Modern Phytomedicine: Turning Medicinal Plants intoDrugs.

Medicinal preparations derived from natural sources, especially from plants, have been in widespread use since time immemorial. Ancient texts of India and China contain exhaustive depictions of the use of a variety of plant-derived medications.In fact, plants remain the main source of medicines for a large proportion of the world’s population, particularly in the developing world, despite the advent of the pharmaceutical chemistry during the early twentieth century, which brought with it the ability to synthesize an enormous variety of medicinal drug molecules and al-lowed the treatment of previously incurable and/or life threatening diseases.Not surprisingly, chemically synthesized drug gained popularity and became the basis of pharmaceutical industry. Over the years, however, synthetic drugs have been plagued by unwanted side-effects, toxicity, and inefficiency, among other problems. In addition, the search for new drugs against a variety of illnesses through chemical synthesis and other modern approaches has not been encouraging. These factors, as well as the emergence of new infectious diseases, the proliferation of disorders such as cancer, and growing multidrug resistance in pathogenic microorganisms, have prompted renewed interest in the discovery of potential drug molecules from medicinal plants.
Herbal medicine is now globally accepted as a valid alternative system of therapy in the form of pharmaceuticals, functional foods, etc., a trend recognized and advocated by the World Health Organization (WHO). Various studies around the world, especially in Europe, have been initiated to develop scientific evidence- based rational herbal therapies. Though ancient medical treatises have documented a large number of medicinal plants, most have remained undocumented and uncharacterized, the knowledge of their use being passed down from generation to generation by word of mouth. New plant sources of medicine are also being discovered.
Here we have made an attempt to bring together recent work and current trends in the field of modern phytomedicine from different parts of the world. Although there are a number of blogs available on medicinal plants and phytocompounds, this blog has unique contributions in the form of chapters from experts in the field starting from the concept of phytoscience, screening biological activities against problematic infectious agents such as multidrugresistant bacteria, fungi, and viruses. Discussion of types of herbal remedies, problems associated with herbal medicines, such as efficacy, adulteration, safety, toxicity, regulations, and drug delivery etc. are included as contributions by different learned experts.
Today’s use of medicinal plants and bioactive phytocompounds worldwide and our scientific knowledge of them comprises the modern field of the “phytosciences.” The phytosciences have been created from the integration of disciplines that have never been linked before, combining diverse areas of economic, social, and political fields, chemistry, biochemistry, physiology, microbiology, medicine, and agriculture. The field is unique among the biomedical sciences in that instead of testing a hypothesis, in the phytosciences researchers try to determine whether plants commonly used in traditional medicine brings benefits for health and, if so, what their mechanisms of action are.
Despite the common belief that phytocompounds are safe, they all have inherent risks just like synthetic compounds. Thus it is within the scope of the phytosciences to elucidate side-effects, appropriate doses, identify bioactive phytocompounds and ways of extraction and conservation. Besides these, legal aspects regarding regulation of the prescription and commercial sale of medicinal plants are a matter of debate all around the world. The varied regulations in different jurisdictions regarding the prescription and sale of these products add confusion to the formal use of phytocompounds.
As a multidisciplinary science, research in the phytosciences is almost unlimited, which makes it impossible to discuss all aspects of this emerging science in just one page. Therefore, we have focussed here mainly on the antimicrobial activity of bioactive phytocompounds, discussing their use against multidrugresistant (MDR) bacteria and fungi, their mechanisms of action, and their interactions with macromolecules and potential for toxicity in mammalian cells. Technical aspects regarding the development of fast and reliable methods of extraction, high output screening systems, and bioautography of essential oils and crude extracts and fractions have also been discussed. Problems related to the efficacy, stability,drug delivery systems and quality control are also commented on.Overall this chapter aims to provide a better understanding of the modern field of the phytosciences and its application in the world today.

Phytotoxicity and Detoxification(P & D)

Coir dust is the remaining waste product when long fibers are
extracted from coconut husk. It constitutes the short fibers and mesocarp pith of coconuts. Because coir dust has many characteristics, such as high water-holding capacity and slow decomposition, it has been extensively used as an environmentally friendly substitute for natural peat in potting media. In addition, coir dust has been used as a soil amendment.

