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Molecular Cardioprotective Effects of Curcumin

March 2018

DOI:10.19080/CTBEB.2018.12.555845

Authors:

Mohammad A. I. Al-Hatamleh

Universiti Sains Malaysia

Mohammad Ariff Tengku

Universiti Sultan Zainal Abidin | UniSZA

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djusts multiple cell signaling pathways as well. Many types of research and clinical trials have proven the pharmacokinetics and effects of curcumin against several chronic diseases in human. Turmeric is used because of its multifunctional properties. One of its roles is played in medicinal sciences as it is used to treat the bacterial infection, inflammation, any digestive disorders and burns and it has also been used in many traditional spices in several countries especially in Asia. In our study, we mainly focused on the effects of curcumin on the cardiovascular system and atherosclerosis as diet has many roles in modulating the risk of development of several diseases.

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Mini Review

Volume 12 Issue 4 - March 2018

DOI: 10.19080/CTBEB.2018.12.555845

Curr Trends Biomedical Eng & Biosci

Molecular Cardioprotective Effects of Curcumin

Maira Siddiqui1, Yumna Jawaid1, Al-Hatamleh MAI2, Tengku MA3, Alshajrawi OM2, Ilyas MN2, Rao SK3, Majid L4,

Zubaidi AB2, Nordin Bin Simbak2 and Atif AB2*

1Jinnah University for Women, Pakistan

2Faculty of Medicine, Universiti Sultan Zainal Abidin, Malaysia

3Institute for Community (Health) Development, Universiti Sultan ZainalAbidin, Malaysia

4Department of Chemical Pathology, Pakistan

Submission: February 12, 2018; Published: March 14, 2018

*Corresponding author: Atif Amin Baig, 2Faculty of Medicine, Universiti Sultan Zainal Abidin, Kuala Terengganu, Malaysia, Tel:

Email:

Introduction

Curcumin is recognized as a strong anti-microbial agent

which vigorously prevent from many chronic diseases like

cancer, cardiovascular, diabetes, obesity and neurological and

autoimmune diseases [1]. Turmeric (Curcuma Longta) is a well-

known herb which is cultivated in the southern and southwestern

tropical area region. Turmeric is categorized in the ginger family.

It is very popular in Iran, China, India, Malaysia, Polynesia and

Thailand. It is frequently used in curry and soups etc due to its

unique sensory properties [2]. Such comestible plants are of

   

are non-nutritive chemical present in plants which take their

active role to restrain macro chemical and anatomical process in

the body of living organisms [3].

Curcumin (diferuloylmethane) is a major compound

present in Turmeric (Curcumin longa) which is an Indian spice.

Curcumin is known for its pharmacological activity [4]. The

active compound present in curcumin is curcuminoid which is

predominant phenol and provides identical bright yellow color

to turmeric. The total concentration of curcuminoid present

in curcumin is about 75% of total curcuminoids present in

turmeric. C21H20O6 is the chemical formula of curcumin it has

branched structure. Curcumin has tripartite functions, not only

it is used as spice it is also used for its pigments and its medical

purposes since a long period [5]. In research, it is mentioned that

   

  

functions at a time and it even doesn’t have any side effect. It can



Curcumin is a well-known polyphenol which has an anti-

  

antioxidant, wound healing, and anti-microbial characteristics

[8]. According to study which was carried since past quarter

century, the pharmacokinetics, effectiveness and protective

nature of curcumin’s capability of curing diseases was

determined [9].

Multifaceted Barrier against Heart Diseases

Curcumin is considered as a vital antioxidant that takes

part in improving heart health. It maintains endothelial

functions of the body with are directly related to cardiovascular

diseases [10]. The endothelium produces some vasodilator and

vasoconstrictor functions which help in maintaining the activity

     

function is directly linked to the long lasting effects of cardio

vascular diseases. Some compounds in food can disturb the

functioning of these vasco promoters such as Lipids usually low-

density lipoprotein and cholesterol may interfere the functioning

of vascopromoter by minimizing the bioavailability of nitric acid



as kappa [11].

