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\def\RunningAuthor{Ajah O. et al.}
\firstPage{2454}
\articleType{Review Article}
\receivedDate{29 Feb 2020}
\acceptedDate{28 Apr 2020}
\revisedDate{25 Apr 2020}
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\title{\textbf{Medicinal Plants with Cardioprotective Potency and Some Possible Cardiac Biomarkers for Monitoring and Diagnosing Myocardial Infarction: A Review}}
\author{Ajah~O\textsuperscript{*},  
            Omodamiro~O~D, 
            Christian~E~Odo~\\[5pt]{Pharmacology Unit, Department of Biochemistry, Michael Okpara University of Agriculture, Umudike, Umuahia Abia State, Nigeria}}

\begin{abstract}
Following the increasing rate of Cardiovascular diseases, actions have been taken and geared towards the discovery of new leads (drugs) since the existing drugs treat and manage some of these Cardiovascular ailments but with proven adverse effects on the side of the patients. Coronary artery disease which is also called Ischemic heart disease is a crucial problem worldwide, and it's known as a major non-transmissible disease. A good example of ischemic heart disease is acute myocardial infarction (MI), and its manifest due to inequality between coronary blood supply and myocardial demand. Sustained ischemia causes myocardial infarction, which leads to myocardial cell death. Cardiac biomarkers are enzymes/proteins that are used as essential tools in cardiology for primary and secondary prevention, diagnosis and management of acute myocardial infarction and other heart-related issues. The treatment and management of diseases in the African continent are achieved mostly with traditional medicine, and Plants are known to contain active components which possess medical properties that are harnessed for the treatment of different diseases. So many medicinal plants have shown to be potent in the treatment and management of this life-threatening condition known as acute myocardial infarction (heart attack). Some research-proven cardioprotective plants and possible tools for evaluating their potency are reviews in this article. 
\end{abstract}\def\keywordstitle{Keywords}

\begin{keywords}Cardioprotective,\newline Myocardial infarction,\newline Cardiac biomarkers,\newline Diagnosis
\end{keywords}
\twocolumn[ \maketitle {\printKwdAbsBox}]
\makeatletter{\raggedright\textsuperscript{*}Corresponding Author\par Name:\ Ajah~O~\\ Phone:\ +23408064055271~\\  Email:\ ajah.obinna90@gmail.com
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\section{Introduction}
Following the increasing rate of Cardiovascular diseases, actions have been taken and geared towards the discovery of new leads (drugs) since the existing drugs treat and manage some of these Cardiovascular ailments but with proven adverse effects on the side of the patients.

The treatment and management of diseases in the African continent are achieved mostly with traditional medicine and Plants are known to contain active components which possess medical properties that are harnessed for the treatment of different diseases \unskip~\citep{1108045:22250709}. Human survival is next to impossible without the heart. Significant reduction or blockage in the blood supply to the heart cause myocardial infarction and necrosis of myocytes is the pathological indication of myocardial infarction \unskip~\citep{1108045:22250559}. Several cardiac biomarkers can be used to monitor the effectiveness of any cardioprotective medicinal plant and for the diagnosis of myocardial infarction and other heart-related issues \unskip~\citep{1108045:22250680}. This article reviewed some of the medicinal plants with cardioprotective potency and possible cardiac biomarkers for monitoring and diagnosing myocardial infarction. 

\textbf{Cardioprotective Properties of some Medicinal Plants}

\textit{\textbf{Moringa plant}}

Moringa plant is a herbaceous plant commonly used and widely known for its medicinal effects. A report from \unskip~\cite{1108045:22250647} revealed that \textit{Moringa oleifera } has some cardioprotective activity where the aqueous extract of \textit{Morning oleifera } was administered to the Isoproterenol induced rats and it showed significant activity in lowering the cholesterol in the rats. Further study confirmed its cardioprotective activity in rats, where it reveals that the antioxidant defense system of the butanolic fraction of \textit{Moringa oleifera } could be responsible for\textit{\space } the Protection of the myocardium \unskip~\citep{1108045:22250611}. \textit{Moringa oleifera} leaf also has the ability to reduced cardiac function biomarkers in rats. \unskip~\cite{1108045:22250609} reported that \textit{Moringa oleifera} increased serum HDL-C and reduced AST which are pointers that \textit{Moringa oleifera} leaf extract might exhibit cardioprotective action as well. 

