Abstract

Background: Cardiovascular diseases (CVD’s) are a group of chronic heterogeneous diseases of the heart and blood vessels that evolve gradually throughout life.. Cameroon’s mortality rate of CVDs in 2017 was at 11.85%. Most often MI is caused by plaque rupture of an atherosclerotic plaque with thrombus formation in obstructive coronary MI and in fewer instances caused by spontaneous coronary dissection, coronary artery embolism, vasospasm, and stress induced cardiomyopathy in non-obstructive MI.

More than 90% of the risks of MI are accounted for by modifiable risk factors such as hyperlipidemia, smoking, physical inactivity, diabetes mellitus and obesity. Conventional medications such as statins used in the treatment of hyperlipidemia and management of myocardial infarction although well tolerated by the human system, have many adverse effects.

Objective: the study aimed to investigate the cardioprotective effect of the Kalanchoe pinnata in a combined model of high-fat diet induced myocardial infarction. The objectives were to optimize a hyperlipidemic model and establish a combined model of hyperlipidemia and myocardial infarction, asses the cardioprotective effect of the extract and evaluate its impact on hyperlipidemia in the combined model.

Materials and Methods: This study utilized a randomized experimental design with a total of 36 animals divided into different treatment groups. The animals were subjected to a high-fat diet to induce hyperlipidemia, followed by the administration of isoprenaline to induce MI the aqueous extract of Kalanchoe pinnata was administered at varying doses (KP50, KP100, and KP200) to different groups, while the negative controland positive control groups were also included. Blood samples were collected at specific time points to measure total cholesterol, triglycerides, LDL-cholesterol and HDL-cholesterol levels

Results: The results demonstrated significant decreases in total cholesterol levels for the neutral control group in the 6th and 9th weeks compared to the 4th week (p<0.001). The negative control group also showed significant decreases in the 6th and 9th weeks (p<0.0001 and p<0.05, respectively) compared to the 4th week. The KP50 group exhibited a significant decrease in the 6th week (p<0.001) compared to the 4th week, while KP100 showed a significant decrease in the 6th week (p<0.05). KP200 displayed significant decrease in the 6th and 9th week(p<0.001) compared to the 2nd week.

Recommendations: These findings highlight the potential of kalanchoe pinnata as a therapeutic agent in managing hyperlipidemia and reducing the risk of cardiovascular diseases. Further studies are needed to elucidate the underlying mecahnisms of action and evaluate its long term effects.

Conclusion: The aqueous extract of kalanchoe pinnat exhibited  promising cardioprotectrive effects in the combined model of hyperlipidemia and and myocardioal infarction. These findings contribute to the growing body of knowledge on natural compounds with potential therapeutic applications in cardiovascular disease.

CHAPTER ONE

INTRODUCTION

1.1.  Background of the Study

Cardiovascular diseases (CVD’s) are a group of chronic heterogeneous diseases of the heart and blood vessels that evolve gradually throughout life [1]. CVD’s are one of the four major non-communicable diseases that seriously affect worldwide public health and are the leading cause of global death with an estimated loss of 17.9 million lives each year [2].

CVD is a broad term that encompasses a list of congenital and acquired pathologies with the most common being coronary artery disease (CAD), cerebrovascular disease, peripheral arterial disease, cardiomyopathy, inflammation of the heart caused by infections, rheumatic and congenital heart diseases [3, 4].

Damage caused by CVD’s to the arteries of organs such as the brain, and heart are highly associated to the build-up of fatty deposits in the arteries and also blood clots which reduce blood flow to these organs [5]. Apart from the major causes of CVD’s, there exist a list of risk factors both modifiable and non-modifiable such as physical inactivity, dyslipidemia, hyperglycemia, high blood pressure, obesity, kidney dysfunction, age, gender, and genetic background[6] which contribute to the growth of CVD’s. One of the most common causes of CVD’s is the coronary artery disease (CAD) that manifests as narrowed or occluded major arteries due to a number of reasons such as rupture of an atherosclerotic plaque, a diseased endothelium, low-grade inflammation and lipid accumulation[1].

CAD is one of the most common CVD’s found to be the leading cause of death in both the developed, low and middle-income countries[7]. CAD is a condition that refers to the inadequate supply of blood and oxygen to the myocardium due to occlusion of the coronary arteries (arteries that supply the heart with blood, nutrients and oxygen) caused by plaque formation in the lumen of the coronary arteries[8].  Complete occlusion of the coronary arteries that supply a particular portion of the heart caused by a blood clot or imbalance in the blood supply and oxygen demand ratio of the heart results in myocardial infarction (MI) referred to as necrosis of the heart muscle[9].

