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Back to the roots: a quantitative survey of herbal drugs in Dioscorides' De Materia Medica (ex Matthioli, 1568).

ABSTRACT

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.

Keywords:

Europe

Herbal medicine

History

Mediterranean

Pharmacopoeia

Renaissance

Introduction

Over the past decade, research on medicinal plants has increasingly turned to historical medico-botanical texts both to study the development of pharmacopoeias as well as to identify candidate species for drug discovery (e.g. Adams et al., 2011; Buenz et al., 2005; dal Cero et al., 2014; Lardos and Heinrich, 2013; Leonti et al., 2010; Touwaide, 2010). There is a broad consensus that ancient herbals such as Dioscorides' De Materia Medica and Galen's De simplicium medicamentorum facultatibus have influenced and guided the development of Mediterranean and European herbal medicine (Mann, 1984; Riddle, 1985; Tschirch, 1910). In addition, recent diachronic studies traced back elements of contemporary herbal medicine to Dioscorides' De Materia Medica (dal Cero et al., 2014; De Vos, 2010; Lardos et al., 2011; Leonti et al., 2015, 2009). Despite the profound influence on western herbal medicine, the content of De Materia Medica has hitherto not been quantitatively assessed.

This paper presents a comprehensive survey of the herbal remedies described in the Renaissance translation of De Materia Medica by Pier Andrea Matthioli (1568) and analyzes botanical, therapeutic and diachronic patterns. Moreover, we introduce a software-assisted technique allowing for a transparent extraction of textual information. Given Dioscorides' importance, a systematic assessment and reappraisal of De Materia Medica may help to better contextualize research in phytotherapy and herbal medicine. In particular, this study may guide research on novel phytotherapeutic agents, inform safety evaluations and help to prove tradition of use in the context of drug regulation (Helmstadter and Staiger, 2014).

Dioscorides' De Materia Medica

Dioscorides of Anazarbos (Asia Minor; 1st century CE) is the author of De Materia Medica, which is the most detailed pharmacognostic guide from the ancient Mediterranean world passed down (Riddle, 1980). In about 800 chapters Dioscorides monographed over 600 different kinds of plants, 35 animals and 90 minerals, and summarized what was considered to be the consensus on efficacious medicine (Riddle, 1971). To compile the treatise, Dioscorides drew on previous writings, his own experience as a physician as well as on local traditions in the Mediterranean and the Near East (Riddle, 1985:3-4; Scarborough, 2012). Based on geographical references in the text, Dioscorides' compilation is thought to be the fruit of extensive journeys while the predominant but contentious view is that he travelled as a military physician of the Roman army (Riddle 1985:2-4; Scarborough and Nutton, 1982:213-217).

The historical impact of De Materia Medica is epitomized by the fact that for over one and a half millennia its content has been extensively copied, edited and translated into different languages (Riddle, 1980). By the end of the 15th century, this development resulted in a myriad of complexly interrelated Greek, Latin, Syriac and Arabic manuscripts that circulated in the Mediterranean and the Near East (Riddle, 1980). Apart from these copyedited texts, Dioscorides also influenced many medieval codices as well as Arab scholars such as Serapion the Elder (9th century), Avicenna (980-1037), and Ibn al-Baitar (1197-1248), whose scripts temporarily eclipsed De Material Medica in popularity (Riddle, 1980; Stannard, 1966). Dioscorides' reception in Europe was restored in the late 15th--16th centuries. During that time Renaissance humanists recovered ancient Latin and Greek botanical manuscripts (Palmer, 1985; Reeds, 1976; Stannard, 1966), which thanks to the advent of book printing techniques were disseminated amongst a wider public, also in different European vernaculars (Reeds, 1976).