\textit{\textbf{Vernonia amygdalina}}

V. amygdalina (bitter leaf) is a widely used local plant in Nigeria. It is used for both therapeutic and nutritional purposes.

\unskip~\cite{1108045:22250589} reported that \textit{aqueous} extract of \textit{V. amygdalina } exerts significant protection against oxidative stress induced by the Red dye adulterated palm oil. \unskip~\cite{1108045:22250587} reported that \textit{Ocimum gratissimum } and \textit{V. amygdalina } possess some cardiac protection on Streptozomycin induced rats, although the cardiac activity of \textit{Ocimum gratissimum} was higher than \textit{V. amygdalina.}

\textit{\textbf{Garcinia kola}}

Bitter kola is a much-appreciated ingredient in African traditional medicine. Kolaviron has been revealed to exhibit many pharmacological effects such as antioxidant, antiatherogenic, antihepatotoxic, antidiabetic etc.

A study conducted by \unskip~\cite{1108045:22250585} revealed that kolaviron has the ability to reduce cholesterol both in the heart. Hence, \textit{Garcinia kola} can be used as a dietary supplement in the prevention and treatment of heart diseases.

Furthermore, both cardiac glycosides and steroidal compounds were found in\textit{ G. kola} extracts responsible for the treatment of chest pain and cardiac infection. More also, a review by \unskip~\cite{1108045:22250559} described the effect of \textit{Garcinia kola} on isoproterenol-induced neurosis in rats with a decrease in elevated biomarkers. Additionally, \textit{Garcinia kola} contains a vasoactive substance that has blood pressure reducing effect.

\textit{\textbf{Anarcadium occidentale}}

\textit{Anacardium occidentale} Linn is a plant belonging to the family Anacardiaceae. The plant has been used as folkoric medicine in the treatment of inflammation, diabetes, hypertension etc. \unskip~\cite{1108045:22250337}, in his study with \textit{A. Occidentale} in rats, revealed the antihypertensive activity (hypertension which is a risk factor that can cause heart failure, heart attack or even any possible cardiovascular diseases) Hexane extract of the plant. It is also worthy to note that the bark stem extract of \textit{Anacardium occidentale } has shown hypotensive activities i\textit{n vivo} and cardio-inhibitory activities \unskip~\citep{1108045:22250337}

\textit{\textbf{Mucuna puriens}} \textit{\space }

\textit{Mucuna pruriens}, generally known as velvet bean, belongs to the family Fabaceae. Different parts of the plant possess valuable medicinal properties in the traditional system of medicine. A studies by \unskip~\cite{1108045:22250264} stated that methanol extract of \textit{Mucuna pruriens} pre-co-treatment prohibited nearly entire parameters of isoproterenol persuaded myocardial necrosis in rats. Therefore, the protection of the heart against isoproterenol encouraged myocardial necrosis was through sustaining endogenous antioxidant enzyme actions, which provides scientific proof of the traditional values.

\unskip~\cite{1108045:22250262} conducted an interesting study were the rats involved were induced with snake venom and was pretreated with \textit{M. puriens } extract. The results demonstrated a protective effect of \textit{Mucuna pruriens} pretreatment against snake venom poisoning, which may involve a direct action on the heart. \textit{M. pruriens} seed may have a unique cardioprotective agent with potential therapeutic value. Another confirmatory study carried in Malaysia where the rats were injected with snake venom and pretreated with \textit{Mucuna puriens} extract. The result suggested that injection of \textit{Mucuna pruriens } confers protection against C. rhodostoma venom \unskip~\citep{1108045:22250262}.

\textit{\textbf{Zingiber officinale}}

Ginger botanically called Zingiber officinale Roscoe and from the family, Zingiberaceae is one of the world's best-known spices, and it has also been universally used throughout history for its health benefits. Ginger has cardioprotective potential and can decrease cardiac biomarkers. 

Another study by \unskip~\cite{1108045:22250261} confirmed the cardioprotective action of ginger, where the findings suggested that the ethanol extract of ginger exerted significant cardioprotective effects by maintaining the enzyme marker activities and preserving the myocardium integrity. The use of ginger in the treatment of heart diseases has also been reported \unskip~\citep{1108045:22250261}.