Curr Trends Biomedical Eng & Biosci 12(4): CTBEB.MS.ID.555845 (2018) 001

Abstract

Curcumin is a polyphenolic compound of turmeric. It is considered best to use in our daily lives because of its therapeutic property and

it adjusts multiple cell signaling pathways as well. Many types of research and clinical trials have proven the pharmacokinetics and effects of

curcumin against several chronic diseases in human. Turmeric is used because of its multifunctional properties. One of its roles is played in



traditional spices in several countries especially in Asia. In our study, we mainly focused on the effects of curcumin on the cardiovascular system

and atherosclerosis as diet has many roles in modulating the risk of development of several diseases.

Current Trends in Biomedical Engineering & Biosciences

How to cite this article: Atif AB, Maira S, Yumna J, Al-Hatamleh MAI, Tengku MA et.al. Molecular Cardioprotective Effects of Curcumin. Curr Trends

Biomedical Eng & Biosci. 2018; 12(4): 555845. DOI: 10.19080/CTBEB.2018.12.555845.

002

Some recent studies show that curcumin may reduce the

risk of complicated heart attack and strokes by preventing the

development of atherosclerosis, or clogged arteries not only

         

against many other risk factors, including reducing chronic

       



Key to a good heart health

Curcumin is an excellent compound that is suitable for

the patients who have gone through the heart attack or heart

surgeries because its impacts on the genes and help in quick

recovery they take part in cardiac repair and proper cardiac

functioning [14].

Reduction in plaque buildup

Turmeric is known for curing a wide range of heart-related

disorders that occur due to plaque buildup and clot formation

in the arteries of the heart because turmeric can avert clot

formation and prevent plaque buildup. Usually, heart diseases

occurred due to blood clots in the arteries while turmeric takes

part to prevent this blockage and ultimately it lowers the risk of

heart attacks [7,14].

Reduction in bad cholesterol

Curcumin can also help in reducing the bad cholesterol as it

prevents the clotting of blood platelets as it is the main culprit of

heart diseases. It sends signals to the livers which enhance the

production of messenger RNA [7,12]. The main goal of turmeric

is to increase HDL level and decrease LDL level. The increased

LDL level results in blockage of the arteries. Curcumin helps the

liver to remove bad cholesterol so that the risk of heart attack

can be minimized [7,12].

Preventing atrial/ventricular arrhythmias

The provocative effects of curcumin have the possibility

of preventing the atrial arrhythmias and it also plays a role to

correct the pathway of Ca (2+) homeostasis which can lead in

the prevention of some ventricular arrhythmias that prevent

chances of heart attack and stroke.

Studies on Curcumin Prole

         

curcumin shows an anti-cancer effect in living organisms mainly

in animals and humans. It has been reported that curcumin

suppresses the carcinogenic activity of abnormal cells that cause

cancer in colon, breast, oesophagus, duodenums, oral cavity and

liver as well as prostate.

Curcumin used in Asia for its many therapeutic effects on

human health. In one study, protective effects of curcumin on

cardio health were demonstrated. And it was suggested that it

has a wide range of molecular targets including various healing

       

carcinogenic [15].

Similarly, another study showed that 10mg of curcumin

  

levels and increased the serum HDL levels in patients with

atherosclerosis.

Curcumin & Diabetic Cardiovascular Complications

Diabetic cardiovascular or diabetic heart disease refers to a

heart disease in a person who has diabetes. And here we have

mentioned some complications of diabetic cardiovascular. In one

study it was found that increased oxidative stress is linked to

the pathogenesis of chronic diabetic complications. In another

study, it was suggested that nitric oxide (NO) pathway plays role

in generating free radicals.

Curcumin because of its remarkable anti-oxidant property

has shown its effects on NO pathway oxidation in order to

control the generation of free radicals. It seizes the reaction by



development of cardiovascular complications in diabetes in a

study.