Because unripe nuts are usually soaked in brine to make the fiber easier to extract, the problem of excess salinity with some coir dust products has been recognized. The physical and chemical properties of coir dusts varied significantly with source, degree of grinding, screen size, and age. With increasing needs in production of coir-based media and as a soil amendment, the use of coir dust is currently shifting from the aged coir dusts, e.g., 100 year old Sri Lankan coir, to young, even fresh, coir dusts.

The use of fresh coir dusts can involve serious problems of high salinity , and phytotoxicity. In a comparative study of peat and other media for containerized forest tree seedlings, it was found that no plant of E.urophylla survived and growth of E. deglupta wasseverely retarded in coir dust media. Unfortunately, the salinity and phytotoxicity of the coir dust were not determined. One possibility for the phytotoxicity could be the phenolic compounds in the coir dust, like uncomposted sawdust and bark if the Cl content in the coir dust was normal.

The phytotoxicity of the potting substrates based on barks and
sawdusts has been extensively studied and varies with species and age of source trees. Most of the barks and sawdusts used in potting media contain phytotoxins which were found to be phenolic compounds. It was found that catechin, procyanidins B-1 and B-3, and 3,5,30,40-tetrahydroxystilbene and its glucoside from Pinus radiata bark and ellagitannins from sawdust of E. regnans and E. camaldulensis were responsible for the phytotoxicity. Addition of a phenol-fixing compound to aqueous substrate extracts markedly reduced the phytotoxicity.

P & D -- MATERIALS AND METHODS

Fresh coir dust, coconut shell and aged coir dust were obtained from

the Philippines. Some chemical properties of the samples were determined
using the Australia Standard methods To evaluate the phytotoxicity of coir
dust and coconut shell, a rapidbioassay method was used with lettuce
because the plant is a most sensitive species.

The moist sample of 50mL was weighed and placed in a petri dish to depth
about 9mm for the bioassay. The moisture of the sample was estimated
by its weight and bulk density. According to its moisture, water was
added to the petri dish to the water holding capacity of the sample. Ten
lettuce seeds were sown on the surface of the media in the petri dish. The
petri dish was covered with lid and incubated at room temperature
for 7 days. Finally, the root length was measured since the
roots were more sensitive to phytotoxins than shoots of lettuce. A known
nontoxic medium consisting of 0.5 L moist peat moss, 0.5 L sand, 4 g L1
dolomite, 0.75 gL1 KNO3, 1.0 gL1 single superphosphate, and


Sample pH (1:1.5) EC Cl

Fresh fine coir dust (0.25–1 mm) 6.11 0.80 450
Fresh coarse coir dust (1–2 mm) 5.89 0.60 300
Fresh coir dust (mixture) 5.90 0.68 364
Aged coir dust (unscreened) 5.89 0.51 300
Fresh coarse coconut shell (2–4 mm) 6.47 0.71 100
Fresh fine coconut shell (<2mm) 6.05 1.74 425 0.6 gL1 mixture of micronutrients as a bioassay control. There were two replications in the bioassay procedure. The phytotoxicity was expressed as the percentage of root length in the sample to the control. There was no fungal growth in petri dishes.To investigate the effects of incubation time, temperature and amendments on the phytotoxicity of fresh coir dust and shell, the samples of fresh coir and coconut were treated by (i) moistening with 500mLL1 water (moist), (ii) liming with 5 gL1 calcium carbonate(limed) and with 500mLL1 water, and (iii) plus 0.5 g L1 ferrous sulphate (limedþFe). The treated samples were kept in plastic bags and incubated in an incubator the dark and at different constant temperature systems. The samples were taken for bioassay every week for several weeks. After incubation, pH and EC of the incubated samples were determined in the suspension of sample and distilled water at the ratio of 1:1.5 .

Detoxification of Coir Dust

The root elongation was affected by incubation time in a moist, limed and limed with addition of  FeSO4 . At moisture of 50% (v/v) the phytotoxicity of both coir dust and coconut shell decreased  with incubation time. After 10 weeks incubation at 20C, the percentages of root length in media to control increased from 17.7 to 65.1% for fresh fine coir dust (0.5–1 mm), from 29.8 to 62.6% for fresh coarse coir dust (1–2 mm) and from 61.1% to 86.6% for fresh coconut shell (2–4 mm). A similar result was found in a mixture of fresh coir dust samples.

