DERMATOLOGY’S BOTANICAL HERITAGE

Scott A. Norton, MD, MPH, MSc

Chief of Dermatology

Walter Reed Army Medical Center

Washington DC 20307

Office (202) 782 9486

FAX 202 782 9118

scott.norton@na.amedd.army.mil

Words: 5260

References: 63

The opinions and assertions contained herein are those of the author

and not necessarily those of the Department of Defense.

Funding sources: none.

This article originally appeared as a chapter in Dermatologic Botany by Javier Avalos (ed).

Copyright 1999 by Taylor & Francis Group LLC. Reproduced with permission of Taylor &

Francis Group LLC in the format Journal via Copyright Clearance Center

1

Along the bank of the river . . .will grow all kinds of trees [whose] fruit will be used for food and

their leaves for medicine. Ezekiel 47:12

INTRODUCTION

"Dermatologic Botany” addresses mainly the harmful or injurious effects of plants upon

the skin. This chapter serves to remind readers of the beneficent role of plants in dermatology

(and medicine in general) throughout history. Many of my patients and colleagues know of my

interest in botany and often ask if I use (or “believe in”) herbal medicines or medicinal plants.

My short answer is, “Of course, but perhaps not as you think.” My full answer, a discourse on

the historical and continuing harmonious relationship between plants and dermatology,

constitutes this chapter.

The disciplines of medicine and botany have been closely allied through most of

man’s history. For millennia, healers depended on the helpful properties of plants and were by

necessity accomplished botanists.[1,2] For centuries, herbals (manuals of pharmacognosy in

which the therapeutic properties of plants are cataloged) served as the standard treatises of

Western medicine. Healers in both Western and non-Western models of medicine relied – and

still rely – on medicinal plants. In developing nations approximately 80% of the populations are

still treated with traditional medicines made from natural products with little or no processing.[3]

From 1959 to 1980, medications derived from vascular plants account for one-quarter of all out-

patient prescriptions in the United States.[3] Since 1980, roughly half of the medications

submitted to the FDA were derived from natural products.[4]

Medical botany was once a core course in medical education but physicians trained today

in the modern biomedical fashion are often unaware of medicine’s botanical heritage. With the

rise of the chemical industry in the mid-19th century, the fields of medicine and botany began to

evolve separately. The pharmacologically-active components of plants were often extracted and

analyzed in the laboratory. Once the chemical structures were identified, chemists were often

able to fully synthesize the desired product. This obviated the need to collect useful plants from

the wild or from cultivation and led to the further divergence between botany and medicine.

Biochemists were also able to develop novel substances whose molecular structures were

unknown in nature. These were developed for industrial uses, such as textile dyes, but the

pharmacoactivity of these new compounds was recognized and many entered the conventional

pharmacopoeia. Today synthetic medications have largely replaced natural products and many

2

physicians now regard plant-derived medications such as digoxin, morphine, ipecac, and atropine

as curious remnants from the antiquated days of medicine.

NATURAL PRODUCTS AND ETHNOBOTANY

In the past two decades, however, there has been a reawakened appreciation of the

pharmacoactive properties of natural products. Perhaps the most widely-known examples of

plant-products entering the modern pharmacopoeia are the development of chemotherapeutic

agents. Vinblastine and vincristine from Madagascar’s rosy periwinkle (Catharanthus rosea)

and paclitaxel from the Western yew tree (Taxus brevifolia) are now standard elements in our

battles with cancer. The interest in medicinal plants usually follows one of three avenues: a

popular interest in herbal medicines, ethnobotanical investigations among traditional peoples,

and pharmacological investigations involving combinatorial chemistry. In Europe, particularly

France and Germany, herbal medications have long been part of the standard formularies. More

recently, it has been recognized that millions of Americans (and billions of their health care

dollars) are engaged in alternative or complementary medical practices, much of which uses

natural products.[5] The medical and scientific, social and economic, legal and regulatory

consequences of these practices are still evolving.[6]

Ethnobotany has re-emerged as a medically sound and potentially profitable source of

new medications. Hundreds of reports appear in the medical literature each year on the

physiologic activity of phytochemicals in laboratory animals or in vitro. Most endeavors seek

new agents for antiviral, antibacterial, and chemotherapeutic purposes. The ethnobotanist’s

principle is that there are innumerable plants and plant-products whose therapeutic activity is

recognized by traditional healers but whose pharmacological activity has not yet been recognized

by Western medical science.[7] Ethnobotanical investigations require interdisciplinary skills in

plant taxonomy, cultural anthropology, biochemistry, pharmacology, linguistics, and medicine.

[2,8]

The search for and the development of potentially valuable natural products is called

bioprospecting. This was one of the major themes of the 1992 United Nations “Earth Summit” in

Rio de Janeiro. The United Nations Convention on Biological Diversity that arose from the

Summit endorses the proposal that nations (and their indigenous peoples) retain intellectual

property rights to biologic products derived from endemic plants and animals. Indigenous

3

peoples whose knowledge and skills are used in the development of a new product figure

prominently in this Convention.[2]

Dermatological remedies are a particularly appropriate avenue for ethnopharmacologic

pursuit because the ethnopharmacopoeia of many populations are directed toward skin diseases.

