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Medicinal Plants for Holistic Health and Well-Being

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Medicinal Plants for Holistic Health and Well-Being

Academic Press is an imprint of Elsevier

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This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein).

Notices

Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary.

Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility.

To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein.

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1. Traditional Medicine: The Ancient Roots of Modern Practice

Anna-Mari Reid, Carel B. Oosthuizen, Bianca D. Fibrich, Danielle Twilley, Isa Anina Lambrechts, Marco Nuno de Canha, Sunelle Rademan and Namrita Lall

1.1

2.

2.5

3. Fighting the Inevitable: Skin Aging and Plants

3.1

D. Fibrich and Namrita Lall

3.1.4

3.1.5

4. Exploiting Medicinal Plants as Possible Treatments for Acne Vulgaris

Isa Anina Lambrechts, Marco Nuno de Canha and Namrita Lall

4.1

4.1.7

4.2 Why Use Plants for the Treatment of Acne Vulgaris?

4.2.1

4.2.2

4.3 Essential Oils for the Treatment of

4.3.1 Plant Essential Oils Traditionally Used and Commercially Available for the Treatment of Acne

4.4 Scientific Reports on Plants Against Propionibacterium acnes

4.4.1

4.4.2

4.5

5. Medicinal Plants as Alternative Treatments for Progressive Macular Hypomelanosis

Analike Blom van Staden and Namrita Lall

5.1

5.1.3

5.1.4

5.1.5

5.2

5.3

5.4

5.5

5.4.1

5.4.3

5.5.1

5.5.2

5.5.3

5.6

6. The Role of Medicinal Plants in Oral Care Dikonketso Bodiba, Karina Mariam Szuman and Namrita Lall

6.1

6.2

6.3

6.3.1

6.3.2

6.4

6.5

6.6 Plant Products Produced

6.6.2

6.6.3

Rinses and Herbal Mouthwash

6.7 Reported Antibacterial and Antifungal Activity of Medicinal Plants and Phytochemical Compounds

6.7.1 Heteropyxis dehniae Suess.

6.7.2 Syzygium aromaticum (L.) Merr. & L.M. Perry

6.7.3 Vaccinium vitis-idaea L.

6.7.4 Cinnamomum verum J. Presl

6.7.5 Melaleuca alternifolia Cheel

6.7.6 Azadirachta indica A. Juss.

6.7.7 Euclea natalensis A.DC

6.7.8 Diospyros lycioides Desf.

6.7.9 Mentha longifolia L.

6.7.10 Zantedeschia aethiopica (L.) Spreng.

7. Can Medicinal Plants Provide an Adjuvant for Tuberculosis Patients?

Carel B. Oosthuizen, Anna-Mari Reid and Namrita Lall

7.1

7.2

7.3

7.1.1

7.1.3

7.1.4

7.3.4

7.4

7.5

8. Medicinal Plants Used in the Treatment of Superficial Skin Infections: From Traditional Medicine to Herbal Soap Formulations