Matthioli's renaissance commentary

Arguably the most important Renaissance commentator of Dioscorides, both in terms of popularity and textual output, was Siena (Italy) born Pier Andrea Matthioli (1501-1578) who dedicated large parts of his life to the study of medicine and botany (Kuhnel, 1962; Leonti et al., 2010; Riddle, 1980). Upon reception of his medical degree from the University of Padua in 1523 and after having collected additional experience as a surgeon in Rome, Matthioli soon became personal physician of Archduke Ferdinand I of Austria and his successor Maximilian II (Kuhnel, 1962; Stannard, 1966). Under their patronage Matthioli worked intensively on his commentary on De Materia Medica, which he first published in 1544. This and all his subsequent editions of De Materia Medica are based on Jean Ruel's (1474-1537) Latin translation from 1516 of the Greek editio princeps (printed by Aldus Manutius in Venice in 1499). One of the reasons for Matthioli's popularity was that his commentary had a high practical value for readers who were concerned with legibility of the text rather than with philological accuracy (Stannard, 1969). Moreover, Matthioli included plant identifications in the form of multilingual vernaculars. Following his initial success Matthioli soon started producing further versions of his text in Latin and multiple European vernaculars, making available classical herbal tradition to a wider audience. An extensive network of correspondents provided Matthioli with notes and specimens, which helped to improve his commentary. In addition, from 1554 onwards, Matthioli equipped his work with woodcuts, which further facilitated the identification of the described simples (Riddle, 1980; Stannard, 1969). Overall, Matthioli's commentary on Dioscorides (It.: discorsi, Lat.: commentarii) enjoyed wide success among professionals, such as physicians, pharmacists and plant collectors, without sufficient command of Latin. According to Matthioli's dedicatory letter to the Archduchess of Austria, the combined print run of all pre-1568 Italian versions together totaled at least 30,000 copies (Matthioli, 1568). Even long after Matthioli's death his commentary continued to be printed so that by the end of the 17th century about 60 different editions, reprints and translations had been published in Italian, Latin, German, French and Czech (Fabiani, 1872). Consequently, Matthioli was regarded as the dominant interpreter of Dioscorides and his translation and commentary remained the main pharmaceutical reference for Italian pharmacists and physicians until the end of the 17th century (Cosmacini, 1997:264; Ferri, 1998).

Materials and methods

The medico-botanical analysis of historical texts poses several methodological challenges such as the modern interpretation of past pathologies and the identification of pre-Linnaean plant descriptions (Lardos, 2015; Touwaide, 2010). Data sourced from pre-scientific texts are by their nature interpretations limiting their objective evaluation. Therefore, we consulted previously proposed methods to ensure the reliability of the generated data as far as possible (Buenz et al., 2004; Evergetis and Haroutounian, 2015; Lardos et al., 2011; Touwaide, 2010). In the following we describe the employed methodology and exemplarily point out specific problems and explain how these were addressed.

Text source

This study is based on Matthioli's (1568) translation of De Materia Medica in the form of a five-volume facsimile printed by the Stabilimento Tipografico Julia in Rome between 1967 and 1970, henceforth referred to as "De Materia Medica". This was Matthioli's first Italian edition with enlarged woodcuts (Stannard, 1969). We chose Matthioli's translation as a proxy for Dioscorides' text because (I) unlike the current standard edition (Wellmann, 1906-1914), Matthioli (1568) facilitates the identification of the often scantly described simples; (II) Matthioli's medico-botanical expertise imparts authority resulting in practical yet qualified interpretations; and (III) it is written in Italian and therefore easily accessible to readers without any knowledge of Latin or Ancient Greek. Particularly the 1568 edition was selected because it is available in facsimile and one of Matthioli's later and thus repeatedly revised versions of the text. The content analyzed in this study comprises only Matthioli's translation of Dioscorides' text printed in roman type. Matthioli's italicized commentaries on Dioscorides' chapters were not considered as these contain Renaissance knowledge (Fig. 1). Of all 831 chapters attributed to Dioscorides we only included those 531 that deal with single botanical substances (i.e. plant simples or drugs). Chapters dealing with drugs derived from animal (inch human), mineral, fungal, algal or other sources, as well as processed plant parts (e.g. distillates, pickles or colophony) and compound drugs (e.g. unguents, incense mixtures or flavored wines) were disregarded. Moreover, we excluded unspecific (e.g. generic woods or resins) and spuriously described botanical drugs.

