Ethnomedicine and neuropsychopharmacology in Mesoamerica, 2021
The burden of disease caused by mental and neurological disorders is increasing globally, to a di... more The burden of disease caused by mental and neurological disorders is increasing globally, to a disproportionate degree in Latin America. In contrast to the many psychoactive plants with a use history in Mesoamerican cultures, the translation to the wider population of knowledge around numerous botanicals used contemporarily by indigenous Mesoamerican societies to treat psychological and neurological disorders did not receive the same attention. Material and methods: We used the previously published Mesoamerican Medicinal Plant Database to extract species and associated botanical drugs used as treatments for illnesses associated with the nervous system by Mesoamerican cultures in Belize, Guatemala, and Mexico. With the critical use of published pharmacological literature, the crossculturally most salient genera are systematically reviewed. Results: From 2188 plant taxa contained in the database 1324 are used as treatments for illnesses associated with the nervous system. The ethnomedical data was critically confronted with the available biomedical literature for the 58 cross-culturally most salient genera. For a considerable proportion of the frequently used taxa, preclinical data are available, mostly validating ethnomedicinal uses. Conclusion: This quantitative approach facilitates the prioritization of taxa for future pre-clinical, clinical and treatment outcome studies and gives patients, practitioners, and legislators a fundamental framework of evidence, on which to base decisions regarding phytomedicines.
The relevance of quantitative ethnobotanical indices for ethnopharmacology and ethnobotany, 2022
As an interdisciplinary field of research ethnopharmacology draws on methodologies and methods fr... more As an interdisciplinary field of research ethnopharmacology draws on methodologies and methods from a variety of disciplines. A range of ethnobotanical indices are frequently used to transform primary data obtained through field studies into statistical measures. These indices are claimed to serve as a proxy for efficacy or drug discovery (Fidelity Level 'FL') and to show the importance of botanical drugs and plants used as medicines (Relative Importance 'RI', Use Value 'UV' or Cultural Importance Index 'CI', Cultural Value Index 'CV', Relative Frequency of Citation 'RFC'). This is, however, doubtful, as these indices have not been developed by statisticians, nor by pharmacologists while a proof of concept is lacking. Moreover, the question whether a simple number can summarize the cultural value or importance of plants is not only mathematical but also epistemological. Material and methods: The FL, RI, UV/CI, CV and the RFC are shortly reviewed. Their statistical rigour is explained and the relevance for ethnobotany, ethnopharmacology and drug discovery discussed. Results: The effect of the sample size on the dispersal of data and the differential probability of botanical drugs being used for the different categories of use are not being considered by these indices. They lack statistical rigour and are simple percentage calculations. Moreover, important factors influencing plant use, such as the availability of pharmaceutical drugs, or the severity of diseases covered by the use-categories, are not accounted for. Conclusion: Especially unexperienced and young researchers may be ensnared by using ethnobotanical indices to describe their field data. However, the cultural value and importance of plants in general, and more specifically, of medicinal plants and botanical drugs cannot be summed up by numbers. The discussed indices encrypt parts of the primary data but fail to show the value or importance of plant use because the reasons for which plants are valued or important to people are far more complex than what the formulations of these indices suggest. The indices also lack the power to pinpoint plant species or botanical drugs for drug discovery that contextualized primary data has. Botanical drugs may be useful for a range of disorders or only for specific indications, according to their pharmacologic properties. Therefore, the exclusiveness of therapeutical applications (FL) does not serve as a proxy for effectiveness. The solution is to use and understand the contextualized primary data.
Chemosensory qualities of botanical drugs are important cues for anticipating physiologic consequ... more Chemosensory qualities of botanical drugs are important cues for anticipating physiologic consequences. Whether a botanical drug is used for both, food and medicine, or only as medicine depends on taste preferences, nutritional content, cultural background, and the individual and overall epidemiological context. Material and methods: We subjected 540 botanical drugs described in De Materia Medica having at least one oral medical application to a tasting panel. The 540 drugs were grouped into those only used for medicine (388) and those also used for food (152). The associations with chemosensory qualities and therapeutic indications were compared across the two groups. We considered 22 experimentally assessed chemosensory qualities and 39 categories of therapeutic use groups. We wanted to know, 1): which chemosensory qualities increase the probability of an orally applied botanical drug to be also used for food ? 2): which chemosensory qualities augment the probability of an orally applied botanical drug to be only used for medicine? and 3): whether there are differences in therapeutic indications between orally applied botanical drugs also used for food (food drugs) and botanical drugs applied exclusively for medicinal purposes (non-food drugs) and, if yes, how the differences can be explained. Results: Chemosensory qualities augmenting the probability of an orally applied botanical drug to be also used for food were sweet, starchy, salty, burning/hot, fruity, nutty, and cooling. Therapeutics used for diarrhoea, as libido modulators, purgatives, laxatives, for expelling parasites, breast and lactation and increasing diuresis, were preferentially sourced from food drugs while drugs used for liver and jaundice, vaginal discharge and humoral management showed significant negative associations with food dugs in ancient Greek-Roman materia medica. Conclusion: Therapeutics used for ailments of body organs involved in the digestion of food and the excretion of waste products showed a tendency to be sourced from food drugs. Arguably, the daily consumption of food offered the possibility for observing post-prandial physiologic and pharmacologic effects which led to a high therapeutic versatility of food drugs and the possibility to understand benefits of taste and flavour qualities. The difference in chemosensory qualities between food drugs and non-food drugs is demarcating the organoleptic requirements of food rather than that of medicine.
