The use of plant secondary metabolites as natural products

Author: Iloka Benneth Chiemelie

Published: 15th-December-2014

Chapter 1

Introduction

The human race has been highly dependent on plants over the centuries as a common source of food. On the same ground, plant has also been viewed as a significant source of secondary metabolites, and these metabolites have been used for pharmaceutical, agrochemical, fragrance, flavour, biopesticides and additive sources for foods. Studies have also shown that about 80% of an approximated 30 thousand natural products that are currently known are of plant origin (Ruiu et al., 2008; Saxena, 1989; Schaffazick, 2006). In terms of measuring the structures, the numbers of known chemical structures have been estimated to be in at least four times greater than those of microbial origin. Dating back to 1985, 2600 of the 3500 newly identified chemical structures are from higher plants. Recent studies have also shown that 121 of the prescription drugs that are clinically available across the world are from plant origin (Ong, 2004).

A different survey conducted to understand the usage of medicines from plant origin in the USA revealed an increase of such from about 3% as of the 1991 study in the population to over 37% in 1998 (Brevoort, 1998), and this has created a subsequent rise in the sales of plant medicine in the USA to US$ 3 billion per annum (Rharrabe, 2008). Even presently, there is a recorded study that 75% of the world’s population rely on plants as a source of their traditional medicine. Even in the USA market where most of the pharmaceutical products are dominated by chemicals, it has also been recorded that 25% of the pharmaceutical products are actually derived from plant chemicals (Ong, 2004; ICH, 1996). Thus, the expectation is that plants will continue their strive in providing novel products and also chemical models for new drugs both presently and in the coming centuries as a result of the fact that the chemistry of most of the plant products are yet to be characterized (Hussain, 1990). Besides the pharmaceutical approaches, plants have also been used for agrochemical, fragrance, flavour, biopesticides and additive sources for foods as noted earlier.

Purpose of research

Considering the advancement in technologies, biotechnological products are fast on the rise and the needs to advance the system in such a way that efficiency is provided with the extraction process has been called a “necessity,” because it is the right key to understanding the characteristics of plants that have not been analysed and also defining new usage of the secondary metabolites from these plants.

On the ground of the above description, the main purpose of this research is to understand ways that the secondary metabolites of plants are actually used. Such an analysis will also involve defining what secondary metabolites of plants are; how they are extracted and stored; and how they are classified in terms of their values and kind of plants extracted from.

Significance of research

From the background review, it can be seen that the human race depends heavily on plants for both food and shelter with such expanding in recent years into areas like medicinal, agrochemical, fragrance, flavour, biopesticides and additive sources for foods. Also, it was noted that majority of the plants across the world has not been classified as useful for a number of reasons such as their medicinal and health value, and these plants also have higher potential of being used as natural products. Thus, it becomes a necessity that the ways plants’ secondary metabolites can be used is understood. This is because such an understanding will help advance the research being conducted on the usage potential, define new usages and create higher volume for adoption. Thus, this paper is significant for researchers, academicians, practitioners and the general public at large.

Research question

In order to address the research purpose above, a number of questions will be asked as the background for the overall research process and these questions are:

1.      What are plant metabolites?

2.      What are the differences between primary and secondary metabolite?

3.      Can the secondary metabolites be used as natural products?

4.      What kind of natural products can the secondary metabolites be used for?

Research objectives

The main objectives of this research are reflected in the questions above and they are:

1.      To understand what plant metabolites are;

2.      To differentiate between secondary and primary metabolites;

3.      To demonstrate whether plant metabolites can be used as natural products; and

4.      To understand the kind of natural products that the secondary metabolites can be used for.

Organization of study

This research is organized into 5 chapters with the first chapter as the introduction. The introduction presents a clear overview of what the research is all about by discussing the purpose and significance of the research. This is further explained by the research question and objectives which are broadened the understanding of the research purpose and framework.

The second chapter is the review of literatures and the purpose of this chapter is present theoretical background and understanding on the research topic. This is done by conducting a reflective study of what past literatures and researchers have discovered in the area of study and also highlighting some of the expected outcome from this present study.

The third chapter is the methodology and this chapter discusses how the research will be conducted by analysing the sources of data and the overall approach that will be utilized in the primary study. The fourth chapter is the analysis of the findings from the primary research. In this study, the research was primarily based and the sources of information are primary source as the research didn’t conduct experimental study. Thus, the chapter four actually present the analysis of the findings discovered from this primary sources.

The final chapter is the chapter five and it is the conclusion of the study. In this chapter, the overall finding from the study where analysed and summarized with recommendations also made with respect to how the study can further be improved in further related researches.