However, the incubation for up to 10 weeks at moist condition was insufficient to detoxify both coir dust samples . The change with incubation time for moist coconut shell lasted up to 5 weeks . Liming had been shown to further reduce the phytotoxicity of fresh coir dusts and coconut shell . The liming increased the process of detoxification of fresh coir dusts and coconut shell. Limed fresh coir dust (1–2 mm), a mixture of coir dust samples and fresh coconut shell (2–4 mm) had been fully detoxified by incubation at 20C for 3 weeks. For the limed fresh fine coir dust (0.5–1 mm), a minimum of 6 weeks was needed .

Compared with liming, addition of FeSO4 tended to decrease the phytotoxicity of coir dust and coconut shell, but it was not significant for fresh fine coir dust (0.5–1 mm)  and for a mixture of coir dusts. The process of detoxification was affected by incubation temperature. For a moist mixture of seven coir dust samples, high incubation temperature  could decrease its phytotoxicity, while for the mixtures with addition of lime or plus FeSO4, high incubation temperature was found to be effective only in the initial 2 weeks . In a potential potting mix of 50% aged coir dust and 50% coconut shell (0.5–2 mm), incubation at high temperature  was found to reduce phytotoxicity more effectively than at low temperature .

Incubation for 6 weeks at  was sufficient to fully detoxify the amended potting mix .Because the fine coconut shell (<0.5 mm) contained 33 mg L1 phenolic compounds , the root elongation in the mix containing the fine coconut shell was severely inhibited. With incubation at 20C the percentage of root length in the mix to control was increased onlyfrom 19.6 to 37.2% .

Bioactive Phytocompounds and Future Perspectives

The integration of herbal medicine into modern medical practises, including treat-ments for infections and cancer, must take into account the interrelated issues of quality, safety, and efficacy [64]. Quality is the paramount issue because it can af-fect the efficacy and/or safety of the herbal products being used. Current product quality ranges from very high to very low due to intrinsic, extrinsic, and regulatory factors. Intrinsically, species differences, organ specificity, diurnal and seasonal variations can affect the qualitative and quantitative accumulation of active chemical constituents in the source medicinal plants. Extrinsically, environmental fac-tors, field collection methods such as cultivation, harvest, post-harvest transport,and storage, manufacturing practises, inadvertent contamination and substitution,and intentional adulteration are contributing factors to the quality of herbal medicinal products. Source plant materials that are contaminated with microbes, microbial toxins, environmental pollutants, or heavy metals; or finished products that are adulterated with foreign toxic plants or synthetic pharmaceutical agents can lead to adverse events. Substandard source materials or finished products will yield therapeutically less effective agents. Herbal medicine quality can also be attributed to regulatory practises. In a number of countries, herbal medicines are unregulated, which has led to product quality differences.

     Product quality improvement may be achieved by implementing control measures from the point of medicinal plant procurement under Good Agricultural Practises (GAPs) and the manufacture of the finished botanical products under Good Manufacturing Practises (GMPs), plus postmarketing quality assurance surveillance. The lack of pharmacological and clinical data on the majority of herbal medicinal products is a major impediment to the integration of herbal medicines into conventional medical practise. For valid integration, pharmacological and especially, clinical studies, must be conducted on those plants lacking such data. Adverse events, including drug–herb interactions, must also be monitored to promote a safe integration of efficacious herbal medicine into conventional medical practises.
For the developing countries, the approval as drugs of standardized and formu-
lated plant extracts might be the starting point of an innovative and successful local pharmaceutical industry, which can compete with the large pharmaceutical companies, not only for the treatment of minor diseases, but also for the treatment  of severe and life-threatening diseases. It can be stated that the major activities of natural products research of the past decades have clearly demonstrated that natural products represent an unparalleled reservoir of molecular diversity to drug discovery and development, and are complementary to combinatorial libraries.The major disadvantage is the time taken to isolate and to characterize the activecomponents from the extracts. By improving the diversity and quality of sample source and screen suitability, by accelerating dereplication and by automating and standardizing early isolation steps, the effectiveness of natural products research can be enhanced. The efforts to establish collaboration between universities and local pharmaceutical companies to produce new medicines with scientific proof of safety, quality and efficacy are relevant to progress in this area. This interaction
between the pharmaceutical industry and the universities has in turn stimulated the appearance of preclinical pharmacological studies and of well-controlled and randomized clinical trials to prove their worth. Furthermore, emphasis on domestication, production, and biotechnological studies, followed by genetic improvements to medicinal plants, are other fields of science that emerge from such progress in the use of medicinal plants in the world. Scientists have dedicated significant efforts to the publishing of both basic and clinical studies on herbal medicines, and thus certainly will create the scientific basis for the physician’s prescription of herbal drugs. In spite of this, so far insufficient data exist to provide an accurate assessment of the quality, efficacy, and safety of most of the herbal medicines currently available on the market. For all these reasons, a great effort in training more scientists in the relevant areas is still necessary in order to establish rational and sustainable exploitation of the world’s biodiversity.

