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Journal of Ethnopharmacology 107 (2006) 134–142

Survey of medical ethnobotanicals for dental and oral medicineconditions and pathologies

Michael D. Colvard a,∗, Geoffrey A. Cordell a,b, Rodrigo Villalobos c, Gina Sancho c,Doel D. Soejarto b,d, William Pestle e, Tatiana Lobo Echeverri f,

Kathleen M. Perkowitz g, Joanna Michel b

a Department of Oral Medicine and Diagnostic Sciences, College of Dentistry, University of Illinois at Chicago,801 South Paulina, Chicago, IL 60612, United States

b Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago,833 Wood Street, Chicago, IL 60612, United States

c Facultad de Odontologıa, Universidad Latina de Costa Rica, San Pedro Montes de Oca, Costa Ricad Department of Botany, Field Museum of Natural History, Chicago, IL 60605, United States

e Department of Anthropology, Field Museum of Natural History, Chicago, IL 60605, United Statesf Escuela de Quimica, Universidad Nacional de Colombia, Medellın, Colombia

g Dewitt & Parke Holland Horticulture Fellow, Chicago Botanical Garden, 1000 Lake Cook Road, Glencoe, IL 60022, United States

Received 28 November 2005; received in revised form 18 March 2006; accepted 3 April 2006Available online 18 April 2006

Abstract

Ethnomedical questionnaires were distributed in Chicago, Costa Rica, and Colombia to identify the most common over-the-counter (OTC) plantor plant-based products advocated for treating oral pain, ulcerative conditions, and cancer within these locations. Over 100 plants or plant-basedherbal preparations and commercial products, purchased from local botanical markets and pharmacies, were advocated for the treatment of oralmedicine conditions. Locally familiar and common language names were attributed to the plant products at the time of purchase. Plant products orplant-based commercial products containing plant-based essential oils, anesthetic constituents, and or chemical compounds recommended as OTCoral medicine preparations were systematized, tabulated, and correlated with the published phytotherapeutic literature. Though pharmacognosticresearch is available for some of the species collected, further ethnographic research is needed to correlate common names with the accuratetaxonomic identification for each plant species. Furthermore, epidemiological research is needed to verify the use and standardized dosage for OTCethnomedicine preparations for oral medicine conditions. Pharmacognostic research and clinical trails which can verify taxonomy, dose, safety,active principles, and efficacy of these OTC oral medicine products must be enhanced in order to verify the claimed validity in contemporary,global, oral medicine practice.© 2006 Elsevier Ireland Ltd. All rights reserved.

Keywords: Dentistry; Oral medicine; Analgesia; Ethnopharmacology; Ethnomedicine; Public health; Piperaceae; Anisillo

1. Introduction

Humans, for millennia, have placed various plants and plant-based products into the oral cavity as a way to deliver chem-ical compounds for various stimulant, medicinal, and hallu-cinogenic effects. Archeological (Harshberger, 1896; Soleckiand Shanidar, 1975; Dimbleby, 1978; Minnis, 2000), anthropo-

∗ Corresponding author. Tel.: +1 312 996 7480; fax: +1 312 355 2688.E-mail address: colvard@uic.edu (M.D. Colvard).

logical (Rivers, 1924; Caudill, 1953; McElroy and Townsend,1989; Johnson and Sargent, 1990; Wiley and Hofman, 1994;Pelto and Pelto, 1997; Sullivan and Hagen, 2002; Oxenhamet al., 2002), and contemporary pharmacognostic research(Schultes, 1977; Cordell, 1981; Callejas, 1986; Cordell, 2000;Jaramillo and Manos, 2001; Newman et al., 2003; Colvard et al.,2006), continue to reveal the human dependence on the naturalworld for sources of plant and animal based medicinal com-pounds (Fabricant and Farnsworth, 2001; Cordell and Colvard,2005.). The co-dependency between humans and the botanicalworld continues to promulgate scientific inquiry into: (1) foster

0378-8741/$ – see front matter © 2006 Elsevier Ireland Ltd. All rights reserved.doi:10.1016/j.jep.2006.04.005

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M.D. Colvard et al. / Journal of Ethnopharmacology 107 (2006) 134–142 135

increased conservation of planetary biomes (Pennington et al.,2004,) and bio-diversity protection efforts (Cordell, 2000, 2002,2003; Hamilton, 2003; Cordell, 2004; Cordell and Colvard,2005; Soejarto, 2005); (2) increase the planetary ecological sta-bility (Millennium Ecosystem Assessment, 2005); (3) definecooperative benefits sharing between entities to protect naturalresources from bio-piracy (Soejarto et al., 2005); (4) strengthenan ethnomedicine theory which attempts to elucidate a coherent,integrated, and safe ethnomedical public health policy (Bodekerand Kronenberg, 2002; Northridge and Mack, 2002; Cordelland Colvard, 2005); and (5) advocate for a scientifically effi-cacious clinical ethnomedicine practice (Eisenberg et al., 1998;Eskinazi, 1998a, 1998b; Eskinazi and Muehsam, 2000; Little,2004). Sustainable ethnomedicine, for the global community, isperceived as one approach to protect the planetary biodiversity,and subsequently, the global health of the animal and humanpopulations (Cordell and Colvard, 2005).