Curcumin & atherosclerosis

The medicinal property of curcumin in reducing the serum

cholesterol level may protect against the pathological changes

occurring with atherosclerosis. Atherosclerosis arises from

various bodily processes that are characterized by either

      

       

Smooth Muscle Cells) are the important cellular components

of vascular media, and from a study, it came to know that its

migration and proliferation lead to the formation of neointima

(a thickened layer formed by migration of vascular cells) renders

vessels particularly sensitive to atherosclerosis [17,18]. That’s



development of atherosclerosis. Curcumin has such potential to

be effective in this case [19].

Curcumin & the cardiovascular system

Curcumin decreases the severity of pathological changes

and thus protects from damage caused by myocardial infarction.

Curcumin improves Ca2+ -transport and its slippage from the

cardiac muscle sarcoplasmic reticulum, thereby raising the

possibility of pharmacological interventions to correct the

defective Ca2+ homeostasis in the cardiac muscle.

Curcumin & its consequence on lipid metabolism

Curcumin increases the alpha-tocopherol level and lowers

the low-density lipoproteins and in vivo interaction between

curcumin and tocopherol augments the bioavailability of vitamin

E and reduces cholesterol levels. Curcumin binds with egg and

soy-phosphatidylcholine, which in turn make a contractual with

divalent metal ions to offer antioxidant activity.

Conclusion

The pharmacological properties and application of curcumin

are now making progress very rapidly. According to one clinical

Current Trends in Biomedical Engineering & Biosciences

How to cite this article: Atif AB, Maira S, Yumna J, Al-Hatamleh MAI, Tengku MA et.al. Molecular Cardioprotective Effects of Curcumin. Curr Trends

Biomedical Eng & Biosci. 2018; 12(4): 555845. DOI: 10.19080/CTBEB.2018.12.555845.

003

study curcumin show its remarkable effects in almost all of

the major organ systems of the human body. It also acts as an

antioxidant by scavenging free radicals and giving a healthy life.

By the addition of curcumin to our daily life, we can get rid of

several health disorders mainly heart which plays a vital role to

maintain the body functions by supplying blood.

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Nov 2015
CRIT REV FOOD SCI

Turmeric (Curcuma Longa) is a type of herb belonging to ginger family, which is widely grown in southern and south western tropical Asia region. Turmeric, which has an importance place in the cuisines of Iran, Malesia, India, China, Polynesia and Thailand, is often used as spice and has an effect on the nature, color and taste of foods. Turmeric is also known to have been used for centuries in India and China for the medical treatments of such illnesses as dermatologic diseases, infection, stress and depression. Turmeric's effects on health generally are centered upon an orange-yellow colored, lipophilic polyphenol substance called 'curcumin', which is acquired from the rhizomes of the herb. Curcumin is known recently to have antioxidant, anti-inflammatory, anti-cancer effects and, thanks to these effects, to have an important role in prevention and treatment of various illnesses ranging notably from cancer to autoimmune, neurological, cardiovascular diseases and diabetic. Furthermore, it is aimed to increase the biological activity and physiological effects of the curcumin on the body by synthesizing curcumin analogues. This paper reviews the history, chemical and physical features, analogues, metabolites, mechanisms of its physiological activities and effects on health of curcumin.