In traditional societies in tropical areas, skin disorders are ubiquitous, conspicuous, and cause

considerable morbidity. Skin diseases are classifiable (although not necessarily in accordance

with a biomedical system) and amenable to observation for response to treatment. Accordingly

the dermatologist should take great interest in ethnopharmacologic endeavors. On the other hand,

the interest of Western pharmaceutical corporations is usually more toward the major causes of

morbidity and mortality in developed countries, such as cancer, diabetes, heart disease, and

infectious diseases. In many cases, the molecular structure of the medication is unchanged but

the product is fully synthesized to achieve large quantities more efficiently than through crude

extractions. In other cases, the molecular structure of the crude product has been modified,

improving the drug’s efficacy and safety (such as the development of atracurium from curare, the

Amazonian arrow poison obtained from Chondrodendron tomentosum (Menispermaceae).[9]

LITERATURE ON BOTANICAL DERMATOLOGY

A survey of books held at National Library of Medicine (NLM) on the topics of plants

and medicine suggests an overwhelming appreciation (at least among medical writers) of the

beneficial contributions of plants to human health. As of mid-1998, the NLM held roughly 4000

books on plants and medicine. Of these, 3596 books (91%) were on beneficial plants and 359

books (9%) were on harmful plants. In contrast, the dermatological literature has a strong bias

against plants. Of the NLM’s 22 volumes on plants and the skin, half are about harmful plants.

Furthermore, all six books written in English and published in Western nations were on the toxic

effects of plants on the skin.

“Dermatologic Botany” and its major predecessors [10-12] are among the volumes that

focus on the harmful effects of plants on the skin. Similar earlier works give the impression that

plants can have either of two consequences: bad or neutral. The subtitle of Mitchell and Rook’s

opus, Botanical Dermatology is Plants and Plant Products Injurious to the Skin.[10] Their

preface explains that “man’s primitive ancestors . . .must have noticed that whilst some plants

were harmful to everyone who handled them, others produced ill effects in only a few.”

Benezra’s volume tells us, “In our everyday life, we are surrounded by plants. . . . Many of these

4

plants have an adverse skin effect. Although most of the isolated and classified 3000,000 plant

species are harmless to the skin, some can be blamed for provoking contact dermatitis.”[11]

This theme distorts the historically harmonious association of plants and the skin. So it is

with great pleasure that I add this brief chapter to review some of the beneficial interactions

between plants and the skin: the ways that dermatologists use plants and the ways that plants

protect and heal the skin.

PLANTS AND THE SKIN

The most obvious ways in which plants maintain the health of our skin are also the most

overlooked ways: food, clothing, and shelter. In the West, we generally do not consider food as

medicine but it is -- both prophylactically and therapeutically. Most western dermatologists have

not seen patients with deficiency diseases of scurvy, pellagra, hypovitaminosis A, and

kwashiorkor yet these conditions still appear in epidemic proportions among refugees and

displaced people. Nutritional diseases continue to ravage the skin (and every other organ) of

millions of people. The inclusion of proper plant-derived foods in the basic or supplemental diet

will prevent or eradicate these disorders. Furthermore, there is evidence that specific plants in the

diet may protect against cancers, usually visceral cancers, but possibly melanoma and non-

melanoma skin cancer as well. Examples of putatively protective plants include those with

abundant non-soluble fiber or with anti-oxidative properties (such as cruciferous vegetables).[13]

Worldwide, most clothing is made from plant fibers, especially cotton. Clothing, of

course, serves as barrier protection for the skin, protecting it from the physical elements of cold,

water, sunlight, rough objects, noxious plants and animals, and infectious organisms. Shelter

protects people from the same elements as do clothing but collectively and at a distance. Homes

for the vast majority of people worldwide are still made mainly from wood and other plant

materials.

Continuing the theme of the obvious but overlooked interactions between plants and

dermatologists, let me add that the paper and ink of this text (and that in every document you

read or prepare) comes from plants. The photographic film that one uses to capture images of

one’s patients has a base of cellulose acetate that comes from eucalyptus trees (Eucalyptus,

Myrtaceae).[14]

EXAMPLES OF PLANTS IN DERMATOLOGIC THERAPY

5

This remainder of this chapter will review the role of vascular plants in dermatology

today. Fungi, once considered plants, are now classified as their own Kingdom and so their

invaluable contributions to medicine as sources of antibiotic agents (most famously penicillin but

virtually every antibacterial antibiotic as well), antineoplastic agents (e.g., bleomycin and

adriamycin), and immunomodulating agents (e.g., cyclosporine) will not be covered here.

Pyrethrum and pyrethroids (such as permethrin) are natural or semisynthetic derivatives,

respectively, of wild chrysanthemum, Tanacetum cinerariifolium (Asteraceae), native to

mountains of the Balkan peninsula. Legend has it that bouquets of dried plants were placed

around homes to deter insect infestations. Pyrethrum was used during World War I as an insect

repellent both on the skin and to impregnate clothing, tent canvas, and mosquito nets. The

demand for the product by the world’s armies led to the establishment of plantations throughout

tropical mountainous areas such as Kenya, Ecuador, and Papua New Guinea. The products

continue to be used as repellants but more recently semi-synthetic derivatives have been

developed for direct application to the skin as scabicides and pediculicides.