Extensive ethnomedical, ethnopharmacological, and epi-demiological research clearly indicate the continued global med-ical norm of traditional medicine (Anonymous, 2002; Bodekerand Kronenberg, 2002; Northridge and Mack, 2002; Hamilton,2003; Millennium Ecosystem Assessment, 2005). Traditionalmedicine or TM (defined as indigenous health care systems),and complementary and alternative medicine or CAM (definedas healing systems outside mainstream bio-science dependentmedical systems), or TM/CAM care, remain global standards ofmedical and dental care, particularly in less developed countries(Anonymous, 2002; Anonymous, 2003; Hamilton, 2003).

The majority of world’s nations and populations obtain andderive the vast preponderance of therapeutic chemical com-pounds used as primary care medicines from plants and or plantderivatives (Iraskin et al., 2002; Anonymous, 2002; Anonymous,2003; Millennium Ecosystem Assessment, 2005). Epidemio-logical research reveals that as much as 70–80% or more ofthe global population uses TM/CAM care, with the majorityreliant on herbs and plants (Anonymous, 2002; Anonymous,2003; Hamilton, 2003). This trend is likely to increase as globalpopulations increase in various countries.

Even within affluent communities, and those mid-economiclevel communities who have access to clinical trial-basedmedicine or dental care, TM/CAM comprises almost 50% ofall health care, with the majority being, herbal-based care(Hamilton, 2003; Millennium Ecosystem Assessment, 2005).This global reliance on plants extends to the pharmaceuticalindustry. Grifo and Rosenthal (1997) report that within thepharmaceutical product armamentarium, 57% of the top 150proprietary drugs used in the USA as prescription medicines arederived from plants or plant based compounds.

Fabricant and Farnsworth (2001), Cordell et al. (2001), andNewman et al. (2003) provide excellent systematic and tax-onomical inventories of the current medicinal plant speciesused globally as primary sources of pharmaceutical compounds.Numerous leading ethnopharmacological researchers have com-piled taxonomic lists and catalogs elucidating active biologicalmolecules and healing compounds within plants (Newman et al.,2003). The efficacy of TM/CAM ethnobotanical information toproduce medical and dental remedies has led many academic and

corporate researchers to discover new compounds (from plantsand plant products) that have led to new pharmaceuticals. Thus,ethnomedicine plants, in history, and in modern day science,continue to provide clear public health benefits (Iraskin et al.,2002; Bodeker and Kronenberg, 2002; Northridge and Mack,2002; Hamilton, 2003; Millennium Ecosystem Assessment,2005; Cordell and Colvard, 2005); retain truly significant sci-entific value (Fabricant and Farnsworth, 2001; Newman etal., 2003), and consequently warrant further significant globalresearch efforts to determine safety and efficacy.

2. Dentistry and oral medicine ethnobotanicals

No baseline catalog describing the plants used for the eth-nomedical treatments of oral medicine diseases and conditionsexists. There is a significant paucity of published researchdescribing the ethnography, ethnomedicine, ethnopharmacol-ogy, and evidence-based clinical applications of plant-basedmedicines used specifically for dentistry, oral pains, and oral dis-eases. Most publications describe anecdotal dental therapeuticapplications of the current medicinal uses of plants. These papersrecapitulate various descriptive dental therapies attributed toclassical herbs (Yatsu, 1985; Boisyvon, 1986; Jacobsen andCohan, 1998; Ocasio et al., 1999). Other dental papers reviewthe medical effects of various plant drug–synthetic drug interac-tions (Karimi, 1999; Fugh-Berman, 2000; Elvin-Lewis, 2001).The availability of readily accessible, pharmaceutically activeherbal remedies, along with concerns for botanical sourced andsynthetic sourced drug interactions and safety, has led manyresearchers to report synergistic interactions (Fugh-Berman,2000). More commonly, reference books describe the possi-ble medical applications and dental implications of botanicals(Johnson, 1999; Peirce, 1999; Blumenthal et al., 2000; Fosterand Duke, 2000; Roth and Lindorf, 2002; Gage and Pickett,2005).

Only a few papers document the role of plants used tradi-tionally in dentistry, oral medicine, and/or in the treatment andcure of oral and maxillofacial conditions and/or pain (Ogura etal., 1982; Makapugay et al., 1983; Wiley and Hofman, 1994;Wynbrandt, 1998; Eversole et al., 2000; Casagrande, 2000;Padilla et al., 2000; Oxenham et al., 2002; McFerren et al., 2002;Martin-Duce, 2002; Meyers et al., 2002). Ethnopharmacologyresearchers have detailed the specific effects that many plantshave as non-cariogenic sweeteners (Kinghorn et al., 1998). Someoral medicine researchers have reported in vivo clinical patholo-gies associated with botanical products (Eversole et al., 2000).Alonge et al. (2003) and Colvard et al. (2006) have appliedelectron microscopic histopathology techniques to determinethe safety of chewed botanicals used as sources of stimulantsand or as oral medicines.

