Cure and prevention of cardiovascular diseases: herbs for heart

Abstract

Herbs contribute to more than 60-70% in development of modern medicines in the world market either directly or indirectly. The herbal treatments for congestive heart failure, systolic hypertension, angina, atherosclerosis, cerebral insufficiency and venous insufficiency etc. has been known since ancient times. Unlike allopathic medicines, Ayurveda medicines are considered safe, however, the adverse reactions of herbal drugs is also reported. In this paper, we have compiled 128 herbs and their parts that have medicinal value to prevent, alleviate or cure heart disease related disorders. Jaccard Neighbour-joining cluster analysis using Free Tree software was used to assess the relative importance of plants in context with its healing potential for heart related disease. Based on the medicinal value in context with the heart, five major clusters of the selected 128 herbs were made. Correlation of the distance between herbs revealed that most of these herbs were found to have more than one medicinal property. The distance in dendogram depicted closeness of properties curing heart disease; as less the distance between two medicinal plants or two groups they will more close to cure particular heart disease. During drug development, a medicinal plant can be replaced by another plant of same group or by another plant of its neighbour group but from same pedigree. Thus, in case of non-availability of herbs or if it belongs to the category of rare, threatened, and endangered species, such method may add to new ways of drug development.

Introduction

According to WHO, cardiovascular diseases (CVDs) kill 17.9 million people per year, accounting for 31% of all global deaths. Heart attacks and strokes account for 80% of CVD deaths [1]. Populations in low and middle income countries (LMICs) contribute 75% of the CVD deaths [2]. It is predicted that by 2030 more than 22.2 million people will die annually from CVDs. Due to high prevalence of CVD among older adults in LMIC, population with CVD has increased and become a major challenge in future for the health care system. The therapeutic potential of herbs in healthcare system is well known in all over the world whether it is for diseased state or proper maintenance of health [3, 4]. Since Ayurvedic medicines belong to natural sources, they are considered safe compared with allopathic medicines. However, many adverse reactions of herbal drugs is also reported [5, 6]. Ayurvedic medicines can cause adverse effect if the patients continue to take medicines with no monitoring. Prolonged use or overdose of herbal medications lead to side effects e.g. high risk of cardiovascular events. A major drawback is the lack of information on the social and economic benefits on the industrial utilization of medicinal plants [7, 8]. The standard pharmacovigilance techniques (WHO guidelines) when applied presents challenges such as the ways in which herbal medicines are regulated, used, named, and perceived [9]. Very often patient undergo medication with Allopathic and Ayurvedic medicines simultaneously and dose-related responses are rarely measured and reported. Conventional pharmacovigilance tools, such as prescription-event monitoring and the use of computerized health record databases, for evaluating the safety of herbal medicines has limitations too. Reporting of adverse events possibly caused by herbal and traditional medicines in an extensive manner is needed for the systematic and rational use of drugs [9].

Since herbal medications do not require proof of efficacy and safety and there is lack of enough clinical data on herbal medication although, most of the herbs demonstrate an effect on biological mechanisms [10]. Clinical studies so far on herbal medications are limited in sample size and its impact on relevant clinical outcomes is not much studied. There is increased risk of side effects as it is not tested in pregnant women and children. Sometimes there is even contamination with other conventional medications and there also exists risk of drug interactions. Even substitution with alternative plant species is also reported. Enough and improved knowledge herbal medications is essential. Also, there should be transparency between patient- physician and possible benefits, side effects should be discussed. Thus, herbal drug development is possible only if there is development of standardized herbal products.

The present study was conducted to assess the relative importance of herbs that has medicinal potential to regulate heart and cure related disease. This may add to enhance drug discovery approaches for its promotion and development i.e. to generate safety data-either before or after marketing of the formulation.