                                                                       Chapter 2

Review of literatures

Natural products: an introduction

In accordance with the Royal Society for Chemistry (2010), natural products are organic compounds formed by living system. The elucidation process of these compounds coupled with their chemistry, synthesis and biosynthesis form a s very major areas in organic chemistry. These compounds were also described to be naturally occurring and can be divided into three major categories. The first of these categories is the compounds that occur in all cells and also play significant role which is central to metabolism and reproduction of those cells. These compounds are made up of the nucleic acids and the common amino acids as well as sugar. Generally, they are described as primary metabolites. The second category is those that are high in molecular weight polymeric materials such as cellulose, lignin and the proteins that actually form these cellular structures. The final category are compounds that are made of up of limited space ranges and they are known as secondary metabolites. Majority of the primary metabolites yield out their biological effect in the cell or organism that where they were actually produced. On the other hand, the secondary metabolites have in most cases attracted interest due to their biological effects on other organisms.

Primary and secondary metabolites (natural products)

Biosynthesis is a process in plant that involves breakdown of proteins, nucleic acids, fat and carbohydrates, and this process is very important to all living organism; and known as primary metabolism which is done by compounds known as primary metabolites (Dewick, 2002). However, the process by which a given organism actually biosynthesizes compounds known as secondary metabolites (natural products) is something that has been perceived as unique to organism and can also be described as the expression of how species are individual and it is known  as secondary metabolism (Dewick, 2002). On a general ground, secondary metabolites are not that important for growth, the development or productive process in living organism and they are produced either because the organising is adapting to its surrounding environment or that the organism is producing them as a form of defensive mechanism to act against predators in order to assist the organism towards survival (Maplestone et al., 1992). The biosynthesis of secondary metabolites is gotten from the basic photosynthetic process, glycolysis and also the Krebs cycle that are used to form biosynthetic intermediates that will eventually yield the formation of secondary metabolites that are also known as natural products (Colegate and Molyneux, 2008). Thus, it can be seen that while the number of building blocks actually seem limited, the actual process of forming secondary metabolites are infinite in nature. The most vital building block adapted in the process of the biosynthesis of secondary metabolites are those that are gotten from the intermediate as: Acetyl coenzyme A (acetyl-CoA), shikimic acid, mevalonic acid and 1-deoxyxylulose-5-phosphate. These enzymes are actually involved in a number of varying mechanisms and reactions that are done through countless biosynthetic pathways (Sarker et al., 2006).

There are also hypothesis that secondary metabolism makes use of amino acids and the acetate together with shikimate pathways for the production of “shunt metabolites” (intermediates) that have been grown through a biosynthetic route, and this results in the actual biosynthesis of the secondary metabolites (Sarker et al., 2006). The causes of modifications in the biosynthetic pathways can be either natures (such as viruses and changes in the environment) or unnatural causes (such as chemical or radiation) in the plants efforts to actually adapt to a given organism or provide longevity for that particular organism (Sarker et al., 2006). Basically, secondary metabolism is a unique biosynthesis of natural products that is actually produced through numerous terrestrial and marine organisms, providing the characteristic chemical structures that contains an array of biological activities.

Classes of secondary metabolites

Still on the same study by Royal Society for Chemistry (2010), it was made known that secondary metabolites will normally seem to be bewilderingly diverse at first sight. However, it was made known that most of these compounds actually belong to a number of families and these families have their own respective structural features that arises from the way in which they are actually built up in nature, which is from their real biosynthetic nature. Secondary metabolites can be classified into:

1.      Polyketides and fatty acids

2.      Terpenoids and steroids

3.      Phenylpropanoids

4.      Akaliods

5.      Specialized amino acids and peptides

6.      Specialized carbohydrates

The formation of polyketides is done via the linear combination of acetates (ethanoate) units that are gotten from the acetyl co-enzyme A, which is the building block of the whole formation process. Steroids and Terpenoids are naturally formed from the isoprenoid C₅ units that are gotten from isopentenyl (3-methylbut-3-en-1-y1) pyrophosphate. The linking of the C₅ is done naturally in a head-to-head placement approach. They also possess a structure that features branched chains. There are also a further group of natural products that contain phenylpropanoid (C₆-C₃) unit. 

The amino acids function as the foundation of the peptides and proteins. While these acids are normally perceived as primary metabolites, some unusual amino acids are quite restricted in terms of their occurrence. Some of the antibiotics such as penicillin are also formed from small amount of peptides (Royal Society for Chemistry, 2010). The alkaloids are group of natural products that are structurally diverse and they contain nitrogen. The nitrogenous portions of the alkaloids are gotten via amino acids like ornithine, tryptophan, lysine, and tyrosine.

Although sugar (carbohydrates) like glucose is normally primary metabolites, there are also some sugars that are very much limited in their occurrence. Some of these sugars that are less common are attached to the natural products as a part of a glycoside. Non-sugar proteins are referred to as aglycone, and they can be polyketide, terpenoid, or alkaloid.