Capsaicin is the natural substance that carries the essential fieriness of hot peppers.[15] It

is found only in several members of the genus Capsicum (Solanaceae). The action of capsaicin

when applied to the skin is to deplete sensory nerve fibers of Substance P which renders the

nerves incapable of transmitting pain sensations. Consequently capsaicin compounds are used to

treat cutaneous dysesthesias associated with postherpetic neuralgia, diabetic neuropathy, reflex

sympathetic dystrophy, Raynaud's phenomenon, notalgia paresthetica, and hemodialysis-related

pruritus.[16]

Nearly all antibacterial agents in use today are derived from fungi. The story of penicillin

is well-known; many other antibiotics such as cephalosporins were developed in similar yet more

purposeful ways. Several fully synthetic antibiotics, such as sulfa compounds, emerged from the

biochemical industry. But the only regularly used antibacterial derived from a higher plant in

modern times has been chaulmoogra which was prescribed in the treatment of leprosy.[17]

Chaulmoogra oil is extracted from the seeds of several closely related plants in the genus

Hydnocarpus (Hydnocarpaceae) found in scattered areas in southeast Asia. This plant entered

Western medicine through a true combination of ethnobotany and bioprospecting (although long

before either term was in use). British physicians working in India in the mid-1800’s reported on

the local use of an oil made from the crushed seeds of certain trees found in the Kerala hills. The

6

substance was used in several forms by local healers to treat leprosy. For the next half-century,

Western supplies of chaulmoogra were obtained from bazaars in India and Indochina but the oils

were often in low supply and poor quality. The United States Department of Agriculture

dispatched Joseph Rock, a botanist at University of Hawaii, to southeast Asia to collect viable

chaulmoogra seeds for the establishment of plantations on the Hawaiian islands. Rock succeeded

and the oil subsequently obtained from his trees supplied American leprosaria for decades.

Ultimately chaulmoogra was replaced replacement by a fungus-derived products, rifampicin, and

a fully synthetic product, dapsone.

Podophyllin is a crude extract from the mayapple, Podophyllum peltatum

(Berberidaceae), that grows wild in forested hills over much of the eastern half of the United

States. A closely-related species, Podophyllum hexandrum (syn P. emodi), is found in

mountainous areas of southwestern China, a disjunct distribution that is found with a number of

primitive flowering plants such as magnolia and star anise. The mayapple has a plum-sized

yellowish-green fruit that ripens in late spring hence its name. North America Indians used the

fruit as part of their pharmacopoeia, ingesting it as an emetic and purgative. The use of a crude

extract of podophyllin to treat warts was first practiced in New Orleans in the 1930s. Recently a

purified preparation of one of the active ingredients, podophyllotoxin, was approved for

dispensing. The compound appears to cause mitotic arrest in actively dividing cells, the sort

found in warts and some neoplasms. Indeed, a semisynthetic derivative of mayapple, etoposide

(also called VP16), that is administered parenterally to treat cancers such as small cell carcinoma

of the lung and refractory testicular tumors. A recent report suggests that etoposide may be

useful in the treatment of cutaneous Langerhans cell histiocytosis.[19]

Corticosteroids are the most frequently prescribed class of medications in dermatology

yet they have been widely available for perhaps only the past 40 years. The history of

commercial steroids is a fascinating tale of botanical exploration to find an exploitable source of

sapogenins from which steroids could be derived.[20] Until recently, almost all steroid products

(sex steroids and glucocorticoids) were derived from one of several species of wild Mexican

yams (e.g., Dioscorea mexicana, D. composita, and D. floribunda, Dioscoraceae) that contained

sufficient diosgenin for practical conversion into an active substance. Subsequently, pathways

from soybean precursors were developed and many of the products are marketed with the cachet

of being a “natural” product in both the prescription (such as Ogen, estropipate) and non-

7

prescription markets (dehydroepiandrosterone sulfate or DHEAS sold under many trade names at

health food stores).

Antimalarial substances derived from quinine have changed the history of man and,

consequently, the face of the earth. The oft-repeated early history of quinine or peruvian bark is a

mixture of truth and legend[21] but the extract from the bark of the Cinchona (especially C.

calisaya, Rubiaceae) tree has contributed greatly toward the conquest of malaria and has

consequently enabled dense inhabitation of the humid tropics and subtropics. Unfortunately the

plasmodia are acquiring resistance to quinine and its descendants but these products are part of

the dermatologist’s core formulary still. In 1894, a physician tried quinine to treat the cutaneous

lesions of discoid lupus erythematosus on the assumption that quinine would cause

vasoconstriction and clear the plaques.[21] Successes here led to trials over the next century of

various natural and synthetic antimalarials in other connective tissue diseases, photosensitivity

disorders, and sarcoidosis.

Colchicine is an alkaloid derived from the autumn crocus, Colchicum autumnale. The

plant is endemic to regions in the eastern Mediterranean but is now cultivated worldwide for

both its ornamental and its therapeutic properties. Colchicine is the classic treatment for gout but

is also used in neutrophilic disorders. It appears that colchicine interferes with mitoses and has

other immunomodulating effects. A variety of seemingly disparate disorders such as gout, oral

aphthae, Behcet’s disease, familial Mediterranean fever (and associated amyloidosis), and

primary biliary cirrhosis can be controlled although not cured with colchicine.