Materials and methods

Plants having medicinal properties for treatment of various heart diseases were extracted from secondary database search e.g. Google Scholar, PubMed and published research articles. Based on this, dataset of 128 different medicinal plants were further grouped and assessed for its relative medicinal potential to regulate and treat heart disease (Table 1 [12-27] http://www.nmpb.nic.in/, https://en.wikipedia.org/wiki/Scutellaria#Traditional_use). The percentage of plant parts used for the treatment of heart disease were further assessed (Fig. 1). Heart disease and the Plant uses were categorised in three parts: Plants used in only one diseases of heart, two disease of heart, three diseases of heart were grouped together (Table 2 [27]). Jaccard Neighbour-joining dendrogram were obtained through collected dataset of 128 different plants useful for heart disease ailment, computed performed with the help of Free Tree software version 0.9.1.50 and FigTree version 1.2.2. And mathematical consensus tree so obtained after 1000 replicates of bootstrap. Herbs were recorded as ‘1’ for present or ‘0’ for absent of a particular medicinal property related to heart. The objective of the cluster analysis was to develop sub grouping of plants on the basis of their properties to treat heart disease. This method of clustering not only clusters sample, but also it clusters various clusters that were formed earlier in the clustering process. In this method, each sample or variable was treated as a cluster of 1 and the closest two clusters are joined to form a new cluster [28].

Table 1 List of plants, its habit and parts used for treatment of heart disease

Fig. 1

The percentage of plant parts used for the treatment of Heart Disease

Table 2: Heart disease and the Plant Uses (A-C)

Results

In this paper we have listed 128 plants, its habit and parts used for treatment of heart disease (Table 1). Comparative analysis of parts used of percentage of total plants showed that root and rhizome is the most frequently used plant parts followed by leaves, while gum being the least frequently used plant parts in context with ailment of heart disease (Fig. 1). The order (maximum to minimum) of plant parts used for heart disease ailment is root and rhizome-leaf-stem-flower-fruit and seed-other parts-gum (Fig. 1). Analysis of plants used for various types of heart diseases showed that only one plant i.e. Crocus sativus L. has the potential to cure five types of heart disease-hypertension, heart attack and reduction in blood fat, anti-oxidant and cardiac tonic thus indicating its relevancy in context with cardiovascular diseases (Table 2). Similarly, plants having medicinal property to cure four heart disease category were also few (Table 2). Maximum number of plants were found to be in category of curing only one heart disease type. Very few plants were observed to have medicinal property capable of treating multiple heart disease type (Table 2).

Cluster analysis based on Jaccard Neighbour-joining dendrogram using collected dataset of 128 herbs useful for heart with the help of Free Tree software version 0.9.1.50 and FigTree version 1.2.2. and mathematical consensus tree was obtained after 1000 replicates of bootstrap (Fig. 2). Five major clusters of the selected 128 herbs were observed on the basis of their medicinal value in context with heart. Within a cluster most of herbs showing similar properties and medicinal similarity negatively correlated with the cluster distance. Correlation of the distance between herbs also revealed that most of these herbs were found to have more than one medicinal property (Fig. 2).

Fig. 2

The dendogram depicts 128 different medicinal plants having property to cure some type of heart disease/ailment. The medicinal plants in one group shows that they have similar properties to cure same heart disease. The distance in dendogram depicts closeness of properties curing heart disease; as less the distance between two medicinal plants or two groups they will more close to cure particular heart disease

Discussion

A variety of modern medicines have been developed from herbs that are being used by native people [29]. Herb serve as both preventive and therapeutic purposes of many diseases. Use of herbs for cardiovascular diseases such as congestive heart failure, systolic hypertension, angina pectoris, atherosclerosis, cerebral insufficiency, and arryhythmia is prevalent since ancient time [30]. Herbs has been a continuing source for medicine e.g. antineoplastic drug paclitaxel derived from Taxus brevifolia, digitoxin from Digitalis purpurea, reserpine from Rauwolfia serpentina etc [1]. These herbs are used for treatment of cardiovascular diseases. Use of herbal medicine though exist since past decade, this system of medicine has several lacunae. For example, herbal medicine lack scientific evidence or assessment. Many of the herbal medicines have toxic effects and major drug-drug interactions too. Therefore, in-depth research is needed to understand the pharmacological activity of the herbs. In this paper, cluster analysis of the potential herbs for heart with its ability to treat various heart related diseases was done to understand the possible combination of the herbs that may help in the development of more effective drug formulation that the existing one. As mentioned in the results section, almost every part of the herb has a medicinal property, although root and rhizome is most frequently used plant parts.