The perception of taste and flavour (a combination of taste, smell, and chemesthesis), here also ... more The perception of taste and flavour (a combination of taste, smell, and chemesthesis), here also referred to as chemosensation, enables animals to find high-value foods and avoid toxins. Humans have learned to use unpalatable and toxic substances as medicines, yet the importance of chemosensation in this process is poorly understood. Here, we generate tasting-panel data for botanical drugs and apply phylogenetic generalised linear mixed models to test whether intensity and complexity of chemosensory qualities as well as particular tastes and flavours can predict ancient Graeco-Roman drug use. We found chemosensation to be strongly predictive of therapeutic use: botanical drugs with high therapeutic versatility have simple yet intense tastes and flavours, and 21 of 22 chemosensory qualities predicted at least one therapeutic use. In addition to the common notion of bitter tasting medicines, we also found starchy, musky, sweet, and soapy drugs associated with versatility. In ancient Greece and Rome, illness was thought to arise from imbalance in bodily fluids or humours, yet our study suggests that uses of drugs were based on observed physiological effects that are often consistent with modern understanding of chemesthesis and taste receptor pharmacology. eLife assessment This valuable study links the "taste" of botanicals to their application as medicines used by the ancient Greco-Roman society. The authors used phylogenetic linear mixed models in a Bayesian framework to test the relationships between taste qualities, intensities, complexities, and therapeutic use. The evidence supporting the conclusions is solid, although there is a minor weakness concerning the somewhat inconsistent method of botanical preparation and presentation to the taster panelists; subjective bias and robustness of the participants' responses might have been overlooked. The study may be of broad interest to pharmacologists and scientists working on drug discovery, particularly those interested in natural products.
Organoleptic properties, and more specifically chemosensory cues, have been shown to guide therap... more Organoleptic properties, and more specifically chemosensory cues, have been shown to guide therapeutic applications of medicinal plants. Humoral qualities, on the other hand, are widely believed to be an abstract concept, mainly applied post hoc to validate therapy. However, the nexus between humoral qualities, chemosensory properties, and medicinal plant uses has never been systematically assessed. To systematically analyse the correlations between chemosensory properties, humoral qualities, and medicinal uses of selected botanical drugs. The issue was approached experimentally via an organoleptic testing panel, consisting of Zoque healers in Chiapas, Mexico. The healers smelled and tasted 71 selected herbal drugs and subsequently commented on their humoral qualities and therapeutic uses. The resulting dataset is analysed for correlations between these variables using Bayesian statistics. Qualitative data on the characteristics and role of the hot-cold dichotomy complement the quan...
Ethnopharmacological relevance: ''Nothing in biology makes sense except in the light of evolution... more Ethnopharmacological relevance: ''Nothing in biology makes sense except in the light of evolution'' 1 The historical legacy and relevance of ethnopharmacology in drug discovery is undisputed. Here we connect the parameters influencing the selection of plant derived medicines by human culture with the concept of evolution. Aim of the study: In the present contribution we compare global data with local data and try to answer the questions, to what extent are the taxonomic clades included in indigenous pharmacopoeias associated with certain ailment groups, and to what extent can ecology and phylogeny, which we consider a proxy for chemical relatedness and convergence, account for the observed bias? Materials and methods: We use an approximated chi-square test (w 2) to check for associations between 12 ethnomedical use-categories and 15 taxonomical clades. With cluster analyses we test for correlations between phylogeny and use-categories. We compare the 67 drug-productive families identified by Zhu et al. ,2 with the medicinal flora of the Popoluca and the APG database and compare our results with the phylogenetic target classes evidenced by Zhu et al. Furthermore, we compare the medicinal flora of the Popoluca with the world's weeds (cf. Holm et al.) 3 and discuss our results in relation to anthropological rationales for plant selection. Results: The null-hypothesis ''species from the 15 taxonomic clades are selected proportionally to their share in the treatment of the twelve organ-and symptom-defined use-categories'' is rejected. The cluster dendrogram for the clades shows that the use patterns are to a certain extent associated with Angiosperm phylogeny. With the occurrence of 53 families the 67 drug-productive families are overrepresented in the regional flora of the Popoluca. The importance of these families in terms of their share is even more pronounced with the medicinal flora holding around 70% of all individual Popoluca informant responses. Conclusions: The overall phylogenetic use pattern is influenced by both the inherent pharmacological properties, which depend on phylogeny, biogeography, ecology and ultimately allelopathy, and on culture-specific perception of organoleptic properties. The comparison of the 67 drug-productive Viridiplantae families with the ethnopharmacopoeia of the Popoluca and the APG database, shows that ''traditional'' pharmacopoeias and plant-derived drugs are obtained from widespread and species-rich taxa. This is not a function of family size alone. We put forward the theory that as a function of Contents lists available at SciVerse ScienceDirect
... During 16 months of ethnobotanical fieldwork, about 600 medicinal species used by the ... tra... more ... During 16 months of ethnobotanical fieldwork, about 600 medicinal species used by the ... trabajo es de particular interes, ya que permite una comparaci6n intercultural con los ... Estos hallazgos apoyan la teoria de la transmisi6n inter-cultural de este conocimiento, posiblemente ...