One facet that limits the acceptance and publication of eth-nomedical and ethnopharmacology papers for oral medicine isthe lack of proper recording of the ethnographic componentwithin oral medicine, as defined by Soejarto (2005). A secondsignificant drawback is the lack of clinical documentation of theethnomedical treatments for the oral pathologies experienced bypeople in their actual cultural and eco-political settings. Elkin

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and Elisabetsky (2005) clearly indicate the necessity for properdocumentation within actual cultural and eco-political settings.To the knowledge of the authors of this paper, only a few papersexist which follow, ethnographic, ethnomedical, ethnopharma-cological, and/or pathological analysis of botanical medicinesas they relate specifically to dental and oral medicine conditions(Wiley and Hofman, 1994; Pelto and Pelto, 1997; Eversole et al.,2000; Casagrande, 2000; Sullivan and Hagen, 2002; Oxenhamet al., 2002; Alonge et al., 2003; Colvard et al., 2006).

Since no baseline ethnomedical data exists describing plantsor plant-based products used empirically as oral medicines,this paper details an initial ethnographic, ethnomedical, andethnopharmacological sampling effort to identify, catalog, andtabulate the most common over-the-counter (OTC) plant reme-dies advocated by rural farmers, botanical healers from selected‘common markets’, and staff at local Farmacia’s as treatmentsfor oral pain and ulcerative oral medicine conditions in North,Central, and South America.

3. Methods and materials

Following guidelines detailed by Soejarto (Soejarto andFarnsworth, 1989; Soejarto et al., 2004; Soejarto et al., 2005;Soejarto, 2005), a 5-year cooperative intellectual property andbenefit sharing Memorandum of Agreement (MOA), was signedbetween the University of Illinois at Chicago (UIC), Chicago,IL, and Universidad Latina de Costa Rica (ULATINA), SanPedro Montes de Oca, Costa Rica; which follows the bio-prospecting guidelines defined by the Intellectual PropertiesOffice, Office of the Vice Chancellor for Research (OVCR),University of Illinois at Chicago and the Rector’s Office ofULATINA. This MOA follows United Nations Convention onBiological Diversity guidelines (Soejarto et al., 2005). Further-more, the University of Illinois at Chicago (UIC), InstitutionalReview Board (IRB) protocol number 2005-0193, held by oneof us (Colvard) follows principles defined by Soejarto (2005) forfield ethnographic survey research for ethnopharmacology. ThisIRB approval reflects mutually negotiated ethical guidelinesaccepted by the Ethical Review Committee of the UniversidadLatina de Costa Rica (ULATINA) and details the collaborativeefforts of the authors of the faculty’s of the UIC College of Den-tistry and the Universidad Latina de Costa Rica (ULATINA),College of Odontologia. The IRB guidelines for this researchallow for ethnographic surveys and the collection and samplingof ethnomedical plants used to treat oral medicine conditions,as advocated by the rural peoples, botanical healers, and oralhealth professionals within Costa Rica. This clinical surveyof TM/CAM used in Central and South America to treat oralmedicine conditions is listed with the United States NationalInstitutes of Health (NIH) Clinical Trials registry service at:(http://www.clinicaltrials.gov/ct/show/NCT00200837).

Collaboration with the farming brothers Kilo and Mario San-doval, Route #32, Provincia de Limon, Costa Rica, was criticalfor collecting fresh plant material for common name verificationand for comparative studies with herbarium voucher specimens.The common or typical (“tico”) usage name of all the plantentities collected within Costa Rica were compared and corre-

lated to phytochemical and ethnobotanical databases from theUnited States Department of Agriculture (USDA), AgriculturalResearch Service (ARS), and the Germplasm Resource Infor-mation Network (GRIN), as well as the Tico EthnobotanicalDictionary, maintained by Dr. James Duke (http://www.ars-grin.gov/duke/dictionary/tico/a.html).

Plant entities were identified and systematized at the taxo-nomic level of family, and, where possible, genus. Plants weresystematized, tabulated, and correlated to the reported heal-ing actions for each plant product. Selected plant specimensthat were collected in the field, are held, in a dried state, ina secure location at ULATINA; awaiting further processing asvoucher specimens for the Herbarium Nacional in San Jose andThe Field Museum of Natural History Herbarium in Chicago.These plants and/or photographs of plants were cross referencedwith voucher specimens held at the Herbario of the MuseumNacional de Costa Rica, San Jose, Costa Rica; the Herbarioat the Universidad de Antioquia, in Medellin, Colombia, andThe Field Museum of Natural History, Chicago, IL. Photo-graphic records of all the plants claimed and collected as treat-ments of oral medicine conditions are held by the appropriateauthors.

The most common, (OTC) botanical-based oral medicinepreparations advocated for inflammations, ulcers, oral pain andanxiety were purchased from local herbal markets, health foodstores, and selected pharmaceutical chains in San Jose, CostaRica, Medellin, Colombia, and Chicago, Illinois.

