Food drugs as drivers of therapeutic knowledge and the role of chemosensory qualities.

ETHNOPHARMACOLOGICAL RELEVANCE: 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.

Taste shaped the use of botanical drugs.

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.

In ancient times people used trial and error to identify medicinal plants as being effective. Later, diseases were believed to arise from imbalances in body fluids (or 'humours'), and botanical drugs were thought to restore this balance through the power of their taste. Modern science rejects this theory but does recognise the importance of chemosensation ­ our sensitivity to chemicals through taste and smell. These senses evolved in humans to help us seek out nutrients and avoid toxins and may also have guided the ancient uses of botanical drugs. There are many records of historical medicinal plant use and ailments, which makes it possible to explore possible relationships between therapeutic uses of botanical drugs and their chemosensory qualities. To investigate if therapeutic uses of botanical drugs could indeed be predicted by taste and flavour, Leonti, Baker et al. collected 700 botanical drugs identified in an ancient text, named De Materia Medica, which dates back to the 1^st century CE. The researchers asked volunteer tasters to classify the botanical drugs using 22 taste descriptions, such as bitter, aromatic, burning/hot, and fresh/cooling. The volunteers were also asked to score the strength of these tastes. Leonti, Baker et al. then used statistical modelling to see if the participant's taste descriptions could be used to predict the therapeutic uses of the drugs identified in the ancient text. This revealed that of the 46 therapeutic indications described in the text, 45 showed significant associations with at least one taste quality. Botanical drugs with stronger and simpler tastes tended to be used for a wider range of therapeutic indications. This suggests that chemosensation influenced therapeutic expectations in ancient, prescientific medicine. The study of Leonti, Baker et al. brings ancient medicine to life, offering valuable insights into the chemosensory aspects of medicinal plants and their potential applications in modern medicine. A next step would be to explore whether these insights could have relevance to modern science.

Ethnomedicine and neuropsychopharmacology in Mesoamerica.

ETHNOPHARMACOLOGICAL RELEVANCE: 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 cross-culturally 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.

Traditional Herbal Medicine in Mesoamerica: Toward Its Evidence Base for Improving Universal Health Coverage.

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.

Integrating nutrition and physical activity promotion: A scoping review.

BACKGROUND: This paper investigates actions that combine nutrition and physical activity which hold potential for 'double duty action' to tackle multiple forms of malnutrition simultaneously. Expanding on previous research on single component actions, we assessed the state of the literature to map integrated interventions across the life course to analyse potential double duty effects, and identify knowledge gaps and needs for future design, implementation, evaluation and research for effective double duty action. METHODS: A scoping review of peer-reviewed and grey literature was conducted to explore the pathways that extend from combined physical activity and nutrition promotion interventions, with potential synergistic effects on outcomes other than obesity. Electronic databases were searched for studies published between 1 January 2010 and 31 January 2020. Out of 359 articles retrieved, 31 peer-reviewed and 5 grey literature sources met inclusion criteria. Findings from 36 papers reporting on 34 interventions/initiatives were organised into 6 categories, based on implementation across multiple stages of the life course. Double-duty potential was assessed through a further stage of analysis. FINDINGS: This review has identified actions that hold potential for tackling not only obesity, but healthy diets, sedentary behaviour and quality of life more generally, as well as actions that explicitly tackle multiple forms of malnutrition. Importantly, it has identified crucial gaps in current methods and praxis that call for further practice-oriented research, in order to better understand and exploit the synergistic effects of integrated interventions on outcomes other than obesity. CONCLUSIONS: Findings from across implementation settings suggest that even in situations where interventions are aimed at, or framed in terms of, obesity prevention and control, there are unexploited pathways for broader outcomes of relevance to nutrition and health and wellbeing more generally. Future design and evaluation of multisectoral approaches will benefit from an explicit framing of interventions as double-duty oriented.

The historical development of pharmacopoeias and the inclusion of exotic herbal drugs with a focus on Europe and Brazil.