Murunwa Madzinga, Quenton Kritzinger and Namrita Lall

8.1 Superficial Skin Infections 256

8.1.1 Common Superficial Fungal Infections (Mycoses)

8.1.2 Common Bacterial Skin Infections

8.1.3 Prevalence of Skin Infections Worldwide

8.1.4 Prevalence of Skin Infections in Africa

8.1.5 Current Treatments of Skin Infections

8.2 South African Plants Used in the Treatment of Bacterial and Fungal Skin Infections

8.2.1 Elephantorrhiza elephantina (Burch.) Skeels (Eland’s Bean)

8.2.2 Melianthus comosus Vahl (Honey Flower)

8.2.3 Dicoma anomala Sond. (Fever Bush)

8.2.4 Kigelia africana (Lam.) Benth. (Sausage Tree)

8.2.5 Ekebergia capensis Sparrm. (Cape Ash)

8.2.6 Diospyros mespiliformis Hochst. ex A.DC. (African Ebony, Jackleberry)

8.2.7 Aloe ferox Mill. (Bitter Aloe)

8.2.8 Warburgia salutaris (G. Bertol.) Chiov. (Pepper-Bark, Fever Tree)

8.2.9 Senecio serratuloides DC. (Two-Day Plant)

8.3 Herbal Soaps Infused With Plants Extracts

8.4 Conclusion

9. Garlic (Allium sativum) and Its Associated Molecules, as Medicine

Carel B. Oosthuizen, Anna-Mari Reid and Namrita Lall

9.1 Introduction: Allium sativum and Its Historical Relevance

9.2 Product Development

9.3 Research Findings of Garlic Extracts

9.3.1 Biological Properties

9.3.2 Nutritional Value

9.3.3 Antibacterial

9.3.4 Cardiovascular

9.3.5 Immune Stimulatory Effect

9.3.6 Cancer Treatment

9.3.7 Clinical Significance

9.4

10. Maximizing Medicinal Plants: Steps to Realizing Their Full Potential

10.1 Maximizing the Value of Medicinal Plants

10.1.1 Educate the Global Population About the Use of Plants in Medicine

10.1.2 The Use of Medicinal Plants Stemming From Ethnomedicinal Origin Needs to Be Fully Understood and Scientifically Validated

10.1.3

List of Contributors

Isa Anina Lambrechts, University of Pretoria, Pretoria, South Africa

Analike Blom van Staden, University of Pretoria, Pretoria, South Africa

Dikonketso Bodiba, University of Pretoria, Pretoria, South Africa

Bianca D. Fibrich, University of Pretoria, Pretoria, South Africa

Quenton Kritzinger, University of Pretoria, Pretoria, South Africa

Namrita Lall, University of Pretoria, Pretoria, South Africa

Murunwa Madzinga, University of Pretoria, Pretoria, South Africa

Marco Nuno de Canha, University of Pretoria, Pretoria, South Africa

Carel B. Oosthuizen, University of Pretoria, Pretoria, South Africa

Sunelle Rademan, University of Pretoria, Pretoria, South Africa

Anna-Mari Reid, University of Pretoria, Pretoria, South Africa

Karina Mariam Szuman, University of Pretoria, Pretoria, South Africa

Danielle Twilley, University of Pretoria, Pretoria, South Africa

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Foreword

Yet another book about plants as medicine? Surely an overabundance of books on the subject already exists? However, I am confident that this new title, Medicinal plants for holistic health and well-being, is in a league of its own. The promotion of plant-derived products to treat all kinds of maladies under the banner of being “natural,” and therefore by implication safe and desirable to use, is the order of the day. Unfortunately, claiming such health benefits without proper scientific support has undeniably caused some reputational damage to the noble idea of promoting plants as medicine. This new book by Prof. Lall et al., however, is sure to not only bring much credibility to the scientific study of plant medicines but would also contribute toward its promotion as an exciting field of research, especially among students. The book is also special in that it is a true team effort, conceived and written by a research leader of note and several of her postgraduate students and colleagues. It is a celebration of the trials and tribulations of scientific investigation, ultimately culminating in the excitement and reward of discovering a new pharmacologically active compound or of a new commercially released natural product that can be recommended with confidence.

This publication also bears testimony to what can be achieved by a supervisor and mentor of postgraduate students through sound and inspiring leadership and much hard work. I met Namrita Lall when she was still a botany student and was struck by her enthusiasm for her studies. Through hard work and several years later, Namrita Lall is a distinguished professor in Medicinal Plant Science at the University of Pretoria. She is truly passionate about evaluating the wonders of medicinal plants and not only values and respects available information on biocultural usage in her research but also takes it beyond by proving the efficacy of plant-derived products and eventually developing valuable pharmaceutical and cosmeceutical products. This is further substantiated by the various recognitions she has already received, including the Distinguished Young Women in Science Award (2011) from the Department of Science and Technology, South Africa, and more recently, the Order of Mapungubwe (2014), South Africa’s highest civilian honor granted by the President of the country, for achievements in the international arena that have served the country’s interests.