Natural products for treatment of illness

From the onset, traditional medication process form the root of medication practice and this was followed by a transformation into clinical, pharmacological and chemical studies as the solution to health related issues (5). The syntheses of anti-inflammatory agent, acetylsalicyclic acid (1) which are gotten from natural products, salicin (2) which drop off from the back of willow tree Salix alba L. Der Marderosian, and Beutler, 2002]  are probably the most common and famous examples of traditional medicines that dates up till this moment. Investigations done on  Papaver somniferum L. (opium poppy) is the foundation from which numerous alkaloids where isolated including morphine (3), which is an important and commercial drug that was first reporting in 1903 as shown in figure 2.1 below. In the 1870s, crude morphine that were gotten from the plant P. somniferum was heated up in acetic anhydride in order to produce diacetylmorphine (heroin) and they were readily found to be converted to codeine (painkiller). There are historical documentations that the Sumerians and Ancient Greeks made use of extracts from poppy for medicinal purpose, and the Arabians described opium as an additive drug (Der Marderosian, and Beutler, 2002). Another compound that has been traced back to Europe in the 10^th century is Digitalis purpurea L. (foxglove), but it was until the 1700s that the active constituent digitoxin (4), a form of cardiotonic glycoside discovered to be capable of enhancing the cardiac conditions, as such improving the actual cardiac contractibility strength. Digitixin (4) and its analogue has been used for long for the management of congestive failure of the heart and they have also been shown to have detrimental effects on the long term and this is the main reason why they are being replaced by other medicines for the treatment of heart related deficiencies (Der Marderosian, and Beutler, 2002). Quinine is an anti-malaria drug (5) that was approved by the US FDA in 2004, and it is actually isolated from the bark of Cinchona succirubra Pav. Ex Klotsch with its usage coming in over the centuries for the treatment of malaria, fever, indigestions, mouth and throat diseases as well as cancer. A formal adoption of the bark of the plant for the purpose of treating material is a phenomenon that begun back in the 1800s and the British started an actual worldwide cultivation of the plant for the same and other related purposes (Der Marderosian, and Beutler, 2002). Pilocarpine (6) is another secondary metabolite that is found in Pilocarpus jaborandi (Rutaceae) is an L-histidine-derived alkaloid, that has for long been used as a form of clinical drug for the treatment of chronic open-angle glaucoma and closure-angle glaucoma for the more than 100 years. The oral formulation of the same Pilocarpine was approved by the US FDA for the treatment of dry mouth (Xerostomia), which is a side effect that is caused by the radioactive therapy of the head and neck cancers and also used for the purpose of stimulating sweat glands in order to measure the actual concentration of sodium and chloride as can be seen from the figure (2.1) below (Aniszewski, 2007).

Figure 2.1 Acetylsalicyclic acid (1), Salicin (2), Morphine (3), Digitoxin (4), Quinine (5) and Pilocarpine (6).

Over the years, there have been numerous documentations about plants with regards to their medicinal uses. Plants have evolved and adapted over millions of years ago when it comes to withstanding bacteria, insects, weather, and fungi in order to produce secondary metabolites that are diverse in their structure. The ethnopharmacological properties of these plants have also been used mainly for medical purpose and they serve as the route for early discoveries made in drugs [Fellows and Scofield, 1995; McRae, 2007]. In accordance with the records presented by the World Health organization (WHO), it was shown that 80% of people that across the world still put high hopes and reliance on traditional medicines from plants as their primary source of health care across the globe (Farnsworth et al., 1985), and 80% of 122 plants that have been discovered are related to their original ethnopharmacological purpose [Fabricant and Farnsworth, 2001]. The associated knowledge when it comes to traditional medicine (be it in the complementary of alternative herbal products) has led to the promotion of extra investigations of medicinal plants as a potential source of medicines and has also led to the actual isolation of numerous natural products that have now become pharmaceutical products.

For instance, Taxol® (Purvis, 2000) is the mode widely used drug for breast cancer, and it is isolated from the bark of Taxus brevifolia (Pacific Yew). The United States Department for Agriculture (USDA) first made collection of the back part as their exploratory plant screening program at the country’s National Cancer Institute (NCI) see figure (2.2) below (Purvis, 2000) for the purpose of understanding how the plant can be used for cancer treatment. The bark from about three nature for over 100 years old plants are needed for the purpose of providing a gram of the drug (Purvis, 2000) and it should also be understood that the treatment of cancer requirement can demand up to 2 grams of the drug. Current demand for the drug is in the region of about 100–200 kg per annum (i.e., 50,000 treatments/year) and this has led to its current synthetic production process (Dewick, 2002).

