A New Look at Medicinal and Aromatic Plants

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    A New Look At Medicinal And Aromatic Plants*

    kos MthUniversity of West Hungary,

    Faculty of Agriculture and Food Industry

    Vr 2.9200 MosonmagyarvrHungary

    Keywords: medicinal plants, collection, cultivation, standards, safety, efficacy, and

    quality, trends, modern technologies, sustainability

    Abstract

    Herbs, Medicinal and Aromatic Plants (MAPs) have maintained their traditional

    basic curative role while new trends seek natural alternatives with lesser side effects to

    using conventional drugs. Besides their similarly traditional culinary and food industryuses, MAPs are intensively consumed as food supplements (food additives). In animal

    husbandry, feed-additives are used to replace synthetic chemicals and production

    increasing hormones.

    Nearly unlimited and increasing huge demand have lead to the overexploitation

    of natural resources, thus endangering not only plant species but incomes, even

    livelihoods ,especially in developing countries.

    A New Look, a different holistic focus and R+D action is needed to sustain an

    energetic and socio-economically sound MAPs sector.

    Guided by international standards (e.g.: ISSC-MAP, GA(C)P, FairWild), the

    sustainable exploitation and management of MAP natural resources have become an

    imperative from both environment protection and socio-economic points of view.

    The raw material supplies should be secured by conserving and improving the

    germplasm of cultivated species, and using both in situand/or ex-situtechnologies.

    There is a strong demand on the domestication/introduction into cultivation of presently

    wildcrafted species. Sophisticated in vitro propagation and breeding (selection)

    technologies aided by advanced phytochemical and molecular biological analytical

    techniques can farther assist this progress

    There is also a need to ensure the quality of medicinal plant products by using

    modern control techniques and applying suitable standards. Based on the already

    available modern sample preparation techniques (e.g.: SPME, SFE, PLE, MAE and

    SME), the study of the plant metabolome has already yielded successes. Advances inplant genomics and metabolite profiling, also seem to offer unprecedented possibilities in

    exploring the extraordinary complexity of plant biochemical capacity. State-of the art

    genomics tools can be used to enhance the production of known target metabolites

    and/or to synthesize entire novel compounds in cultivated plant cells by the so-called

    combinatorial biochemistry.

    Ultimate goal of these efforts should be to help improve the traceability and

    safety (reliability) of natural products, as well as the appropriate policies and legal

    frameworks to guide the protection, production (including organic production), trade,

    and applications of medicinal and aromatic plant materials.

    *Invited lecture: at 28. International Horticultural Congress, Lisbon, August 22

    27, 2010to be published in Acta Horticulturae

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    INTRODUCTION

    Herbs, Medicinal and Aromatic Plants (MAPs) have been utilized in various forms,

    since the very early periods of mankind. Early forms as complemented by the up to-date areas

    of utilization constitute powerful drivers for the exploitation of these natural resources that -for a long-long timehad been wasted in an unrestricted manner.

    Todays huge demands counterpointed with the already rather limited availability andexhaustion of natural resources brings up the necessity to make a renewed approach to MAPs,

    to reconsider our ideas regarding R + D, production and utilization, especially from the

    viewpoint of sustainability.

    THE ROLE OF MAPS IN MODERN SOCIETIES

    The initial basic curative role of MAPs has been maintained due to traditional,

    economic and other practical reasons. With almost half of the worlds population (i.e.: threebillion people) living in poverty, earning less than two US dollars per day, even to date, ca.

    80 % of the worlds population still relies primarily on traditional medicines.For many, i.e. ca. 900 million people living in rural areas, deriving their income

    mainly from agriculture and other related activities, MAP collection and/cultivation plays an

    important role as an income generating factor.

    MAPs have maintained their importance also for the modern pharmaceutical

    industry. According to WHO (1998) statistics, currently one-fourth of all prescribed

    pharmaceuticals in industrialized countries contain compounds that take their origin, directly

    or indirectly (via semi-synthesis), from plants. 11% of the 252 drugs considered as basic and

    essential by WHO are exclusively derived from flowering plants.

    In the developed parts of the world, a new trend has emerged, i.e.: to seek natural

    alternatives to using conventional drugs, food and cosmetics, etc. with lesser side effects. As

    a result, MAPs are intensively consumed in the form of food supplements and food additives.