ETHNOPHARMACOLOGICAL RELEVANCE: 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.

Ethnopharmacology of Love.

Background: Elixirs conferring eternal youth or inducing amatory and erotic attraction have been searched for without success. Lovesickness is a widespread affliction resulting from unrequited love and/or the impossibility for physical and emotional union. The symptoms are reflections of altered dopamine, serotonin, noradrenaline, testosterone and cortisol levels and range from frenzy and intrusive thinking to despair and depression, sharing traits with the neurochemistry of addiction and compulsive behavior disorder. Although it can seriously impact the quality of life, lovesickness is currently not considered in official disease classification systems. Consequently, no official therapeutic guidelines exist, leaving subjects to seek the cure on their own. Methods: We review literature of the past 2000 years dealing with the concept, diagnosis and the healing of lovesickness and contextualize it with neurochemical, ethnomedical, and ethnographic data. Since neurobiological and pharmacological connections between the love drive and the sex drive exist, we review also the literature about herbal an- and aphrodisiacs, focusing on their excitatory or calmative potential. Results: An overall consensus regarding socio-behavioral regimes exists for dealing with lovesickness from historical through contemporary literature. The herbal drugs used for treating lovesickness or inducing love passion do not possess the alleged properties. The pharmacological effects of aphrodisiacs are heterogeneous, including dopaminergic and adrenergic activities, but there is no evidence for any serotonergic effects. The libido-regulating properties of anaphrodisiacs seem to be associated with sedative and toxic effects or decreasing testosterone levels. CB2 receptors expressed on dopaminergic neurons of the ventral tegmental area, part of the brain's reward circuit, implicated with addiction, orgasm and strong emotions such as love, might constitute a new therapeutic target. Conclusion: The common food additive and CB2 agonist ß-caryophyllene might have the potential to attenuate dopaminergic firing, quenching the reward and thus motivation associated with romantic love. From Greek mythology to modern history, cultural expressions and implications of love, sex and procreation is and was organized along hierarchical lines that put men on top. The neuronal predispositions and activities associated with falling in love will probably forever remain nature's and Eros' secret.

The taste of heat: How humoral qualities act as a cultural filter for chemosensory properties guiding herbal medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: 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. AIM OF THE STUDY: To systematically analyse the correlations between chemosensory properties, humoral qualities, and medicinal uses of selected botanical drugs. METHODS: 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 quantitative analysis, facilitating meaningful interpretation. RESULTS AND DISCUSSION: The results reproduce and extend the findings of previous studies, which established specific correlations between chemosensory cues and nosological units. The key predictors of drugs' therapeutic uses, however, are their humoral qualities, which are themselves conditioned by taste and smell. These findings appear to be valid for drug samples known to the participants as well as for unfamiliar samples. Thus, this study establishes the role of the hot-cold dichotomy as an important cultural filter connecting organoleptic properties and therapeutic uses of herbal drugs. CONCLUSIONS: There is considerable cross-cultural consensus in Mesoamerica for the specific correlations described in this study. Given the continued pervasiveness of the hot-cold dichotomy, humoral qualities and the underlying organoleptic properties ought to be increasingly considered in the design of pharmaceutical products as well as public health strategies. Such culturally appropriate adjustments may considerably improve the perceived quality and effectiveness of healthcare.

Reverse ethnopharmacology and drug discovery.

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 ethnopharmacology" 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).

Acculturation and ethnomedicine: A regional comparison of medicinal plant knowledge among the Zoque of southern Mexico.