Claimed analgesic, anti-inflammatory, or anti-anxiety activ-ity was corroborated (or not) with documented phytotherapeuticcompound identification and bioactivity for each plant product.Data were recorded in tabular format and cross-referenced withcontemporary, peer-reviewed pharmaceutical literature sources,found in such databases as the University of Illinois at Chicago,College of Pharmacy, Natural Products Alert Database(http://www.uic.edu/pharmacy/depts/pmch/napralert), andthe Food and Drug Administration (FDA) “Med Watch”(http://www.fda.gov/medwatch) database.

Constituent essential oils, flavoring compounds, anestheticconstituents, and chemical compounds were identified, sur-veyed, systematized, tabulated, and correlated to the reportedhealing actions. Biological and clinical claims for compoundswere also cross-matched and correlated to standard references(Blumenthal et al., 1998; Blumenthal et al., 2000; Dionne et al.,2001; Dewick, 2002; Krinsky et al., 2003; Dyer et al., 2004;Schulz et al., 2004; Gage and Pickett, 2005; Wynn et al., 2005),which could describe bioactive secondary metabolites with doc-umented clinical activity.

4. Results

Specific plants used for analgesia/anesthesia (Table 1),inflammations (Table 2), and anxiety (Table 3) were corre-lated to their common names, botanical family, and wherepossible, botanical genus and species. Each plant productwas cross referenced with published literature which describesknown constituent essential oils, flavoring compounds, anes-thetic constituents, and biologically active chemical compounds.

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Table 1Plants with claimed analgesic/anesthetic activity for oral medicine

Comman name Plant species Family Claimed therapy Metabolites ULATINA samples

Anestesia Ottonia frutescens Piperaceae Pain, inflammation Piperovatine YesAnicillo Piper species Piperaceae Pain, inflammation Piper alkaloids YesAnisillo Piper species Piperaceae Pain, inflammation Piper alkaloids YesArnica Arnica montana Asteraceae Pain, inflammation Helenalin YesBetle Piper betle Piperaceae Pain Alkaloids YesCapsicum Capsicum annuum Solanaceae Pain Capsiacinoids YesChilcuague Heliopsis longipes Asteraceae Pain, inflammation Affinin YesChile Picante Capsicum annuum Solanaceae Pain, inflammation Capsiacinoids YesChilmecatl Heliopsis longipes Asteraceae Pain, inflammation Affinin YesChinchillia (Anicillo) Tagetes minuta Asteraceae Pain, inflammation Flavonoids YesClove Eugenia caryophyllus Myrtaceae Pain, inflammation EugenolsCoca Erythroxylum coca Erythroxylaceae Pain Cocaine alkaloidsCoca Erythroxylum novagranatense Erythroxylaceae Pain Cocaine alkaloidsCordinsillo Piper species Piperaceae Pain Alkaloids YesDormilona Mimosa pudica Fabaceae Pain Linoleic acid YesFeverview Tanacetum parthenium Asteraceae Pain ParthenolideGinger Zingiber officinale Zingiberaceae Pain, inflammation ZingibereneMarijuana Cannabis sativa Cannabaceae Pain, anxiety CannabinoidsMeadowsweet Filipendula ulmaria Rosaceae Pain, inflammations Salicylic acidMenthol Mentha piperata Lamiaceae Pain, itching, anxiety MentholMyrrh Commiphora myrrha Burseraceae Pain, itching, anxiety FuranosesquiterpenesPeppermint Mentha piperita Lamiaceae Pain, itching, anxiety MentholPoppy Papaver somniferum Papaveraceae Pain Morphine alkaloidsPrickly Ash Zanthoxylum clavaherculis Rutaceae Pain, sialogogue Nitidine alkaloidsRed pepper Capsicum annuum Solanaceae Pain Capsiacinoids YesReine de la Noche Datura arborea Solanaceae Pain Tropane alkaloids YesRhubarb (Chinese) Rheum palmatum Polygonaceae Pain, inflammations Anthracenes, tanninsSalvia Salvia divinorum Lamiaceae Pain, anxiety Salvinorin ASaragundi Cassia alata Fabaceae Pain, inflammations AnthraguinonesSauquillo (Anisillo) Hedyosmum bonplandianum Chloranthaceae Pain Kaempferol, alkaloidsTobacco Nicotiana tabacum Solanaceae Pain, stimulant Nicotine alkaloids YesWillow bark Salix alba Salicaceae Pain and inflammations Salicin, salicylic acidWintergreen Gaultheria procumbens Ericaceae Pain, anxiety Methyl salicylate

Plant-based commercial products were identified (Table 4) andinclude country of origin, manufacturer, and claimed content list(Table 4).

5. Discussion

Botanical-based medicines, with their structurally and con-formationally diverse molecular constituents, have been uti-lized by human cultures for millennia (Lloyd and Lloyd, 1911;Goodman, 1994; Schultes, 1977; Wynbrandt, 1998; Sullivanand Hagen, 2002). Research suggests that the ability of ani-mal and human species to utilize botanically-sourced, bioactivecompounds and secondary metabolites to ameliorate medicalconditions may reflect co-evolutionary adaptation (Nebert andDieter, 2000; Sullivan and Hagen, 2002). Modern anthropolog-ical research suggests that early indigenous peoples and heal-ers used experimentation and observation, along with positiveimmunological responses to plant usage, to determine whetheranimals and humans would (mutually) survive plant usage,ingested plant compounds, and their derivatives, and wouldcontinue to use the effective plant species and propagate theircontinued existence, as a form of sustainable health care. Theneed to return to the concept of the sustainable resourcing ofmedicinal agents has been restated (Cordell and Colvard, 2005).