The story of psoralen-containing plants in dermatology is well known. In both Egypt and

India, people with vitiligo ate seeds from particular plants in the parsley family (Umbelliferae or

Apiaceae) and exposed themselves to sunlight. Depigmented areas became sunburned and often

blistered, after which the pigment occasionally returned. One of these plants, Psoralea

corylifolia, gave its name to the class of agents, psoralens, that are now used in the treatment of

several photoresponsive dermatoses, such as psoriasis. Most psoralen used for medical purposes

comes from Bishop’s weed (Ammi majus), native to parts of southern Europe, north Africa, and

southwest Asia.[22-24]

The precursor of anthralin used in the treatment of psoriasis was a natural preparation

called Goa powder or chrysorobin. It was obtained from the bark and wood of several closely

related trees, particularly the araroba (Vataireopsis araroba Leguminosae), found along Brazil’s

8

Bahia coast.[25] Portuguese traders took the tree from their New World colony and established

it in their Indian colony of Goa, hence the medication was also known as Goa powder. In the

mid-to-late 1800’s, chrysorobin entered the dermatologist’s formulary as a treatment for several

papulosquamous diseases but soon was recognized for its antipsoriatic properties. A seatrade

blockade of Germany during World War I led to the synthesis of anthralin, the most effective

component of chrysorobin, by that nation’s biochemists.[26]

Azelaic acid, a byproduct of processed cereal grains (Graminae), has several properties

that make it useful in dermatology. It interferes with tyrosinase and hence can be used as a

topical agent to treat benign pigmented lesions such as melasma. It is also mildly bacteriostatic

and anti-inflammatory and is used in the treatment of mild acne vulgaris although its precise

mechanism of action is not known.[27]

Traditional Chinese medicine is a rich source of herbal medicines. Most Chinese

medicines are combinations of several herbs, often animal parts. These are administered under

the philosophy that the collective or synergistic properties of the herbs are what is beneficial.

This differs from the Western biomedical paradigm in which there are extractable and

identifiable pharmacologically-active ingredients. Western dermatologists seem most interested

in the Chinese approach to treating psoriasis and atopic dermatitis.[28,29] Issues of plant

identification, potency of the materials, and purity of the concoctions makes these products

difficult for Western pharmacologists to analyze and assess. There are dangers of uncritical

enthusiasm and many reports of toxic adulterants in traditional Chinese medicines.[30-32]

It has been noted recently that ulcerative colitis is uncommon in cigarette smokers. It

appears that in some way, tobacco is protective or therapeutic. The likeliest explanation is that

nicotine, an alkaloid found in tobacco (Nicotiana tabacum, Solanaceae), has some hitherto

undetected salutary properties. Open trials of topical nicotine in the treatment of a cutaneous

manifestation of ulcerative colitis, namely pyoderma gangrenosum, also show some benefit.[33]

Oats can be made into an antipruritic remedy; the oatmeal bath is used as a palliative for

intensely itchy conditions such as severe atopic dermatitis. The Latin name for oats, Avena sativa

(Graminae) gives a clue for the trade name of the most commonly used form of oats. Other

antipruritic agents include menthol from mint (Mentha spp., Labiatae) and camphor from several

trees (especially in Lauraceae and Myrtaceae), although these agents are now synthesized. These

are both mild topical anesthetics that can help reduce severe itching.

9

Papain, an enzyme from papaya (Carica papaya, Caricaceae) is often touted as and used

for the treatment of minor envenomations (such as from jellyfish or fire ants) to denature the

toxic proteins, despite uncertain evidence.[34] Papain has also been used for enzymatic

debridement of leg ulcers.[35]

Aloe vera (Aloe vera, Agavaceae) is one of the most popular of the botaniceuticals. Aloe

is used as direct application of freshly cut aloe leaves. Extracts of tissue juices are also prepared

for commercial products. There are pharmacologically active substances in aloe vera that may

promote wound healing and retard bacterial growth.[36]

Most flavorings, fragrances, colorings, and many of the vehicles in which topical and oral

medications are prepared are derived from plants.[37] Tincture of benzoin is made from the

storax tree, Styrax (Styracaceae). Alcohol, used in so many fashions, is a byproduct from the

grain industry. Balsam of Peru is derived from the black balsam tree, Myroxylon balsamum var.

pereirae, which naturally occurs in lowland forests of central America although it is now grown

in plantations throughout the tropics. The useful product, balsam, is a viscous liquid with a

vanilla-like odor that is used in perfumes.

Other topical preparations prepared from plants include liniments, rubifacients,

astringents, emollients, and counterirritants such as turpentine, capsaicin, salicylates, menthol,

and thymol.[37] Rubifacients are preparations that increase the cutaneous blood flow. Salicylic

acid is used as both a rubifacient and as a keratolytic compound in many formulations. By

legend, the original source of salicylic acid was the bark of willow trees (in Latin, willow is

Salix). Later salicylates were obtained from Spiraea (Rosaceae) but a century ago, a synthetic

version was made “without Spiraea (a-spiraea),” hence the name “aspirin.” Witch hazel from

Hamamelis virginiana (Hamamelidaceae) is an astringent, used to calm external hemorrhoids.