Figure 2.2. Paclitaxel (Taxol®) (19) and baccatin III (20)

Natural products as insecticides

Insecticides have for long served as the cornerstone upon which the management of pest are actually based, and they are also likely to maintain the same function so long as they continue to be inexpensive and effective chemicals (Hayves, 1988). Natural products have been used since the ancient time as botanical invectives. On a general ground, all the plants have developed a unique chemical complex that they use in protecting themselves from different kinds of pests and these chemicals are referred to as allelochemicals. Thus, it can easily be seen that pests will serve as a source of diverse group of complex chemical structures that can be seen in almost all the forms of biological activity. For thousands of years, the reliance of agricultural practices have been on crop rotation or mixed cropping as a form of optimizing natural pest control. Thus, the concept of natural pesticides is something that arose earlier alongside development of agriculture (Dayan et al., 2009). The compendium of medicine which is referred to as the Ebers Papyrus of c. 1600 B.C., and it comprises of both organic and chemical substances that were mainly recommended for usage as insecticides (Panagiotakopulu et al., 1995). These medicines have been documented in both the Ancient Greek world and Chinese medicine and serves as the right proof of pest control right from the earliest days (Dayan et al., 2009; Yang &Tang, 1988).

                                                                        Chapter 3

Materials and method

Research purpose

Right from the introductory chapter, the purpose of this research was highlighted and it is to understand how plant’s secondary metabolites are used as natural products. The understanding is designed to analyse the concepts for such uses, history and current applications. As such, this is also the same purpose of the primary research and it is designed to present an analysis of the usages in terms of documented and experimental studies.

Research approach

The approach for this research is secondary based. The implication is that information will be sourced from previous studies but such sourcing will be done form reliable sources such as plant related journals that have tested the research topic in the past. Thus, it can be said that the source will be primary sources but the same purpose of the research will be reflected from the whole study.

Reliability and validity

Considering the importance of this research topic, it is important to understand that data to be used in the analysis need to be very much reliable and valid as of the time of the study and this is basically the main framework governing this study. Information will be sourced only from validated and reliable sources such as journals that have been done from government departments and other biotechnology units across the world. The gathered information will then be compared against each other and picked up only if similarities exist as a clear proof of the validity of such studies.

Ethical consideration

In a research such as this where information are gathered entirely online, a number of ethical issues prevail and it is important to understand these issues as well as ways that they will be resolved in order to ensure quality in the delivery of data and findings from the research. In this study, ethical issues exist in terms of representation of information as to the rightful author and research that made such discoveries. Since this is secondary research, it is important that all the information presented in the study are brought to light based on the actually findings and authors that made such discoveries. Thus, the researcher puts this into consideration and extra measure is undertaken with the view of ensuring that all the materials used in this study are properly sourced.

Chapter 4

Findings

Introduction

Following the guidelines that have been established in the research materials and methods above, a number of findings were made and this purpose of this chapter is to present an analysis of the findings from the research. Thus, the focus will be on understanding how plant’s secondary metabolites can be used as natural products with reference to past studies in this field.

Combining plant’s secondary metabolites for drug discovery

System biology is without much doubt an emerging field in the biotechnology system and it is a field that encompasses tools that have been developed in the period following genomics revolutions which can be in the form of transcriptiomics, glycomics, flucomics, and proteomics; all developed with the ambition of characterizing all gene and cell products which also include mRNA, glycan structures, proteins and metabolites in the most comprehensive manner possible. The main objectives of metabolomics is to developed an observation that is unbiased with a high level of analytical tools that can be reproduced and followed by data analysis in order to locate the level of correlations existing between all the variable data loaded into the study. In the currently emerging field of metabolomics, the understanding from research is that there is no single analytical technique that can be used to profile all the low molecular weight metabolites. The emerging field is actually a combination of analytical chemistry, biochemistry and other sophisticated information that enable the analysis of small molecules (metabolites) in their thousands within a given biological system. In consideration of the fact that extracts of the metabolites are very compels and also given the huge chemical diversity present in metabolites, it can easily be seen that there is no single platform and methodology for analysing metabolites, making it impossible to analyse all the metabolites in a given system simultaneously. Thus, there is a need to apply a number of separation chemistry in order to actually achieve the highest level of comprehensiveness in the analysis (Roessner and Beckles, 2009).

As a result of the improved level of sensitivity, advancement and resolutions in hundreds of instrumentation compounds can now be simultaneously analysed with a refined informatics tools developed for the purpose of extracting information from the resulting data, adopting filtering algorithm to deduce the background noise, detecting and integrating peaks throughout larger sets of data and normalizing and transforming the resulting data matrices before any form of statistical analysis can then be conducted (Roessner et al., 2011). The most difficult challenge when it comes to metabolomics is the ability to identify and detect signals in line with their chemical nature. Even at the moment, 60 to 80% of the compounds already detected are still unknown [Roessner et al., 2011; Beckles., 2011] and a number of initiatives have been implemented by the metabolomics community with regards to tacking this issue by adopting measures like creating large mass spectral or NM spectral libraries that can be used as reference.

In any case, the fact is irrespective of the approach used in terms of extracting natural products and the fact still remains that they are a great source of drug used in the treatment of numerous illness. In most of the applications where they have been adopted, there are indications that their adaptation stretches far back to hundreds of years ago and as such it has helped increase understanding on how plant’s metabolites can be extracted and used as medicinal products.

