms and therapies,” Frontiers in Physiology, vol. 8, p. 600, 2017. View at: Publisher Site | Google Scholar
  159. V. Mallika, B. Goswami, and M. Rajappa, “Atherosclerosis pathophysiology and the role of novel risk factors: a clinicobiochemical perspective,” Angiology, vol. 58, no. 5, pp. 513–522, 2007. View at: Publisher Site | Google Scholar
  160. W. Y. W. Lee, L. C. M. Chiu, and J. H. K. Yeung, “Cytotoxicity of major Tanshinones isolated from Danshen (Salvia miltiorrhiza) on HepG2 cells in relation to glutathione perturbation,” Food and Chemical Toxicology, vol. 46, no. 1, pp. 328–338, 2008. View at: Publisher Site | Google Scholar

Copyright © 2019 Xinyu Yang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

More related articles

No related content is available yet for this article.
PDF Download Citation Citation
Download other formatsMore
ePub
XML
Order printed copiesOrder
Views8394
Downloads1342
Citations

Related articles

No related content is available yet for this article.

Article of the Year Award: Outstanding research contributions of 2020, as selected by our Chief Editors. Read the winning articles.