Not only are we as humans dependent on green plants for our existence but also, like all organisms, we share with them what Charles Darwin has aptly referred to in a broad and metaphorical sense as the “Struggle for Existence.”

It always amazes that green plants, being essentially converters of radiant energy from the sun into a chemical form that serves as potential food for innumerable consumers, still manage to exist out there. Their survival, in the face of the threat of being consumed, is due in no small part to their remarkable ability to create a defense arsenal of chemicals that far exceeds our own. Fortunately some health threats faced by both plants and humans have broadly similar causes, making plants excellent candidates to search for chemicals to serve our own needs. Moreover, the chemical diversity in plants is so vast that they are the ideal source for chemical prospecting to discover novel compounds for human application. Through trail and error over millennia, much useful information about the health benefits of plants has been discovered by humans of all cultures. Such indigenous knowledge, though sadly fast disappearing if not already extinct in many societies, provides a rich source of ideas for scientific studies aimed at the development of safe and effective products for the pharmaceutical and cosmetic industries. Using the ethnomedicinal approach as a point of departure not only saves a great deal of time and resources in modern drug discovery but also encourages the forging of relationships between scientists and the communities holding the key to invaluable traditional knowledge.

This accessible and well-illustrated book gives a clear, comprehensive, and up-to-date introduction to the various usages and scientific validation of medicinal plants against a selection of common health conditions from across the globe. It brings together scientific studies conducted worldwide by scientists and students, including Prof. Lall’s research team, and reports on several leads derived from plants used for specific purposes in traditional medicine. It provides a hands-on approach for evaluating the efficacy of medicinal plants for various conditions. The book eloquently captures the excitement of understanding natural and social phenomena of plants as a valuable resource with exceptional promise in the field of medicine. Current trends show increased popularity of natural products over their heavily commercialized synthetic counterparts. Many factors have spurred this popularity, including increased perceived safety. However, the misconception that plants pose no hazardous toxicity or other negative side effects needs to be corrected. Despite this, plants hold many advantages. For instance, they often offer multiple benefits in the treatment of a health condition and not only target specific symptoms.

True to its objectives and especially by endorsing the value of traditional knowledge and the power of the scientific method, this book indeed succeeds in highlighting the wonder of plants in holding solutions for many human health problems. I highly recommend it to prospective students, teachers, and scientists at all levels, to entrepreneurs, practitioners, and people working in the pharmaceutical and cosmeceutical industries, and to anyone else interested in medicinal plant science. It should prove, especially, useful to students embarking on a research project and also to established researchers as information on the usage of medicinal plants and the scientific validation thereof has been culled from

various sources. Although the work is in the first instance aimed at an academic audience, informed members of the public keen to learn more about the discovery and testing of new medicines should also find it a highly informative read. I would like to congratulate Prof. Lall and her team on a book I believe makes a significant contribution to the field of modern drug discovery.

Abraham E. van Wyk University of Pretoria

May 2017

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Chapter 1 Traditional Medicine: The Ancient Roots of Modern Practice

Anna-Mari Reid, Carel B. Oosthuizen, Bianca D. Fibrich, Danielle Twilley, Isa Anina Lambrechts, Marco Nuno de Canha, Sunelle Rademan, Namrita Lall

