Potential of herbal constituents as new natural leads against helminthiasis:A neglected tropical disease

Kiran D. Patil, Shashikant B. Bagade, Sanjay R. Sharma, Ketan V. Hatware

NMIMS, School of Pharmacy and Technology Management, Shirpur, India

Keywords:Neglected tropical diseases Herbal constituents Helminthiasis Herbal anthelmintics

ABSTRACT The WHO reports that billions of people and animals in tropical and subtropical regions are affected by helminthiasis as neglected tropical disease. It is predominant in underdeveloped areas; nevertheless, the increase in the number of travelers and migrants has made this infection more common. The current mass drug treatment produces severe side effects and many strains of helminths are resistant to them. None of the chemotherapeutic drugs meets the ideal requirements of anthelmintics, such as broad spectrum of activity, single dose cure, free from side effect and cost-effectiveness. Today, many researchers are screening the traditional herbal system in search of the anthelmintic herbal constituents which overcome all the problems of synthetic drugs. Several researchers proclaim anthelmintic activity of herbal medicines by using different experimental models. The present review demonstrates natural product drug discovery, outlining potential of herbal constituents from natural sources as natural leads against helminthiasis.

1. Introduction

Human beings have relied on the Mother Nature throughout the ages for the treatment of a wide range of diseases. In particular, herbal drugs have formed the basis of sophisticated traditional medicinal systems. The earliest records from 2 600 BC,approximately 1 000 plant-derived substances were documented in Mesopotamia. Most of them are still used today for the treatment of ailments like tropical diseases[1].

Neglected tropical diseases (NTDs) are among the seventeen life threatening endemic ailments that occur in tropical and subtropical regions covering 149 countries[2]. Billions of people were affected with the NTDs and people died from these infections is more than half million every year[3-6]. The infections mainly affect peoples who live on less than US$ 2 per day or under the World Bank poverty level of US$ 1.25 per day[7]. Helminthiasis is one of the major public health problems and development challenges,and it is estimated that each species affect more than one billion people all over the world and is classified as neglected tropical disease by WHO[8,9]. It is mainly associated with poverty and is most predominant in the poorest populations of the developing countries. Helminthiasis is one of the major reasons behind poverty of these countries as it affects the pregnancy, child growth,worker productivity, and outcome[10,11]. In these regions, it mainly contributed to malnutrition, anemia, eosinophilia, pneumonia and reduced physical and intellectual abilities[11-13]. Moreover, it offers very less profit for pharmaceutical industries in returns of huge investment on research and development of new chemical entities[14].

Helminthiasis is the most common infection caused by worms,which is mainly divided into two phyla. Nemathelminths are nematodes, e.g. hookworms (Ancylostoma duodenale) and roundworms (Ascaris lumbricoids). Platyhelminths are flatworms divided into the cestode, e.g. tapeworms (Taenia solium, Taenia saginata) and the trematode e.g. flukes (Schistosoma mansoni and Schistosoma hematobolium)[15].

2. Helminths affecting humans

The helminths affect approximately more than 1.45 billion people across the globe. Among them, Ascaris lumbricoides affects more than 819 million, Trichuris trichiura affects over 465 million and hookworm (Necator americanus and/or Ancylostoma duodenale)affects over 439 million peoples worldwide[16]. Helminthiasis leads to malnutrition and anemia, which retard children’s mental and physical growth[17], significantly contribute to school absenteeism[8].Helminths mainly reside in gastrointestinal tract and can also infect liver and other organs. The infection is generally spread through contaminated soil with helminths and their eggs in the areas with poor sanitation[18]. Helminths is a large veterinary health problem to farm yard animals and responsible for 3%-8% of their weight loss and 28% of death[19].

Table 1 shows the prevalence of helminthiasis in three major continents. It has been observed that African and Asian are affected more compared to America. This data supports the statement that helminthiasis is more common in developing countries than developed countries.

3. Conventional drug therapy for helminthiasis

The current mass drug treatment of helminths produces side effects(Table 2) like abdominal disturbances, nausea, vomiting, headache,diarrhea, weight loss and many of the drugs are not recommended to use during pregnancy[20]. Consequently agranulocytosis and teratogenicity are major adverse effects of the conventional medicines. None of the chemotherapeutic drugs meets the ideal requirements of anthelmintic such as broad spectrum of activity,single dose cure, free from side effects and cost effectiveness.Moreover, the increase of resistance[21], toxic residue of synthetic drugs, less availability and high cost requires the search for alternative medicinal system to overcome associated problems.