Other examples of such besides those discussed in the review of literature is that plant metabolites are currently in a number of anti-tumour clinical trials with examples such as ingenol 3-O-angelate (21) which is a derivative of polyhydroxy diterpenoid ingenol that is extracted from the sap of Euphorbia peplus and is currently being texted as a potential chemotherapeutic agent against skin cancer as a clinical development by Peplin biotech that will be used as a tropical treatment of some kinds of skin cancer (as shown in the figure 4.1 below) [Kedei et al., 2004; Ogbourne et al., 2004]. PG490-88 (22) (14-succinyl triptolide sodium salt), a semisynthetic analogue of triptolide is a diterpene-diepoxide extracted from Tripterygium wilfordii is used as an autoimmune and inflammatory diseases therapy presently in China [Kiviharju et al., 2002; Fidler et al., 2003]. Another deliberative is Combretastatin A-4 phosphate (23), which is gotten from the South African Bush Willow, Combretum caffrum and it functions as an anti-angiogenic agent that produces vascular shutdowns in tumours (necrosis) with the present phase of the test being in II of clinical trials as shown in the figure 4.1 below [Newmand and Cragg, 2005; Holwell et al., 2002].

Figure 7. ingenol 3-O-angelate (21), PG490-88 (22) and Combretastatin A-4 phosphate (23).

The AIDS pandemic of the 1980s forced numerous organizations alongside the National Cancer Institute (NCI) to start exploration of numerous natural products as a potential source of drugs that will be used to address these health issues. In the course of the study, more than 60 thousand of extracts from plants and other marine organisms have been tested against lymphoblastic cells that are infected with HIV-1. The class of compounds known as calanolides represents the most important result that was gathered from this test. As amatter of fact, the isolation of calanolide A (24) and calanolide B (25) from the Calonphyllum species, along with prostratin (26) from Homalanthus nutans, have all progressed into clinical and preclinical developments (see figure 4.2 below) [68–70].

Figure 4.2: Calanolide A (24), Calanolide B (25) and Prostratin (26).

From the above analysis, it can be seen that plants’ metabolites represents a huge improvement in the area of drug discovery and as such it is being practices across the globe for the core of numerous drugs as well as in clinical trials as potential cure of blood related and vascular diseases such as AIDS. As such, this metabolites are now very significant when it comes to improving the health of humans because it represents a significant increase in the science of the medical field.

Use of plants’ metabolites (natural products) as phytochemical sources and for insecticidal activity

The increase in demand for natural products has further intensified in the past couple of decades as these products have been found to possess extensive biological active compounds and are also being considered as an important alternative strategy when it comes to ensuring sustainable inset management and pest control in the agricultural field, as a result of their high level of biodegradability and potentials when it comes to being used in integration for numerous management programs (Rattan, 2010). A review of literature as presented above have shown that there are a number of biological activity of numerous plant compounds on a high number of pathogens and arthropods. Roark (1947) conducted an old review with focus on agriculture and described 1200 plants species in the process that have also been listed in current literatures as possessing potential insecticidal values. These studies has also exposed in the process, a number of botanical insecticides that exist in different families such as Meliaceae, Agavaceae, Lamiaceae, Rutaceae, Cactaceae, Asteracae, Labiatae, etc., also including a broader species of bioactive fungicides, nematicides, acaricides, insecticides and carcinogenic (Shaalan et al., 2005). Some of the botanical extracts that have insecticidal interests are described in the Table 4.1 below. Possibilities also exist when it comes to identifying extracts that come prepared from the roots, stems, branches, flowers, fruits, seeds, leaves and a host of other sources of plants, showing differences in terms of their biological activities against insect pests (with regards to the way they act and react within specific settings), and they also come in large volume of diversity in terms of the phytochemical techniques they employ in the process of producing these materials, differences in their chemical profile and numerous other compositions that are assayed in their formulations.

Table 4.1: potential plants’ metabolites and their insecticidal features

Source plant	Organ	Insects they kills	Experimental study
Aglaia odorata Yucca periculosa	Leaves Barks	Spodoptera littoralis Spodoptera frugiperda Sitophilus oryzae Tribolium castaneum	Nugroho et al., 1999 Torres et al., 2003
Ocimum gratissimum	Oils	Oryzaephilus urinamensis Rhyzopertha dominica Callosobruchus chinensis Sitophilus zeamais	Ogendo et al., 2008

 Actually, it is never hard to make identifications of botanical extracts that show some sort of activity against pests and insects. Within the planet universe, the Meliaceae family has been the centre of attraction when it comes to such identifications. This family is made up of 50 different genes and 1400 kinds of species with most of these species distributed within the Pan-tropics zone. The ones that show a higher level of insecticidal activities within these genes include Aglaia, Aphanamixis, Azadirachta, Garapa, Cedrela, Chukrasia, Dysoxylum, Guarea, Khaya, Melia, Soymida, Swietenia, Trichilia, and most of the plants within this family are tress and known for their quality in the timber industry (Benerji &Nigam, 1984).