Data management

Data extraction from De Materia Medica was done in ATLAS.ti (version 7.5.4), a proprietary software commonly used in the social sciences to explore and manage large amounts of unstructured primary data. We chose this tool because it allows for rapid extraction of text quotes from a written source and for linking these quotes to interpretative codes, which in our case were therapeutic categories of use. By coding our data this way, we could thus separate the original text (the emic or historical perspective) from our biomedical interpretation (the etic or scientific perspective) and maintain our analysis transparent (Leonti and Weckerle, 2015). Plant uses were extracted and databased through line-by-line reading of a digitized and OCRed (optical character recognition) version of Matthioli (1568). The PDF version of Matthioli (1568; Books 1-6) can be found in the supplementary material.

The basic units of analysis were single uses of herbal drugs, including insect repellents, poisons and foods. For each usage mentioned in the text we recorded (I) the chapter number, (II) the putative botanical identity, (III) the reported plant part, (IV) the described symptom, ailment or specific use (V) the mode of administration, (VI) our modern (viz. biomedical) interpretation of the described symptom or ailment as well as (VII) the category of use under which we filed the specific use. Each recorded combination of the variables I-V was counted as one individual (therapeutic) use. Data conversion and plotting were done using R and several add-on libraries (Feinerer and Hornik, 2015; R Core Team, 2016; Thuiller et al., 2014; Wei, 2013; Wickham, 2015).

Classification of historical uses

The following eleven plant parts or products were differentiated: Ashes (i.e. charred plant matter), barks, exudates (incl. gums, resins and saps), flowers (incl. inflorescences and parts thereof), fruits (incl. parts thereof), herbs (incl. branches and shoots), leaves, oils (e.g. olive oil), seeds (incl. seed-like fruits), subterranean parts (incl. bulbs, rhizomes, roots and tubers) and wood (incl. pith). Seed-like fruits, such as Apiaceae indehiscent schizocarps or Urtica spp. achenes, were classified as seeds.

The modes of administration were divided into four groups: Internal (e.g. infusions and pills), external (e.g. baths, mouthwashes, ointments and poultices), fumigations (incl. smokes and steams) and clysters (incl. enema, pessaries and suppositories). Therapeutic uses were classified into organ-, symptom- and ailment- defined categories of use largely following the bioprospecting-oriented classification scheme proposed by Staub et al. (2015). The applied 21 categories of use comprise; Andrology (incl. male fertility), antidotes (internally applied), cardiovascular problems (incl. both suppositories and internal applications against hemorrhoids), dermatology (e.g. abscesses, cosmetics, skin inflammations, tumors, wounds and external applications against hemorrhoids and animal bites/stings), fever (incl. malaria), food (incl. spices), gastroenterology (e.g. carminatives, colics, diarrhea, dysentery, liver and spleen), gynecology (incl. female fertility), libido regulators (i.e. aphrodisiacs and anaphrodisiacs), musculoskeletal ailments (e.g. cramps, fractures, gout, hematoma and spasms), neurology (incl. psychosomatic ailments), ophthalmology (i.e. eye problems), oral cavity (e.g. dentistry, gums and tonsils), others (e.g. magic, indefinable pathologies, unspecific inflammations, veterinary medicine and uses related to humoral pathology without any link to specific organs), otology (i.e. ear problems), parasites (e.g. lice, scabies and tapeworms), poisons (e.g. hunting or fish poisons), repellents (e.g. against insects), respiratory system (e.g. asthma, coughs, dyspnea and tuberculosis), rhinology (incl. epistaxis and polyps) and urology (e.g. diuretics, dropsy, kidneys and painful urination). This classification system was chosen particularly to facilitate future comparative and quantitative studies. It is noteworthy, however, that the leveling of historical terms to fit biomedical categories may misrepresent ancient Mediterranean medical concepts and disease delimitations.