    Recently, the use ofphytogenic feed-additives (i.e.: in animal welfare and nutrition)

    is also gaining on popularity (Franz et al., 2005).

    In view of the controversial, constantly rising, demand on raw materials and limited

    resources, a new approach to MAP production and exploitation is desirable.

    Recent achievements in (medicinal) plant research (e.g.: biology, chemical analytics),

    have opened up new horizons to our knowledge on MAPs, their genetic/physiological traits,

    etc. As a result, new methods, technologies have emerged that ultimately may modernize both

    production and utilization including the standardization and quality assurance of MAP derived

    produces.

    Present review is aimed at highlighting some of the main elements of MAP research,production and utilization that have been greatly affected by changes and deserve, therefore,

    more attention

    ORIGIN OF MAP RAW MATERIAL RESOURCES

    Wild crafted MAPs vs. biodiversity conservation

    The primary resource for raw materials is wild-crafting. Some over nine tenth of

    MAPs used are traditionally gathered in the so called Third World countries. The natural

    resources of MAPs are, however, limited and this has already lead to the overexploitation of

    natural resources endangering both the survival of an increasing number of species and

    valuable incomes, especially for rural households in developing countries.

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    - The number of endangered species is increasing menacinglyAccording to IUCN (The World Conservation Union) the greatest risk of extinction

    occurs in those regions of the world (e.g.: Asia, Africa, Indonesia), where medicinal plants are

    still widely used. A global estimate of endangered plant species (Graham, 2002) indicates that

    13 % of global flora is at the risk of extinction with 22 - 47 % of the worlds plants

    endangered.The belated growth in international awareness about the declining supplying capacity

    of the world's medicinal plants, the over-harvesting of natural resources, the destructive

    harvesting practices accompanied by habitat loss, forest degradation of habitats, etc. have

    brought about alarming problems to biodiversity.

    - The sustainable use of natural resourcesThe imperative for the sustainable use of natural r esourceswas first recognized by

    the Chiang Mai Declaration (1988) that had expressed alarm over the consequences in the

    loss of plant diversity. It highlighted "the urgent need for international cooperation and

    coordination to establish programs for the conservation of medicinal plants to ensure that

    adequate quantities are available for future generations. It has also called for a need tocoordinate conservation actions based on both in situ and ex situ strategies.

    The subsequent two decades have been marked by several far ther declarations and

    sets of recommendationscalling for the Conservation and Sustainable use of biodiversity

    including also medicinal plants.

    The Convention of Biological Diversity (CBD), an international, legally binding

    treaty reached at the Earth Summit, in Rio de Janeiro (1992), established the following main

    goals: the conservation of biological diversity, the sustainable use of its components, and the

    fair and equitable sharing of the benefits from the use of genetic resources . The CBD coming

    into force in 1993, secures rights to control access to genetic resources for the countries in

    which those resources are located. In view of the objective to enable lesser-developed

    countries better benefit from their resources and traditional knowledge, the CBD rules thatbio-prospectors are required to obtain informed consent to access such resources, and must

    share any benefits with the biodiversity-rich country.

    Despite of several positive changes, the target agreed by the worlds Governments in2002, to achieve by 2010 a significant reduction of the current rate of biodiversity loss at theglobal, regional and national level as a contribution to poverty alleviation and to the benefit of

    all life on Earth, has not been met, yet (Figure 1.).

    METHODS/STANDARDS FOR THE SUSTAINABLE MANAGEMENT OF MAP

    RESOURCES

    Several field-based methods have been developed for the sustainable harvest,

    assessment and monitoring of MAPs. Limiting the harvest to a sustainable level requires an

    effective management system including annual harvest quotas, seasonal or geographical

    restrictions and restriction of harvest to particular plant parts or size classes. In many cases

    harvesting techniques need to be improved, since collecting methods are often crude and

    wasteful, resulting in loss of quality and reduction in price (Iqbal, 1993; Vantomme in Anon.