Extraction and HTS of Crude Plant Extracts

Medicinal plants have formed the basis of health care throughout the world since the earliest days of humanity and are still widely used and have considerable importance in international trade. Recognition of their clinical, pharmaceutical, and economic value is still growing, although this varies widely between countries. Plants are important for pharmacological research and drug development, not only when bioactive phytocompounds are used directly as therapeutic agents, but also as starting materials for the synthesis of drugs or as models for pharmacologically active compounds.

High-throughput screening, often abbreviated as HTS, is a method of scientific experimentation especially relevant to the fields of biology and chemistry. Through a combination of modern robotics and other specialized laboratory hardware, it allows a researcher to effectively conduct hundreds of scientific experiments at once. In essence, HTS uses a brute-force approach to collect a large amount of experimental data, usually observations about how some biological entity reacts to exposure to various chemical compounds in a relatively short time. A screen, in this context, is the larger experiment, with a single goal to which all this data may subsequently be applied.

Just like drugs of synthetic origin, bioactive phytocompounds range from simple to complex structures. Either way, the evaluation of a bioactive phytocompound or a natural product leads to benefits from modern HTS for the generation of analogs . Thus, paradoxically, the same combinatorial chemistry that initially caused the decline in natural product screening now promises to be an essential tool in rejuvenating it. Academic groups in particular are used to allocating significant resources of time and staff towards the total synthesis of bioactive phytocompounds. The ability to adapt such routes for the preparation of analogs is an obvious strategy for leveraging the initial expenditure, and is now increasingly evident in the literature. Because of the stricter timelines, large-scale combinatorial programs

Currently, almost every large pharmaceutical company has established HTS infrastructures and possesses large combinatorial compound libraries, which cover awide range of chemical diversity. However, the ability to detect the desired biological activity directly in the HPLC effluent stream and to chemically characterize the bioactive phytocompound on-line, would eliminate much of the time and labor taken in the fraction collection strategy. This way, cycle times, expenses, and the isolation of known or undesirable compounds would be reduced dramatically, allowing natural products to be screened in an efficient and cost effective manner

Antimicrobial Bioactive Phytocompounds

Different approaches to drug discovery using higher plants can be distinguished random selection followed by chemical screening; random selection followed by one or more biological assays; biological activity reports and ethnomedical use of plants . The latter approach includes plants used in traditional medical systems; herbalism, folklore, and shamanism; and the use of databases. The objective is the targeted isolation of new bioactive phytocompounds. When an active extract has been identified, the first task to be taken is the identification of the bioactive phytocompounds, and this can mean either a full identification of a bioactive phytocompound after purification or partial identification to the level of a family of known compounds


For screening selection, plants are collected either randomly or by following leads supplied by local healers in geographical areas where the plants are found. Initial screening of plants for possible antimicrobial activities typically begins by using crude aqueous or alcohol extractions followed by various organic extraction methods. Plant material can be used fresh or dried. The aspects of plant collection and identification will be discussed further in this chapter. Other relevant plant materials related to antimicrobial activity are the essential oils. Essential oils are complex natural mixtures of volatile secondary metabolites, isolated from plants by hydro or steam distillation and by expression (citrus peel oils). The main constituents of essential oils , along with carbohydrates, alcohols, ethers, aldehydes, and ke-tones, are responsible for the fragrant and biological properties of aromatic and medicinal plants. Due to these properties, since ancient times spices and herbs
have been added to food, not only as flavoring agents but also as preservatives. For centuries essential oils have been isolated from different parts of plants and are also used for similar purposes.

Drying medicinal plant material directly on bare ground should be avoided. If a concrete or cement surface is used, the plant materials should be laid on a tarpaulin or other appropriate cloth or sheeting. Insects, rodents, birds and other pests,and livestock and domestic animals should be kept away from drying sites. For indoor drying, the duration of drying, drying temperature, humidity and other conditions should be determined on the basis of the plant part concerned and any volatile natural constituents, such as essential oils. If possible, the source of heat for directs drying (fire) should be limited to butane, propane or natural gas, and temperatures should be kept below 60 °C . If other sources of fire are used, contact between those materials, smoke, and the medicinal plant material should be avoided.

