Cardiovascular benefits of Momordica charantia in cholesterol-fed Wistar rats

Cardiovascular diseases result from the death of cardiac tissues due to prolonged and severe ischemia [1]. The occurrence also correlates with genetic and behavioral dispositions to atherosclerosis [2]. Significant increase in morbidity and mortality due to cardiovascular diseases are often associated with aortic and carotid atherosclerotic disease and stroke [2]. Conventionally, cardiovascular diseases such as myocardial infarction and atherosclerosis are treated or managed with the administration of orthodox drugs or by surgical intervention. These conventional procedures are often associated with unpleasant side-effects and complications. In a view to mitigating these side effects, the search for alternative and safer remedy have become the focus of many researchers. Medicinal plants have been acclaimed to be safe as an alternative form of therapy. They have been harnessed as phyto-remedy since the dawn of civilization and some herbs have emerged as a mainstay of man’s pharmacotherapy.

The World Health Organization in 2013 [3] estimated that 80% of inhabitants of developing countries rely on plant-based drugs because they are natural and supposedly innocuous with little or no side effects. In ethnomedicine, M. charantia has been acclaimed to have a broad spectrum of activities in the management and treatment of cardiovascular disorders, diabetes, inflammation, etc [4] Commonly called bitter gourd or Balsam pear, M. charantia belongs to the Cucurbitaceae family and grows in the tropical area. It is native to tropical and subtropical Africa. It is popularly consumed as vegetable and has been acclaimed to possess high medicinal values. M. charantia has been reported to contain active phytochemicals which are responsible for its therapeutic activities. An example is the protection against atherosclerosis by regulating blood cholesterol. It has been proposed that the crude extract of Momordica charantia, as well as Momordicatin (which is obtained from the fruits of Momordica charantia) may be considered as potential sources of new chemotherapeutics [4]. However, there is dearth of scientific information about the determination of the safe dose and possible cardiovascular benefits of this plant. In this study, we investigated the possible cardiovascular benefits of M. charantia using standard scientific methods.

In Table 1, the phytochemical screening of Momordica charantia shows the presence of some phytochemicals such as alkaloids, flavonoids, saponins, steriods, terponoids, tanins and anthroquines and cardiac glycosides. The results also indicate comparatively, the highest concentration of alkaloids in the plant extract.

Myocardial infarction and atherosclerosis are major manifestations of cardiovascular diseases with high rate of morbidity and mortality globally. Nature has made available certain therapeutic agents of plant origin capable of protecting or improving cardiovascular health. This may provide an avenue to reduce cholesterol without recourse to synthetic drugs and their undesirable side-effects. Due to the long historical utilization of ethnomedicinal plants by humans, useful data on the acute and sub-acute toxicity evaluations of medicinal plants or extracts derived from them should be accessed. This is necessary to ensure the certainty of their safety to humans and also set the criteria for choosing a safe dose in humans [9]. Preliminary analysis of some phytochemical constituent of the extract of M. charantia revealed the presence of high amounts of alkaloids, flavonoids and cardiac glycosides. Other phytochemicals of biochemical importance and cardiovascular relevance found include saponins, steroids, terpenoids tannins and anthraquinones. As observed in our study, we infer that the presence of saponins, tannins and other hypolipidemic phytocomponents such as flavonoids in the extract could account for its bioactivity.

Our preliminary toxicity (acute and chronic) study of M. charantia (although not published) revealed that; the oral administration of the plant extract at different doses (up to 12,000 mg/kg body weight) for 14 days did not cause any signs of toxicity, morbidity or mortality in the experimental rats. Toxicological evaluation involving sub-acute, acute and chronic studies are often employed for the evaluation of the undesirable side effects of exposure to medicinal plants over a period of time [10]. These investigations provide useful information on target organ toxicity and can be used to determine appropriate dose regimens for longer term investigations in humans [11]. It has been reported that significant changes in body weight gain and internal organ weights are direct and sensitive indices of toxicity after exposure to a toxic substance [12‐14]. We did not observe any significant changes in the behavior of the test animals, as well as their food consumption habits. The body weight changes as well as relative organ weights of the experimental rats (both male and female) did not differ significantly from those of the control rats. It may therefore be appropriate to infer that M. charantia is relatively safe with respect to its use in ethnomedicine. M. charantia is widely used in ethnomedicine; however, studies investigating its biological properties and mechanisms of action are still insufficient. Different therapeutic indications of the plant in ethnomedicine are found in literature, especially its pharmacological activities in the control of diabetes, viral infections and cancer [15]. M. charantia is a medicinal herb which possesses various bioactive compounds with health benefits [16].