    2002). In addition, clarification of the access and user rights to the resources providing MAPs

    is part of the essential baseline information (FAO 1995; Leaman et al. 1997; Prescott-Allen

    and Prescott-Allen, 1996; Schippmann, 1997; WHO, IUCN and WWF, 1993).

    a. I nternational Standard on Sustainable Wil d Collection of MAPs (ISSC-MAP)To date, the most widely accepted collection standard, with a focus on the species. Its

    mission is toensure the long term survival of medicinal and aromatic plant populations intheir natural habitats, while respecting the traditions, cultures and livelihoods of all

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    stakeholders if the process. Through its holistic approach, the ISSC-MAP is aimed at

    bridging the gap between the existing broad conservation guidelines and management plans

    for local conditions. It is meant to provide guidance for sustainable wild collection of

    MAPs and also a basis for audit and certification in wild collection (incl. the organic

    sector). Ultimately, the standard is expected to have several benefits: e.g.: substantially

    contribute to the livelihood improvement of those involved in wildcrafting of MAPs, serveas a communication tool for the industry, serve as a guideline for MAP protection, harvest,and monitoring. For collectors, it can offer both insurance against resource and market

    failures, and for consumers, reliability of claims about ecological and social sustainability.

    Most importantly, at the level of species and habitats, it can contribute to maintaining

    biodiversity.

    b.Guideli nes for Good Agri cultur al (and Collection) Practice of MAPs (GA(C)PGood Agricultural and/or Collection Practices (e.g.: EUROPAM, 2006) for medicinal

    plants are the first step in quality assurance, on which the safety and efficacy of herbal

    medicinal products directly depend. Harvesters of wild plants must apply collection practices

    that address not only their need to gain economic benefits from the sale of wild-harvested

    plants, but also make sure that each of the collected species survives. In addition to preservingplant populations, harvest practices must also minimize damage to local habitats.

    These practices are also expected to play an important role in the protection of natural

    resources of medicinal plants for sustainable use.

    c. FairWildInitiated by the Swiss Import Promotion Organization (SIPPO), FairWild is a

    verification system that offers a comprehensive guidance framework and certification option

    for all sustainably collected wild plant, fungi and lichen species worldwide. FairWild

    Standard covers both ecological sustainability (based on the ISSC-MAP1) and aspects of fair

    trade as well as social sustainability.

    The FairWild Standard is implemented either by the FairWild Foundation (2010)

    and/or its partners. Although specifically designed for wild collection situations, FairWild

    also includes the collection of plants, lichens or fungi or parts or products thereof on

    cultivated land, if the target species for collection are only a by-product and not the target of

    cultivation.

    SIPPO supports small and medium-sized enterprises (SMEs) from emerging markets

    and markets in transition to access the Swiss and European markets.

    d. Domestication/I ntroduction into cul tivation of endangered speciesIn view of the complex and manifold possible implications (e.g.: biodiversity

    conservation, management and quality assurance), as well as sustainability issues, to date,

    MAP domestication/introduction into cultivation are increasing considered as methods that

    could secure the reliable raw material supplies. As a consequence, in addition to conservingand farther improving the germplasm of traditionally cultivated species, the

    domestication/introduction of farther crops is needed.

    In this process, in situ and/or ex-situ production technologies play a decisive role.

    Sophisticated in vitro micropropagation and breeding (selection) technologies aided by

    advanced phytochemical and molecular biological analytical techniques can farther assist this

    progress.

    It is a special feature of MAPs selection and breeding that besides the usual breeding

    goals - e.g. to increase plant yields - the quality of active principle content plays an important

    role.

    The amount and quality (composition) of these metabolites is influenced by ecological

    factors, it can undergo ontogenetic and diurnal changes, it can be accompanied by the

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    accumulation / translocation of metabolites between various organs (intra individual

    variability of active principles), etc.

    Due to the high costs of the relevant chemical analyses, the breeding of MAPs can be

    rather costly while frequently also the effect of influencing factors must be investigated in the

    course of breeding.

    These and also farther (here not discussed) considerations have led to the elaborationof new analytical methods with the advantage, that they can be used in the subsequent chains

    of quality assurance. It is well known that even to-date, quality related problems (e.g.: lack of

    consistency, safety and efficacy) seem to be overshadowing the potential genuine health

    benefits of several herbal products. One of the major causes for this can be related to the lack

    of simple and reliable analytical techniques and methodologies of quality assessment (Huie,

    2002).

    TRENDS IN THE QUALITY ASSESSMENT OF MAPS

    According to certain authors (Nyiredy, 2002), the major goals of medicinal plant

    research include: a/ qualitative and quantitative assessment and analysis of plant chemical

    components, b/ isolation of plant derived fractions and molecules c/ optimization of theproduction of plant bioactive principles. In order to achieve these, the plant materials need to

    be made suitable for analysis by using appropriate sample-preparation techniques.