A report by \unskip~\cite{1108045:22250259} revealed that hyperlipidemia has an adverse effect on cardiac functions, oxidative stress and antioxidant status. However, ethanolic extract of ginger is known to have antioxidant, hypolipidemic and androgenic effect as well as cardio-protective action in hyperlipidemic rats. 

\textit{\textbf{Allium sativum}}

Garlic (Allium sativum) is a well-known medicinal plant that grows in all parts of the world and the bulb is extensively used in both traditional and general medicine. \unskip~\cite{1108045:22250256} reported that chronic oral administration of garlic homogenate protected the rat heart from in vitro ischemic reperfusion injury. allicin which is a principal bioactive compound of garlic juice, may be responsible for the protective role \unskip~\citep{1108045:22250256}.

Findings by \unskip~\cite{1108045:22250253} provide evidence that administration of Garlic extract can protect the heart through reducing oxidative stress and controlling cardiac Na+/K+ -ATPase activity and Ca2+ levels, hence confirming the myocardial protective ability of Garlic. 

A study by \unskip~\cite{1108045:22250220} stated that Garlic oil has a cardioprotective activity, which was evident in its ability to low the levels of serum marker enzymes and lipid peroxidation and elevation the levels of GSH \unskip~\citep{1108045:22250220}.\textit{}

\textit{\textbf{Allium cepa}}

\textit{Allium cepa} belong to the family Liliaceae, cultivated for over five thousand years and have been used in herbal medicine and as an indispensable flavouring agent and as a vegetable.

An \textit{in vivo } study by \unskip~\cite{1108045:22250219} showed that ISO produced significant myocardial injury and administration of \textit{A. cepa} in the dose of 400mg/kg significantly restored the damage parameters (HR, R-R interval, Troponin-I, Creatine kinase-MB, glutamate-pyruvate transaminase, and oxidative stress markers). Also, \unskip~\cite{1108045:22250218} further confirmed in their study that \textit{A. cepa} leaves possess some cardioprotective function in which there were a significant reduction in ALP, LDH and CK levels together with protection histoarchitectural changes. Additionally, \textit{Allium cepa } leaves extract possesses antioxidant and cardioprotective activity, which might be due to flavonoids and anthocynidins when administered to Doxorubicin-induced rats. 

\textit{\textbf{Curcuma longa}}

The rhizomes of turmeric botanically called Curcuma longa L. and from a family Zingiberaceae, play an essential role as an ill-health remedy. \unskip~\cite{1108045:22250216}, in their research work, isolated some bioactive compounds from curcuma longa and investigated its cardioprotective activity, and the result showed that the formulated curcumin-nisin based nanoparticle confers a significant level of cardio-protection in the guinea pig and is nontoxic. Another study confirms its activity in Doxorubicin-induced cardiotoxicity in rats where \textit{Curcuma longa} revealed significant protection, which was proven by a significant reduction in mortality, CK-MB and LDH activities \unskip~\citep{1108045:22250214}.

According to \unskip~\cite{1108045:22250212}, Curcuma longa has cardioprotective effects, which are most likely due to antioxidant and free radical scavenging activity. Hence, \textit{Curcuma longa} can be used as a home remedy that reduces premature death resulting from myocardial infarction \unskip~\citep{1108045:22250212}. Furthermore, curcumin alone and its combination with piperine showed significant protection against Cylophosphamide-induced myocardial toxicity. 

\textit{\textbf{Hibiscus sabdariffa}}

\textit{Hibiscus sabdariffa} from the Malvaceae family is cultured and grown naturally in tropical regions. This plant is reported to be used in different countries as a cooking and curative ingredient. In a study by \unskip~\cite{1108045:22250210}, the protective effect of \textit{Hibiscus sabdariffa} on Doxorubicin-induced cytotoxicity in H\ensuremath{_{9}}C\ensuremath{_{2}} cardiomyoblast cells was conducted and the findings revealed that pretreatment with \textit{hibiscus sabdariffa} extract significantly decreased cell apoptosis after 24 hr at a concentration of 31.25-250 \ensuremath{\mu }g/mL which suggested that \textit{H. sabdariffa} could have cardioprotective effects on Doxorubicin-induced toxicity partly by antiapoptotic activity.