BACKGROUND De Materia Medica written by Pedanios Dioscorides (1 century CE) has shaped European a... more BACKGROUND De Materia Medica written by Pedanios Dioscorides (1 century CE) has shaped European and Mediterranean herbal medicine to a large extent. Despite its fundamental importance for modern medico-botanical traditions the content of this work has never been systematically assessed. PURPOSE We present a quantitative survey of the botanical drugs described in De Materia Medica (ex Matthioli, 1568) and identify overall therapeutic, diachronic and botanical patterns. The extracted data may serve as a baseline and help to better contextualize research on herbal drugs and phytotherapy. METHODS Therapeutic uses of herbal drugs were extracted through line-by-line reading of a digitized version of the treatise. For each plant usage mentioned in the text we recorded (I) the chapter number, (II) the putative botanical identity, (III) the plant part, (IV) the symptoms or disease, (V) the mode of administration, (VI) our biomedical interpretation of the ancient ailment or disease description as well as (VII) the organ- and symptom-defined category under which the use was filed. SECTIONS An introduction to Dioscorides' De Materia Medica and Matthioli's Renaissance commentary is followed by a description of the employed methodology. The results and discussion section introduces the generated database comprising 5314 unique therapeutic uses of 536 plant taxa and 924 herbal drugs. Separate subsections address salient patterns such as the frequent recommendation of Fabaceae seeds for dermatology, Apiaceae seeds as antidotes and Apiaceae exudates for neurology and psychosomatic disorders as well as the heavy reliance on subterranean parts as drugs. CONCLUSIONS The therapeutic knowledge described in De Materia Medica (ex Matthioli, 1568) offers unique insights into classical Mediterranean epidemiology and herbal medicine. Drugs that lost importance over time as well as remedies used for diseases now controlled by preventive medicine and industrially produced drugs may be interesting starting points for research on herbal medicine and drug discovery. Apart from promoting future data mining, the study may also help to prove the tradition of use, which is required for the regulatory approval of certain herbal products.
In spite of the rich bio-cultural diversity found in the Neotropics relatively few herbal drugs n... more In spite of the rich bio-cultural diversity found in the Neotropics relatively few herbal drugs native to South America are included in the global pharmacopoeia. Material and methods: In the attempt to historically explain the inclusion of herbal drugs into official pharmacopoeias we consider the disparate epidemiology and cultural evolution of the New and the Old World. We then trace the development of pharmacopoeias and review forces that worked towards and against the synchronization of pharmacopoeias and highlight the role of early chemical and pharmacological studies in Europe. Finally, we compare the share of exotic and native herbal drug species included in the Brazilian Pharmacopoeia with the share of exotic and native species included in the European Pharmacopoeia as well as those used for products registered with ANVISA. Results: The domination of Eurasian herbal drugs in the European Pharmacopoeia seems to be conditioned by the geographical extension of Eurasia, which facilitated the interchange of materia medica and the creation of a consensus of use since ancient times. At the time of the Conquest the epidemiology of the Amerindian populations resembled that of pre-agriculturalist societies while no written consensus around efficacious medicine existed. Subsequently, introduced and well-tried plant species of the Old World gained therapeutic importance in the New World. Conclusion: The research focus in Europe and the US resulted in a persistence of herbal drugs with a historic importance in the European and US pharmacopoeias, which gained a status as safe and efficacious. During the last decades only few ethnopharmacological field-studies have been conducted with indigenous Amerindian groups living in the Brazilian Amazon, which might be attributable to difficulties in obtaining research permissions. Newly adopted regulations regarding access to biodiversity and traditional knowledge as well as the simplified procedure for licencing herbal medicinal products in Brazil prospects an interesting future for those aiming at developing herbal medicine based on bio-cultural diversity and respecting the protocols regulating benefit sharing. an estimated 90,000 to 110,000 plant species (Antonelli and Sanmartín, 2011), half of which occur in the Amazon basin (Hubbell et al., 2008). With up to 50,000 species, Brazil has the largest flora in the Neotropics (Lewinsohn and Prado, 2005; Shepherd, 2003; Ulloa et al., 2017). Besides a rich biodiversity around 300 Amerindian groups (including ca. 900,000 individuals) associated with 274 different languages are living
The cross-cultural exchange of plant resources between societies across the globe added to the di... more The cross-cultural exchange of plant resources between societies across the globe added to the diversification of medicinal floras and pharmacopeias. Understanding how and why people select plants for medicine is still a common focus and topic addressed by the interdisciplinary research fields of ethnobotany, anthropology, ethnopharmacology, ethnomedicine, pharmacy, phytochemistry, and pharmacognosy. Here, we scrutinize recently reviewed ethnobotanical theories and hypotheses, which focus on the selection of plants as medicine by putting them into historical, ecological, and pharmacological perspective. We contextualize the availability, versatility, and diversification hypotheses, often presented in association with the inclusion of non-native species or imported herbal drugs into medicinal floras or ethnopharmacopeias. We also discuss the relevance of the concept of utilitarian redundancy and the apparency hypothesis, as well as the appropriateness of various statistical models applied for assessing non-random plant selection. It appears that the concept of utilitarian redundancy has been applied in a too reductionist and uncritical way, while the apparency theory is conceptually inconsistent and contradictive allowing for multiple interpretations. While the availability, versatility, and diversification hypotheses are not contextualized historically, they are used to explain retrospectively deliberate and well-documented human activities and cultural developments. Therefore, considering the cultural history and the pharmacology of plants is essential for the formulation of hypotheses related to the selection of plants as medicine and food. Ecological research questions applied to human-plant relationships should consider the historical impact of human culture as a framework and confounder to be integrated into the analysis.
Summary Globally, more than six million people are infected with Trypanosoma cruzi, the causative... more Summary Globally, more than six million people are infected with Trypanosoma cruzi, the causative protozoan parasite of the vector-borne Chagas disease (CD). We conducted a cross-sectional ethnopharmacological field study in Bolivia among different ethnic groups where CD is hyperendemic. A total of 775 extracts of botanical drugs used in Bolivia in the context of CD and botanical drugs from unrelated indications from the Mediterranean De Materia Medica compiled by Dioscorides two thousand years ago were profiled in a multidimensional assay uncovering different antichagasic natural product classes. Intriguingly, the phylobioactive anthraquinone hotspot matched the antichagasic activity of Senna chloroclada, the taxon with the strongest ethnomedical consensus for treating CD among the Izoceño-Guaraní. Testing common 9,10-anthracenedione derivatives in T. cruzi cellular infection assays demarcates hydroxyanthraquinone as a potential antichagasic lead scaffold. Our study systematically uncovers in vitro antichagasic phylogenetic hotspots in the plant kingdom as a potential resource for drug discovery based on ethnopharmacological hypotheses.