ETHNOPHARMACOLOGICAL RELEVANCE: In rural areas of Mexico the impact of modernization has changed healthcare and health seeking behaviour to varying degrees. This has rarely been accounted for when discussing and comparing medicinal floras. The ethnomedical system of the Zoque has never before been systematically studied. AIM OF THE STUDY: The objective of this study was to document medical practices and medicinal plant knowledge of the Zoque of Chiapas and Oaxaca, the latter being more strongly affected by acculturation. The medicinal floras are compared in order to detect similarities and differences and establishing links to the cultural transformation. METHODS: Research was carried out in a total of nine Zoque municipalities, attempting to adequately represent the cultural and ecological diversity of the Zoque territory. Standard anthropological and ethnobotanical methods were used for data collection. The recorded medicinal uses were classified into 17 disease categories according to emic medical concepts. In each category, the recorded taxa were rank-ordered based on number of use-reports and the informant consensus factor was calculated. The characteristics of the disease categories and the most salient taxa were compared across the two field sites. RESULTS AND DISCUSSION: A total of 6598 use-reports on 544 species have been collected. With the strongly acculturated Zoque of Oaxaca we have documented a considerably less extensive medicinal flora. The ethnopharmacopoeias of the two Zoque groups share 144 species. These species are of over-proportionate salience, accounting for two-thirds of the total use-reports. In both field sites gastrointestinal disorders are of particular importance, followed by women's diseases, respiratory diseases and musculoskeletal ailments. Children's and spiritual illnesses seem to have lost their importance in Oaxaca, as the underlying concepts are often considered backwards and superstitious. CONCLUSION: While it is difficult to establish a quantitative causal relation between acculturation and medicinal plant knowledge, in qualitative terms there are clear indicators for the changes acculturation has brought about in the medical system of the Zoque of Oaxaca. The results suggest the development of an increasingly homogenized pan-Mesoamerican medicinal flora.

Delivery of liquorice extract by liposomes and hyalurosomes to protect the skin against oxidative stress injuries.

Liquorice extract, obtained by percolation in ethanol of Glycyrrhiza glabra L. roots, was incorporated in liposomes and hyalurosomes, new phospholipid-sodium hyaluronate vesicles, and their protective effect against oxidative stress skin damages was probed. As a comparison, raw glycyrrhizin was also tested. All the vesicles were small in size (≤ 100 nm), with a highly negative zeta potential ensuring long-term stability, and able to incorporate a high amount of the extract. In vitro tests showed that the liquorice extract loaded in vesicles was able to scavenge DPPH free radical (80% inhibition) and to protect 3T3 fibroblasts against H2O2-induced oxidative stress, restoring the normal conditions. By contrast, glycyrrhizin showed poor antioxidant activity, and was not able to efficiently counteract the oxidative effect of H2O2. In addition, the incorporation of the liquorice extract into the vesicular systems promoted the proliferation and migration of 3T3 fibroblasts, favouring the closure of the scratched area. In vivo anti-inflammatory tests on mice confirmed the ability of the proposed nanosystems to improve the local efficacy of the extract, favouring the re-epitelization process.

From cumulative cultural transmission to evidence-based medicine: evolution of medicinal plant knowledge in Southern Italy.

In Mediterranean cultures written records of medicinal plant use have a long tradition. This written record contributed to building a consensus about what was perceived to be an efficacious pharmacopeia. Passed down through millennia, these scripts have transmitted knowledge about plant uses, with high fidelity, to scholars and laypersons alike. Herbal medicine's importance and the long-standing written record call for a better understanding of the mechanisms influencing the transmission of contemporary medicinal plant knowledge. Here we contextualize herbal medicine within evolutionary medicine and cultural evolution. Cumulative knowledge transmission is approached by estimating the causal effect of two seminal scripts about materia medica written by Dioscorides and Galen, two classical Greco-Roman physicians, on today's medicinal plant use in the Southern Italian regions of Campania, Sardinia, and Sicily. Plant-use combinations are treated as transmissible cultural traits (or "memes"), which in analogy to the biological evolution of genetic traits, are subjected to mutation and selection. Our results suggest that until today ancient scripts have exerted a strong influence on the use of herbal medicine. We conclude that the repeated empirical testing and scientific study of health care claims is guiding and shaping the selection of efficacious treatments and evidence-based herbal medicine.