Thymol, an extract from thyme, Thymus vulgaris (Labiatae), has been used as a fungistatic agent

for fungal infections of nails. The oils that one applies to the skin as lubricants, moisturizers, and

emollients are often plant-based as is the glycolic acid now used in skin resurfacing. Evening

primrose oil and green tea extracts enjoy waves of popularity among both the public and the

medical community for their actions on several inflammatory conditions.

EXAMPLES OF PLANTS IN DERMATOLOGIC DIAGNOSIS

Some of the simplest diagnostic tests that use plant products are sensory testing with

wisps of cotton when one suspects leprosy and the acetowhitening technique to check for genital

10

epithelial growths, such as warts. Acetic acid, of course, is a byproduct of common fermentation

of any of a number of plant sources.

Several histochemical stains are derived from plants. The most widely used stain is

haemotoxylin, a natural dye, in combination with eosin, a synthetic dye. Haematoxylin is derived

from the red-colored heartwood of the logwood tree, Haematoxylum campechianum

(Leguminosae), a scrub tree indigenous to southern Mexico but now planted commercially on

several Caribbean islands.[38] An extract of the wood was used as a traditional textile dye by

Indians of the region. In the 16th and 17th centuries, Spanish and English mercantile ships vied for

supplies of logwood to produce textile dyes for much of Europe. The chemical structure of

hematoxylin is known but attempts at commercial synthesis have been unsuccessful. The product

remains in use today much as it was by Virchow 130 years ago.

Alizarin red is one of several histochemical stains that are used to detect dermal calcium

in disorders such as pseudoxanthoma elasticum and calcinosis cutis.[39] The original alizarin

was prepared from the madder plant, Rubia tinctorum (Rubiaceae), and was originally used as a

textile dye. Nowadays a synthetic product, chemically identical, is used instead in

histochemistry.

Many agents used in immunohistochemistry are derived from plants.

Phytohemagglutinins and lectins are naturally-occurring proteins that adhere to glycoproteins on

the surface of red blood cells. This confers upon these substances the curious ability to

agglutinate red blood cells in vitro.[40] Examples of phytohemagglutinins that are used in

dermatologic immunopathology are concanavalin A (jackbean, Canavalia ensiformis), peanut

antigen (Arachis hypogaea), Ulex europaeus (European common gorse) antigen, and soybean

(Glycine max) lectin. U. europaeus antigen helps identify the vascular origins of tissues. Not all

plants with lectins are botanically related but most (including all those listed above) are from the

pea family, Leguminosae. Pokeweed (Phytolacca americana, Phytolaccaceae) mitogen is used in

an assay to test B-cell origin of lymphocytes. Gallotannin or tannic acid, derived from oak galls

(a sort of tumorous response to insect invasions), enhances fixation of specimens for electron

microscopy and immunoelectron microscopy.[41] Peroxidases derived from several plants,

horseradish (Amoracia rusticana, Cruciferae) in particular, are used in immunohistochemistry

and a number of other diagnostic tests.

OTHER NATURAL PRODUCTS IN DERMATOLOGY

11

Biochemists have had tremendous accomplishments in the duplication of natural

chemicals and the creation of new ones. Nature, however, remains the consummately innovative

and prolific producer of useful substances. The biochemical machinery of plants and animals far

exceeds that which man has identified to date or what computers can generate. Nature also

provides the finest combinatorial chemists in the form of her most diverse class of organisms: the

insects. The myriad phytochemicals (such as alkaloids and flavonoids) often serve as

chemoattractants or chemorepellants. There is an evolutionary chess game that exists between

plants and insects (or between any two organisms that have an ecological relationship). When an

herbivore, such as an insect, feeds on a plant, natural selection favors the plants with defenses,

chemical (e.g., alkaloids) or physical (e.g., thorns). The herbivorous insects digest, metabolize,

and transform the phytochemicals to their own advantage. Occasionally these insect-modified

substances serve useful functions for humans also. Insect-modified products used in dermatology

include silk sutures made from threads that the silkworm (Bombyx mori) makes from mulberry

leaves (Morus spp., Moraceae); cantharone for the treatment of warts from blister beetles

(Cantharus vesicatoria); mucicarmine for histology made from excreta that the cochineal bug

(Dactylopius spp.) deposits on its host plant, the nopal cactus (Nopalea, Cactaceae); beeswax

used in some topical preparations and honey once used to clean deep ulcers. The full

opportunities afforded by other insect-modified substances has not been well explored. Until

recently, we have rarely capitalized on the biochemical abilities of insects. Other than the

medical uses listed above, we know that some honeys have psychoactive properties. Bees

transfer traces of phytochemicals from the nectar of psychoactive plants.[42] Medicine Man, a

1992 movie starring Sean Connery, elaborated on this theme with the story of a serendipitous

anticancer treatment that was extracted from an nectar-feeding insect inadvertently blended into

an Amazonian herbal remedy.

Vertebrate sources also provide a number of natural products regularly used in

conventional dermatology. Examples include injectable bovine collagen, glycerin from animal

fat, lanolin from sheep’s wool, suture made from sheep intestines (catgut), and sodium

morrhulate for sclerotherapy from cod liver oil.

