Traditional Approaches to Wound Healing

GERARD C. BODEKER, EdD TERENCE J. RYAN, DM, FRCP CHI-KEONG ONG, PhD

n Vietnam, where the cost and availability of modern medical care have ensured that the less expensive traditional remedies also continue to be widely used, there is an expression that traditional (i.e., indigenous) medicine costs the equivalent of a chicken. Modern medicine costs one cow. And hospitalization costs the family its herd of cows. The economic reality of each is evident. Traditional medicine, used widely by rural communities in most developing countries, serves as a mainstay for everyday health care for the majority of the worlds population. The World Health Organization (WHO) estimates that between 60 80% of the population in most developing countries rely on traditional medicine for their everyday health care. Despite this fact, official interest in traditional medical practices has been low, and WHO has cut its own support of the topic.1 Cost is a major factor throughout the world in the continued, widespread use of traditional health systems. Familiarity is another. When explanations for disease and methods of treatment are culturally familiar, they may persist even with the availability of modern medicine. In many countries, villagers will adopt a pluralistic approach to health care, using modern medicine to treat symptoms and traditional medicine to address what they perceive to be the underlying causes of a condition. In rural areas of developing countries, wounds and dermatological conditions constitute one of the five most common reason for people seeking medical care.2 Rural people sustain injuries working in the fields; burns from cooking and sleeping near fires; leg ulcers resulting from untreated wounds, diabetes, and leprosy; injuries incurred in conflicts; and, increasingly, injuries resulting from traffic accidents. While there is emerging recognition of the clinical potential for traditional treatments to be harnessed in the case of wounds
From the Global Initiative For Traditional Systems of Health, Green College, Oxford University, Oxford, United Kingdom. Address correspondence to Dr. G.C. Bodeker, Oxford University, Institute of Health Sciences, Health Services Research Unit, Oxford, OX2 6HG, UK. 1999 by Elsevier Science Inc. All rights reserved. 655 Avenue of the Americas, New York, NY 10010

and dermatological conditions, there has been a significant lack of research and clinical and policy interest in this field. There are three main reasons for this neglect. First, wounds are not included in the WHOs priority disease areas, even though delayed healing of wounds and chronic inflammation is a feature of diseases such as leprosy, syphilis, AIDS, leishmaniasis, and filariasis. With the exception of those wounds associated with sexually transmitted diseases, most wounds fall outside the WHO definition of infectious diseases. However, such common conditions as burns, injuries, and tropical ulcers are the basis for much of the day-to-day need for care in most developing countries. Second, traditional health systems, where considered at all, are viewed by most medical authorities as being best suited for use with chronic, low-level conditions rather than in acute conditions. This view persists despite the fact that traditional approaches have served as a principle source of care in the treatment of trauma in such countries as Vietnam.3 Third, injuries and chronic wounds tend to be treated locally. For example, the most effective use of traditional herbal medicines in primary health care in Thailand was found to be in their role in self-medication. Herbal medicines offer a low-cost intervention in the early treatment of disease and the care of wounds.4 In a clinic in northern Madagascar, where herbalists and medical doctors work side by side, because of the shortage of drugs and the efficacy of local herbal treatments, the third most common reason for people seeking care (after malaria and gastrointestinal disorders) is for treatment for skin conditions and wounds. Traditional wound treatments are used in four out of five cases, and wound healing appears to be faster in those using traditional medicines than in those using modern wound treatments.5 As is clear from the following section, much of the research into traditional medicine has been pharmacological or experimental. Very little direct clinical or observational research has been done, particularly into the large number of wound-healing treatments used by traditional societies. While biomedical research has as a cornerstone the identification of a single active principle in a plant or complex mixture, this is viewed by tradi0738-081X/99/$see front matter PII S0738-081X(98)00056-X

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tional practitioners as a reductionistic approach that misses the synergism or interactive effects of the multiple ingredients in a complex mixture. There is a need for the development of research methodologies that will give traditional methodologies a chance to validate their pharmacological principles rather than to recast these in the light of a reductionistic explanatory model. The fact that so much of the research in industrialized country laboratories is aimed at this single cause has meant that the complexity of the influences on disease hidden in the hosts response to a noxious agent is given far less weight. The role of peoples beliefs as to causation and the fact that such beliefs can influence healing is also the object of little research. Drug availability (i.e., how effective remedies are made available to those who need them) is given too little attention. In this context, it is reasonable to ask of what use is a magic bullet if it can only be afforded by and delivered to an elite few?