MI is the most severe clinical manifestations of CAD with sudden cardiac death and remains the leading cause of mortality with its global prevalence approaching 3 million deaths annually. MI leads to irreversible damage of the cardio myocytes due to interruption of oxygen supply [10] which arises from coronary artery occlusion.

Most often MI is caused by plaque rupture of an atherosclerotic plaque with thrombus formation in obstructive coronary MI and in fewer instances caused by spontaneous coronary dissection, coronary artery embolism, vasospasm, and stress induced cardiomyopathy in non-obstructive MI [11]. More than 90% of the risks of MI are accounted for by modifiable risk factors such as hyperlipidemia, smoking, physical inactivity, diabetes mellitus and obesity[12]. Hyperlipidemia is an established strong risk factor of MI, it is a most commonly acquired condition but can be solely due to hereditary factors[13].

Hyperlipidemia is a heterogeneous group of disorders characterized by elevated levels of lipids (triglycerides, cholesterol, or both) in the blood stream[14]. Also identified as dyslipidemia, a disorder in which the concentration of triglyceride and cholesterol-carrying lipoproteins exceed their normal limit in the blood plasma [15].

Causes of hyperlipidemia maybe genetic, environmental or both, which makes it to be further classified into primary and secondary hyperlipidemia which may occur as a result of high intake of food rich in fats and cholesterol, a genetic defect or other underlying diseases such as diabetes mellitus, hypothyroidism, and obstructive liver disease[13, 14]. Hyperlipidemia affects heart structure and function by complex mechanisms of chronic inflammation, which lead to high oxidative stress levels and injury[16]. Treatment of hyperlipidemia reduces the risk of MI [17].

Conventional medications such as statins used in the treatment of hyperlipidemia and management of myocardial infarction  [18, 19] although well tolerated by the human system, have many adverse effects such as rhabdomyolysis, sleep disturbances and, liver injury [20], which has made researchers move towards conventional and alternative medicine.

Over the recent decades the use of alternative and conventional medicines especially medicinal plants in the treatment of diseases such as hyperlipidemia and CVD’s has increased [21].  80% of the emerging world’s population relies on medicinal plants for primary health care according to the World Health Organization (WHO) [22]. Medicinal plants are important in pharmacological research and drug development due to the presence of pharmacologically active compounds (phytochemicals) [20]. Several epidemiological studies have shown that medicinal plants that contain phytochemicals such as flavonoids and polyphenols have a protective effect against CVD’s and hyperlipidemia [23]. Kalanchoe pinnata is a succulent medicinal herb with many common names such as air plant, miracle leaf, cathedral bells, and life plant, rich in phytochemicals such as alkaloids, triterpenes, glycosides, flavonoids, cardienolides, steroids, bufadienolides and lipids.

Its fleshy dark green leaves contain an active group of chemicals called bufadienolides (bryotoxin A, B, C) making them to possess antibacterial, antitumorous, cancer preventative and insecticidal properties [24]. The aqueous extract of its leaves possess anti-inflammatory, antioxidant, antiallergic, analgesic, antidiabetic [23], antihypertensive activities, and cardioprotective effects [25]. This study is aimed at assessing the protective effect of kalanchoe pinnata against hyperlipidemia combined with myocardial infarction in Wistar rat models.

1.2.  Problem Statement

Cardiovascular disease is the leading cause of global death [26].  Cameroon’s mortality rate of CVDs in 2017 was at 11.85% [27]. CVDs are predicted to overtake infectious diseases as a leading cause of death by 2030 due to its rising burden[28]. MI is a globally relevant public health problem and the leading cause of disability and death among major cardiovascular diseases; it is not just a disease of the elderly in developed countries but also affects the working-age adults globally and is a growing problem in low and middle-income countries [29]

Being ranked as one of the greatest risk factors that contributes to the prevalence of MI, the  prevalence of hyperlipidemia ranges from 5.2 to 89.9% in Africa [30] . Most of the lipid disorders (80%) are associated with diet and lifestyle. The dietary habits of populations in low-to-middle-income countries have rapidly shifted to less-healthy diets. These consist of processed foods, away-from-home food intake, and increased use of edible oils and sugar-sweetened beverages [28].

1.3. Research questions

1. Does the aqueous extract of Kalanchoe pinnata have hypolipidemic activity?
2. Does the aqueous extract of Kalanchoe pinnata have cardioprotective effects in a combined disease state of hyperlipidemia and myocardial infarction?

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