University of Pretoria, Pretoria, South Africa

Chapter Outline

1.1 The Use of Plants in Medicine: A Historic Tale 1

1.2 Traditional Medicine Is a Crucial Part of African Heritage 3

1.3 Traditional Medicine in South Africa 5

1.4 Development of Modern Herbal Preparations 7 References 10

1.1 THE USE OF PLANTS IN MEDICINE: A HISTORIC TALE

Plants have been around longer than mankind; naturally, they would be one of the first resources exploited for their medicinal value. In ancient times, the etiological agents of disease were unknown to man, and hence the use of plants as medicinal sources became the product of trial and error, ultimately unveiling valuable medicinal plants. The resulting knowledge of this trial and error formed the root system from which modern medicine would eventually stem. The earliest records of plants used in medicine date back 5000 years to a Sumerian clay slab describing 12 recipes for drug preparation, referring to over 250 plants! Even more interestingly, it describes plants still commonly used in modern times such as the poppy and mandrake (Petrovska, 2012). The Mandrake, Mandragora officinarum, contains the alkaloid hyoscine, responsible for the use of Mandrake in Greek medicine as a surgical anesthetic. The presence of this powerful hallucinogenic alkaloid is what led to the association of the Mandrake with the supernatural (Carter, 2003). The effects of the mandrake, supernatural or not, are what led to the incorporation of mandrake as a

medicinal plant into many additional rituals and traditional medicine practices. The popularity of mandrake and the legends surrounding its use extend beyond medicine into the world of film, where it was interestingly incorporated into the popular film, Harry Potter and the chamber of secrets

Although difficult, the World Health Organization (WHO) has harnessed the characteristics and elements of traditional medicine, drawing from descriptions as far back as the evidence allows even to modern traditional medicinal practices, to formulate a definition, which describes traditional medicine as “a holistic term encompassing diverse health practices, approaches, knowledge and beliefs incorporating plant, animal and/or mineral based medicines, spiritual therapies, manual techniques and exercises applied singularly or in combination to maintain well-being, as well as to treat, diagnose or prevent illness.” Ultimately and more simplistically, traditional medicine refers to any form of indigenous healthcare system with ancient roots, cultural bonds, trained healers, and a theoretical construct. Examples include Ayurveda, Unani, Kampo, Shamanism, and traditional Chinese medicine (Fabricant & Farnsworth, 2001). The use of plants in medicine by specific ethnic groups is termed ethnobotanical medicine (Farnsworth, 1994a,b). A medicinal plant is thus any plant with alleged medicinal value that is used by Western standards or which contains components that are used as drugs (Laird & Kate, 2002). In industrialized countries, adaptations of traditional or ethnobotanical medicine are termed “Complementary” or “Alternative” medicines where complementary medicine refers to the use of medicinal plants in conjunction with a Western medicinal treatment, and alternative medicine refers to the use of a medicinal plant or plant-based medicine in place of Western medicine (WHO, 2003). Western medicine is distinguished from traditional medicine by the fact that it considers only ailments of the physical body, based on the principles of technology, science, knowledge, and clinical analysis developed in Northern America and Western Europe (Richter, 2003).

Medicinal plants and plant-derived medicines are used globally to treat various ailments. In modern society, these medicines are not only used by traditional cultures but are also gaining popularity under Western civilization. Currently there is a trend in natural alternatives as a source of new commercial products to synthetic chemicals. Although the use of plants as medicine is often underestimated, awareness of the active components of plants, which enable them to perform healing functions, needs to be increased. These active components, called phytochemicals, exist as they are required by the plant itself for specific functions. Generally, these phytochemicals are classified as secondary metabolites as they are not crucial for the survival of the plant but rather render a secondary beneficial function that provides the plant with a selective advantage. More than 100,000 such secondary metabolites have been isolated and characterized, many of which have been implemented as active ingredients in common medicines or have provided a basis for the development of synthetic actives that are incorporated into medicines (Rates, 2001).

More than 50% of drugs that are clinically used in the world are derived from natural products and their derivatives, with 25% being from higher plants.

When considering ∼250,000 higher plant species globally, only 10,000 have documented medicinal uses, of which only 150–200 are actually incorporated into Western medicine (McChesney, Venkataraman, & Henri, 2007), it becomes increasingly evident that plants possess a great potential avenue for exploration.