Difficulties with the translation of historic terms for diseases and symptoms into modern biomedical terminology were resolved by consulting Matthioli's (1568) vocabulary included in volume five as well as the Vocabolario degli accademici della Crusca (online, 2015). In this context, it is important to mention that spleen disorders were treated as gastrointestinal (and not lymphatic) conditions because in Ancient Greek medicine the spleen was variously regarded co-responsible for humoral balance and thus possibly perceived as being related to the proximate digestive system (Paraskevas et al., 2016). This is in line with the finding that textual mentions of spleen afflictions in De Materia Medica usually appear along with gastrointestinal problems in the narrower sense. Also, special attention was given to mentions of nerves ("nervi"), since due to the ancient confusion between nerves, tendons and ligaments (Haubrich, 2003:156) the addressed organ can only be interpreted through the context. Several obscure historical pathologies could not be translated unequivocally into modern terms and were thus included in the category of 'others'. One of these is "rotti e spasimati" (including the less frequent variant "fraccassati e spasimati"), which literally translates into "(the) ruptured and (the) spastic." Based on the fact that textual mentions of rotti e spasimati were often preceded by respiratory conditions such as cough and followed by abdominal ailments such as side stitch, we initially hypothesized that this disease may translate into some advanced form of tuberculosis. However, since rotti and spasimati also occurred as isolated symptoms (of which the former, "/ rotti" (i.e. "(the) ruptured"), was left unclassified and the latter, "/ spasimati" (i.e. "(the) spastics"), was counted as a musculoskeletal ailment) the compound term was assumed to represent symptoms of unknown pathology.

Plant identifications

Plant identifications were established by crosschecking the descriptions in De Materia Medica with the Flora Europaea (Tutin et al., 1968-1993) and the pharmacognostic discussions presented in Berendes (1902 and references therein). Berendes (1902) reviews the botanical identifications of the Dioscoridean simples proposed by authorities such as Theophrast (ca. 371-287 BCE), Pliny (23-79 CE), Sibthorp (1758-1796) and Sprengel (1766-1833). In cases where the kind(s) of plant(s) described in a single chapter (e.g. book IV, chap. 96: Dell'Ortica) was (were) found to correspond to two or more closely related taxa (e.g. Urtica dioica L., U. membranacea Poir. ex Savigny, U. pilulifera L., U. urens L.) we limited our interpretation to one inclusive scientific taxon (e.g. Urtica spp.) per chapter. In other cases, where clearly distinguishable species were treated in one chapter (e.g. in Book I, Chap. 132: De tutte le Mele (on all apples)), these were identified separately (i.e. as Citrus medica L., Cydonia oblonga Mill., Malus domestica Borkh., Prunus arme niaca L, Primus persica (L.) Batsch). Species names were checked against The Plant List 1.1 (2013 and references therein) and family names follow the Angiosperm Phylogeny Group 4 (APG IV, 2016).

Results and discussion

General patterns

In total 536 plant taxa including 924 drugs were recorded. Of these, 316 taxa could be identified to the species level including 563 drugs, 128 taxa were identified to the genus level including 234 drugs and 27 taxa were only identified to the family level including 37 drugs. For 65 taxa, including 90 drugs, no identification was possible. Arbutus unedo L. (Arbuto; book I, chap. 139) and Calystegia sepium (L.) R. Br. (Smilace liscia; book IV, chap. 147) are not recommended for any use and were thus not considered. Overall, 5314 medical uses (i.e. unique combinations of a specific taxon, plant part, route of administration and specific use) were recorded for the 536 mentioned taxa. Internal applications such as pills or infuses (2655 uses) and external applications such as poultices, sitz baths or eye drops (2350 uses) prevail, while enemas, suppositories and pessaries (235 uses) as well as steams and fumigations (74 uses) are less frequent (Fig. 2). The categories including most uses are dermatology (1216), gastroenterology (805), gynecology (615), urology (437), respiratory system (374) and neurology (269; Fig. 2). Both a compact and a full dataset of the recorded plant taxa, plant parts and therapeutic uses are presented in the supplementary material (Tables S1 and S2).