The quality of health care in Mesoamerica is influenced by its rich cultural diversity and charac... more The quality of health care in Mesoamerica is influenced by its rich cultural diversity and characterized by social inequalities. Especially indigenous and rural communities confront diverse barriers to accessing formal health services, leading to often conflicting plurimedical systems. Fostering integrative medicine is a fundamental pillar for achieving universal health coverage (UHC) for marginalized populations. Recent developments toward health sovereignty in the region are concerned with assessing the role of traditional medicines, and particularly herbal medicines, to foster accessible and culturally pertinent healthcare provision models. In Mesoamerica, as in most regions of the world, a wealth of information on traditional and complementary medicine has been recorded. Yet these data are often scattered, making it difficult for policy makers to regulate and integrate traditionally used botanical products into primary health care. This critical review is based on a quantitative analysis of 28 survey papers focusing on the traditional use of botanical drugs in Mesoamerica used for the compilation of the “Mesoamerican Medicinal Plant Database” (MAMPDB), which includes a total of 12,537 use-records for 2188 plant taxa. Our approach presents a fundamental step toward UHC by presenting a pharmacological and toxicological review of the cross-culturally salient plant taxa and associated botanical drugs used in traditional medicine in Mesoamerica. Especially for native herbal drugs, data about safety and effectiveness are limited. Commonly used cross-culturally salient botanical drugs, which are considered safe but for which data on effectiveness is lacking constitute ideal candidates for treatment outcome studies.
Globally, more than six million people are infected with Trypanosoma cruzi, the causative protozo... more Globally, more than six million people are infected with Trypanosoma cruzi, the causative protozoan parasite of the vector-borne Chagas disease (CD). In Bolivia, CD is hyperendemic and a major health problem among indigenous communities. Although botanical drugs are used widely among different ethnic groups in Bolivia, studies challenging the hypothesis that effective antitrypanosomal medicinal agents were identified empirically are lacking. We conducted a cross-sectional ethnopharmacological field study in Bolivia among different ethnic groups in the Chaco, Chiquitanía and Inter-Andean valleys. We compared botanical drugs used in Bolivia in the context of CD with botanical drugs from unrelated indications from the Mediterranean De Materia Medica (DMM) compiled by Dioscorides two thousand years ago. A total of 775 ethyl acetate plant extracts with and without ethnomedical indications for CD treatment were profiled against T. cruzi epimastigote and procyclic T. brucei proliferation, ...
Origanum ehrenbergii Boiss., an endemic plant to Lebanon, is widely acknowledged in Lebanese trad... more Origanum ehrenbergii Boiss., an endemic plant to Lebanon, is widely acknowledged in Lebanese traditional medicine. The aim of the present study was to evaluate the influence of the drying method, region, and time of harvest on yield and chemical composition of O. ehrenbergii essential oils (EOs). Plants were harvested monthly throughout 2013 and 2014, from two different regions, Aabadiye and Qartaba, then dried using two drying methods: lyophilization and shade-drying at 4 °C. EO was extracted by hydrodistillation and analyzed by GC/MS. GC-MS data, combined with independent component analysis (ICA) and common component and specific weight analysis (CCSWA), showed that drying techniques, region of harvest, and soil composition have no effect on the chemical composition of O. ehrenbergii EOs. Of the factors analyzed, only harvesting time affected the EO composition of this species. High and stable amounts of carvacrol, associated with reliable antimicrobial activities, were detected i...
What are the minimum methodological and conceptual requirements for an ethnopharmacological field... more What are the minimum methodological and conceptual requirements for an ethnopharmacological field study? How can the results of ethnopharmacological field studies be reported so that researchers with different backgrounds can draw on the results and develop new research questions and projects? And how should these field data be presented to get accepted in a scientific journal such as the Journal of Ethnopharmacology? The objective of this commentary is to create a reference that covers the basic standards necessary during planning, conducting and reporting of field research. We focus on conducting and reporting ethnopharmacological field studies on medicinal plants or materia medica and associated knowledge of a specific people or region. The article highlights the most frequent problems and pitfalls, and draws on published literature, fieldwork experience, and extensive insights from peer-review of field studies. Research needs to be ethical and legal, and follow local and nationa...
Ethnomedicine and neuropsychopharmacology in Mesoamerica, 2021
The burden of disease caused by mental and neurological disorders is increasing globally, to a di... more The burden of disease caused by mental and neurological disorders is increasing globally, to a disproportionate degree in Latin America. In contrast to the many psychoactive plants with a use history in Mesoamerican cultures, the translation to the wider population of knowledge around numerous botanicals used contemporarily by indigenous Mesoamerican societies to treat psychological and neurological disorders did not receive the same attention. Material and methods: We used the previously published Mesoamerican Medicinal Plant Database to extract species and associated botanical drugs used as treatments for illnesses associated with the nervous system by Mesoamerican cultures in Belize, Guatemala, and Mexico. With the critical use of published pharmacological literature, the crossculturally most salient genera are systematically reviewed. Results: From 2188 plant taxa contained in the database 1324 are used as treatments for illnesses associated with the nervous system. The ethnomedical data was critically confronted with the available biomedical literature for the 58 cross-culturally most salient genera. For a considerable proportion of the frequently used taxa, preclinical data are available, mostly validating ethnomedicinal uses. Conclusion: This quantitative approach facilitates the prioritization of taxa for future pre-clinical, clinical and treatment outcome studies and gives patients, practitioners, and legislators a fundamental framework of evidence, on which to base decisions regarding phytomedicines.
