Where Do We Go New Antidiabetic Plants

Diabetes mellitus (diabetes) is a disease of worldwide significance and increasing prevalence. Plant materials have played an important role in the traditional treatment of diabetes, particularly the type II (non-insulin-dependent) form. In many regions of the world, herbal remedies continue to be more accessible and affordable than conventional drugs and represent the first line of treatment available to a diabetes patient. Concurrently, within societies with well-developed, modern health care systems, demand is growing for herbal remedies to complement prescribed, modern therapies for many diseases, including diabetes.

This volume is the first detailed compilation of information from across the world on plants used traditionally to treat diabetes and the scientific methods by which they can be and have been investigated. The book is divided into three main themes. It begins with an introduction to diabetes mellitus by a consultant physician and a major updated review and discussion of scientific information pertaining to traditional antidiabetic plants compiled by authors from the Royal Botanic Gardens, Kew, London. For those interested in performing research in this field, the next chapters provide an outline of clinical, in vivo, and in vitro methods for assessing antidiabetic activity of plant materials. Then follows a set of chapters by an international group of authors that describe traditional plant remedies used in Asia, the Americas, Africa, Europe, and Australia. The final chapters emphasize the role of particular phytochemical groups in the treatment of diabetes.

The potential role of plants in treating or preventing the complications of diabetes, is mentioned in the chapters on Chinese and Kampo medicines, a Western herbalist's perspective, and flavonoids, xanthones, and other antioxidant polyphenols. This latter chapter and that on plant polysaccharides highlight the important role of dietary plant materials in the prevention and control of diabetes. Indeed, it is believed that changes in diet from traditional plant foodstuffs containing beneficial components to richer, more processed and "junk" food is responsible for the increasing prevalence of diabetes worldwide.

A number of important points emerge from this volume. It is apparent that diversity as well as similarity can be found in the use of plants across the world. Understandably, each region of the world has developed a materia medica of antidiabetic remedies based on the local flora. However, the use of certain plants such as Momordica charantia L. (bitter melon) and Trigonella foenum-graecum L. (fenugreek) appears in more than one region. Climatic factors and cross-cultural communication play a role here. Generally, the use of a particular plant in a number of regions is strong evidence for its effectiveness. Diversity is also seen in the range of plant families and types of phytochemicals associated with antidiabetic activity. At the same time, certain groups, such as alkaloids, saponins, xanthones and flavonoids, and nonstarch polysaccharides appear to have effects of particular significance in diabetes treatment.

The extent to which various antidiabetic plants have been studied differs widely. For some (e.g., fenugreek, bitter melon, or gymnema [Gymnema sylvestre R. Br.]), detailed studies in humans, animals, and in vitro have resulted in the isolation of active compounds with recognizable modes of action. An interesting finding is that plants typically have more than one active component, often associated with more than one mode of action. Additive or synergistic effects between components undoubtedly occur, conforming to the view of traditional herbalists that the activity of a medicinal plant cannot be reproduced by the isolation of a single active component. Nevertheless, identification of actives and modes of action are important for drug development, and for the validation, standardization, and rational use of traditional herbal remedies.

To what extent has knowledge of traditional antidiabetic plants influenced the development of new antidiabetic drugs? Apart from the conventional drug metformin, which is based on the structure of galegine (a component of the European antidiabetic herb Galega officinalis L.), no new antidiabetic drugs derived from higher plants have been introduced into the market. This is rather surprising, given the large number of antidiabetic plants available and the wealth of documented information about them. One factor may be that research in the pharmaceutical industry has lately been heavily based on high-throughput in vitro screening programs. The capacity of these systems to handle large numbers of samples has led to random screening rather than selection from ethnobotanical materials. Complex extracts of natural products are, understandably, less attractive to the industry than screening single compounds from synthetic libraries because a "hit" would need to be followed up by isolation and identification of the active compound within the extract.

Legal access to plant material from other countries and conservation issues as covered by the Convention on Biodiversity and other international agreements are additional limiting factors. As a result, natural products derived from microbial sources have featured much more extensively in screening programs than have higher plants, let alone traditional plant remedies. A final factor is that high-throughput assays tend to be highly focused in their target mechanism and that, although effective in diabetes, the plant material may not work in that particular way. An alternate, more successful approach (pioneered by a smaller company) was to test ethnobotanically selected plants in vivo in experimental diabetic animals for initial determination of activity. This was followed by in vivo and in vitro testing to guide further fractionation. This approach has led to the identification of a number of active compounds as candidates for drug development. New investigational drugs must pass many hurdles relating to efficacy and toxicity issues before they are approved for use in the clinic; this, too, is a confounding factor in the introduction of new antidiabetic drugs from plant sources.

Much research on antidiabetic plants has been undertaken in academia. Indeed, the majority of the data described in this volume on activity and active components of these plants is from this source. This situation is likely to continue and, hopefully, increase in response to the growing prevalence of diabetes worldwide. Academia has traditionally been more inclined to follow ethno-botanical leads, but much of the early research led to publications rather than patents. A greater awareness of intellectual property issues coupled with greater synergy with the pharmaceutical industry may well lead to the development of new drugs from this route.

If not conventional drugs — what about herbal remedies for diabetes? Plant remedies have been and are being used by diabetic patients throughout the world. Research suggests that using an antidiabetic plant in whole form or as complex extracts may offer many benefits due to the presence of multiple active components. Of considerable benefit would be well researched herbal products based on traditional preparation methods and standardized to contain effective levels of the most important components for activity. Given the limited resources of most of the companies producing herbal products, research into these agents is, again, most likely to take place in an academic setting or by government-sponsored agencies as in many developing countries. It is also necessary for medicine's regulatory authorities to develop special criteria for the evaluation and licensing of herbal antidiabetic products. Finally, patients and health care providers need to be educated in the use of these products as sole or complementary treatments for diabetes in order to ensure their safe and effective use.

It is the hope of the editor that this volume will be of value to all those with an interest in antidiabetic plants and that it will facilitate the application of traditional knowledge to treatment of diabetes in modern and future times.

All the authors who contributed to this volume are very gratefully acknowledged.

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