Most drugs (894 derived from 512 taxa) are derived from Mediterranean floristic elements including those species previously introduced. Central European elements are represented by the aromatic alpine species Valeriana celtica L. and Sedum roseum (L.) Scop, (syn.: Rhodiola rosea L.). A smaller number (30 drugs derived from 24 taxa) are exotics that have been imported from Africa, Arabia, Central Asia, Himalaya or the indo-Malayan ecozone. This shows that ancient Mediterranean herbal medicine was deliberately enriched with foreign materia medica (Miller, 1969; Touwaide and Appetiti, 2013). Most drugs stem from subterranean organs (212), seeds (190), herbs (165) and leaves (161; Fig. 3). The drugs derive from members of 109 vascular plant families with Asteraceae (46 species; 74 drugs), Apiaceae (44 taxa; 85 drugs), Lamiaceae (36 taxa; 44 drugs),

Fabaceae (27 taxa; 35 drugs) and Rosaceae (20 taxa; 40 drugs) comprising the most taxa.

Medico-botanical patterns

To characterize therapeutic preferences the associations between taxonomy, plant part and category of use were analyzed (Figs. 4-7, S1-2). Apiaceae are frequently cited for gastroenterology (91), gynecology (90), urology (72) as well as neurology (45). Apiaceae seeds are important as antidotes (20) and their exudates frequently recommended for musculoskeletal ailments (19). Lamiaceae are often mentioned for gastroenterology (66), dermatology (65) and gynecology (62), while specifically Lamiaceae herbs and leaves are dominant for the treatment of the respiratory system (31). Other associations include the use of Fabaceae seeds for dermatology (55), Rosaceae fruits for gastroenterology (20), Araceae subterranean parts for ophthalmology (12) and Amaryllidaceae drugs for rhinology (10). The drugs described in De Materia Medica show high taxonomic and therapeutic diversity indicating a comprehensive snapshot of ancient Mediterranean herbal medicine. The symptoms and ailments addressed largely match the therapeutic spectrum of a general practitioner rather than that of a military physician. This was already observed by Riddle (1985:2-4) who noted that the high frequency of gynecological uses combined with the few treatments for battle wounds is unusual for an army doctor. Apart from this hint at Dioscorides' professional life, the overall picture of therapeutic uses allows inferences about the epidemiology in the Roman Empire in the 1st century CE. Many uses cover infectious diseases such as abscesses (111), dysentery (82), and ear infections (16) as well as infestations by scabies (59) and tapeworms (37), which indicate poor sanitation and hygiene. Moreover, the large number of uses for envenomations (193) and the presence of animal repellents (31) reflect ecologically less controlled environments. The sporadic mention of remedies against tertian and quartan fever (11) testifies to the prevalence of malaria in the Mediterranean.

Important categories of use

Dermatological uses are the most frequent (1216; Fig. 2) and cover ailments such as ulcers (205), abscesses (107), animal stings and bites (only topical applications; 106), wounds (60), erysipelas (58), burns (42), tumors (31), gangrene (26), fistula (25), skin inflammations (25), indurations (24), carbuncles (21), chilblains (19), pustules (17) and dandruff (16). The remedies for these conditions are taxonomically diverse, including 438 different drugs derived from 319 plant taxa. Fabaceae seeds account for a comparably high number of uses in this category (55; Fig. 5) and comprise peas (Pisum sativum L.), chickpeas (Cicer arietinum L.), lentils (Lens culinaris Medik.), fenugreek (Trigonella foenum-graecum L.), bitter vetch (Vi'cia ervilia (L.) Willd.) and lupine (Lupinus spp.). Legume seeds contain significant amounts of protease inhibitors (Birk, 1996) that may beneficially modulate epidermal homeostasis, which is dysregulated in various skin disorders (de Veer et al., 2014).