The cosmetic industry has incorporated dozens of animal derived products into creams,

lotions, emollients, polishes, shampoos, and especially into antiaging products. Collagen from

shredded calfskin, elastin from bovine neck ligaments, hyaluronic acid from a variety of bovine

12

and avian organs, oils from bird fat, and keratin from bovine, ovine, and porcine sources. More

mysterious ingredients include extracts from mammalian brains, placentae, amniotic fluid, and

pancreases that are used in some cosmeceutical preparations.[43,44]

THE FUTURE OF NATURAL PRODUCTS IN DERMATOLOGY

Every month’s scientific publications report various natural products that have

pharmacologic activity in vivo or in vitro. Some of these report early investigations; others

describe clinical trials. Nevertheless, most of these will not reach the commercial market as the

overall success ratio of tested products to marketed products is very low. Recent reports include

a fern extract with possible application in the treatment of vitiligo; a birch extract in the

treatment of melanoma; castor bean extract in the treatment of cutaneous T-cell lymphoma; and a

coffee bean extract in the treatment of HIV infection.[45-48]

Another promising endeavor is to use plant cell cultures to produce recognized or novel

phytochemicals. A novel way to administer vaccines to people is via genetically engineered

foodplants such as the potato or banana. Oral administration is a practical way to immunize

patients.[49] Measles, chickenpox, diphtheria, and tetanus are examples of vaccine-preventable

diseases in which the skin figures prominently in either the disorder or its acquisition.

The role of vitamins is changing from protection from deficiency diseases to now

consider more active role as antioxidants [50] in which vitamins protect not only from their

respective deficiency diseases but serve as antioxidants to protect from aging and degenerative

conditions. A number of cosmeceutical preparations include Vitamins A, B complex, C, and E.

[51]

HERBAL MEDICINES, BOTANICEUTICALS, AND ENTREPENEURS

There is a burgeoning commercial market for herbal remedies known as botaniceuticals.

The manufacturers of these products vaunt them for one’s health and appearance. No regulatory

agency has established a definition for botaniceuticals and the Dietary Supplement Health and

Education Act (DSHEA) prevents the United States Food and Drug Administration from

regulating most of these products as long as the manufacturer does not claim prevention,

diagnosis, treatment, or cure of a disease. The manufacturers’ claims of safety and efficacy, often

stated evasively, need more critical examination by both the target market and by health

agencies.[52] The claims of efficacy that accompany many herbal medicines are impressive but

the research substantiating them, regrettably, is not (Angell). An example of this is topical

13

creams that contain plant-derived methylxanthines (caffeine and theophylline) that purportedly

reduce “cellulite.”[53] Furthermore, the notion that natural products are inherently purer or safer

than manufactured products is false[54] and is aimed at a wishful but naïve and credulous

market. There are few assurances for the purity and consistent potency of the herbal medications,

hence innumerable episodes of toxicities from their use. Harm may arise from impurities

(contamination, intentional adulteration, and misidentification)[30,31,54-56] but most problems

are caused by the intrinsic pharmacological activity of the herbs.[57] Then again,

phytomedicines in the conventional pharmacopoeia have their hazards as well when consumed in

the wrong dose or manner. Digitalis can be toxic as can cocaine, opium, and virtually every plant

product. Pharmacologically-active plants (such as tobacco) and plant derivatives (such as

alcohol) are among the main threats to human health today. The Ames test shows us that

seemingly innocuous plants, even lettuce, have mutagenic properties.[58] Herbal preparations,

sold under the guise of a natural beneficence may not be as innocent as some would have us

believe.[57]

Many physicians, myself included, believe that there should not be two forms of

medicine, one conventional and one alternative.[52] Most of what is considered alternative

medicine has never been tested in a scientific rigorous and intellectually honest manner. If an

alternative technique or method or remedy can be shown safe and effective, it would then be

embraced as mainstream medicine. In the case of natural products, most practitioners with

biomedical training believe an important step is to extract and identify the pharmacologically

active ingredient (or ingredients) to better understand its actions and the insights it might offer

for disease pathophysiology, prevention, and treatment.

CONSERVATION, BIODIVERSITY, AND PRESERVATION OF INDIGENOUS

CULTURES

Many in the medical community believe it is incumbent on us for many reasons to take

an active role in conservation concerns.[2,59-61] are an estimated 10-20 million species of

plants, animals, and other organisms on earth.[62] Perhaps only one-tenth of these species,

however, have been identified and named. A much smaller fraction of these have been assessed

for economic utility, such as possible medical contributions. An alarming concern is that half of

all species may become extinct in the next half-century – possibly destroying any opportunity

that these will become economically useful. How then can we improve the chances of survival

14

for the remaining millions of species? Population biology and ecological principles show that our

pursuit should not be merely to save individual species but to save entire environments. An

appropriate metaphor is that organisms are threads in a delicate fabric of life; disruption of one

thread may cause the entire the entire fabric to unravel and sunder. One cannot simply preserve

fragments of an ecosystem; scattered bits of remnant habitats, such as small parks, are less able

to sustain species diversity and environmental complexity than are a smaller number of larger

preserves.[63] At first glance, this may appear to be commercially untenable but economic

analyses have shown that sustainable enterprises in preserved lands (vs. timber, mining, and the

ruinous effects of single-cycle tropical agriculture) can generate more revenue than intensive use

– and its consequent destruction – of habitats.[61] Consequently one should pursue the

preservation of entire environments, not to simply focus on selected economic or charismatic

species alone.