Herbs have more than one medicinal property i.e. it has the potential to prevent or cure more than one disease as demonstrated in our results. For example, only one herb Crocus sativus L. was found to have medicinal property with the potential to treat five heart disease type-hypertension, heart attack, reduction in blood fat, anti- oxidant, and cardiac tonic. Role of this herb against cardiovascular diseases is related to their antioxidant and anti-inflammation effects [31]. Crocus sativus is found to have antihypertensive and normalizing effect on blood pressure [32]. It is known to possess a potent inhibitory effect on heart rate and contractility of guinea pig heart via calcium channel-blocking effect [33]. Other studies also support cardiovascular effects of saffron and its components [34].

Three herbs-Citrus medica L., Crataegus monogyna, Elettaria cardamom possess medicinal property with the potential to treat four heart disease type. Citrus medica L. “Otroj” (Brain citron), is a member of Rutaceae family. Evidence supports its cardioprotective potential due to its potent antioxidant and free radical scavenging activity [35]. Crataegus species is shown to represent a safe, effective, nontoxic agent in the treatment of cardiovascular disease and ischemic heart disease (IHD) [36]. Its mechanism of action include direct scavenging of reactive oxygen species, enhanced superoxide dismutase, and catalase activities, antioxidant activity, down regulation of caspase 3 gene etc. [36]. Crataegus monogyna are rich in polyphenols and both of its leaves and flowers or alternatively the fruit are used medicinally [37]. It helps to regulate both high and low blood pressure, in addition to slowly breaking down cholesterol and fat deposits in the body [37]. It increases conversion rates of LDL or “bad” cholesterol into HDL or “good” cholesterol in the liver and improves blood and oxygen supply to the heart muscle. In cases of congestive heart failure and circulatory disorders, Hawthorns is prominently being used in a holistic approach to heal the body itself [37]. It plays a role in alleviating irritation and swelling of the blood vessels. Study has shown that small cardamom Elettaria cardamom effectively lowers blood pressure, increases fibrinolysis, and boosts antioxidant status in stage 1 hypertensive patients without affecting blood lipids or fibrinogen levels [38]. A rat study has also demonstrated the ability of cardamom oil to restore lipid homeostasis in the presence of hypercholesterolemia [39]. This study has shown reduction in atherogenicity index by dietary intervention with cardamom powder and cardamom oil hence, the cardioprotective potential of cardamom [39]. The bark of Terminalia arjuna has been demonstrated to show cardioprotective effects against doxorubicin induced cardiotoxicity by increased coronary artery flow and protection of myocardium against ischemic damage [40]. Terminalia chebula pericap has also been reported to have cardioprotective activity [41].

The dendogram obtained for 128 medicinal plants by Jaccard Neighbour joining dendogram method depicts 128 different medicinal plants having property to cure some type of heart disease/ailment. The medicinal plants in one group showed to have similar properties to cure same heart disease. The distance in dendogram depicts closeness of the properties curing the heart disease; less the distance between two medicinal plants or two groups, the more it is closer to cure particular heart disease. During drug development, a medicinal plant can be replaced by another plant of same group or by another plant of its neighbour group but from same pedigree (like garlic, turmeric and safflower) on the basis of their similar properties of curing that particular heart disease. Thus, in case of non-availability of the herbs or if it belongs to the category of rare, threatened, and endangered species, such method may add to new ways of drug development. During drug development, if any medicinal plant shows adverse effect, it can be replaced by a plant with similar medicinal potential, suitable for the same drug composition based on cluster analysis.

Generally, herbal medicines is considered harmless as it is derived from natural sources, however, adverse reaction of herbal medicines is also reported. For example, bleeding is the adverse effect of the herbal drug, Ginko biloba. Similarly, gastrointestinal disturbances, allergic reactions, fatigue, dizziness, confusion, dry mouth, photosensitivity are the adverse effect of the herbal drug St. John’s wort. Lack of information on the social and economic benefits on the industrial utilization of medicinal plants is the major drawback in development of the medicinal plant-based industries in developing countries [7, 8].

Medicinal plants are the oldest known health-care products and its importance in the primary health care of individuals and communities in both developed as well as developing countries is increasing. However, further research is needed to find compounds of interest in these plants that can be used as safe and effective medicines to treat heart disease.

Conclusion

More scientific research on these plants is needed in order to find new drugs for the treatment of cardiovascular diseases that have no or few side effects.