For this study, particular reference will be given to Azadirachta indica A. Juss (Meliaceae) (Neem tree), and both present and past researches have shown that numerous mechanisms of action exist in terms of adopting it as an insecticidal control agent. There are over 100 compounds that have been isolated from different parts of Neem (Luo et al., 1999). Additionally, it is common to find a wide range of biological activities, which will include their anti-feedant effects on insects as well as their properties with respect to regulating growth. In most recent studies conducted, there are evidence that chemical compositions of these Neem seeds have also witnessed an intensive exploration following their prove as an excellent source of wide varieties of chemicals that are very useful for the purpose of managing pestiferous insects (Kumar et al., 2003). Over 500 insects and pests have also been listed as being sensitive to seed extracts from Neem (Morgan, 2009). Basically, these biological characteristics are as a result of the terpenoid compounds that numerous papers have also reported to contain bitter substances, which are popularly referred to as limonoids as shown in the figure 4.3 below (Luo et al., 1999; Siddiqui et al., 1999; Siddiqui et al., 2001).

Figure 4.3: The main metabolite of Neem is a limonoid known as azadirachtin

Basically, the understanding from the above discussion is that plant metabolites are significant compounds for insecticidal activities. This is in line with the earlier discussions presented in the review of literatures where it was made known that in the course of by their biodiversity, plants have developed a number of resistance and adaptations to the insects that exist in their ecosystem. Thus, it can easily be understood that such development when applied rightfully will ensure that these insects are also protected against in the biological sense. Thus, it can be seen from the above discussion that plant metabolites represent significant natural products for pest and insect management and it is even much better can the chemicals used because they are biodegradable.

Besides the earlier of pharmacology and insecticidal usages, plants’ metabolites are also used in other areas such as usage as fragrance and food additive. However, these usages still reference its agricultural application and the implication is that the most common areas where plant metabolites are used are for pharmacological and agricultural purposes. Basically, this is understandable because plants on their own represent agricultural products and it is expected that their usages will also be related to this field. Additionally, agricultural products are used for medicinal purpose, making it a common understanding that plants metabolites will also be used in that earlier as well.

Chapter 5

Conclusion

In the course of this study, the purpose of the research was discussed in the introductory page and the purpose was defined to be to gain an understanding of how secondary metabolites from plants can be used as natural products. Basically, plants are known to undertake the process of photosynthesis in which the primary metabolites are the compounds released while the secondary metabolites are the compounds used in the process of such photosynthesis. Thus, it is more like the waste gotten from a photosynthesizing plant.

Such an understanding was further expanded in the review of literature where it was made known that a number of researches have been done in the past and there are also those being conducted presently with regards to how the secondary metabolites of plants can be used as a natural product. The understanding from both past and present researches is that their usages come in two broad areas of pharmacology and agriculture.

In order to further understand the usage of plant metabolites as natural products, primary research was designed in order to compare between past literatures, studies and experiments with respect to how the secondary metabolites are currently being used and can also be used in the future. Necessary ethical measures were taken into consideration in order to ensure that the sources for the information are documented and the actual findings analysed as presented in the study.

Following the research design, a number of findings were but the significance of such is reflected in the understanding that secondary metabolites are used primarily for medical and agricultural purposes. In terms of the medical aspect, it was found that plants in the past have been used for centuries in the cure of numerous diseases and as such UK and USA advance such application by actually expanding the cultivation of relevant plants that serve those purposes cross the world. The growth of such adoption increased and it also lead to a subsequent increase in clinical testing for plants’ metabolites. Increase in technology has also increase the extraction and isolation level of such metabolites for easier collection and usage in the medical settings. Besides its high use for drugs, they are also used as insecticides. Basically, plants have developed a number of features over the years to fight insect attacks and these features are currently being extracted to function as natural and biodegradable insecticides, which makes it better than that of chemical insecticides.

In conclusion, plants’ metabolites are very significant agricultural products to the human race and their importance is reflected in the area of agriculture and pharmacology. They play significant role in human life with respect to providing sources for drugs used to cure numerous illnesses, being effective insecticides and also used as food additives and for fragrance production. The advancement in biotechnology has also increased the efficiency and effectiveness for research through an increase in the extraction and isolation efficiency.

References

Aniszewski, T. Alkaloids—Secrets of Life. In Alkaloid Chemistry, Biological Significance, Applications and Ecological Role; Elsevier Science: Amsterdam, The Netherlands, 2007; p. 334.

Beckles, D.M.; Roessner, U. Plant Metabolomics—Applications and opportunities for agricultural biotechnology. In Plant Biotechnology and Agriculture: Prospects for the 21st Century; Altmann, A., Hasegawa, P.M., Eds.; Elsevier/Academic Press: Boston, MA, USA, 2011.

