ReviewCurcumin as a potential protective compound against cardiac diseases
Graphical abstract
Introduction
According to the 2016 Heart Disease and Stroke Statistics report, cardiac diseases are currently the leading causes of mortality in both developed and developing countries and, to a large extent, surpass cancer and cerebrovascular-related deaths worldwide [1]. Cardiac diseases consist of a broad spectrum of diseases, such as myocardial ischemia, cardiomyopathy, hypertension, and arrhythmia, all of which resulted in 17.3 million deaths (31.5%) in 2013 compared to 12.3 million (25.8%) in 1990 [2]. According to a WHO/FAO report (1974), Indian populations who ingest between 2 and 2.5 g turmeric daily are healthier and have lower risk of cardiac diseases [3]. This suggests that cardiac diseases are preventive and depend largely on eating habits, further supporting curcumin as a therapeutic candidate for cardiac diseases.
The last decade has witnessed a surge in the use of plant-derived products (also known as phytochemicals or phytoceuticals) that serve as preventive and therapeutic drugs against various diseases. Turmeric (Curcuma longa), a type of spice in curry dishes, is a major ingredient of mustard preparations used as a garnish in the United States. Turmeric was first used almost 3000 years ago as an anti-inflammatory agent and was introduced to the Europe and North America in the 14th century. In Ayurvedic medicine, turmeric has been used to treat common colds, coughs, jaundice and other common diseases [4]. Curcumin [1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione], also known as diferuloylmethane, is a well-known dietary polyphenol found in turmeric. It was first discovered approximately two centuries ago when Vogel and Pelletier reported the isolation of a “yellow coloring-matter” from the rhizomes of turmeric and named it curcumin. Thereafter, it was identified by Rougghley and Whitting in 1973 [5] and came into view of researchers progressively. The major curcuminoids present in turmeric are curcumin (curcumin I) demethoxycurcumin (curcumin II), bisdemethoxycurcumin (curcumin III), and cyclocurcumin (curcumin IV) [6], [7]. Initially, it was proven that the anti-inflammatory effects of curcumin are comparable to the classical drugs hydrocortisone, phenylbutazone, and ibuprofen. Notably, curcumin almost produces no toxicity in humans compared to common anti-inflammatory drugs but may decrease white blood cell count, promote ulcer formation and intestinal bleeding. Moreover, curcumin has an immense bactericidal effect that can meet the standards and effects of antibiotics. Curcumin exerts protective effects on a variety of diseases such as cardiac diseases [8], cancer [9], diabetes [10], Alzheimer’s disease [11], rheumatoid arthritis [12], and psoriasis [13]. Our laboratory has discovered that curcumin is a protective compound against myocardial ischemia [14] and endothelial injury [15], whereas its relationship with cardiac diseases has not been well reviewed. Therefore, further understanding of the mechanisms by which curcumin produces these effects may aid in experimental studies and provide therapeutic avenues for cardiac diseases.
In this review, we first provide a basic background of cardiac diseases and curcumin and continue with the description of pivotal actions of curcumin in embryonic heart development. Secondly, we introduce the biological actions of curcumin in cardiac diseases, including its anti-oxidative, anti-apoptotic, and anti-inflammatory actions. Thirdly, curcumin can exert its beneficial effects in myocardial ischemia, diabetic cardiomyopathy, hypertrophic cardiomyopathy, arrhythmia, and doxorubicin-related cardiotoxicity. Ultimately, we will discuss the clinical evidence, negative effects, remaining obstacles and advancement, further directions and prospective applications of curcumin. This review highlights recent advances and provides a comprehensive picture of curcumin, which may be helpful in drug design and clinical therapy of cardiac diseases.
Section snippets
Curcumin and embryonic heart development
Embryonic heart development is a crucial process throughout the whole growth stage, the dysfunction of which may contribute to postnatal cardiomyopathy or congenital heart disease. Previous studies have revealed that curcumin mediates histone acetylation and the expression of cardiac transcription factors, ultimately controlling the progress of normal heart development [16], [17], [18]. Relevant mechanisms involve: 1) curcumin activating the NO signaling and inhibiting the acetylation of
Oxidative stress
Oxidative stress is a pathophysiological process manifesting as the overproduction of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in response to oxidative stimuli. The heart is a highly energy-consuming organ and utilizes much energy whereas the energy storage only sustains the heart for a few minutes under energy crisis, which underscores the high vulnerability of the heart to oxidative stimuli. As discussed above, curcumin has traditionally been regarded as an
Myocardial ischemia/reperfusion injury
Myocardial ischemia/reperfusion injury (IRI) following cardiac surgery and myocardial infarction is a primary cause of heart failure and cardiac mortality [14]. As previously mentioned, curcumin inhibits oxidative stress [34], apoptosis [14], and inflammation [52] and exerts cardioprotective effects upon IRI, thereby reducing the release of cardiac lactate dehydrogenase (LDH) and creatine kinase (CK) and improving post-ischemic cardiac function. Curcumin also exerts definitive protective
Clinical evidence of curcumin
Accumulating clinical evidence has revealed that curcumin possesses a variety of beneficial properties in cancer, inflammatory bowel disease, rheumatoid arthritis, and other disorders [79], [80], [81]. However, few studies have been conducted in patients with cardiac diseases. Herein, we would like to provide a comprehensive review on the clinical evidence of curcumin.
Wongcharoen’s group recruited and randomly allocated 121 consecutive patients undergoing coronary artery bypass grafting (CABG)
Conclusions
Initially, we proposed a hypothesis that curcumin is a protective molecule against cardiac diseases, as curcumin is a well-known dietary polyphenol and protective drug against cardiac diseases through attenuating oxidative stress, apoptosis, and inflammation. Through these mechanisms, curcumin exerts protective effects against several cardiac diseases, including myocardial ischemia, diabetic cardiomyopathy, hypertrophic cardiomyopathy, arrhythmia, and doxorubicin-related cardiotoxicity.
Disclosure
None
Acknowledgement
This work was supported by the National Natural Science Foundation of China (81500263, 81600306, 81403182, 81200133), China Postdoctoral Science Foundation (2016T90973 and 2015M572681), Jiangsu Top Expert Program in Six Professions (2013-WSN-032, 2014-WSN-048), Jiangsu Province Health Department Program Grant (Z201411), Key Project supported by Medical Science and technology development Foundation, Nanjing Department of Health (JQX14006, YKK12056).
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These authors contributed equally to this work.