The WHO considers 252 drugs “basic” 11% of these (∼28) originate exclusively from plants, with a significant amount of the remaining synthetic drugs being derived from natural precursors (WHO, 2003). This further exemplifies the importance of plants in healing, across both pharmaceutical and cosmeceutical industries. The vast amount of plants that have yet to be explored outlines the importance of research in medicinal plants, and when considering what has been accomplished with what knowledge we do possess, it becomes very clear that the possibilities are endless and much to be sought after (Verpoorte, 1998).

Natural and herbal medicines have shown their potential over synthetic drugs by mostly having fewer side effects and lower levels of toxicity. Pharmacologically natural medicines have also shown their importance in their use as starting material for drug synthesis or directly as therapeutics. Natural medicines can also function as models for pharmacologically active compounds that may possess higher activity and less toxicity than their synthetic counterparts (Verma & Singh, 2008).

Not only do plants serve as potentially great alternatives to synthetic drugs and therapies, but natural plant-based therapies have also become increasingly popular, setting the benchmark for a more natural and safe platform. Reasons for this increased popularity include inefficiencies or hazards posed by conventional synthetic therapies, adverse side effects, affordability, and accessibility. Folk medicine and increased ecological awareness recently have also encouraged the idea that natural products may be less harmless (Rates, 2001).

1.2 TRADITIONAL MEDICINE IS A CRUCIAL PART OF AFRICAN HERITAGE

Traditional medicine, on the African continent, dates back ∼4000 years. It was once the sole medicinal system; however, even in recent times for some, it remains the dominant system with an estimated 80% of the African Member States population use traditional medicine as a primary source of health care. Africans have used traditional medicine for hundreds of years as a form of health care. In South Africa it is estimated that there are ∼27 million individuals who use traditional medicine. It has been calculated that from these individuals who use traditional medicine, they use it ∼4.8 times/year, which equates to an average of about 157 g of plant material for each treatment and 750 g/ year. In South Africa, indigenous plants are mainly used and this equates to ∼20,000 tons being used each year from at least 771 plant species that have been recorded. There are a range of plant parts used, which are collected from forests, grasslands, woodlands, and thickets (Fig. 1.1; HST, 2015).

The WHO estimates that of the plants harvested for medicinal use, about 86% of the plant parts harvested results in death of the plant, which has a huge

4 Medicinal Plants for Holistic Health and Well-Being

impact on sustainability. The decrease in availability of plants increases the time taken to find these plants and increases cost of the material. Common plants such as Scilla natalensis (Fig. 1.2) cost about R53/kg and scarce plants such as Salacia kraussii can reach up to R4,800/kg. There is also a big trade in plants from South Africa with neighboring countries such as Zimbabwe and Mozambique (HST, 2015).

Bark

Roots

Bulb

Whole plant

Leaves and stems

Tubers

Combina on of parts

FIGURE 1.1 Percentage of plant parts used in traditional medicine in South Africa (HST, 2015).
FIGURE 1.2 Scilla natalensis, a commonly used medicinal plant traded at approximately R50/kg (Shebs, 2007a,b).

1.3 TRADITIONAL MEDICINE IN SOUTH AFRICA

South Africa has much to be explored as it is one of the richest temperate flora globally, comprising 24,000 specific and infraspecific taxa from 368 plant families. More than 10% of the Earth’s vascular plant flora is offered by Southern Africa on less than 2.5% of its total surface area (Germishuizen & Meyer, 2003). South Africa, being one of the richest centers of plant biodiversity, has an excellent historic research base to begin with, gathered from a long history of traditional medicine implementing ∼5700 different plant taxa (out of 24,000), of which 3000 are medicinally recognized (Mulholland, 2005).

Some popular South African plants often used include Aloe ferox, also commonly known as the bitter aloe, Kaapse aalwyn, or umhlaba (Fig. 1.3A).