    Earlier, the chemical analysis of medicinal plants meant mainly the assessment of the

    total amount of certain groups of compounds, (e.g.: total-flavonoid content), whereas the

    recent results in the development of modern separation techniques, especially those of the

    high throughput gas-, and liquid-chromatography, have rendered possible the more accurate

    separation and subsequent quantitative measurement of chemical components (Bisset and

    Wichtl, 2001).

    Sample preparation is regarded as the crucial first step in the chemical study of

    medicinal plants, either for basic scientific (e.g. plant breeding, physiological topics) or

    applied (e.g.: raw materials for the pharmaceutical industry) purposes. In addition, the modernmethods are also indispensible in order to improve the acceptance of MAPs, i.e.: facilitate

    their reliable consumption, either as home remedies (e.g.: in the form of over-the-counter drug

    products) or their utilization as raw materials by the pharmaceutical industry, etc.

    The need to ensure the quality of medicinal plant products by using modern control

    techniques and applying suitable standards (WHO, 1998) has been worded also by the World

    Health Assembly - in resolutions WHA31.33 (1978), WHA40.33 (1987) and WHA42.43

    (1989).

    RECENT DEVELOPMENTS (METHODS) OF NATURAL PRODUCT CHEMISTRY

    Sample preparati on techniques

    The elaboration of modern sample-preparation techniques, as a precondition of plantextraction and analysis, plays an important role in the efforts of ensuring and providing high-

    quality herbal products. The modern techniques include solid phase micro extraction

    (SPME), supercritical-fluid extraction (SFE), pressurized-liquid extraction (PLE),

    microwave-assisted extraction (MAE) and surfactant-mediated extraction (SME) (Huie,

    2002).

    Over the past 50 years, spectroscopic methods coupled with good extraction

    techniques have significantly contributed to the success of natural product chemistry. E.g.: in

    the analysis of essential oil containing herbs (where medicinal properties can be related to the

    volatile constituents in the plant matrix), gas chromatography (GC) is frequently used for

    determination of the volatile composition. The inclusion of a fractionation step before GC

    analysis can help avoid the disadvantages of commonly used sample-preparation techniques

    (e.g. distillation and liquid solvent extraction that generally require large amounts of organic

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    solvents and man labor). Headspace (HS) sampling, though destructive in nature, is regarded

    as well suited for the fractionation of volatile compounds from complex solid matrices such as

    plant materials.

    As another promising method, supercritical fluid extraction (SFE) seems to offer high

    selectivity, minimum degradation of thermally labile analytes and the elimination of the use

    of hazardous organic solvents. SFE has been used for many years for the extraction of volatilecomponents, like essential oils and aroma compounds from plant materials, on an industrial

    scale. Recently, the application of this technique has started to attract wide interest for sample

    preparation before chromatographic analysis.

    Pressurized liquid extraction (PLE) using subcritical water extractant seems to be

    promising especially in the case of analytes with a wide range of polarity. Its main advantages

    are: that water is inexpensive and non-toxic, environment friendly.

    These techniques are not restricted to plant sources but they are also applied to

    microbial and even fungal sources of metabolites.

    Analytical vs. Rapid Analytical Methods

    Hardly less than a decade ago, a new array of analytical methodologies andtechnologies evolved and were introduced to the analysis of microbial, plant and animal

    metabolomes. (Metabolome= complete collections of all low molecular weight compounds in

    a cell). The size of plant metabolome varies greatly. It is estimated that the plant kingdom has

    approximately 200,000 primary and secondary metabolites (Fiehn, 2002).

    As plant secondary metabolites occur usually in low concentrations, these

    sophisticated technologies look promising and have already been successfully applied in their

    analytics.

    A rough overview of available analytical methods for the study of MAPs is given in

    Table 1.

    Above methods have several relevant advantages, among them the most importantbeing rapidity, the ability to select high-quality single plants from populations, progenies

    (e.g.: crossing experiments), as well as industrial uses for quality checks and supervision, etc.