In those days Hezekiah was sick and near death . . . . Then Isaiah said, “Let them take a lump of

figs and apply it as a poultice on the boil, and he shall recover. Isaiah 38:21

15

REFERENCES

1. Schultes, R. E. The future of plants as sources of new biodynamic compounds, in Plants in the development of modern medicine, Swain T, Ed., Harvard University Press, Cambridge, 1972, 103-124.

2. King, S. R., Carlson, T. J., Moran, K., Biological diversity, indigenous knowledge, drug discovery and intellectual property rights: creating reciprocity and maintaining relationships. J Ethnopharmacol, 51, 45, 1996.

3. Balandrin, M. F., Klocke, J.A., Wurtele, E. S., Bollinger, W.H. Natural plant chemicals: sources of industrial and medicinal materials. Science, 228, 1154, 1985.

4. Marwick, C., Nature’s agents help heal humans – some now take steps to reciprocate. JAMA 279, 1679, 1998.

5. Eisenberg, D. M., Kessler, R. C., Foster, C., Norlock, F. E., Calkins, D.R., Delblanco, T. L., Unconventional medicine in the United States: prevalence, costs, and patterns of use. N Engl J Med, 328, 246, 1993.

6. Lipp, F. J., The efficacy, history, and politics of medicinal plants. Alternative Therapies, 2, 3641, 1996.

7. Cox, P. A., Balick, M. J., The ethnobotanical approach to drug discovery. Scientific Am, 1994, 82, 1994.

8. Davis, W., One river: explorations and discoveries in the Amazon rain forest. New York, Simon and Schuster, 1996.

9. Anonymous. Pharmaceuticals from plants: great potential, few funds. Lancet 343, 1513, 1994.

10. Mitchell, J., Rook, A., Botanical dermatology: plants and plant products injurious to the skin, Greengrass, Vancouver, 1979.

11. Benezra, C., Ducombs, G., Sell, Y., Foussereau J., Plant contact dermatitis, B. C. Decker, Toronto, 1985.

12. Lovell, C., Plants and the skin, Blackwell, London, 1993.

13. Mukhtar H., Agarwal R., J Investig Dermatol Symp Proc 1, 209, 1996.

14. Morris, K., Celebrating the vegetable kingdom, Lancet, 352, 660, 1998.

15. Norton, S. A., The useful plants of dermatology. V. Capsicum and capsaicin. J Am Acad Dermatol 39, 626, 1998.

16. Markovits, E., Gilhar, A., Capsaicin – an effective topical treatment in pain. Int J Dermatol 36, 401, 1997.

17. Norton, S. A. The useful plants of dermatology. I. Hydnocarpus and chaulmoogra. J Am Acad Dermatol 31, 683, 1994.

18. Miller, R. A., Podophyllin, Int J Dermatol 24, 491, 1985.

19. Helmbold, P., Hegemann, B., Holzhausen, H.-J., Klapperstuck (umlaut over u), T., Marsch, W. C., Low-dose oral etoposide monotherapy in adult Langerhans cell histiocytosis. Arch Dermatol, 134, 1275, 1998.

20. Norton, S. A., The useful plants of dermatology. III. Dioscorea, Strophanthus, and corticosteroids. J Am Acad Dermatol, 38, 256, 1998.

21. Wallace, D. J., The history of antimalarials. Lupus 5 (Suppl 1), S2, 1996.

22. Fitzpatrick, T. B., Pathak, M. A., Historical aspects of methoxsalen and other furocoumarins. J Invest Dermatol 32, 229, 1959.

16

23. Benedetto, A. V., The psoralens: an historical perspective. Cutis 20, 469, 1977.

24. Duke, J. A., Bishop’s weed (Ammi majus L., Apiaceae), Economic Botany, 42, 442, 1988.

25. Lewis, G. P., Legumes of Bahia. Royal Botanic Gardens, Kew, 1987, 215.

26. Ashton, R. E., Andre, P., Lowe, N. J., Whitefield, M., Anthralin: historical and current perspectives. J Am Acad Dermatol 9, 173, 1983.

27. Mackrides, P. S., Shaugnessy, A. F. Azelaic acid therapy for acne. Am Family Phys 54, 2457, 1996.

28. Atherton, D. J., Sheehan, M. P., Rustin, M.H.A., Whittle, B., Guy, G., Treatment of atopic eczema with traditional Chinese medicinal plants. Pediatr Dermatol 9, 373, 1992.

29. Koo J., Traditional Chinese medicine for psoriasis in the US? National Psoriasis Foundation Bull, 26(6), 4, 1995.

30. Horowitz, R. S., Feldhaus, K, Dart, R. C., Stermitz, F. R., Beck, J. J., The clinical spectrum of jin bu huan toxicity. Arch Intern Med, 156, 899, 903.