Traditionally it has been reported to be used as a laxative, for conjunctivitis, eczema, arthritis, and stress and hypertension and is now sold commercially as a laxative. An interesting medicinal plant reported to have many uses traditionally is Boophone disticha, commonly referred to as gifbol, bushman poison bulb or leshoma. Dried outer scales are used as a dressing for boils, septic wounds, and postcircumcision wounds. It is also thought to draw out pus. Mild decoctions are prepared for relief from headaches, eye conditions, weakness, and abdominal complaints, while stronger decoctions are used as hallucinogens and sedatives. Interestingly, examination of a 2000-year-old Khoisan mummy revealed scales

(E)

and

FIGURE 1.3 A few popular medicinal plants reported in folk medicine for their use in treating various conditions, from skin conditions to stomach complains and infections. (A) Aloe ferox, bitter aloe (Shebs, 2009), (B) Cinnamomum camphora, the camphor tree (Starr & Starr, 2009), (C) Datura stramonium, thornapple (Zell, 2009), (D) Harpagophytum procumbens, devil’s claw (Pidoux, 2005),
Hypericum perforatum, St John’s wort (Blanc, 2011),
(F) Sutherlandia frutescens, cancer bush (Humert, 2009).

of the bulb to be used for mummification purposes. Catharanthus roseus, the Madagascar periwinkle or isisushlungu has traditionally been used to treat diabetes; however, two alkaloids present within the plant are commercially available for the treatment of cancer in combination with chemotherapy. The camphor tree, Cinnamomum camphora, has been reported to be used traditionally for the treatment of heart conditions, colds and fevers, respiratory complaints such as pneumonia, inflammatory conditions, infections, diarrhea, and hysteria (Fig. 1.3B). Topical applications act as a counterirritant and antiseptic. The thornapple, Datura stramonium has traditionally been used for pain associated with boils, gout, abscesses, rheumatism, asthma, wounds, and as a hypnotic, and aphrodisiac (Fig. 1.3C). Commercially, alkaloids from this plant are used for the treatment of motion sickness, Parkinsonism as well as eye drops. Harpagophytum procumbens, the devil’s claw or sengaparile, is traditionally used in the treatment of arthritis, rheumatism, digestive complaints (Fig. 1.3D). Pharmacologically it has been confirmed as an analgesic and antiinflammatory agent. St John’s wort, Hypericum perforatum has been used for diarrhea, gout, rheumatism, and as an antidepressant (Fig. 1.3E). Oily extracts may be topically applied to wounds. Pharmacological evaluation has revealed H. perforatum to act as an antidepressant and antimicrobial agent. The cancer bush, Sutherlandia frutescens, has commonly been used in the Cape region of South Africa for the treatment of cancers and stomach complaints (Fig. 1.3F). Topically it has also been applied to ailments concerning the eye as well as wounds, and it has also been noted to be effective in the treatment of colds and influenza, varicose veins, chicken pox, piles, liver problems, inflammation, and backache. It has been attributed anticancer activity too.

For the provision of health care and medicine, many options exist within South Africa ranging from Western medicine, Western fringe practitioners, selftreatment, pharmaceuticals, faith healing, and traditional medicine (Dauskardt, 1990). Traditional medicine is a network of knowledge strongly supported by many individuals. It is therefore, very valuable for the information that is known to be passed on for many generations. Many modern Western medicines owe their existence due to the exploitation of all the components and structures of active substances that form part of medicinal plants.