Pain relief, and in particular oral pain relief, is one of themost ubiquitous anthropological human experiences for whichplants have been used. Wynbrandt (1998) reviewed the 5000BCE Babylonian medical treaties, the medical texts of EmperorShen Nung (3700 BCE), the 2500 BCE medical treatments ofHesi-Re (“the greatest of those that deal with teeth and of thephysicians”), and the 1500 BCE Papyrus Ebers, all of whichoutline and describe the significant roles numerous familiesof plants play in providing analgesic (loss of pain), anxiolytic(stress reduction), and anesthetic (loss of sensation) treatmentsfor dental and medical conditions. Goodman (1994) reviewedthe multiple roles that tobacco entities, from the Solanaceae fam-ily, have played in the medical ethnobotany of oral medicine andmedicine. Numerous other plants, for example: betel nut fromthe Arecaceae (palm) family (Oxenham et al., 2002; Sullivanand Hagen, 2002), purple cone flower (Echinacea augustifo-lia) from the Asteraceae (Wiley and Hofman, 1994), khat fromthe Celastraceae family, kava kava and other Piper plants fromPiperaceae (Sullivan and Hagen, 2002), coca from the Erythrox-ylaceae (Lloyd and Lloyd, 1911; Goodman, 1994; Schultes,1977; Wynbrandt, 1998; Sullivan and Hagen, 2002), opiumderived alkaloids from the Papaveraceae (Sullivan and Hagen,2002); various peppers (capsaicin) from the Solanaceae (Cordelland Araujo, 1993; Padilla et al., 2000), and even cherries from

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Table 2Plants with claimed anti-inflammatory activity for oral medicine

Common name Plant species Family Claimed treatment Metabolites ULATINA samples

Aloe Aloe vera Liliaceae Oral ulcers/inflammations Anthracenes, carbohydrates YesAnestesia Ottonia frutescens Piperaceae Oral ulcers/inflammations Piperovatine YesAngelica Angelica archangelica Apiaceae Sialagogue FurocoumarinsAnnatto Bixa orellana Bixaceae Oral ulcers/inflammations BixinAnisillo Piper auritum Piperaceae Oral ulcers/inflammations Piper alkaloids YesAnisillo Piper marginatum Piperaceae Oral ulcers/inflammations Piper alkaloids YesArnica Arnica montana Asteraceae Oral ulcers/inflammations Helenalin YesBuckwheat Fagopyrum esculentum Polygonaceae Oral ulcers/inflammations RutinCalendula Calendula officinalis Asteraceae Oral ulcers/inflammations TriterpenoidsCamptotheca Camptotheca acuminata Nyssaceae Oral ulcers/inflammations CamptothecinCelery seeds Apium graveolens Apiaceae Oral ulcers/inflammations PhthalidesChamomile Anthemis nobilis Asteraceae Oral ulcers/inflammations BisabololChickweed Stellaria media Caryophyllaceae Oral ulcers/inflammations Vitamin C, rutinChicle Manilkara sapota Sapotaceae Sialogogue LatexChilcuague Heliopsis longipes Asteraceae Oral ulcers/inflammations Affinin YesChilmecatl Heliopsis longipes Asteraceae Oral ulcers/inflammations Affinin YesChinchillia (Anicillo) Tagetes minuta Asteraceae Oral ulcers/inflammations Flavonoids YesDandelion Taraxacum officinale Asteraceae Sialogogue TaraxacinDon quai Angelica polymorpha Apiaceae Oral ulcers/inflammations Coumarins, bergaptenGarlic Allium sativum Liliaceae Oral ulcers/inflammations Alliin, allicin YesGinger Zingiber officinale Zingiberaceae Oral ulcers/inflammations ZingibereneGotu kola Centella asiatica Apiaceae Oral ulcers/inflammations MadecasossidesHierba mora Solanum nigrum Solanaceae Oral ulcers/inflammations GlycoalkaloidsJaborandi Pilocarpus jaborandi Rutaceae Sialagogue PilocarpineLicorice Glycyrrhiza glabra Fabaceae Oral ulcers/inflammations Glycyrrhetic acidMeadowsweet Filipendula ulmaria Rosaceae Oral ulcers/inflammations Salicylic acidOnions Allium cepa Liliaceae Oral ulcers/inflammations Alliin, allicin YesNeem Azadirachtia indica Meliaceae Oral ulcers/inflammations Azadirachtin, tanninsNettles Urtica dioica Urticaceae Oral ulcers/inflammations Hydroxyoctadecatrienic acidPeriwinkle (lesser) Vinca minor Apocynaceae Oral ulcers/inflammations Tannins, vincaminePine Bark Pinus palustris Pinaceae Oral ulcers/inflammations TerpineolPrickly Ash Zanthoxylum clavaherculis Rutaceae Sialogogue Nitidine alkaloidsPrimrose oil Oenothera biennis Onagraceae Oral ulcers/inflammations GLA, linoleic acidRaspberry Rubus idaeus Rosaceae Oral ulcers/inflammations TanninsRhubarb (Chinese) Rheum palmatum Polygonaceae Oral ulcers/inflammations Anthracenes, tanninsSage Salvia officinalis Lamiaceae Oral ulcers/inflammations Thujone, camphorSangre de Drago Croton draco Euphorbiaceae Oral ulcers/inflammations Alkaloids YesTargua Croton lechleri Euphorbiaceae Oral ulcers/inflammations Alkaloids YesTea Tree Melaleuca alternifolia Myrtaceae Oral ulcers/inflammations Terpinene, cineoleTurmeric Curcuma longa Zingiberaceae Oral ulcers/inflammations CurcuminoidsWillow bark Salix alba Salicaceae Oral ulcers/inflammations Salicin, salicylic acid