Further study by \unskip~\cite{1108045:22250208} confirmed the consumption of \textit{Hibiscus sabdariffa} attenuated the cardiotoxicity induced by Adriamycin. \textit{Hibiscus sabdariffa } also has potential effects as a cardioprotective agent in diabetes condition.

A recent study by \unskip~\cite{1108045:22250206} suggested that the treatment with an infusion from \textit{Hibiscus sabdariffa} calices protects the cardiac function from damage by ischemia and reperfusion through the antioxidant activities of the substances it possesses. 

\textbf{Some Biomarkers for Evaluation of Myocardial Infarction}

The following are enzymes and proteins used in the analysis of myocardial infarction, of which elevation in their value indicates cardiac cell injury.

\textbf{Troponin}

This is the best commonly useful biomarker for myocardial injury. The cTn complex comprises 2 subunits{\textemdash}C, I, and T which together regulate calcium-mediated interaction of actin and myosin, leading to the contraction and relaxation of striated muscle \unskip~\citep{1108045:22250198}. Troponin I~(cTnI) and troponin T (cTnT) are extremely specific for myocardial damage because they are found only in cardiac muscle \unskip~\citep{1108045:22250095}. Damage to the cardiac myocyte leads to the continued rise in peripheral levels of troponin. After infarction, cTn remains detectable for days (4{\textendash}7 days for cTnI and 10{\textendash}14 days for cTnT) \unskip~\citep{1108045:22250095}.

\textbf{Creatine Kinase MB (CK-MB)}

In the 1970s and 1980s, CK-MB was the standard for the diagnosis and quantitative assessment of myocardial infarction \unskip~\citep{1108045:22250026}. CK is an enzyme that catalyzes the reversible transformation of creatine and ATP to creatine phosphate and ADP \unskip~\citep{1108045:22250026}. Creatine kinase (CK) is mainly found in the heart, skeletal muscles, and brain. The heart, a muscle that frequently contracts without a break, has a high energy requirement. Thus, when the heart muscle dies during myocardial infarction, it discharges many molecules into the bloodstream, one of the more abundant being CK. There are three types of CK called isoenzymes: CKMM, found in skeletal muscle and heart; CK-MB, found in the heart and rises when the heart muscle is damaged; and CK-BB, found mostly in the brain \unskip~\citep{1108045:22250007}.

\textbf{Glucagon-like Peptide 1}

Glucagon-like Peptide 1, a gut incretin hormone with the ability to induce postprandial insulin secretion, can be used in the prediction of acute myocardial infarction. Glucagon-like Peptide 1 were recently found to be elevated in acute myocardial infarction. It is commonly used in monitoring the risk of a heart attack in a patient with diabetes \unskip~\citep{1108045:22250006}

\textbf{Lactate dehydrogenase (LDH)}

LDH is expressed in many organs and well known to have five isoenzymes. The heart has LDH1, but it lacks specificity due to its presence in skeletal muscle, stomach, erythrocytes, kidney, brain, and pancreas. It surges within 6{\textendash}12 hours from the onset of chest pain, peaks over 1{\textendash}3 days, and returns to normal values within 8{\textendash}14 days \unskip~\citep{1108045:22249978}.

\textbf{Aspartate amino transferase (AST)}

This was the initial biomarker used in the diagnosis of acute myocardial infarction (AMI) but is not currently used because of its non-specificity to the heart. \unskip~\citep{1108045:22249978}
    
\section{Conclusion}
Cardiovascular diseases (CVDs) are regarded as the main cause of death worldwide and are mostly refers to Myocardial infarction, angina pectoris, hypertension, stroke and other circulatory diseases. Medicinal plants have been used for centuries to combat many health challenges and are also a useful component in the pharmaceutical industries. The treatment and management of acute myocardial infarction using medicinal plants have been proven by Researchers and simple tools for the diagnosis of myocardial infarction have also been established. Some of the biomarkers for the evaluation and management of Myocardial infarction are Troponin, CK-MB, Glucagon-like Peptide 1, Lactate dehydrogenase, AST and ALT. 
\section*{Acknowledgement}All the authors whose articles were reviewed are sincerely appreciated and apologizes goes to authors that have actually done research on the cardioprotective effect of the plant but were not reviewed.

\textbf{Conflict of Interest}

The authors declare that they have no conflict of interest.

\textbf{Funding Support}

The authors declare that they have no funding support for this study.
    

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