South African traditional medicine is strongly associated with the use of herbs and multiremedies that are bestowed by the traditional healer known as a “sangoma” or “izinyanga” with strong spiritual components (Richter, 2003). Traditional healers may be divided into diviner-mediums (diviner-diagnostician) and herbalists (healers) (Jolles & Jolles, 2002). The differences between these divisions can be highlighted when considering the roles of each; for example, the diviner or isangoma diagnoses the patient generally through a spiritual means, therefore, serving as a communication medium between the patient and ancestral powers. This may be achieved through a trance state or through the throwing of bones (Dauskardt, 1990). The herbalist, or inyanga, is trained through an apprenticeship with an established herbalist and provides the correct herbs to be used for treatment. Although theoretically they appear easily distinguished,

various sets of legislation, the history of South Africa and the encroachment of Western medicinal practices have blurred the lines separating the roles between these two (Richter, 2003).

The history of investigating the phytochemical potential of plants in South Africa can be attributed to the importance of stock farming, the risk that many diseases posed toward the stock farming industry, and the catastrophic effects this could have on the economy. Diseases such as “slangkop” poisoning, “stywe siekte,” “vermeersiekte,” and “gifblaar” poisoning resulted in the deaths of livestock due to their grazing on poisonous plants (Marais, 1944; Rindl, 1924; Theiler, 1911; Vahrmeyer, 1982). For that reason, halfway through the 20th century, extensive research was done to understand the nature of these deaths. However, it was only in the 1990’s that a noticeable shift occurred in the field of research that wished to explore the use of traditional medicine and plants in the development of many products from pharmaceuticals to cosmeceuticals (Mulholland, 2005).

Several collaborative efforts between research organizations and traditional healers have found hundreds of plant species with the potential for drug development. Medicinal plants have played a major role in the traditions and lives of many people all over the world and from all walks of life. Plants that were used medicinally by various people and tribes had initiated the development of traditional healthcare systems such as Ayurveda and Unani, which have formed a key part of mankind for thousands of years (Gurib-Fakim, 2006). Today the medicinal importance of higher plants is still recognized with natural products and their derivatives having a 50% share of all drugs in clinical use (Gurib-Fakim, 2006).

1.4 DEVELOPMENT OF MODERN HERBAL PREPARATIONS

The development of modern herbal preparations involves many steps, namely identification of the plant material, authentication, collection, testing, standardization, processing, and finally, marketing. Each step has been developed in response to questions and concerns surrounding the use of herbal products.

The identification of medicinal plants may be through traditional knowledge systems (ethnopharmacology), on the basis of their plant family or through random selection. While random selection is somewhat inefficient in terms of time and resources, selecting a plant based on the traditional knowledge or plant family is more effective. Selection based on the plant family would be based on literature revealing other members of the plant family showing some medicinal value. The ethnomedicinal approach provides the greatest advantage above the aforementioned methods in that, it gives specific information about a specific species. Utilizing such methods, however, may lead to problems when moving forward into the second step of herbal production, authentication. This is because misidentification of the plant material may occur, especially in instances where closely related species exist. In such instances, a trained taxonomist is employed to correctly identify the plant species. The implications

of misidentification may be severe where toxic plants are concerned and have implications in the treatment of the condition in question, showing no activity and ultimately being considered an ineffective treatment.