Problems with Herbal Drugs Preparations(1):-

The number of reports of patients experiencing negative health consequences caused by the use of herbal medicines has increased in recent years . Analysis and studies have revealed a variety of reasons for such problems. One of the major causes of reported adverse events is directly linked to the poor quality of herbal medicines, including raw medicinal plant materials. It has therefore been recog- nized that insufficient attention has been paid to the quality assurance and control of herbal medicines .

Quality control directly impacts the safety and efficacy of herbal medicinal products . The implementation of good agricultural and collection practises for medicinal plants is only the first step in quality assurance, on which the safety and efficacy of herbal medicinal products directly depend, and also plays an important role in the protection of natural resources of medicinal plants for sustainable use. Some reported adverse events following the use of certain herbal medicines have been associated with a variety of possible explanations, including the inadvertent use of the wrong plant species, adulteration with undeclared other medicines
and/or potent substances, contamination with undeclared toxic and/or hazardous substances, overdosage, inappropriate use by health care providers or consumers, and interactions with other medicines, resulting in adverse drug effects .

The safety and quality of raw medicinal plant materials and finished products depend on factors that may be classified as intrinsic  or extrinsic . Inadvertent contamination by microbial or chemical agents during any of the production stages can also lead to deterioration in safety and quality. Medicinal plants collected from the wild population may be contaminated by other species or plant parts through misidentification, accidental contamination, or intentional adulteration, all of which may have unsafe consequences. The collection of medicinal plants from wild populations can give rise to additional concerns related to global, regional, and/or local over-harvesting, and protection of endangered species. The impact of cultivation and collection on the environment and ecological processes, and the welfare of local communities should be considered .

It is well established that intrinsic and extrinsic factors, including species differences, organ specificity, diurnal and seasonal variation, environment, field collection and cultivation methods, contamination, substitution, adulteration, and processing and manufacturing practises greatly affect botanical quality. Intrinsically, botanicals are derived from dynamic living organisms, each of which is capable of being slightly different in its physical and chemical characters due to genetic influence.

Diurnal and seasonal variations are other intrinsic factors affecting chemical acumulation in both wild and cultivated plants. Depending on the plant, the accumulation of chemical constituents can occur at any time during the various stages of growth. In the majority of cases, maximum chemical accumulation occurs at the
time of flowering, followed by a decline beginning at the fruiting stage. The time of harvest or field collection can thus influence the quality of the final herbal product.

There are many extrinsic factors affecting the qualities of medicinal plants. It has been well established that factors such as soil, light, water, temperature, and nutrients can, and do, affect phytochemical accumulation in plants, The methods employed in field collection from the wild, as well as in commercial cultivation, harvest, post-harvest processing, shipping, and storage can also influence the physical appearance and chemical quality of botanical source materials.

Contamination by microbial and chemical agents , as well as by insect, animal, animal parts, and animal  xcreta during any of the stages of source plant material production can lead to lower quality and/or unsafe materials. Adulteration of herbal medicines with synthetic drugs represents another problem in product quality.

Problems with Herbal Drugs Preparations(2):-

In the following paragraphs technical aspects of medicinal plant production will be discussed. According to the World health Organization  the botanical identity, scientific name of each medicinal plant under cultivation should be verified and recorded. If available, the local and English common names should also be recorded. Other relevant information, such as the cultivar name, ecotype, chemotype, or phenotype, may also be provided, as appropriate.

For commercially available cultivars, the name of the cultivar and of the supplier should be provided. It’s essential that a voucher botanical specimen used in the experiments be placed in a regional or national herbarium for identification and further consultation by other researchers; it is almost impossible and not advised to publish without the registration numbers. Cultivation of medicinal plants requires intensive care and management. The conditions and duration of cultivation required vary depending on the quality of the medicinal plant materials required. If no scientific published or documented cultivation data are available, traditional methods of cultivation should be followed, where feasible.

Otherwise a method should be developed through research. The principles of good plant husbandry, including appropriate rotation of plants selected according to environmental suitability, should be followed, and tillage should be adapted to plant growth and other requirements. Risks of contamination as a result of pollution of the soil, air, or water by hazardous chemicals should be avoided. The impact of past land uses on the cultivation site, including the planting of previous crops and any applications of plant protection products should be evaluated.