Li et al. in 1994 and Verschuren et al. in 1995 [17, 18] reported a linear correlation between dietary cholesterol intake and mortality from coronary heart disease (CHD). It has also been shown that the administration of dietary cholesterol speeds up the formation of aortic plaques in the apolipoprotein E null mutant mouse [19]. Results of our present study, which focused on the cardiovascular benefits of the plant (M. charantia), shows that the mean total cholesterol, triglyceride and high-density lipoproteins (HDL) of the experimental rats were not significantly affected in all the test groups as compared to the control. It can therefore be inferred that the administration of the extracts and the standard drug (atorvastatin) had similar effect with respect to the reduction of the lipids in the test animals. Previous studies have shown that in mice fed high fat diet (HFD), administration of freeze-dried M. charantia juice was found to reduce adiposity and it was reported that extracts from this plant may reduce visceral obesity [20, 21]. Our findings also show that the mean low-density lipoproteins were significantly lower in the groups given LDMC, cholesterol plus HDMC and coconut oil only as compared with the control group. Low-density lipoprotein is the most important risk factor for development of atherosclerosis and cardiovascular diseases in humans and animals [22‐24]. Our results portend the cardiovascular benefit of the extract as reduction in low-density lipoproteins correlates with decreased risk of cardiovascular diseases. Willeck et al. in 2015 [22] reported observable increases in total cholesterol, triglyceride and LDL-cholesterol, with corresponding decrease in HDL- cholesterol in cholesterol-induced hyperlipidemic rats as compared to the control rats. Pre-treatment with M. charantia resulted in reduced LDL-cholesterol with concomitant increase in HDL-cholesterol. Decrease in LDL-cholesterol and increase in HDL-cholesterol in M. charantia–treated group may be due to inhibition of hepatic cholesterol biosynthesis, increased fecal bile acid secretion, stimulation of receptor-mediated catabolism of LDL-cholesterol, or increase in uptake of LDL-cholesterol from the blood by the liver [25]. These activities may be due to the presence of active phytochemicals with lipid lowering properties in M. charantia. This may also be true since chronic administration of the extract did not significantly alter the total food intake of the treated animals. This suggests that the anti-hyperlipidaemic effects of the extract were not mediated through inhibition of appetite.

Histological examination has been described as the golden standard for evaluating treatments related to pathological changes in tissues and organs [26]. Histological analysis of the heart and aortic branch of the experimental rats show that cholesterol administration induced myocardial degeneration, vascular ulceration and stenosis in the aorta and heavy perivascular infiltrates of inflammatory cells. However, there was amelioration of these deleterious effects to a very appreciable degree or a near normal condition relatively, upon treatment with Atorvastatin and M. charantia, as compared with the control groups. These, among others, also suggest a similar activity between the extract and the standard drug. Our results also support the report that dietary cholesterol contributes significantly to elevation of plasma cholesterol. This has been demonstrated to increase serum and aortic tissue cholesterol and as such predisposes to aortic atherosclerosis or cardiovascular diseases [27, 28].

Our study shows that the extract of M. charantia exhibited hypolipidemic properties, as well as restored and maintained the functional and structural integrity of the tissues of the heart and aorta. It ameliorated the degenerative changes in the myocardium and aortic tissues. The lowering of LDL-cholesterol level and improvement in the histological features of the aorta portend the cardio-protective effect or cardiovascular benefits of M. charantia. However, more detailed and relevant studies are required to give scientific justification to these benefits.