Summary of Research
Research into traditional wound-healing remedies fall into several categories: (1) herbal remedies; (2) the use of animal/insect products as wound-healing agents; and (3) the use of organisms to effect wound debridement through biosurgery.

Herbal Wound-Healing Remedies

Wound care has existed almost certainly as long as Homo sapiens have existed. Many treatments discovered by early civilizations were based on the use of local plants. Thus, the largest class of research conducted to date is on herbal remedies used by different cultures worldwide. Many types of plant remedies are used and are available. In South America, dragons blood is a traditional remedy used for wound healing. This is a blood red, viscous latex which is extracted from various Croton spp. (Euphorbiaceae) by slashing the bark.6 In North America, the spineless prickly pear Opuntia ficus-indica is used to treat wounds. Local communities split open the mucilaginous joints of the plant and either heat the plant and exudate in an oven, or soak it in water and apply the preparation as a poultice on wounds.7 Experiments have shown that dragons blood stimulated contraction of wounds, crust formation, formation of new collagen, and epithelial regeneration. Proanthocyanidins were found in dragons blood and were shown to be responsible for wound contracture and protein precipitation, which is part of the process of crusting.6 In the West Indies, in Jamaica for example, the herbaceous plant Justica pectoralis (Acanthaceae family) is used in folk medicine to treat cuts and wounds. The leaves are bruised, alone or with rum, and applied as a plaster.8,9

Preliminary investigations showed that coumarin was a major component of an acetone extract of this plant. Fresh wounds created on Wistar rats and treated with the extracted coumarin showed attenuated inflammation processes and significantly enhanced healing of wounds compared with controls.8 Europe also has a tradition of using herbal remedies to treat wounds. In Bulgaria, the bark of Fraxinus ornus L. (Oleaceae) is used in folk medicine for wound healing.10 Aloe vera (Aloe barbadensis Miller), has been commonly used not only in Europe but in many other countries worldwide to treat wounds and skin conditions. Its beneficial effects have been demonstrated in in vitro and in vivo studies.11,12 The bark of Fraxinus ornus L. was found to possess hyrdoxycoumarins. The presence of these compounds inhibited Staphylococus aureus and Escherichia coli growth. This explains to some extent its application as a wound-healing agent, since it is of paramount importance to control wound and skin infections by bacteria such as S. aureus, Pseudomonas aeruginosa, and E. coli if successful wound healing is to occur.10 Extracts from Aloe barbadensis (Aloe vera) has been found to penetrate tissue, have anaesthetic properties, have antibacterial, antifungal and antiviral properties, serve as an antiinflammatory agent, and dilate capillaries to increase blood flow.13,14 In vivo analysis of burn injuries show that the mediator of progressive tissue damage was thromboxane A2. Aloe extracts have been shown to be not only a thromboxane A2 inhibitor but was also shown to maintain homeostasis within the vascular endothelium as well as in surrounding tissue.11 Asian traditional medical systems and pharmacopeia are highly developed and many plant remedies for the treatment of wounds can be found in traditional Chinese medicine and in the Ayurvedic tradition of India. In China, a herb that is found in the mountain area of southwest China, known as Lao Xongboa (Rubus pinfaensis Levl. et Vant (Rosaceae)) is used. Aqueous extracts of the herb are employed locally to treat burn wounds.15 In Vietnam, the plant known locally as co hoi (Chromolaena odorata) is used to treat soft tissue and burn wounds. Both aqueous extracts and decoction for the leaves are used for these purposes.16 Phan et al. examined the wound-healing properties of Eupolin, a topical agent produced from the leaves of Chromolaena odorata. Eupolin was found to enhance hemostasis, stimulate granulation tissue and re-epithelialization, and inhibit collagen contraction. These results suggest a mechanism for clinical reports on the effectiveness of Eupolin in reducing wound contraction and scarring, which are critical complications in post-burn trauma. Eupolin was also found to have important antibacterial properties.17 The Le Huu Trac National Institute for Burns in Hanoi uses traditional medicines for treatment of