Gastrointestinal uses (805; Fig. 2) comprise diarrhea (138), dysentery (82) spleen afflictions (80), jaundice (60), abdominal pain and stomachache (76), liver problems (38), flatulence (20), hiccup (13), hematemesis (eleven) and vomiting (eleven) as well as uses as purgatives (62) and carminatives (13). Lamiaceae herbs and leaves (62) as well as Apiaceae seeds (38) are the most frequently recommended simples (Fig. 5) including species like Menta x piperita L., Melissa officinalis L., Origanum vulgare L. and Carum carvi L., which are well known stomachics and carminatives containing large amounts of essential oil (Hansel and Sticher, 2007; Wichtl, 2002). Amelcorn (Triticum dicoccon (Schrank) Schubl.), apart from being called nutritive ("abondantemente nutrisce"), is also praised for its positive (but not further specified) effects on the stomach (book II, chap. 87) and exemplifies the blurred boundaries between ancient dietetics and medicine (Totelin, 2015).

Gynecology is the third largest category of use (Fig. 2) and mainly covers pre- and perinatal uses (204), various uterine and vaginal conditions (131) and applications for controlling the menstrual cycle (71). Explicit abortifacient (17) and contraceptive (four) uses are rare, but as discussed in Riddle (1992:31-32), these may be implied within emmenagogues. Lamiaceae herbs and leaves (51) as well as Apiaceae seeds (36) were the most frequently mentioned drugs in this category (Fig. 5).

The category of nervous system and psychosomatic disorders (269; Fig. 2) includes general analgesics (72), headache (50), soporifics (31), epilepsy (36), fatigue (16), paralysis (11), lethargy (6), frenzy (6), melancholy (3) and mood enhancers (3). Apart from the expected prevalence of Solanaceae (23) and Papaveraceae (17) drugs many uses are based on Apiaceae (45) such as Apium graveolens L., Heracleum sphondylium L., Opopanax spp., Peucedanum officinale L., Pimpinella anisum L., Seseli tortuosum L., three species of the genus Ferula L. as well as the notoriously cryptic Silphium (Laserpitio; book III, chap. 88). This clustering may be due to the presence of coumarins, which are known to have various effects on the central nervous system in vitro and in vivo, including anticonvulsant, anxiolytic, antidepressive, neuroprotective and procognitive activities (Skalicka-Wozniak et al., 2016). Additionally, phenyl propanoids such as myristicin, present in different Apiaceae (Hall, 1973), may contribute to neurological effects (Hallstrom and Thuvander, 1997). Three of the six Crassulaceae drugs are recommended for headache (i.e. the subterranean parts of Sedum roseum as well as the leaves of Aeonium arboreum Webb & Berthel. and Sedum amplexicaule DC.).

Diachronic aspects

While many uses such as those of Lamiaceae drugs for gastroenterology and respiratory problems are still popular today, the applications of drugs with problematic side effects and high risk/benefit ratio (e.g. Aconitum spp., Bryonia spp., Chelidonium majus L., Convolvulus scammonia L., Delphinium staphisagria L.) have disappeared or are less prominent. For the same reason, drugs from the genus Euphorbia (20 derived from nine taxa) are avoided in European herbal medicine today. However, the genus Euphorbia is currently regaining attention in drug discovery (Ernst et al., 2015).

Wetland taxa (e.g. Alisma spp., Cressa cretica L., Hippuris vulgaris L., Lemna minor L., Nuphar lutea (L.) Sm., Persicaria hydropiper (L.) Delarbre, Sparganium spp. and Trapa natans L.) appear to be over-represented in De Materia Medica as compared to modern herbal pharmacopoeias. Changing ecological management regimes resulting in a loss of wetland areas and availability of these drugs are probably the main factor responsible for this shift. Several other drugs, which are less important today, derive from early domesticated crops (e.g. Citrus medica L., Sorbus domestica L., Triticum dicoccon (Schrank.) Schubl. and Vida ervilia (L.) Willd.) and arable weeds (Agrostemma githago L., Bongardia chrysogonum (L.) Spach and Leontice leontopetalum L.). In contrast, several species important in contemporary European phytotherapy as well as for the production of biomedical drugs are apparently not mentioned in De Materia Medica. These include Borago officinalis L., Calendula officinalis L., Digitalis spp. and Humulus lupulus L.