4. Herbal constituents as new natural leads

The World Medicines Situation 2011[22] reports that all the countries uses traditional medicines at some extent, among these,developing countries accounts for 70%-95%. Moreover, at least 25% of all currents drugs are obtained either directly or indirectly from natural origin. According to the herbal medicine market research report 2018, the global market of herbal medicines increasing exponentially to register a compound annual growth rate of 5.88% to reach US$ 129 million by 2023, which was 50 million in 2017[23]. As per the resolution of World Health Assembly(WHA62.13)[24], the member governments are mandatory to conserve, respect and universally communicate the knowledge of traditional medicines. Also, it prepares regulatory policies for development of new innovative traditional medicines to encourage appropriate, harmless, rational and effective uses.

A survey of plant constituents used as drugs in countries with WHO-Traditional Medicine Centers has identified 122 compounds derived from 94 plants, of which 80% were used for therapeutic purposes[1]. There is no doubt that herbs are among the vital natural sources for synthesis of various molecules from simple skeletal structure to complex one. Many popular components are based on traditional drugs, such as quinine (chloroquine& mefloquine), artemisinin, taxol (paclitaxel), camptothecin,khellin, sodium chromoglycate, galegine, metformin, papaverine,verapamil[1,25-27]. Therefore, the WHO paid great attention on new chemical entities to manage NTDs including helminthiasis.

Table 1. Prevalence of different helminthes in major continents.

Table 2. WHO-recommended anthelminthic drugs.

Thus, the present review demonstrates the potential of herbal constituents from different plants sources as new natural leads against helminthiasis (Table 3). The method used for compiling following data consist of articles from the National Center for Biotechnology Information during the period 2005-2019.

It was also observed from the data that phytoconstituents from different plants shown their distinct mechanism of action according to the major chemical group. Table 4 summarizes the anthelmintic mechanism of different phytoconstituents.

Figure 1 shows that around 46 families of plants possess anthelmintic activity. Among them, family Asteraceae has the most plants that show anthelmintic potential. The helminthes used for evaluating anthelmintic activity are given in Figure 2. It has been observed that Haemonchus contortus was the most frequently used test agent for the study of anthelmintic potential.

Subsequently, Figure 3 shows that the major plant parts possessing anthelmintic potential. Among all these parts, leaves have shown more potential than other plant parts.

Moreover, the Figure 4 shows the various methods of extraction used to obtain anthelmintic phytoconstituents from the plants. The aqueous extract followed by methanolic and ethanolic extract have shown more significant anthelmintic potential.

Nevertheless, the anthelmintic potential depends on the presence of major phytoconstituents present in the plants. It has been observed that, tannins (20%) shows more potential followed by flavonoids (19%), phenolic compounds (18%), saponins (12%),alkaloids (11%), various enzymes (8%), metals (2%), glycosides(2%) terpenoids (2%) and other phytoconstituents (3%) are responsible for anthelmintic activity (Table 3).

Figure 1. Anthelmintic agents by plant families.

Table 3. Different in vitro and in vivo anthelmintic studies of herbal constituents.

Table 3. Different in vitro and in vivo anthelmintic studies of herbal constituents (continued).

Figure 2. Anthelmintic studies of various plants.

Figure 3. Anthelmintic activity studied in different parts of plants.

Figure 4. The anthelmintic activity of crude powder and different fractions obtained from plants.

5. Conclusions

The available conventional drugs fails to meet the ideal requirements of anthelmintic effect on all species of helminthes,single dose cure, free from side effects and cost-effective.Moreover, the increase of resistance, toxic impurities from synthetic drugs, less availability with higher cost requires the search for alternative system of medicine to overcome associated problems. The old classical systems of medicine and ethno medical surveys described the use of plants for the treatment of helminthic infection. This traditional knowledge of active herbs revealed effectiveness and safety of medicinal plants. However, their mode of action and the phytoconstituents responsible for the activity is not clearly known. The crude plant extracts, essential oils and isolates containing active principle show significant anthelmintic activity using in vitro and in vivo models. Moreover, to explore bioactivity of anthelmintic plants, further studies are needed, so as to discover different natural sources to emerge cost effective treatment of helminthic infection. The present review surveys literature that report name of plants, their anthelmintic activity and possible constituent that responsible for the bioactivity. The special attention is desired in order to standardize the bioactive plant with quantitative anthelmintic activity. Consequently, the design of palatable herbal preparations is needed to overcome side effects.Hence further study must be carried out to explore different plants of higher efficiency and negligible side effects.

Table 4. Anthelmintic mechanism of different phytoconstituents.

Conflict of interest statement

We declare that we have no conflict of interest.