Classifying diseases and remedies in ethnomedicine and ethnopharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Ethnopharmacology focuses on the understanding of local and indigenous use of medicines and therefore an emic approach is inevitable. Often, however, standard biomedical disease classifications are used to describe and analyse local diseases and remedies. Standard classifications might be a valid tool for cross-cultural comparisons and bioprospecting purposes but are not suitable to understand the local perception of disease and use of remedies. Different standard disease classification systems exist but their suitability for cross-cultural comparisons of ethnomedical data has never been assessed. Depending on the research focus, (I) ethnomedical, (II) cross-cultural, and (III) bioprospecting, we provide suggestions for the use of specific classification systems. MATERIALS AND METHODS: We analyse three different standard biomedical classification systems (the International Classification of Diseases (ICD); the Economic Botany Data Collection Standard (EBDCS); and the International Classification of Primary Care (ICPC)), and discuss their value for categorizing diseases of ethnomedical systems and their suitability for cross-cultural research in ethnopharmacology. Moreover, based on the biomedical uses of all approved plant derived biomedical drugs, we propose a biomedical therapy-based classification system as a guide for the discovery of drugs from ethnopharmacological sources. RESULTS: Widely used standards, such as the International Classification of Diseases (ICD) by the WHO and the Economic Botany Data Collection Standard (EBDCS) are either technically challenging due to a categorisation system based on clinical examinations, which are usually not possible during field research (ICD) or lack clear biomedical criteria combining disorders and medical effects in an imprecise and confusing way (EBDCS). The International Classification of Primary Care (ICPC), also accepted by the WHO, has more in common with ethnomedical reality than the ICD or the EBDCS, as the categories are designed according to patient's perceptions and are less influenced by clinical medicine. Since diagnostic tools are not required, medical ethnobotanists and ethnopharmacologists can easily classify reported symptoms and complaints with the ICPC in one of the "chapters" based on 17 body systems, psychological and social problems. Also the biomedical uses of plant-derived drugs are classifiable into 17 broad organ- and therapy-based use-categories but can easily be divided into more specific subcategories. CONCLUSIONS: Depending on the research focus (I-III) we propose the following classification systems: I. Ethnomedicine: Ethnomedicine is culture-bound and local classifications have to be understood from an emic perspective. Consequently, the application of prefabricated, "one-size fits all" biomedical classification schemes is of limited value. II. Cross-cultural analysis: The ICPC is a suitable standard that can be applied but modified as required. III. Bioprospecting: We suggest a biomedical therapy-driven classification system with currently 17 use-categories based on biomedical uses of all approved plant derived natural product drugs.

Nematicidal activity of furanocoumarins from parsley against Meloidogyne spp.

BACKGROUND: This report describes activity against Meloidogyne spp. and chemical characterisation of the essential oil and methanol extract of Petroselinum crispum aerial parts. The study was based on the hypothesis that P. crispum could be used as an intercrop and soil amendment in tomato culture for nematode control. RESULTS: The methanol extract and the essential oil exhibited significant nematicidal activity against M. incognita, M. hapla and M. arenaria, the first being the most sensitive species, with EC50 /72 h values of 140 ± 15 and 795 ± 125 mg L(-1) for the extract and oil respectively. The most abundant furanocoumarin compounds in the methanolic extract were xanthotoxin, psoralen, bergapten and oxypeucedanin; levels ranged from 1.77 to 46.04 mg kg(-1) wet weight. The EC50 /24 h values of xanthotoxol, psoralen and xanthotoxin against M. incognita were 68 ± 33, 147 ± 88 and 200 ± 21 mg L(-1) respectively. The addition of fresh parsley paste to soil reduced the number of M. incognita females and plant galls on tomato roots; EC50 values were 24.79 and 28.07 mg g(-1) respectively. Moreover, parsley paste enhanced tomato growth in a dose-response manner. CONCLUSIONS: Parsley exhibits promising nematicidal activity as an organic amendment and as a source of nematotoxic furanocoumarins.