Benerji, B. & Nigam, S.K. (1984).Wood constituents of Meliaceae: a review. Fitoterapia, 55, pp. 3-36.

Colegate, S.M.; Molyneux, R.J. Bioactive Natural Products: Detection, Isolation and Structure

Dayan, F.E., Cantrell, C.L., & Duke, S.O. (2009). Natural Products in Crop Protection. Bioorganic & Medicinal Chemistry, 17, pp. 4022–4034.

Der Marderosian, A.; Beutler, J.A. The Review of Natural Products, 2nd ed.; Facts and Comparisons; Seattle, WA, USA, 2002; pp. 13–43.

Determination; CRC Press: Boca Raton, FL, USA, 2008; pp. 421–437.

Dewick, P.M. Medicinal Natural Products: A Biosynthentic Approach, 2nd ed.; John Wiley and Son: West Sussex, UK, 2002; p. 520.

Dewick, P.M. Medicinal Natural Products: A Biosynthentic Approach, 2nd ed.; John Wiley and Son: West Sussex, UK, 2002; p. 520.

Fabricant, D.S.; Farnsworth, N.R. The value of plants used in traditional medicine for drug discovery. Environ. Health Perspect. 2001, 109, 69–75.

Farnsworth, N.R.; Akerele, R.O.; Bingel, A.S.; Soejarto, D.D.; Guo, Z. Medicinal Plants in Therapy. Bull. WHO 1985, 63, 965–981.

Fellows, L.; Scofield, A. Chemical diversity in plants. In Intellectual Property Rights and Biodiversity Conservation—An Interdisciplinary Analysis of the Values of Medicinal Plants; University Press: Cambridge, UK, 1995.

Fidler, J.M.; Li, K.; Chung, C. PG490-88, a derivative of triptolide, casues tumor regression and sensitizes tumors to chemotherapy. Mol. Cancer. Ther. 2003, 2, 855–862.

Hayves, K.F. (1988). Sublethal effects of neurotoxic insecticides on insect behaviour. Annual Review of Entomology, 33, pp. 149-168.

Holwell, S.E.; Cooper, P.A.; Grosios, J.W.; Lippert, J.W., III; Pettit, G.R.; Snyder, S.D.; Bibby, M.C. Combretastatin A-1 phosphate, a novel tubulin-binding agent with in-vivo anti-vascular effects in experimental tumors. Anticancer Res. 2002, 22, 707–712.

Hussain, M., Perschke, H., & Kutscher, R., (1990). The Effect of Selected UV Absorber Compounds on the Photodegradation of Pyrethroid Insecticides Applied to Cotton Fabric Screens. J. Pesticide Sci., 28, pp. 345-355.

ICH [International Conference on Harmonization, FDA, USA]. (1996). Tittle, In: Q2B: Validation of Analytical Procedures: Methodology. Jul/02/2011. Available from: <http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInfor

Kedei, N.; Lundberg, D.J.; Toth, A.; Welburn, P.; Garfield, S.H.; Blumberg, P.M. Characterization of the interaction of ingenol 3-angelate with protein kinase C. Cancer Res. 2004, 64, 3243–3255.

Kiviharju, T.M.; Lecane, P.S.; Sellers, R.G.; Peehl, D.M. Antiproliferative and proapoptic of triptolide (PG490), a natural product entering clinical trials, on primary cultures of human prostatic epithelial cells. Clin. Cancer. Res. 2002, 8, 2666–2674.

Kumar, A.R.V., Jayadevi, H.C., Ashoka, H.J., & Chandrashekara, K. (2003). Azadirachtin use efficiency in commercial neem formulations. Current science, 84, pp. 1459-1464.

Luo, X., Ma, Y., Wu, S., & Wu, D. (1999). Two novel azadirachtin derivatives from Azadirachta indica. J. Nat. Prod., 62, pp. 1022-1024.

Maplestone, R.A.; Stone, M.J.; Williams, D.H. The evolutionary role of secondary metabolites— A review. Gene 1992, 115, 151–157.

mation/Guidances/UCM073384.pdf)>.

McRae, J.; Yang, Q.; Crawford, R.; Palombo, W. Review of the methods used for isolating pharmaceutical lead compounds from traditional medicinal plants. Environmentalist 2007, 27, 165–174.

Morgan, E.D. (2009). Azadirachtin, a scientific gold mine. Bioorganic & Medicinal Chemistry, 17, pp.4096–4105.

Newman, D.J.; Cragg, G.M. In Drug Discovery, Therapeutics, and Preventive Medicine; Zhang, L., Fleming, A., Demain, A.L., Eds.; Humana Press: Totowa, NJ, USA, 2005; p. 74.