    Recently, Schulz (2009) gave an overview of the applications of the so called rapid

    analytical methods (RAM) with a focus on the efficient evaluation of plant genetic resources

    and breeding material of MAPs. According to this, Rapid High-Throughput (RHP) methods

    are capable of simultaneously characterizing several quality parameters and as such reducing

    sample preparation to a minimum. Vibrational spectroscopy methods (attenuated total

    reflectance/Fourier-transform-infrared (ATR/FT-IR), FT-Raman and near infrared (NIR)

    spectroscopy) have a potential for the identification and quantification of valuable, as well as

    carcinogenic substances (e.g.: in different basil chemotypes). The main volatile components

    occurring in the plant samples can be reliably determined in both isolated essential oils orsolvent extracts and the air-dried herbs. MIR (Mid_Infrared Spectroscopy), NIR (Near

    Infrared Spectroscopy) as well as Raman sectroscopy are reported to be suitable for the

    rapid and reliable non-destructive discrimination of plant species or chemotypes.

    High throughput screening (HTS) methods. By using molecular targets, a large

    number of samples (up to 100,000 in 24 h) can be screened for a single activity.

    HTS offers the following new possibilities for natural products: rapid screening of large

    number of extracts (a), it is very suitable for bioassay-guided fractionation (in the past, the

    major bottleneck in studies of active compounds in plant extracts) (b), it has significantly

    increased throughput and reduced assay volumes (c). Key advances over the past few years

    include: new fluorescence methods, detection platforms and liquid-handling technologies.

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    From Metabolomics to Metabolic Engineeri ng

    Cutting edge research in MAPs, nowadays, is also frequently engaged in the study of

    the plant metabolome. We are seeing a shift in gene studies, going from single-gene studies

    towards metabolic pathways, ultimately to the study of the whole-genome (Oksman-

    Caldentey and Inz, 2004).

    With other words the qualitative and quantitative analysis of all metabolites combinedwith new and powerful tools of functional genomics can be used to elucidate biosynthetic

    pathways of natural products.

    As a precondition for Metabolic Engineering, the details involved in the biosynthesis

    of a natural product need to be identified at both enzyme and regulation levels. According to

    the general concept of metabolic engineering certain pathways within a biosynthesis network

    could be stimulated/favored over others (e.g. by over-expressing the crucial enzyme squalene

    synthase gene in Panax ginseng, a stimulating a higher biosynthesis of triterpenes and

    phytosterols).

    Production of designer secondary metaboli tes

    The chemical synthesis of many compounds produced by plants in the form ofsecondary metabolites is already available, still due to their relatively high costs, even to-date,

    most of the pharmaceutically important secondary metabolites are isolated from plants.

    Biotechnological production in plant cell cultures could be an attractive alternative, but even

    currently this has had only limited success because of a limited understanding of how these

    metabolites are synthesized. Recent advances in plant genomics and metabolite profiling,

    however, seem to offer unprecedented possibilities to explore the extraordinary complexity of

    the plant biochemical capacity. State-of the art genomics tools can be used to enhance the

    production of known target metabolites or to synthesize entire novel compounds by so-called

    combinatorial biochemistry in cultivated plant cells (Oksman-Caldentey and Inze, 2004).

    Ultimate goal of these efforts should be to assist the recent upsurge in improving the

    traceability and safety (reliability) of natural products, as well as the appropriate policies and

    legal frameworks to guide the protection, production (including organic production), trade,

    and applications of medicinal and aromatic plant materials (GWP, GAP, GCP, GMP, etc.).

    Literature Cited

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    (GACP) of Medicinal and Aromatic Plants. Brussels, 3rd April, 2006;EUROPAM GACP Working Copy No. 7.3

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    Figure 1 Conservation status of medicinal plant species in different geographic regions

    Table 1 - Analytical methods for the study of medicinal and aromatic plants

    Chromatographic separation methods

    Non-volatile compounds:

    TLC = thin layer chromatography

    HPTLC = high performance thin layer chromatography

    HPLC = high performance liquid chromatography

    Volati le compounds:

    GC = Gas chromatography applying different detectors

    FID = flame ionization detectorNPD = nitrogen-phosphorous detector

    Modern sample preparation techniques linked to fast chromatographic methods

    SPE = Solid Phase Extraction,

    SPME = Solid Phase Microextraction

    SBSE = Stir-Bar Sorptive Extraction

    ASE = Accelerated Solvent ExtractionSFE = Simultaneous Distillation Extraction