The quality and growth of medicinal plants can also be affected by other plants, other living organisms, and by human activities. The introduction of nonindigenous medicinal plant species into cultivation may have a detrimental impact on the biological and ecological balance of the region. The ecological impact of cultivation activities should be monitored over time, where practical. The social impact of cultivation on local communities should also be examined to ensure that negative impacts on local livelihood are avoided. In terms of local income-earning opportunities, small-scale cultivation is often preferable to largescale production, especially if small-scale farmers are organized to market their products jointly. If large-scale medicinal plant cultivation is or has been established, care should be taken that local communities benefit directly from, for example, fair wages, equal employment opportunities, and capital reinvestment.

NBP Against Bacteria/Fungi:

Long before the discovery of the existence of microbes, the idea that certain plants had healing potential, indeed, that they contained what we would currently characterize as antimicrobial principles, was well accepted. Since antiquity, humans have used plants to treat common infectious diseases, and some of these traditional medicines are still included as part of the habitual treatment of various maladies. For example, the use of bearberry  and cranberry juice to treat urinary tract infections is reported in different manuals of phytotherapy, while species such as lemon balm, garlic, and tee tree are described as broad-spectrum antimicrobial agents. That being said, it has generally been the essential oils of these plants rather than their extracts that have had the greatest use in the treatment of infectious pathologies in the respiratory system, urinary tract, gastrointestinal, and biliary systems, as well as on the skin. In the case of Melaleuca alternifolia, for example, the use of the essential oil  is a common therapeutic tool to treat acne and other infectious troubles of the skin.

Antimicrobial resistance is one of the biggest challenges facing global public health. Although antimicrobial drugs have saved many lives and eased the suffering of many millions, poverty, ignorance, poor sanitation, hunger and malnutrition, inadequate access to drugs, poor and inadequate health care systems, civil conflicts and bad governance in developing countries have tremendously limited the benefits of these drugs in controlling infectious diseases. The development of resistance in the responsible pathogens has worsened the situation, often with very limited resources to investigate and provide reliable susceptibility data on which rational treatments can be based as well as the means to optimize the use of antimicrobial agents. The emergence of multidrug-resistant isolates in tuberculosis, acute respiratory infections, and diarrhea, often referred to as the diseases of poverty, has had its greatest toll in developing countries. The epidemic of HIV/AIDS, with over 30 million cases in developing countries, has greatly enlarged the population of immunocompromised patients. The disease has left these patients at great risk of numerous infections and even greater risk of acquiring highly resistant organisms during long periods of hospitalization.

Antibiotic resistance can occur via three general mechanisms: prevention of interaction of the drug with target, efflux of the antibiotic from the cell, and direct destruction or modification of the compound. The emergence of multidrug resistance in human and animal pathogenic bacteria as well as undesirable side-effects of certain antibiotics has triggered immense interest in the search for new antimicrobial drugs of plant origin. Ahmad and Beg  tested alcoholic extracts of 45 traditionally used Indian medicinal plants against drug-resistant bacteria and fungi  both related to the critical prognosis and treatment of infectious diseases in immunocompromised, AIDS and cancer patients. Of these, 40 plant extracts showed varied levels of antimicrobial activity against one or more test bacteria. Anticandidal activity was detected in 24 plant extracts. Overall, broad-spectrum antimicrobial activity was observed in 12 plants . Several other studies have also demonstrated the importance of new bioactive phytocompounds against multidrug-resistant bacteria/fungi.

Useful antimicrobial phytochemicals can be divided into several categories summarized . Scientists from divergent fields are investigating plants anew with an eye to their antimicrobial usefulness. A sense of urgency accompanies the search as the pace of species extinction continues. Laboratories of the world have found literally thousands of phytochemicals which have inhibitory effects on all types of microorganisms in vitro. More of these compounds should be subjected to animal and human studies to determine their effectiveness in whole-organism systems, including in particular toxicity studies as well as an examination of their effects on beneficial normal microbiota.

It would be advantageous to standardize methods of extraction and in vitro testing so that the search could be more systemtic and interpretation of results facilitated. Also, alternative mechanisms of infection prevention and treatment should be included in initial activity screenings. Disruption of adhesion is one example of an anti-infection activity not commonly screened currently. Attention to these issues could usher in a badly needed new era of chemotherapeutic treatment of infection by using plant-derived principles.