Nugroho, B.W., Edrada, R.A., Wray, V., Witte, L., Bringmann, G., Gehling, M., & Proksch. P. (1999). An insecticidal rocaglamide derivatives and related compounds from Aglaia odorata (Meliaceae). Phytochemistry, 51, pp. 367-376.

Ogbourne, S.M.; Suhrbier, A.; Jones, B. Antitumour activity of ingenol 3-angelate: Plasma membrane and mitochondrial disruption and necrotic cell death. Cancer Res. 2004, 64, 2833–2839.

Ogendo, J.O., Kostyukovsky, M., Ravid, U., Matasyoh, J.C., Deng, A.L., Omolo, E.O., Kariuki, S.T., & Shaaya, E. ( 2008). Bioactivity of Ocimum gratissimum L. oil and two of its constituents against five insect pests attacking stored food products. Journal of Stored Products Research, 44, pp. 328–334.

Ong, E.S. (2004). Extraction methods and chemical standardization of botanical and herbal preparations. Journal of Chromatography B, 812, pp. 23-33.

Panagiotakopulu, E., Buckland, P.C., & Day, P.M. (1995). Natural Insecticides and Insect Repellents in Antiquity: A Review of the Evidence. Journal of Archaeological Science, 22, pp. 705-710.

Purvis, W. Lichens; Natural History Museum, London/Smithsonian Institution: Washington D.C., USA, 2000; p. 112.

Rattan, R.S. (2010). Mechanism of action of insecticidal secondary metabolites of plant origin. Crop protection, 29, pp. 913-920.

Rharrabe, K., Amri, H., Bouayad, N., & Sayah, F. (2008). Effects of azadirachtin on postembryonic development, energy reserves and -amylase activity of Plodia interpunctella Hübner (Lepidoptera: Pyralidae). Journal of Stored Products Research, 44, pp. 290– 294.

Roark, RC. (1947). Some promising insecticidal plants. Econ. Bot. 1, pp. 437-445; apud Shaalan, E.A-S., Canyon, D., Younes, M.W.F., Abdel-Wahab, H., & Mansour, A-H. A review of botanical phytochemicals with mosquitocidal potential. Environment International, 31, pp. 1149 – 1166.

Roessner, U.; Beckles, D.M. Metabolite measurements. In Plant Metabolic Networks; Junker, B., Schwender, J., Eds.; Springer: Heidelberg, Germany, 2009.

Roessner, U.; Nahid, A.; Hunter, A.; Bellgard, M. Metabolomics—The combination of analytical chemistry, biology and informatics. In Comprehensive Biotechnology, 2nd ed.; Moo-Young, M., Ed.; Springer: Heidelberg, Germany, 2011; Volume 1, pp. 447–459.

Royal Society for Chemistry (2010), The classes of natural products and their isolation. Available at: www.rsc.org/pdf/tct/natprods1.pdf [Accessed on: 20/10/2013].

Ruiu, L., Satta, A., & Floris, I. (2008). Effects of an azadirachtin-based formulation on the non-target muscoid fly parasitoid Muscidifurax raptor (Hymenoptera: Pteromalidae). Biological Control, 47, pp. 66–70.

Sarker, S.D.; Latif, Z.; Gray, A.I. Methods in Biotechnology: Natural Product Isolation; Satyajit D., Ed.; Human Press Inc: Totowa, NJ, USA, 2006; p. 528.

Saxena, R.C. (1989). Insecticides do neem. In: Insecticides of Plant Origin, Arnason, J.T., Philogène, B.J.R., & Morand, P., pp. 110-135, ACS Symposium Series, 387, ISBN 9780841215696, Washington.

Schaffazick, S.R., Pohlmann, A.R., Mezzalira, G., & Guterres, S.S. (2006). Development of nanocapsule suspensions and nanocapsule spray-dried powders containing melatonin. J. Braz. Chem. Soc., 17, pp. 562-569.

Shaalan, E.A-S., Canyon, D., Younes, M.W.F., Abdel-Wahab, H., & Mansour, A-H. (2005). A review of botanical phytochemicals with mosquitocidal potential. Environment International, 31, pp. 1149–1166.

Siddiqui, B.S. Afshan, F., & Faizi, S. (2001). Three novel tetracyclic triterpenoids of biogenetic interest from the leaves of Azadirachta indica. Tetrahedron, 57, pp. 10281- 10286.

Siddiqui, B.S., Ghiasiddin., Faizi, S., & Rasheed, M. (1999). Triterpenoids of fruit coats of Azadirachta indica. J. nat. Prod., 62, pp. 1006-1009.

Torres, P., Avila, J.G., de Vivar, A.R., García, A.M., Marín, R.C., Aranda, E., & Céspedes, C.L. (2003). Antioxidant and insect growth regulatory activities of stilbenes and extracts from Yucca ericulosa. Phytochemistry, 64, pp. 463–473.

Yang, R. Z., & Tang, C.-S. (1988). Plants used for pest control in China: a literature review. Econ. Bot., 42, pp. 376-406.