Therapeutic Roles of Curcumin: Lessons Learned from Clinical Trials

Article

Full-text available

Nov 2012
AAPS J

Extensive research over the past half century has shown that curcumin (diferuloylmethane), a component of the golden spice turmeric (Curcuma longa), can modulate multiple cell signaling pathways. Extensive clinical trials over the past quarter century have addressed the pharmacokinetics, safety, and efficacy of this nutraceutical against numerous diseases in humans. Some promising effects have been observed in patients with various pro-inflammatory diseases including cancer, cardiovascular disease, arthritis, uveitis, ulcerative proctitis, Crohn's disease, ulcerative colitis, irritable bowel disease, tropical pancreatitis, peptic ulcer, gastric ulcer, idiopathic orbital inflammatory pseudotumor, oral lichen planus, gastric inflammation, vitiligo, psoriasis, acute coronary syndrome, atherosclerosis, diabetes, diabetic nephropathy, diabetic microangiopathy, lupus nephritis, renal conditions, acquired immunodeficiency syndrome, β-thalassemia, biliary dyskinesia, Dejerine-Sottas disease, cholecystitis, and chronic bacterial prostatitis. Curcumin has also shown protection against hepatic conditions, chronic arsenic exposure, and alcohol intoxication. Dose-escalating studies have indicated the safety of curcumin at doses as high as 12 g/day over 3 months. Curcumin's pleiotropic activities emanate from its ability to modulate numerous signaling molecules such as pro-inflammatory cytokines, apoptotic proteins, NF-κB, cyclooxygenase-2, 5-LOX, STAT3, C-reactive protein, prostaglandin E(2), prostate-specific antigen, adhesion molecules, phosphorylase kinase, transforming growth factor-β, triglyceride, ET-1, creatinine, HO-1, AST, and ALT in human participants. In clinical trials, curcumin has been used either alone or in combination with other agents. Various formulations of curcumin, including nanoparticles, liposomal encapsulation, emulsions, capsules, tablets, and powder, have been examined. In this review, we discuss in detail the various human diseases in which the effect of curcumin has been investigated.

Roles of heme oxygenase-1 in curcumin-induced growth inhibition in rat smooth muscle cells

Article

Full-text available

Jul 2007

In vascular smooth muscle cells (VSMCs), induction of the heme oxygenase-1 (HO-1) confers vascular protection against cellular proliferation mainly via its up-regulation of the cyclin-dependent kinase inhibitor p21(WAF1/CIP1) that is involved in negative regulation of cellular proliferation. In the present study, we investigated whether the phytochemical curcumin and its metabolite tetrahydrocurcumin could induce HO-1 expression and growth inhibition in rat VSMCs and, if so, whether their antiproliferative effect could be mediated via HO-1 expression. At non-toxic concentrations, curcumin possessing two Michael-reaction acceptors induced HO-1 expression by activating antioxidant response element (ARE) through translocation of the nuclear transcription factor E2-related factor-2 (Nrf2) into the nucleus and also inhibited VSMC growth triggered by 5% FBS in a dose-dependent manner. In contrast, tetrahydrocurcumin lacking Michael-reaction acceptor showed no effect on HO-1 expression, ARE activation and VSMC growth inhibition. The antiproliferative effect of curcumin in VSMCs was accompanied by the increased expression of p21(WAF1/CIP1). Inhibition of VSMC growth and expression of p21(WAF1/CIP1) by curcumin were partially, but not completely, abolished when the cells were co- incubated with the HO inhibitor tin protoporphyrin. In human aortic smooth muscle cells (HASMCs), curcumin also inhibited growth triggered by TNF-alpha and increased p21(WAF1/CIP1) expression via HO-1-dependent manner. Our findings suggest that curcumin has an ability to induce HO-1 expression, presumably through Nrf2-dependent ARE activation, in rat VSMCs and HASMCs, and provide evidence that the antiproliferative effect of curcumin is considerably linked to its ability to induce HO-1 expression.

Curcumin, The Golden Nutraceutical: Multitargeting for Multiple Chronic Diseases

Article

Sep 2016
BRIT J PHARMACOL

Curcumin, a yellow pigment in the Indian spice Turmeric (Curcuma longa), which is chemically known as diferuloylmethane, was first isolated exactly two centuries ago in 1815 by two German Scientists, Vogel and Pelletier. However, according to the pubmed database, the first study on its biological activity as an antibacterial agent was published in 1949 in Nature and the first clinical trial was reported in The Lancet in 1937. Although the current database indicates almost 9000 publications on curcumin, until 1990 there were less than 100 papers published on this nutraceutical. At the molecular level, this multitargeted agent has been shown to exhibit anti-inflammatory activity through the suppression of numerous cell signalling pathways including NF-κB, STAT3, Nrf2, ROS and COX-2. Numerous studies have indicated that curcumin is a highly potent antimicrobial agent and has been shown to be active against various chronic diseases including various types of cancers, diabetes, obesity, cardiovascular, pulmonary, neurological and autoimmune diseases. Furthermore, this compound has also been shown to be synergistic with other nutraceuticals such as resveratrol, piperine, catechins, quercetin and genistein. To date, over 100 different clinical trials have been completed with curcumin, which clearly show its safety, tolerability and its effectiveness against various chronic diseases in humans. However, more clinical trials in different populations are necessary to prove its potential against different chronic diseases in humans. This review's primary focus is on lessons learnt about curcumin from clinical trials. Linked articles: This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc.