Table 3Over the counter anti-anxiety and hallucinogenic preparations

Common name Plant species Family Claimed therapy Metabolites ULATINA samples

Aconite Aconitum napellus Ranunculaceae Pain, facial paralysis Aconitine, kaempferolAnestesia Ottonia frutescens Piperaceae Pain, inflammation Piperovatine YesAnisillo Piper auritum Piperaceae Pain, oral ulcers, anxiety Piper alkaloids YesAnisillo Piper marginatum Piperaceae Pain, oral ulcers, anxiety Piper alkaloids YesBetel nut Areca catechu Arecaceae Anxiety, stimulant Arecoline alkaloids YesBetle Piper betle Piperaceae Pain Alkaloids YesCoca Erythroxylum coca Erythroxylaceae Pain Cocaine alkaloidsCoca Erythroxylum novagranatense Erythroxylaceae Pain Cocaine alkaloidsKava Piper methysticum Piperaceae Anxiety KavapyronesKhat Catha edulis Celastraceae Anxiety, stimulant CathinoneMarijuana Cannabis sativa Cannabaceae Pain, anxiety CannabinoidsMushrooms Psilocybe mexicana Strophariaceae Pain, anxiety Psilocybin, psilocin YesSalvia Salvia divinorum Lamiaceae Pain, anxiety Salvinorin ASt John’s wort Hypericum perforatum Clusiaceae Anxiety Linoleic acidTobacco Nicotiana tabacum Solanaceae Stimulant, pain Nicotine alkaloids YesYerba Maria Salvia divinorum Lamiaceae Stimulant, pain Salvinorin A

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Table 4Topical oral mucosal applications for oral mucosal anesthesia

Product Manufacturer Active ingredients

Arnica Aleman Labs Bogota, Columbia Arnica, aconitum, belladonna, Bellis perennis, Bryonia alba, calendulachamomilla, dulcamara, echinacea, hamamelis, hypericum, millefoliumphytolacca, symphytum, alcohol, soluble mercury, sulfur

Arnica Labfarve Bogota, Columbia ArnicaAbreva GlaxoSmithKline Pittsburg, PA Synthetic docosonalAnbesol Wyeth Madison, NJ Benzocaine and camphorBenadryl Pfizer Morris Plains, NJ Synthetic diphenhydramineBiocalor Bioland San Jose, Costa Rica Licorice extract, ginsing extract, aleo, augustifolia, eucalytlol, chile, saragundiBlistex Blistex Oakbrook, IL Benzocaine, alcohol, tannic acidCalendula Funat Labs Medillin, Colombia CalendulaCortizone Pfizer Morris Plains, NJ Synthetic hydrocortisoneDr Burt’s Burt’s Bees Durhan, NC Peppermint, coconut oil, lavender oil, rosemary, eucalyptus, comfreyDr Tichenor’s Tichenor’s Antiseptic New Orleans, LA Alcohol, peppermint oil, arnicaGyloxide GlaxoSmithKline Pittsburgh, PA Carbamide peroxideHerbal Mouthwash The Natural Dentist Fort Lee, NJ Echinacea, goldenseal, calendula, aloe, bloodroot, grapefriut seedHurricaine Beutlich Waukegan, IL Synthetic benzocaineHyland’s Standard Homeopathic Los Angles, CA Chamomile, coffee, belladonnaIpsab Heritage Products Virginia Beach, VA Prickly ash, iodine terachloride, peppermint oilsIpsadent Heritage Products Virginia Beach, VA Iodine, prickly ash, stevia, cinnamon, clove, alcoholListerine Pfizer Morris Plains, NJ Thymol, eucalyptol, methyl salicylate and mentholOptifresh Nature’s Plus Melville NY Sorbital, spearmint and peppermint oils, echinacea, olive leaf, neem, citric acidOrajel Del Labs Farmingdale, NY Synthetic dyclonineTea Tree Desert Essence Chatsworth, CA Tea tree oil, aloe, witch hazel, spearmint oil, alcoholTriaminic Novartis Parsippany, NJ PhenolViractin JB Williams Glen Rock, NJ Synthetic tetracaine

the Rosaceae (Angier, 2000); have all served as highly regardedhistorical sources of plant-based oral medicinal remedies. Oralbuccal mastication with saliva is a universal route to ingest andextract bioactive constituents from pain and inflammation reliev-ing plants (Sullivan and Hagen, 2002).

