Herbal drugs in European tradition - A phylogenetic, chemosensory and neuropharmacological approach

Historical texts have emerged as valuable tools to study the therapeutic knowledge of past cultures. Dioscorides’ De Materia Medica (DMM), written in the 1st century CE is one of the most influential historical texts on use of herbal drugs in the Euro-Mediterranean area and inventories over 1000 plant, animal and mineral drugs. Despite the impact of DMM on modern (herbal) medicine the content of this work has never been systematically assessed. This thesis studied the herbal drugs described in DMM (ex Matthioli, 1568) using a multi-disciplinary approach. The aims were I) to analyze the use of botanical drugs in the ancient Mediterranean world; II) to provide historical background data to better contextualize modern herbal medicine; III) to characterize the influence of chemosensory properties of herbal drugs on their therapeutic usage; and IV) to systematically screen herbal drugs in European tradition for cannabinomimetic effects. A quantitative survey of the plant knowledge described in DMM resulted in a database comprising 5314 unique therapeutic uses of 536 plant taxa and 924 herbal drugs. Salient patterns in the data, such as the frequent mention of Apiaceae exudates for the treatment of neurological and mental disorders, are discussed. It is suggested that drugs that lost importance over time, remedies for diseases now controlled by industrially produced drugs and preventive medicine might be interesting starting points for research on herbal medicine and drug discovery. A diachronic analysis estimated the causal effect of the ancient works by Dioscorides and Galen on contemporary herbal medicine in three Italian provinces. The analysis of 87 commonly used medicinal plant taxa suggests that ancient scripts have exerted strong influence on the usage of herbal medicine until today. It is concluded that the repeated empirical testing and scientific study of therapeutic claims guides the selection of efficacious remedies and evidence-based herbal medicine. Methodological problems associated with the classification of pathologies in pre- and non-scientific knowledge systems are addressed. Three different classification systems are proposed and critically discussed in terms of their potential application in ethnobotany and ethnomedicine. Based on the plant descriptions in DMM, botanical fieldwork in the Euro-Mediterranean area (2014 – 2016) resulted in the collection of a botanical library comprising 697 herbal drugs derived from 404 species. Extracts of 436 herbal drugs were bioassayed for inhibitory activity on fatty acid amide hydrolase (FAAH), a major target of the endocannabinoid system. The phytochemistry and ethnopharmacology of the most active hits are discussed in relation to observed ECS modulation. A comparison of cannbinomimetic activity and traditional uses of herbal drugs showed that specific categories of use were at best only weak predictors of the measured FAAH inhibitory effects. To test how taste and smell properties correlate with the therapeutic use of medicinal plants, chemosensory profiles of 697 herbal drugs were experimentally assessed in 4026 sensory trials. Both specific flavor properties and overall flavor bouquet complexity resulted as predictors of plant use. The results support previous claims that the compilation of DMM was guided partly by plant taste and smell. It is suggested that chemosensory cues are important criteria for the selection of food and herbal drugs, supporting and expanding specific flavor use-links reported in the literature. Overall, the results of this thesis perpetuate the view that ancient texts have potential for 1) natural products research; 2) contextualizing contemporary phytopharmacy; 3) theory building in medical anthropology.