Once the correct plant material has been identified as authentic, material should be collected for testing. Collection should be sustainable, a lot of controversy has arisen surrounding the use of medicinal plant parts that cannot be harvested sustainably, such as roots. The material collected for testing may then be comprised of only plant parts, which have previously been reported on, or may be nonselective. For the plant material to be tested, a plant extract needs to be formulated. This is to concentrate the phytochemicals present within the plant material and ensure homogeneity in the sample to be tested. The plant may be extracted using water or organic solvents such as ethanol. Extraction may be through a variety of different mechanisms, including maceration, reflux, solid phase extraction, and supercritical fluid extraction. The extraction and concentration step may result in the concentration of phenolic or acidic compounds, and the effect of these on other active compounds present in the extract should be taken into consideration (Panichayupakaranant, 2011, Chap. 25). The mixture is then put through a filter such that the solvent containing the phytochemicals is separated from the plant pulp. The phytochemical solution is then allowed to dry such that all the solvents are evaporated to dryness, yielding a sticky syrup or powder of concentrated phytochemicals for testing. Authentication of the material as well as quality control, qualitative, and quantitative phytochemical determination should be carried out at all steps, that is to say on the fresh, dried, and powdered plant material as well as on the prepared extract (Panichayupakaranant, 2011, Chap. 25). The consequences involved with not adhering to these important parameters is firstly and most obviously the production of an unstandardized herbal formulation, with diminished or no efficacy, as well as increased potential for toxicity or adverse side effects when consumed (Panichayupakaranant, 2011, Chap. 25). Although an unstandardized herbal formulation may hold reduced efficacy as a disadvantage, standardization of all of the components that go into an herbal formulation should also confirm the absence of adulterants that may be added to enhance the efficacy without the consumer being aware of it. It is very important for the components to be specifically listed as the addition of adulterants do not give a clear indication of the medicinal value of the herbal formulation as an individual entity and may pose side effects to the consumer further down the line if, for example, the adulterant in question poses its own contraindications. This is different from a pure compound in that it is a cocktail of multiple molecules within the plant material.

Although whole extracts containing a phytochemical cocktail often offer the benefit of targeting more than one step in the pathogenesis or progression of any given condition, often also acting as a valued antioxidant, the application is somewhat limited due to the introduction of a vast number of variables that need to be considered. The specificity and target-orientated application of a single

compound allow treatment to exist in a much more comfortable realm, with a drastically lowered number of variables when compared to a whole extract and far fewer biological implications, especially for consumption as a medicine.

Scientific testing is a crucial part of validating the traditional uses associated with the plants concerned. It normally involves a target-specific approach in certain conditions, closely examining the biological pathways involved and the effect of the plant sample on this pathway. Often, more than one test will be performed to evaluate the total activity of the plant sample. In this step toxicity and the adverse side effects of medicinal plants in plant-based formulations compared to synthetic counterparts are evaluated to determine the viability of the plant sample in any given application. Drew and Mayers (1997) classify adverse effects of an herbal formulation as being the result of the intrinsic characteristics (phytochemistry) of the sample or extrinsic factors (which may be the result of processing and manufacturing). For samples showing toxicity the therapeutic efficacy should be determined to determine if the benefit outweighs the cost and by how much. Samples showing a low therapeutic efficacy where the risk of increased adverse side effects exists should be discouraged. Depending on the method of administration, the active components may be incorporated into the medicine either as a pure compound or in the crude extract form as a cocktail containing multiple phyto-constituents. In the instance of compound isolation, the structure of the compound should be identified and checked for batch-tobatch consistency. In the instances where the crude extract is utilized, batch-tobatch consistency is attained through the metabolomic fingerprint of the species or via the identification of biomarkers, which are molecules that are associated with the compound of interest. The formulation of a standardized medicine thus involves both quantitative and qualitative phytochemical analysis.

Generally, two types of standardizations exist, either which aim to quantify the pure compound within an extract or the identification of a single or multiple actives within the extract. The efficacy of the pure compound needs to be evaluated versus the crude extract. The activity may differ greatly as the presence of other components in an extract may enhance or diminish the activity of the compound because the total value of a biological system is not always the sum of its components. Testing of the medicine also includes clinical trials to substantiate the scientific claims. Once it has gone through these steps and remains a good sample, the sample needs to be processed. Processing refers to the processing of the plant material into the form in which it is to be consumed (tablet, cream, ointment, syrup, tea, etc.) and includes cleaning the material and the removal of biological contaminants that may be present. The removal of heavy metals that may be toxic is also crucial in this step. Marketing, of course, is the final step and includes advertising the product to the relevant consumer. At this point, the medicine may be considered commercialized.

Although a great leap for nature, the commercialization step is not without hurdles. Upscaling of growing the plant requires the use of arable land for production. In Agro-countries, which focus a great majority of their resources

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