The relevance of quantitative ethnobotanical indices for ethnopharmacology and ethnobotany, 2022
As an interdisciplinary field of research ethnopharmacology draws on methodologies and methods fr... more As an interdisciplinary field of research ethnopharmacology draws on methodologies and methods from a variety of disciplines. A range of ethnobotanical indices are frequently used to transform primary data obtained through field studies into statistical measures. These indices are claimed to serve as a proxy for efficacy or drug discovery (Fidelity Level 'FL') and to show the importance of botanical drugs and plants used as medicines (Relative Importance 'RI', Use Value 'UV' or Cultural Importance Index 'CI', Cultural Value Index 'CV', Relative Frequency of Citation 'RFC'). This is, however, doubtful, as these indices have not been developed by statisticians, nor by pharmacologists while a proof of concept is lacking. Moreover, the question whether a simple number can summarize the cultural value or importance of plants is not only mathematical but also epistemological. Material and methods: The FL, RI, UV/CI, CV and the RFC are shortly reviewed. Their statistical rigour is explained and the relevance for ethnobotany, ethnopharmacology and drug discovery discussed. Results: The effect of the sample size on the dispersal of data and the differential probability of botanical drugs being used for the different categories of use are not being considered by these indices. They lack statistical rigour and are simple percentage calculations. Moreover, important factors influencing plant use, such as the availability of pharmaceutical drugs, or the severity of diseases covered by the use-categories, are not accounted for. Conclusion: Especially unexperienced and young researchers may be ensnared by using ethnobotanical indices to describe their field data. However, the cultural value and importance of plants in general, and more specifically, of medicinal plants and botanical drugs cannot be summed up by numbers. The discussed indices encrypt parts of the primary data but fail to show the value or importance of plant use because the reasons for which plants are valued or important to people are far more complex than what the formulations of these indices suggest. The indices also lack the power to pinpoint plant species or botanical drugs for drug discovery that contextualized primary data has. Botanical drugs may be useful for a range of disorders or only for specific indications, according to their pharmacologic properties. Therefore, the exclusiveness of therapeutical applications (FL) does not serve as a proxy for effectiveness. The solution is to use and understand the contextualized primary data.
Chemosensory qualities of botanical drugs are important cues for anticipating physiologic consequ... more Chemosensory qualities of botanical drugs are important cues for anticipating physiologic consequences. Whether a botanical drug is used for both, food and medicine, or only as medicine depends on taste preferences, nutritional content, cultural background, and the individual and overall epidemiological context. Material and methods: We subjected 540 botanical drugs described in De Materia Medica having at least one oral medical application to a tasting panel. The 540 drugs were grouped into those only used for medicine (388) and those also used for food (152). The associations with chemosensory qualities and therapeutic indications were compared across the two groups. We considered 22 experimentally assessed chemosensory qualities and 39 categories of therapeutic use groups. We wanted to know, 1): which chemosensory qualities increase the probability of an orally applied botanical drug to be also used for food ? 2): which chemosensory qualities augment the probability of an orally applied botanical drug to be only used for medicine? and 3): whether there are differences in therapeutic indications between orally applied botanical drugs also used for food (food drugs) and botanical drugs applied exclusively for medicinal purposes (non-food drugs) and, if yes, how the differences can be explained. Results: Chemosensory qualities augmenting the probability of an orally applied botanical drug to be also used for food were sweet, starchy, salty, burning/hot, fruity, nutty, and cooling. Therapeutics used for diarrhoea, as libido modulators, purgatives, laxatives, for expelling parasites, breast and lactation and increasing diuresis, were preferentially sourced from food drugs while drugs used for liver and jaundice, vaginal discharge and humoral management showed significant negative associations with food dugs in ancient Greek-Roman materia medica. Conclusion: Therapeutics used for ailments of body organs involved in the digestion of food and the excretion of waste products showed a tendency to be sourced from food drugs. Arguably, the daily consumption of food offered the possibility for observing post-prandial physiologic and pharmacologic effects which led to a high therapeutic versatility of food drugs and the possibility to understand benefits of taste and flavour qualities. The difference in chemosensory qualities between food drugs and non-food drugs is demarcating the organoleptic requirements of food rather than that of medicine.
The perception of taste and flavour (a combination of taste, smell, and chemesthesis), here also ... more The perception of taste and flavour (a combination of taste, smell, and chemesthesis), here also referred to as chemosensation, enables animals to find high-value foods and avoid toxins. Humans have learned to use unpalatable and toxic substances as medicines, yet the importance of chemosensation in this process is poorly understood. Here, we generate tasting-panel data for botanical drugs and apply phylogenetic generalised linear mixed models to test whether intensity and complexity of chemosensory qualities as well as particular tastes and flavours can predict ancient Graeco-Roman drug use. We found chemosensation to be strongly predictive of therapeutic use: botanical drugs with high therapeutic versatility have simple yet intense tastes and flavours, and 21 of 22 chemosensory qualities predicted at least one therapeutic use. In addition to the common notion of bitter tasting medicines, we also found starchy, musky, sweet, and soapy drugs associated with versatility. In ancient Greece and Rome, illness was thought to arise from imbalance in bodily fluids or humours, yet our study suggests that uses of drugs were based on observed physiological effects that are often consistent with modern understanding of chemesthesis and taste receptor pharmacology. eLife assessment This valuable study links the "taste" of botanicals to their application as medicines used by the ancient Greco-Roman society. The authors used phylogenetic linear mixed models in a Bayesian framework to test the relationships between taste qualities, intensities, complexities, and therapeutic use. The evidence supporting the conclusions is solid, although there is a minor weakness concerning the somewhat inconsistent method of botanical preparation and presentation to the taster panelists; subjective bias and robustness of the participants' responses might have been overlooked. The study may be of broad interest to pharmacologists and scientists working on drug discovery, particularly those interested in natural products.