Atherosclerosis – An Inflammatory Disease

Article

May 1996

Ruby Ross

The advanced lesions of atherosclerosis represent the culmination of a specialized form of chronic inflammation followed by a fibroproliferative process that takes place within the intima of the affected artery. Proliferation of smooth muscle cells and generation of connective tissue occur. Proliferation results from interactions between arterial smooth muscle, monocyte-derived macrophages, T lymphocytes, and endothelium. The initial lesion of atherosclerosis, the fatty streak, begins as an accumulation of monocytederived macrophages and T lymphocytes, which adhere and migrate into the intima of the affected artery. Smooth muscle cells, which are present in the intima or which migrate into the intima from the media, then replicate. Monocyte-derived macrophages and T cells also replicate during lesion formation and progression due to the production of cytokines and growth-regulatory molecules. These molecules determine whether there is proliferation and lesion progression or inhibition of proliferation and lesion regression. Several growthregulatory molecules may play critical roles in this process, including platelet-derived growth factor (PGDF), transforming growth factor beta, fibroblast growth factor, heparinbinding epidermal growth factor-like growth factor, and others. PDGF may be one of the principal components in this process because protein containing the PDGF B-chain has been demonstrated within activated lesion macrophages during every phase of atherogenesis. The presence of this growth factor and its receptors on lesion smooth muscle cells creates opportunities for smooth muscle chemotaxis and replication. Smooth muscle proliferation depends upon a series of complex signals based upon cellular interactions in the local microenvironment of the artery. The intracellular signalling pathways for mitogenesis versus chemotaxis are being investigated for smooth muscle. The roles of the cytokines and growth-regulatory peptides involved in these cellular interactions represent critical points of departure for intervention and the development of new diagnostic methods. In addition, magnetic resonance imaging has been developed to demonstrate the fine structure of lesions of atherosclerosis in peripheral arteries not subject to cardiac motion. This noninvasive methodology holds great promise for the future of these approaches.

Endothelial function of the popliteal artery in patients with coronary artery disease

Article

Jan 2001
Atherosclerosis

Coronary artery disease (CAD) is associated more closely with atherosclerosis in the popliteal than in the brachial artery. This case-control study aimed at clarifying whether endothelial dysfunction of patients with CAD can be detected non-invasively in the popliteal artery by means of ischemia-induced flow-mediated dilation (FMD) and cold pressor reaction (CPR), and how it compares with the brachial artery. We further investigated a new mode of evaluation of the CPR. Eleven cases with CAD were compared with 16 matched healthy controls. Popliteal and brachial arterial diameter was monitored by ultrasound for 20 min following ischemia and cold pressor. For CPR, the difference between maximum and minimum diameter was defined as maximum vasomotion. In the popliteal artery, maximum vasomotion and FMD were significantly smaller in cases than in controls, the difference being more pronounced than in the brachial artery, where only maximum vasomotion was significantly smaller. After exclusion of current smokers, only the difference in maximum vasomotion of both arteries remained significant. We conclude that maximum vasomotion may be more sensitive for detection of endothelial dysfunction than FMD. Endothelial dysfunction in patients with CAD is more pronounced in the popliteal artery than in the brachial artery.