Field-based, ethnographic observations (by the authors) ofCosta Rican and Colombian rural peoples reveal that many ruralpeoples in these countries do not have routine access to oralhealth care professionals. Field observations reveal that the ruralpeoples use a wide variety of locally available plant speciesas chewable topical analgesics and anesthetics for pain relief.Within Mexico, Costa Rica, and Colombia, the rural peoplesuse the terms: “anestesia” “anicillo”, “anisillo”, “cordoncillo”and/or, “aniseto” to describe several plants used to numb themouth. Costa Rican local (“tico”) people use the same set oflocal words to identify numerous plants chewed as oral anes-thetic agents, and in particular, the terms “anisillo” and “cor-doncillo”. The plants attributed to these words appear to havediverse constituents able to provide temporary relief and ame-lioration of pain for dental, oral mucosal, and oral ulcerativeconditions.

Casagrande (2000) postulated that indigenous healers use theshape of a known medicinal plant as an aid in furthering sub-sequent medicinal plant selection. Curiously, Costa Rica ticopeople appear to employ a similar process, by attributing anes-thetic capabilities to a plant with certain morphological markers,based upon a known anesthetic plant model that provides topicalanesthesia. Our preliminary ethnomedical and botany fieldworksuggests that the plants used to treat oral pain, in Costa Rica andColombia, have a common set of morphological characteristics.The spike shaped inflorescence of the Piper genus appears toserve as the common, year round, morphological marker used

by rural and indigenous Costa Ricans as the marker of a plantwith potential anesthetic capabilities. The Costa Rican plants,that provide topical local oral mucosal anesthesia, and labeledas “anisillo” and “cordoncillo”, appear to be species within thePiper genus.

The historical global ethnobotany of the Piper family ofplants has provided a wide-ranging source of the global eth-nomedical treatment modalities for the amelioration of painand anoxia. Piper species such as Piper methysticum, Piperbetel, and Piper nigrum have been studied extensively. Numer-ous pharmacognostic and biologically active compounds havebeen elucidated from the Piperaceae family (Parmar et al.,1997; Parmar et al., 1998; Wei et al., 2002). The ethnomedi-cally desired anesthetic activity of kava kava is derived fromthe kava lactones and kawains of Piper methysticum (Schulzet al., 2004). Piper betel, chewed as a masticatory (Heywood,1993), has been shown to possess eugenol compounds (Chenet al., 1995). Piper nigrum (Orav et al., 2004) is purported toprovide pain and anti-inflammatory relief. Piperine, a promi-nent chemical constituent in black pepper (Mujumdar et al.,1990; Dewick, 2002), is reported to inhibit inflammatory painpathways (Stohr et al., 2001). Recently, McFerren et al. (2002)documented anesthetic and anti-inflammatory activity from analkaloid, piperovatine, identified in the Brazilian Piper species,Piper piscatorum, used locally as a water treatment to stun fishfor capture (McFerren and Rodriquez, 1998). Previous pharma-cognostic research has identified the oral anesthetic capabilityof other Piperaceae including Ottonia frutescens (Makapugay etal., 1983) and Piper methysticum, as well as in the Asteraceaespecies Heliopsis longipes (Ogura et al., 1982).

This research is part of an on-going effort to clarify the scopeand of usage of the plant families, and the associated common

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language botanical prototypes, used by indigenous and ruralpeoples of Central and South America to provide anesthetic andpain relieving properties for people without access to allopathicpharmaceuticals. We will conduct further medical anthropolog-ical, taxonomic, and ethnopharmacological studies to elucidateother plant families used for anesthesia, ant-inflammatoryand anti-anxiety purposes. We anticipate phylogenetic PCRanalysis, possibly following the Piper taxonomical workestablished by Callejas (1986) and the phylogenetic model ofJaramillo and Manos (2001) and Jaramillo and Callejas (2004),to clearly elucidate the genetic relationships between thevarious species of plants which are used by the indigenous andthe rural public as public access, plant-based drugs for oral painrelief.

6. Discussion and conclusions

It is well-documented that access, by global populations,to the latest controlled, clinically validated therapies and sub-sequent bio-science based, medical and dental innovationsand treatment protocols is not universal (Anonymous, 2002;Anonymous, 2003; Hamilton, 2003). Significantly, biochem-ical and oil dependent pharmaceutical preparations (Cordelland Colvard, 2005) and medical care, validated by controlled,evidence-based, clinical trials, has not replaced or removed thepersistent need for, and use of, TM/CAM by the vast majorityof the world’s populations (Hamilton, 2003). Access to modernmedical health care and biochemical or oil-sourced syntheticpharmaceuticals will never be widely available to an expandingglobal population (Cordell and Colvard, 2005).