31. Ernst, E., Harmless herbs? A review of the recent literature. Am J Med, 104, 170, 1998.

32. Skolnick, A. A., China is eager to export its tradtional medicine, but some Chinese scientists urge more skepticism. JAMA 276, 1707, 1996.

33. Wolf, R., Ruocco, V., Nicotine for pyoderma gangrenosum. Arch Dermatol, 134, 1071, 1998.

34. Ross, E. V. Jr., Badame, A. J., Dale, S. E. Meat tenderizer in the acute treatment of imported fire ant stings. J Am Acad Dermatol 16, 1189, 1987.

35. Laidet, B., Letourner, M. [Enzymatic debridement of leg ulcers using papain.], Ann Dermatol Venereol, 120, 48, 1993.

36. Klein, A. D., Penneys, N. S. Aloe vera. J Am Acad Dermatol, 18, 714, 1988.

37. Fisher, A. A., Contact dermatitis, 3rd edition, Philadelphia, Lea and Febiger, 1986, p. 167.

38. Norton, S. A. The useful plants of dermatology. II. Haematoxylum and haematoxylin. J Am Acad Dermatol 34, 149, 1996.

39. Norton, S. A. The useful plants of dermatology. IV. Alizarin red and madder. J Am Acad Dermatol, 39, 484, 1998.

40. Leiner, I. E., Seed hemagglutinins. Economic Botany, 18, 27, 1964.

41. Chaplin, A. J., Tannic acid in histology: an historical perspective. Stain Technol 60, 219, 1985.

42. Ott, J. The Delphic bee: bees and toxic honeys as pointers to psychoactive and other medicinal plants. Economic Botany, 52, 260, 1998.

43. Draelos, Z. D., The use of biological additives in cosmetic products. I. Cosmetic Dermatol, 7(2), 16, 1994.

44. Zemstov, A., Gaddis, M., Montalvo-Lugo, V. M., Moisturizing and cosmetic properties of emu oil: a pilot double blind study. Austral J Dermatol 7, 159, 1996.

17

45. Pisha, E., Chai, H., Lee, I.S., Chagwedera, T. E., Farnsworth, N. R., Cordell, G. A., Beecher, C. W., Fong, H. H. Kinghorn, A. D., Brown, D. M., Discovery of betulinic acid as a selective inhibitor of human melanoma that functions by induction of apoptosis. Nature Med, 1, 1046, 1995.

46. Gonzalez ,S., Pathak, M.A., Cuevas, J., Villarrubia, V.G., Fitzpatrick, T.B., Topical or oral administration with an extract of Polypoidum leucotomos prevents acute sunburn and psoralen-induced phototoxic reactions as well as depletion of Langerhans cells in human skin. Photodermatol Photoimmunol Photomed, Lambert/Haertsch, 50, 1997.

47. O’Toole, J. E., Esseltine, D., Lynch, T. J., Lambert, J. M., Grossbard, M. L., Clinical trials with blocked ricin immunotosins. Curr Top Microbiol Immunol 234, 35, 1998.

48. Vlietinck, A. J., De Bruyne, T., Apers, S., Pieters, L. A., Plant-derived compounds for chemotherapy of human inmmunodeficiency virus (HIV) infection. Planta Medica 64, 97, 1998.

49. Wise, J., Plant based vaccines move a step closer. BMJ, 316, 1333, 1998.

50. Keller, K. L., Fenske, N. A., Uses of vitamins A, C, and E and related compounds in dermatology: a review. J Am Acad Dermatol 39, 611, 1998.

51. Mestel, R., Beautiful skin from A to E. Health 12(7), 72, 1998.

52. Angell, M., Kassirer, J. P., Alternative medicine: the risks of untested and unregulated remedies. N Engl J Med, 339, 839, 1998.

53. Dickinson, B. I., Gora-Harper, M. L., Aminophylline for cellulite removal. Ann Pharmacother, 30, 292, 1996.

54. Slifman, N. R., Obermeyer, W. R., Aloi, B. K., Musser, S. M., Correll, W. A. Jr., Cichowicz, S. M., Betz, J. M., Love, L. A., Contamination of botanical dietary supplements by Digitalis lanata. N Engl J Med, 339, 806, 1998.

55. Ko, R. J., Adulterants in Asian patent medicines. N Engl J Med 339, 847, 1998.

56. Drew, A. K., Myers, S. P., Safety issues in herbal medicine: implications for the health professions. Med J Austral, 166, 538, 1997.

57. Huxtable, R. J., The myth of beneficent nature: the risks of herbal preparations. Ann Intern Med, 117, 165, 1992.

58. Ames, B. N., Dietary carcinogens and anticarcinogens: oxygen radicals and degenerative diseases. Science, 221, 1256, 1983.

59. Plotkin, M. J., Conservation, ethnobotany, and the search for new jungle medicines: pharmacognosy comes of age … again. Pharmacotherapy, 8, 257, 1988

60. Bentz, G. D., Medicine’s stake in preserving the tropical rain forest. Southern Med J, 83, 491, 1990.

61. Fellows, L. What are the forests worth? Lancet, 339, 1330, 1992.

62. Anonymous. Biodiversity loss threatens new treatments. BMJ, 316, 1261, 1998.

63. Quammen, D., The song of the dodo: island biogeography in an age of extinctions. New York, Scribner, 1996.

18