Organoleptic properties, and more specifically chemosensory cues, have been shown to guide therap... more Organoleptic properties, and more specifically chemosensory cues, have been shown to guide therapeutic applications of medicinal plants. Humoral qualities, on the other hand, are widely believed to be an abstract concept, mainly applied post hoc to validate therapy. However, the nexus between humoral qualities, chemosensory properties, and medicinal plant uses has never been systematically assessed. To systematically analyse the correlations between chemosensory properties, humoral qualities, and medicinal uses of selected botanical drugs. The issue was approached experimentally via an organoleptic testing panel, consisting of Zoque healers in Chiapas, Mexico. The healers smelled and tasted 71 selected herbal drugs and subsequently commented on their humoral qualities and therapeutic uses. The resulting dataset is analysed for correlations between these variables using Bayesian statistics. Qualitative data on the characteristics and role of the hot-cold dichotomy complement the quan...
Ethnopharmacological relevance: ''Nothing in biology makes sense except in the light of evolution... more Ethnopharmacological relevance: ''Nothing in biology makes sense except in the light of evolution'' 1 The historical legacy and relevance of ethnopharmacology in drug discovery is undisputed. Here we connect the parameters influencing the selection of plant derived medicines by human culture with the concept of evolution. Aim of the study: In the present contribution we compare global data with local data and try to answer the questions, to what extent are the taxonomic clades included in indigenous pharmacopoeias associated with certain ailment groups, and to what extent can ecology and phylogeny, which we consider a proxy for chemical relatedness and convergence, account for the observed bias? Materials and methods: We use an approximated chi-square test (w 2) to check for associations between 12 ethnomedical use-categories and 15 taxonomical clades. With cluster analyses we test for correlations between phylogeny and use-categories. We compare the 67 drug-productive families identified by Zhu et al. ,2 with the medicinal flora of the Popoluca and the APG database and compare our results with the phylogenetic target classes evidenced by Zhu et al. Furthermore, we compare the medicinal flora of the Popoluca with the world's weeds (cf. Holm et al.) 3 and discuss our results in relation to anthropological rationales for plant selection. Results: The null-hypothesis ''species from the 15 taxonomic clades are selected proportionally to their share in the treatment of the twelve organ-and symptom-defined use-categories'' is rejected. The cluster dendrogram for the clades shows that the use patterns are to a certain extent associated with Angiosperm phylogeny. With the occurrence of 53 families the 67 drug-productive families are overrepresented in the regional flora of the Popoluca. The importance of these families in terms of their share is even more pronounced with the medicinal flora holding around 70% of all individual Popoluca informant responses. Conclusions: The overall phylogenetic use pattern is influenced by both the inherent pharmacological properties, which depend on phylogeny, biogeography, ecology and ultimately allelopathy, and on culture-specific perception of organoleptic properties. The comparison of the 67 drug-productive Viridiplantae families with the ethnopharmacopoeia of the Popoluca and the APG database, shows that ''traditional'' pharmacopoeias and plant-derived drugs are obtained from widespread and species-rich taxa. This is not a function of family size alone. We put forward the theory that as a function of Contents lists available at SciVerse ScienceDirect
... During 16 months of ethnobotanical fieldwork, about 600 medicinal species used by the ... tra... more ... During 16 months of ethnobotanical fieldwork, about 600 medicinal species used by the ... trabajo es de particular interes, ya que permite una comparaci6n intercultural con los ... Estos hallazgos apoyan la teoria de la transmisi6n inter-cultural de este conocimiento, posiblemente ...
BACKGROUND De Materia Medica written by Pedanios Dioscorides (1 century CE) has shaped European a... more BACKGROUND De Materia Medica written by Pedanios Dioscorides (1 century CE) has shaped European and Mediterranean herbal medicine to a large extent. Despite its fundamental importance for modern medico-botanical traditions the content of this work has never been systematically assessed. PURPOSE We present a quantitative survey of the botanical drugs described in De Materia Medica (ex Matthioli, 1568) and identify overall therapeutic, diachronic and botanical patterns. The extracted data may serve as a baseline and help to better contextualize research on herbal drugs and phytotherapy. METHODS Therapeutic uses of herbal drugs were extracted through line-by-line reading of a digitized version of the treatise. For each plant usage mentioned in the text we recorded (I) the chapter number, (II) the putative botanical identity, (III) the plant part, (IV) the symptoms or disease, (V) the mode of administration, (VI) our biomedical interpretation of the ancient ailment or disease description as well as (VII) the organ- and symptom-defined category under which the use was filed. SECTIONS An introduction to Dioscorides' De Materia Medica and Matthioli's Renaissance commentary is followed by a description of the employed methodology. The results and discussion section introduces the generated database comprising 5314 unique therapeutic uses of 536 plant taxa and 924 herbal drugs. Separate subsections address salient patterns such as the frequent recommendation of Fabaceae seeds for dermatology, Apiaceae seeds as antidotes and Apiaceae exudates for neurology and psychosomatic disorders as well as the heavy reliance on subterranean parts as drugs. CONCLUSIONS The therapeutic knowledge described in De Materia Medica (ex Matthioli, 1568) offers unique insights into classical Mediterranean epidemiology and herbal medicine. Drugs that lost importance over time as well as remedies used for diseases now controlled by preventive medicine and industrially produced drugs may be interesting starting points for research on herbal medicine and drug discovery. Apart from promoting future data mining, the study may also help to prove the tradition of use, which is required for the regulatory approval of certain herbal products.