The protective role of curcumin in cardiovascular diseases

Article

Mar 2009

Curcumin (diferuloylmethane) is a polyphenol responsible for the yellow color of the curry spice turmeric. It has been used in a variety of diseases in traditional medicine. Modern scientific research has demonstrated its anti-inflammatory, anti-oxidant, anti-carcinogenic, anti-thrombotic, and cardiovascular protective effects. In this review, we focused mainly on the effects of curcumin on the cardiovascular system. The antioxidant effects of curcumin have been shown to attenuate adriamycin-induced cardiotoxicity and may prevent diabetic cardiovascular complications. The anti-thrombotic, anti-proliferative, and anti-inflammatory effects of curcumin and the effect of curcumin in decreasing the serum cholesterol level may protect against the pathological changes occurring with atherosclerosis. The p300-HAT inhibitory effects of curcumin have been demonstrated to ameliorate the development of cardiac hypertrophy and heart failure in animal models. The inflammatory effects of curcumin may have the possibility of preventing atrial arrhythmias and the possible effect of curcumin for correcting the Ca(2+) homeostasis may play a role in the prevention of some ventricular arrhythmias. The preclinical studies from animal to clinical data in human are discussed.

Plaque Rupture in Humans and Mice

Article

May 2007
ARTERIOSCL THROM VAS

Despite the many studies of murine atherosclerosis, we do not yet know the relevance of the natural history of this model to the final events precipitated by plaque disruption of human atherosclerotic lesions. The literature has become particularly confused because of the common use of terms such as "instability", "vulnerable", "rupture", or even "thrombosis" for features of plaques in murine model systems not yet shown to rupture spontaneously and in an animal surprisingly resistant to formation of thrombi at sites of atherosclerosis. We suggest that use of conclusory terms like "vulnerable" and "stable" should be discouraged. Similarly, terms such as "buried fibrous caps" that imply preceding events that are unproven tend to create confusion. We will argue that such terminology may mislead readers by implying knowledge that does not yet exist. We suggest, instead, a focus on specific processes that various forms of data have implicated in plaque progression. For example, formation of the fibrous cap, protease activation, and cell death in the necrotic core can be well described and have all been modeled in well-defined experiments. The relevance of such well-defined, objective, descriptive observations in the mouse can be tested for relevance against data from human pathology.

Curcumin as “Curecumin”: From Kitchen to Clinic

Article

Mar 2008

Although turmeric (Curcuma longa; an Indian spice) has been described in Ayurveda, as a treatment for inflammatory diseases and is referred by different names in different cultures, the active principle called curcumin or diferuloylmethane, a yellow pigment present in turmeric (curry powder) has been shown to exhibit numerous activities. Extensive research over the last half century has revealed several important functions of curcumin. It binds to a variety of proteins and inhibits the activity of various kinases. By modulating the activation of various transcription factors, curcumin regulates the expression of inflammatory enzymes, cytokines, adhesion molecules, and cell survival proteins. Curcumin also downregulates cyclin D1, cyclin E and MDM2; and upregulates p21, p27, and p53. Various preclinical cell culture and animal studies suggest that curcumin has potential as an antiproliferative, anti-invasive, and antiangiogenic agent; as a mediator of chemoresistance and radioresistance; as a chemopreventive agent; and as a therapeutic agent in wound healing, diabetes, Alzheimer disease, Parkinson disease, cardiovascular disease, pulmonary disease, and arthritis. Pilot phase I clinical trials have shown curcumin to be safe even when consumed at a daily dose of 12g for 3 months. Other clinical trials suggest a potential therapeutic role for curcumin in diseases such as familial adenomatous polyposis, inflammatory bowel disease, ulcerative colitis, colon cancer, pancreatic cancer, hypercholesteremia, atherosclerosis, pancreatitis, psoriasis, chronic anterior uveitis and arthritis. Thus, curcumin, a spice once relegated to the kitchen shelf, has moved into the clinic and may prove to be "Curecumin".

Therapeutic potential of curcumin, in medicinal chemistry

Jan 2013
89-99

S Padhye
D Chavan
S Pandey
J Deshpande
K V Swamy

Padhye S, Chavan D, Pandey S, Deshpande J, Swamy KV (2013) Therapeutic potential of curcumin, in medicinal chemistry. Acta Chimica Slovaca 6(1): 89-99.