The study of plants used in oral medicine is at an embryonicstage. Little or no ethnomedical, ethnopharmacological, epi-demiological, or public health survey research has been accom-plished by oral health scientists or public health scientists withrespect to botanical-based oral medicine treatments. Evidencebased research is lacking to establish the identification, use, andstandardized dosage of OTC ethnomedicine compounds for oralmedicine applications. Epidemiological analysis of ethnophar-macological oral medicine efficacy and safety, including ananalysis, which details the safety and efficacy for human use,both locally and globally, is an emerging science. Clinical tri-als, which can verify indications, safety, and efficacy of theseOTC products and compounds must increase in order to jus-tify their role in contemporary oral medicine. Our ethnomedicaland ethnopharmacological survey research continues to identify,catalog, and tabulate the most common natural products, deriva-tives and over-the-counter (OTC) analgesic remedies advocatedfor oral medicine conditions within the North, Central, and SouthAmerica.

Secondly, with regards to the Central American terms“anisillo” and “cordoncillo”, describing a group of South andCentral American plants used to provide oral mucosal anes-thesia; evidence-based taxonomy research (for example, classi-cal morphological taxonomy correlated with polymerase chainreaction-based genetic taxonomy research) is needed to verifythe accurate association of the common language terms with theclinically applied plant species attributed to be Piper species.

Thirdly, no public health survey data, clinical policy, andor health care policy template exists to recommend whetherthis type of plant and therapy is an acceptable alternativeto bioscience-based care. No public health statistical data set(Moerman, 2005) or policy is available to advise the govern-ments of these nations to protect, foster conservation, sustain-ability, or the economic botany of these plants for the future, andas a source of safe sustainable medicines. Scientists, includingBodeker and Kronenberg (2002), Cordell and Colvard (2005),and Moerman (2005) advocate that long term, statistical based,research strategies must be implemented by scientists whocan transcend current discipline specific limitations in researchorthodoxy, with the prime goal to have ethnomedicine andethnopharmacology serve as a platform for global biodiversitysustainability toward a global public health ethic. Only throughthis marriage can ethnomedicine and ethnopharmacology pro-vide sound information to the public on what constitutes goodhealth.

Global deforestation and the loss of planetary biomes haveled to the loss of access to plant based medicinal pharmaceu-ticals, diminished pharmaceutical drug discovery and devel-opment, and, ultimately, to diminished global public health.Consequently, a new economic and public health paradigm isadvocated: The Regional Sustainable Medicinal Plant Econ-omy. This new global public health policy paradigm is beingadvocated to justify increased global biodiversity protectionfor plant based pharmaceutical discovery, the development ofsustainable medicinal natural product drug development pro-grams, and the continued access to medicinal pharmaceuticals bypeople worldwide.

Acknowledgments

The authors extend special recognition and appreciation toCosta Rican farmers Kilo and Mario Sandoval. These gentlemenprovided access to the plants in and around their farm which iswithin the cloud rain forest region of the Guapiles district, andlocated on Route # 32 in the Provincia de Limon, Costa Rica.Their exceptional kindness, support, insight, and access to theplants on their farm is greatly appreciated. We extend specialthanks to Guillermo Guillen, DDS; Melissa Guillen, DDS, theAdministration, and the extended Faculty of the UniversidadLatina de Costa Rica (ULATINA), San Pedro, Costa Rica; fortheir constant support the past 4 years. Special recognition is alsoextended to Mr. Armando Ruiz-Boyer, MS, Staff Botanist withthe Herbario, Museo Nacional, San Jose, Costa Rica, who helpedwith field taxonomy. We thank Mr. Jorge Arce Portuguez, MSc,Cultivos Tropicales, for his support, insight, and access to themedicinal garden plots at EARTH, Costa Rica. We wish to recog-nize the expert insights and collaboration of Dr. Ricardo Callejasof the Universidad Antioquia in Medellin, Colombia; for hisexpert insight on the taxonomy of the Piper and Ottonia species.The authors wish to thank Dr. Mario Lobo, the National Coordi-nator of the Genetic Resources Program, Corpoica, La Selva, inMedellin, Colombia for his expert knowledge and insights withcapsicum. We wish to express our deep gratitude to Dr. RobertMartin, Provost of the Field Museum of Natural History, for his

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support and permission to access to the materials and voucherslocated within the Anthropology and Botany Departments. Wewish to thank Professor James Smith, Boise State University, forhis insights on the genetic phylogeny of various Piper species.We wish to express our great thanks to Ms. Mary Lou Quinn-Beattie of the Natural Products Alert (NAPRALERT) database.Special thanks are reserved for Professor (Emeritus) ShahidAshrafi, botanist and electron microscopist of the Departmentof Oral Medicine and Diagnostic Sciences, College of Dentistry,University of Illinois at Chicago. Recognition and regard goesto Professor (Emeritus) Tommy Gage, Baylor College of Den-tistry, Texas A&M University. Finally, the authors recognizethe financial support the National Institutes of Health (NIH),National Center for Complimentary and Alternative Medicine(NIH/NCCAM Grant K08-AT000987) for funding the prepara-tion of this report.

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