In spite of the rich bio-cultural diversity found in the Neotropics relatively few herbal drugs n... more In spite of the rich bio-cultural diversity found in the Neotropics relatively few herbal drugs native to South America are included in the global pharmacopoeia. Material and methods: In the attempt to historically explain the inclusion of herbal drugs into official pharmacopoeias we consider the disparate epidemiology and cultural evolution of the New and the Old World. We then trace the development of pharmacopoeias and review forces that worked towards and against the synchronization of pharmacopoeias and highlight the role of early chemical and pharmacological studies in Europe. Finally, we compare the share of exotic and native herbal drug species included in the Brazilian Pharmacopoeia with the share of exotic and native species included in the European Pharmacopoeia as well as those used for products registered with ANVISA. Results: The domination of Eurasian herbal drugs in the European Pharmacopoeia seems to be conditioned by the geographical extension of Eurasia, which facilitated the interchange of materia medica and the creation of a consensus of use since ancient times. At the time of the Conquest the epidemiology of the Amerindian populations resembled that of pre-agriculturalist societies while no written consensus around efficacious medicine existed. Subsequently, introduced and well-tried plant species of the Old World gained therapeutic importance in the New World. Conclusion: The research focus in Europe and the US resulted in a persistence of herbal drugs with a historic importance in the European and US pharmacopoeias, which gained a status as safe and efficacious. During the last decades only few ethnopharmacological field-studies have been conducted with indigenous Amerindian groups living in the Brazilian Amazon, which might be attributable to difficulties in obtaining research permissions. Newly adopted regulations regarding access to biodiversity and traditional knowledge as well as the simplified procedure for licencing herbal medicinal products in Brazil prospects an interesting future for those aiming at developing herbal medicine based on bio-cultural diversity and respecting the protocols regulating benefit sharing. an estimated 90,000 to 110,000 plant species (Antonelli and Sanmartín, 2011), half of which occur in the Amazon basin (Hubbell et al., 2008). With up to 50,000 species, Brazil has the largest flora in the Neotropics (Lewinsohn and Prado, 2005; Shepherd, 2003; Ulloa et al., 2017). Besides a rich biodiversity around 300 Amerindian groups (including ca. 900,000 individuals) associated with 274 different languages are living
The cross-cultural exchange of plant resources between societies across the globe added to the di... more The cross-cultural exchange of plant resources between societies across the globe added to the diversification of medicinal floras and pharmacopeias. Understanding how and why people select plants for medicine is still a common focus and topic addressed by the interdisciplinary research fields of ethnobotany, anthropology, ethnopharmacology, ethnomedicine, pharmacy, phytochemistry, and pharmacognosy. Here, we scrutinize recently reviewed ethnobotanical theories and hypotheses, which focus on the selection of plants as medicine by putting them into historical, ecological, and pharmacological perspective. We contextualize the availability, versatility, and diversification hypotheses, often presented in association with the inclusion of non-native species or imported herbal drugs into medicinal floras or ethnopharmacopeias. We also discuss the relevance of the concept of utilitarian redundancy and the apparency hypothesis, as well as the appropriateness of various statistical models applied for assessing non-random plant selection. It appears that the concept of utilitarian redundancy has been applied in a too reductionist and uncritical way, while the apparency theory is conceptually inconsistent and contradictive allowing for multiple interpretations. While the availability, versatility, and diversification hypotheses are not contextualized historically, they are used to explain retrospectively deliberate and well-documented human activities and cultural developments. Therefore, considering the cultural history and the pharmacology of plants is essential for the formulation of hypotheses related to the selection of plants as medicine and food. Ecological research questions applied to human-plant relationships should consider the historical impact of human culture as a framework and confounder to be integrated into the analysis.
Summary Globally, more than six million people are infected with Trypanosoma cruzi, the causative... more Summary Globally, more than six million people are infected with Trypanosoma cruzi, the causative protozoan parasite of the vector-borne Chagas disease (CD). We conducted a cross-sectional ethnopharmacological field study in Bolivia among different ethnic groups where CD is hyperendemic. A total of 775 extracts of botanical drugs used in Bolivia in the context of CD and botanical drugs from unrelated indications from the Mediterranean De Materia Medica compiled by Dioscorides two thousand years ago were profiled in a multidimensional assay uncovering different antichagasic natural product classes. Intriguingly, the phylobioactive anthraquinone hotspot matched the antichagasic activity of Senna chloroclada, the taxon with the strongest ethnomedical consensus for treating CD among the Izoceño-Guaraní. Testing common 9,10-anthracenedione derivatives in T. cruzi cellular infection assays demarcates hydroxyanthraquinone as a potential antichagasic lead scaffold. Our study systematically uncovers in vitro antichagasic phylogenetic hotspots in the plant kingdom as a potential resource for drug discovery based on ethnopharmacological hypotheses.