Soma, food of the immortals according to the Bower Manuscript (Kashmir, 6th century A.D.).

ETHNOPHARMACOLOGICAL RELEVANCE: Food is medicine and vice versa. In Hindu and Ayurvedic medicine, and among human cultures of the Indian subcontinent in general, the perception of the food-medicine continuum is especially well established. The preparation of the exhilarating, gold-coloured Soma, Amrita or Ambrosia, the elixir and food of the 'immortals'-the Hindu pantheon-by the ancient Indo-Aryans, is described in the Rigveda in poetic hymns. Different theories regarding the botanical identity of Soma circulate, but no pharmacologically and historically convincing theory exists to date. We intend to contribute to the botanical, chemical and pharmacological characterisation of Soma through an analysis of two historical Amrita recipes recorded in the Bower Manuscript. The recipes are referred therein as panaceas (clarified butter) and also as a medicine to treat nervous diseases (oil), while no exhilarating properties are mentioned. Notwithstanding this, we hypothesise, that these recipes are related to the ca. 1800 years older Rigvedic Soma. We suppose that the psychoactive Soma ingredient(s) are among the components, possibly in smaller proportions, of the Amrita recipes preserved in the Bower Manuscript. MATERIALS AND METHODS: The Bower Manuscript is a medical treatise recorded in the 6th century A.D. in Sanskrit on birch bark leaves, probably by Buddhist monks, and unearthed towards the end of the 19th century in Chinese Turkestan. We analysed two Amrita recipes from the Bower Manuscript, which was translated by Rudolf Hoernle into English during the early 20th century. A database search with the updated Latin binomials of the herbal ingredients was used to gather quantitative phytochemical and pharmacological information. RESULTS: Together, both Amrita recipes contain around 100 herbal ingredients. Psychoactive alkaloid containing species still important in Ayurvedic, Chinese and Thai medicine and mentioned in the recipe for 'Amrita-Prâsa clarified butter' and 'Amrita Oil' are: Tinospora cordifolia (Amrita, Guduchi), three Sida spp., Mucuna pruriens, Nelumbo nucifera, Desmodium gangeticum, and Tabernaemontana divaricata. These species contain several notorious and potential psychoactive and psychedelic alkaloids, namely: tryptamines, 2-phenylethylamine, ephedrine, aporphines, ibogaine, and L-DOPA. Furthermore, protoberberine alkaloids, tetrahydro-ß-carbolines, and tetrahydroisoquinolines with monoamine oxidase inhibitor (MAO-I) activity but also neurotoxic properties are reported. CONCLUSIONS: We propose that Soma was a combination of a protoberberine alkaloids containing Tinospora cordifolia juice with MAO-I properties mixed together with a tryptamine rich Desmodium gangeticum extract or a blending of Tinospora cordifolia with an ephedrine and phenylethylamine-rich Sida spp. extract. Tinospora cordifolia combined with Desmodium gangeticum might provide a psychedelic experience with visual effects, while a combination of Tinospora cordifolia with Sida spp. might lead to more euphoric and amphetamine-like experiences.

Nematicidal activity of mint aqueous extracts against the root-knot nematode Meloidogyne incognita.

The nematicidal activity and chemical characterization of aqueous extracts and essential oils of three mint species, namely, Mentha × piperita , Mentha spicata , and Mentha pulegium , were investigated. The phytochemical analysis of the essential oils was performed by means of GC-MS, whereas the aqueous extracts were analyzed by LC-MS. The most abundant terpenes were isomenthone, menthone, menthol, pulegone, and carvone, and the water extracts yielded mainly chlorogenic acid, salvianolic acid B, luteolin-7-O-rutinoside, and rosmarinic acid. The water extracts exhibited significant nematicidal activity against Meloidogyne incognita , and the EC50/72h values were calculated at 1005, 745, and 300 mg/L for M. × piperita, M. pulegium, and M. spicata, respectively. Only the essential oil from M. spicata showed a nematicidal activity with an EC50/72h of 358 mg/L. Interestingly, menthofuran and carvone showed EC50/48h values of 127 and 730 mg/L, respectively. On the other hand, salicylic acid, isolated in the aqueous extracts, exhibited EC50 values at 24 and 48 h of 298 ± 92 and 288 ± 79 mg/L, respectively.