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burns. For example, the latex of green papaya contains papain, a proteolytic enzyme. A solution of 210% papain is used for the dressing or continuous moistening of burns and the plant Coscinium usitatum Pierre, Menispermaceae is used to inhibit the growth of S. aureus and Streptococcus proteus.18 Another plant that is widely used in Vietnam, is Cudrania cochinchinensis (Moraceae), where aqueous extracts of fresh leaves are applied to wounds. A research group examined the effect on fibroblast proliferation and the protection of both fibroblast and endothelial cells against oxidative damage by Cudrania cochinchinensis, in an effort to discern the wound-healing mechanisms of this plant.19 Ethyl acetate extracts of this plant were found to protect fibroblasts and endothelial cells against hydrogen peroxide-induced damage. These results suggest that stimulation of fibroblast proliferation and protection of cells against destruction by mediators of inflammatory processes may be ways in which the polyphenolic substances from this plant contribute to wound healing. In India, oil from Azadirachta indica (H-Neem) has been used to treat wounds.20 Work on Rubus pinfaensis Levl. et Vant, showed that the combined activities of ursolic, gallic, and 19a-hydroxyasiatic acids found in the plant against S. aureus and P. aeruginosa probably play a role in its wound-healing properties.15 The question of toxicity is important, when evaluating any wound-healing remedy. Oil from Azadirachta indica was found to be a non-irritant to the skin of rabbits.20 Its lack of subdermal toxicity indicates that it should be safe for external applications on wounds. Finally, the African continent has its own tradition of herbal wound remedies. In Nigeria, for example, young fresh leaves of Spondias mombin and Alchornea cordifolia are shredded into cold water to extract the juice and the cooled solution is used to clean and treat cuts and burns.21 The widely distributed and abundant shrub Aspilia pluriseta is used extensively in Kenya.22 The antibacterial properties of these plants have been well investigated. Aqueous and ethanolic extracts of the leaves from S. mombin and A. cordifolia were found to inhibit the growth of some gram-positive and gramnegative bacteria. In general, ethnolic extracts were found to be more efficacious than aqueous extracts in their level of activity. Once again, it was found that important skin and wound infecting bacteria such as P. aeruginosa, S. aureus, and E. coli were susceptible to aqueous and ethanolic extracts of A. cordifolia. Interestingly, these extracts were active against streptomycin resistant strains of these three types of bacteria.21 Antibacterial properties were also found for the Kenyan plant A. pluriseta. Crude methanol extracts of the plant were shown to have inhibitory activity against E. coli and S. aureus. Three kauranoid acids were isolated that

appear to be the main factors responsible for antibacterial activity.22

Animal Products in Wound Treatment

For 4000 years, the therapeutic properties of honey have been utilized for wound healing.23 The wound-healing properties of honey include antimicrobial activity, ability to absorb edema, the promotion of granulation tissue formation among other functions.23,24,25 These properties were exploited by the ancient Egyptians. Communities in East Africa, including the Maasai, reportedly use honey and other by-products as a traditional wound-healing salve.26 The antibacterial activity of honey is due to hydrogen peroxide, which is an end-product of the enzymatic reaction of glucose oxidase from the bee with the glucose present in honey.24 Qualities which are critical in the capacity of honey to preserve skin grafts27,28 are shared with glycerol. At Mahidol University in Thailand, chronic wounds of 13 patients treated with honey were completely healed in 7 to 38 days. The total micro-organism load of these patients decreased by at least 25% in that time.29 Interestingly, it appears that both the topical use and ingestion of honey will promote wound healing.30 In this study, experimental rats with induced wounds received both oral and topically applied honey. In another set of animal studies, artificially induced wounds in buffaloes were infected with S. aureus and either honey, ampicillin, or an ampicillin-honey mixture was applied to the infected wounds. Effect was greatest with the honey-treated wounds, as measured by the maximal increase in collagen and hydroxyproline content and maximal decrease in hexosamine (amino sugar utilized by granulating tissue) content.31 Frog skin is another animal product that has been used to treat wounds traditionally. Tribal medicine in Nagaland and other forms of Indian medicine use these skins to cover wounds.32 The amphibian skin is known to possess antimicrobial properties.33,34 In Vietnam, the lack of adequate medical supplies to treat napalm burns as a result of the Vietnam war, lead burns surgeons to investigate traditional Vietnamese remedies for burns. They have since successfully reintroduced the use of amphibian skins as temporary grafts for patients with severe skin loss as a result of burns.18 Dressing of experimentally wounded Wistar rats with frog skin, as opposed to controls dressed with cotton gauze showed that healing was faster with the group treated with the frog skins. Biochemical estimations of wound granulation, carried out every two days, until complete healing was achieved, showed that the frog-skin-treated group produced higher levels of hydroxyproline (hence collagen) than the controls.32