The quality of health care in Mesoamerica is influenced by its rich cultural diversity and charac... more The quality of health care in Mesoamerica is influenced by its rich cultural diversity and characterized by social inequalities. Especially indigenous and rural communities confront diverse barriers to accessing formal health services, leading to often conflicting plurimedical systems. Fostering integrative medicine is a fundamental pillar for achieving universal health coverage (UHC) for marginalized populations. Recent developments toward health sovereignty in the region are concerned with assessing the role of traditional medicines, and particularly herbal medicines, to foster accessible and culturally pertinent healthcare provision models. In Mesoamerica, as in most regions of the world, a wealth of information on traditional and complementary medicine has been recorded. Yet these data are often scattered, making it difficult for policy makers to regulate and integrate traditionally used botanical products into primary health care. This critical review is based on a quantitative analysis of 28 survey papers focusing on the traditional use of botanical drugs in Mesoamerica used for the compilation of the “Mesoamerican Medicinal Plant Database” (MAMPDB), which includes a total of 12,537 use-records for 2188 plant taxa. Our approach presents a fundamental step toward UHC by presenting a pharmacological and toxicological review of the cross-culturally salient plant taxa and associated botanical drugs used in traditional medicine in Mesoamerica. Especially for native herbal drugs, data about safety and effectiveness are limited. Commonly used cross-culturally salient botanical drugs, which are considered safe but for which data on effectiveness is lacking constitute ideal candidates for treatment outcome studies.
Globally, more than six million people are infected with Trypanosoma cruzi, the causative protozo... more Globally, more than six million people are infected with Trypanosoma cruzi, the causative protozoan parasite of the vector-borne Chagas disease (CD). In Bolivia, CD is hyperendemic and a major health problem among indigenous communities. Although botanical drugs are used widely among different ethnic groups in Bolivia, studies challenging the hypothesis that effective antitrypanosomal medicinal agents were identified empirically are lacking. We conducted a cross-sectional ethnopharmacological field study in Bolivia among different ethnic groups in the Chaco, Chiquitanía and Inter-Andean valleys. We compared botanical drugs used in Bolivia in the context of CD with botanical drugs from unrelated indications from the Mediterranean De Materia Medica (DMM) compiled by Dioscorides two thousand years ago. A total of 775 ethyl acetate plant extracts with and without ethnomedical indications for CD treatment were profiled against T. cruzi epimastigote and procyclic T. brucei proliferation, ...
Origanum ehrenbergii Boiss., an endemic plant to Lebanon, is widely acknowledged in Lebanese trad... more Origanum ehrenbergii Boiss., an endemic plant to Lebanon, is widely acknowledged in Lebanese traditional medicine. The aim of the present study was to evaluate the influence of the drying method, region, and time of harvest on yield and chemical composition of O. ehrenbergii essential oils (EOs). Plants were harvested monthly throughout 2013 and 2014, from two different regions, Aabadiye and Qartaba, then dried using two drying methods: lyophilization and shade-drying at 4 °C. EO was extracted by hydrodistillation and analyzed by GC/MS. GC-MS data, combined with independent component analysis (ICA) and common component and specific weight analysis (CCSWA), showed that drying techniques, region of harvest, and soil composition have no effect on the chemical composition of O. ehrenbergii EOs. Of the factors analyzed, only harvesting time affected the EO composition of this species. High and stable amounts of carvacrol, associated with reliable antimicrobial activities, were detected i...
What are the minimum methodological and conceptual requirements for an ethnopharmacological field... more What are the minimum methodological and conceptual requirements for an ethnopharmacological field study? How can the results of ethnopharmacological field studies be reported so that researchers with different backgrounds can draw on the results and develop new research questions and projects? And how should these field data be presented to get accepted in a scientific journal such as the Journal of Ethnopharmacology? The objective of this commentary is to create a reference that covers the basic standards necessary during planning, conducting and reporting of field research. We focus on conducting and reporting ethnopharmacological field studies on medicinal plants or materia medica and associated knowledge of a specific people or region. The article highlights the most frequent problems and pitfalls, and draws on published literature, fieldwork experience, and extensive insights from peer-review of field studies. Research needs to be ethical and legal, and follow local and nationa...
Ethnopharmacological relevance: Ethnopharmacological investigations of traditional medicines have... more Ethnopharmacological relevance: Ethnopharmacological investigations of traditional medicines have made significant contributions to plant-derived drugs, as well as the advancement of pharmacology. Drug discovery from medicinal flora is more complex than generally acknowledged because plants are applied for different therapeutic indications within and across cultures. Therefore we propose the concept of "reverse ethnophar-macology" and compare biomedical uses of plant taxa with their ethnomedicinal and popular uses and test the effect of these on the probability of finding biomedical and specifically anticancer drugs. Materials and methods: For this analysis we use data on taxonomy and medical indications of plant derived biomedical drugs, clinical trial, and preclinical trial drug candidates published by Zhu et al. (2011) and compare their therapeutic indications with their ethnomedicinal and popular uses as reported in the NAPRALERT ® database. Specifically, we test for increase or decrease of the probability of finding anticancer drugs based on ethnomedicinal and popular reports with Bayesian logistic regression analyses. Results: Anticancer therapy resulted as the most frequent biomedicinal indication of the therapeutics derived from the 225 drug producing higher plant taxa and showed an association with ethnomedicinal and popular uses in women's medicine, which was also the most important popular use-category. Popular remedies for dysmenorrhoea, and uses as emmenagogues, abortifacients and contraceptives showed a positive effect on the probability of finding anticancer drugs. Another positive effect on the probability of discovering anticancer therapeutics was estimated for popular herbal drugs associated with the therapy of viral and bacterial infections, while the highest effect was found for popular remedies used to treat cancer symptoms. However, this latter effect seems to be influenced by the feedback loop and divulgence of biomedical knowledge on the popular level. Conclusion: We introduce the concept of reverse ethnopharmacology and show that it is possible to estimate the probability of finding biomedical drugs based on ethnomedicinal uses. The detected associations confirm the classical ethnopharmacological approach where a popular remedy for disease category X results in a biomedical drug for disease category X but does also point out the existence of cross-over relationships where popular remedies for disease category X result in biomedical therapeutics for disease category Y (Zhu et al., 2011).
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