Traditional medicines and globalization: current and future perspectives in ethnopharmacology.

The ethnopharmacological approach toward the understanding and appraisal of traditional and herbal medicines is characterized by the inclusions of the social as well as the natural sciences. Anthropological field-observations describing the local use of nature-derived medicines are the basis for ethnopharmacological enquiries. The multidisciplinary scientific validation of indigenous drugs is of relevance to modern societies at large and helps to sustain local health care practices. Especially with respect to therapies related to aging related, chronic and infectious diseases traditional medicines offer promising alternatives to biomedicine. Bioassays applied in ethnopharmacology represent the molecular characteristics and complexities of the disease or symptoms for which an indigenous drug is used in "traditional" medicine to variable depth and extent. One-dimensional in vitro approaches rarely cope with the complexity of human diseases and ignore the concept of polypharmacological synergies. The recent focus on holistic approaches and systems biology in medicinal plant research represents the trend toward the description and the understanding of complex multi-parameter systems. Ethnopharmacopoeias are non-static cultural constructs shaped by belief and knowledge systems. Intensified globalization and economic liberalism currently accelerates the interchange between local and global pharmacopoeias via international trade, television, the World Wide Web and print media. The increased infiltration of newly generated biomedical knowledge and introduction of "foreign" medicines into local pharmacopoeias leads to syncretic developments and generates a feedback loop. While modern and post-modern cultures and knowledge systems adapt and transform the global impact, they become more relevant for ethnopharmacology. Moreover, what is traditional, alternative or complementary medicine depends on the adopted historic-cultural perspective.

Bioprospecting: evolutionary implications from a post-olmec pharmacopoeia and the relevance of widespread taxa.

ETHNOPHARMACOLOGICAL RELEVANCE: "Nothing in biology makes sense except in the light of evolution" 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 (χ(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. 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.) 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 evolution, widespread taxa contain a broader range of accumulated ecological information and response encoded in their genes relative to locally occurring taxa. This information is expressed through the synthesis of allelochemicals with a wide ecological radius, showing broad-spectrum biota-specific interactions, including the targeting of proteins of mammals and primates.

Synthesis and cytotoxic activity of non-naturally substituted 4-oxycoumarin derivatives.

Coumarins are a large family of natural and synthetic compounds exerting different pharmacological effects, including cytotoxic, anti-inflammatory or antimicrobial. In the present communication we report the synthesis of a series of 12 diversely substituted 4-oxycoumarin derivatives including methoxy substituted 4-hydroxycoumarins, methyl, methoxy or unsubstituted 3-aryl-4-hydroxycoumarins and 4-benzyloxycoumarins and their anti-proliferative effects on breast adenocarcinoma cells (MCF-7), human promyelocytic leukemia cells (HL-60), human histiocytic lymphoma cells (U937) and mouse neuroblastoma cells (Neuro2a). The most potent bioactive molecule was the 4-hydroxy-5,7-dimethoxycoumarin (compound 1) which showed similar potency (IC(50) 0.2-2 µM) in all cancer cell lines tested. This non-natural product reveals a simple bioactive scaffold which may be exploited in further studies.

Mild synthetic approach to novel indole-1-carbinols and preliminary evaluation of their cytotoxicity in hepatocarcinoma cells.

A mild and versatile method for the synthesis of some novel indole-1-carbinols has been developed via one-pot reaction of indoles and paraformaldehyde in the presence of an excess of CaO, MgO, ZnO or TiO(2). The solvent-free reaction provided all the indole derivatives in moderate to good yields and short reaction times. Moreover, the effect of some selected indole-1-carbinols on cell proliferation of the hepatoma cell line FaO was evaluated.