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Biosurgery: The Use of Whole Organisms to Treat Wounds

Fly larvae have been deliberately introduced into wounds to promote healing by the Chinese in Yunan, the hill people of Burma, Aborigines in Australia, and the Mayans in Central America.35 Military surgeons, during World War I, reported infestations of wounds by the larvae of certain flies, with apparently promising results.36 Experiences during World War I led surgeons to explore the possibilities of using maggots in wounds. In the late 1920s such larvae were used in hospital medicine, mostly in chronic deep wounds with infections. With the advent of antibiotics and modern medicine, larvae-based methods fell into disfavor but are now undergoing renewal.36 38 Clinical trials and laboratory studies are presently being conducted on the biochemical and clinical properties of maggots for use in the debridement of wounds. Important early observations include the fact that as maggots are photophobic, they achieve good penetration of wound tissue and succeed in burrowing under overhanging wound edges to digest the necrotic tissue found there. Such tissue is normally difficult to remove by conventional surgery. Furthermore, as maggots favor decomposing organic matter as a food source, they tend to devour such material, including any harmful pathogens that may be contained in it.36

Discussion
Since antiquity, mankind has reached into the nearby environment for the means to treat the wounds and topical infections that result from the vicissitudes of everyday living. There is a body of promising research showing the wound-healing properties of a range of different plants, plant mixtures and extracts, animal products, and of whole organisms themselves in the treatment of wounds. What is the point of this information? Ethnobotanists Balick and Cox,39 in an analysis of the diverse uses of plants in traditional societies, point out that approximately one-third of traditional medicines are for skin conditions and wounds, reflecting the widespread call for these remedies (as noted earlier in [2]). At the same time, Balick and Cox point out that a mere 13% of modern drugs are developed to address these conditions. Many of these are antibiotics and steroids, whose cost in industrial countries is high and, in non-industrial countries, is often prohibitive. Clearly, there is much potential to address the common conditions of rural and urban communities in countries which are relatively rich in natural resources and relatively poor in terms of available health care resources, both economic and clinical. The 1990 Arusha Declaration calls for a South-South

cooperation on medicinal plants.40 This would give priority to the optimal utilization of these plants in a standardized form by the people of the developing countries.40 There is also a call for South-South exchange on medicinal plant research methodology, herbal medicine production technology, medicinal plant conservation strategies, and horticulture for commercial production of medicinal plants. Equally important is the strong call for adequate intellectual property rights frameworks designed to protect community, national, and regional knowledge on the use of medicinal plants. A consideration in light of the worlds expanding use of medicinal plants and the increasing loss of medicinal plant biodiversity, is that if supply is to be guaranteed, the raw materials of herbal medicines must be harvested in a sustainable manner and/or cultivated commercially.41 Any endeavor to promote and develop the use of traditional remedies in wound care will naturally require a research infrastructure. At present, biomedicine dominates the medical research budget of all countries, despite the widespread use of traditional medicine by the public. A first step toward comprehensive development of this sector would be the reallocation of research and training budgets to incorporate traditional medicine into their agendas. In this context, it is important to note that there are methodological sensitivities which should be acknowledged in the application of biomedical methodologies to the study of traditional therapies and systems. For example, while biomedical research has as a cornerstone the identification of a single active principle in a plant or complex mixture, this is viewed by traditional practitioners as a reductionistic approach that misses the synergism or interactive effects of the multiple ingredients in a complex mixture.42 Poly-pharmacy is the goal of traditional therapies. There is a need for the application or refinement of research methodologies in a manner which will give traditional health systems the opportunity to validate their own pharmacological principles rather than to recast these in the light of a reductionistic explanatory model. Some basic questions which must be considered in any research strategy designed to evaluate traditional medicines include: Y For whom and for what purpose are the results intended? Y Is research serving the interests of the scientist, the pharmaceutical industry, or the local health system? Y Will the research contribute to increased understanding and a strengthened role for the traditional health systems used by the majority of the worlds population for their basic health care? Y Are the intellectual property rights of the customary

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knowledge holders being respected, legally protected, and compensated appropriately? The need is substantial. From the research considered in this article, it is clear that the potential is great. Commitment from the medical, research, and funding communities is now necessary to place this field on the footing warranted by the plebiscite that exists by virtue of its widespread and enduring utilization and the clear indication of its promise.

17.

18. 19.

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