The few drugs mentioned for cardiovascular problems (13) are mainly remedies for hemorrhoids and varicose veins (8) while two are recommended against cardiac chest pain (i.e. the leaves of raspberry and blackberry), two for vasodilation (flowers and roots of Cymbopogon schoenanthus (L.) Spreng.) and the ash of Ficus carica L. as a blood liquefier. The low number of drugs and uses in this category contrasts with the importance of phytotherapeutics for cardiovascular diseases today and may reflect epidemiological shifts and differences in nosologies and disease etiologies.

With respect to the specific plant organs, drugs derived from subterranean parts, seeds and exudates appear more frequent in De Materia Medica as compared to modern pharmacopeias. Subterranean plant parts may have lost importance as sources for drugs due to their comparably time consuming collection, which is, moreover associated with a negative impact on wild populations. The historical prevalence of these drugs testifies to their past importance and alludes to the so-called rhizotomoi, who were specialist collectors and traders of root drugs. Several plant exudates may have been eliminated from modern herbal medicine because of toxicological concerns or their potential for allergic reactions (Lardos et al., 2011). Moreover, the collection of plant exudates is costly and overharvesting might have compromised their supply. In one case (book III, chap. 88: Laserpitio commonly known as Silphium) this might have even led to the extinction of a species (Koerper and Rolls, 1999).

Via trade, the use of seeds as medicine very probably contributed to the dispersal of germplasm (Beinart and Middleton, 2004, Brockway, 1979:36), which at the same time must have had a self-affirming effect on the transmission of the associated pharmaceutical knowledge. However, the removal of antidotes from the European phytotherapeutic heritage is in part responsible for the reduced importance of seed drugs today. Irrespective of the reasons for why subterranean organs, seeds and exudates became partly obsolete such drugs once formed an important but nowadays neglected part of the Euro-Mediterranean dispensatory. This, together with the fact that seeds, resins and gums are considered unconventional natural resources, potentially rich in yet unknown metabolites (Tulp and Bohlin, 2004), calls for further research on their phytochemistry and pharmacology.

Conclusions

This paper presents a data mining approach and a survey of the herbal drugs contained in Dioscorides' De Materia Medica (ex Matthioli, 1568). Besides human medicine De Materia Medica also covers foods, cosmetics, repellents, poisons and plant uses related to animal husbandry and spiritual practice. By using a systematic data extraction technique we elucidated several salient therapeutic patterns. These include the importance of Fabaceae seeds for dermatology, the frequent mention of Apiaceae seeds as antidotes, the use of Amaryllidaceae bulbs for rhinology, the application of Araceae tubers for ophthalmology and the reliance on exudates from Apiaceae for neurology as well as musculoskeletal ailments. The former existence of the rhizotomoi, who were specialized root collectors and traders in ancient Greece, is reflected in the large number of drugs derived from subterranean plant parts. Moreover, the past importance of wetland species and the frequent uses against envenomations and intoxications mirrors the closer interaction of past societies with their biological environment and different ecological, epidemiological and hygienic conditions. The systematic analysis of herbal texts offers unique insights into past herbal medicine. We suggest that those drugs with discontinued use might represent interesting starting points for drug discovery and the evaluation of ancient herbal medicine. Comparing such data with contemporary herbal medicine and phytotherapy might enhance our understanding of modern practices and help to document the tradition of use, which is required for the regulatory approval of new herbal drugs.

http://dx.doi.org/10.1016/j.phymed.2016.06.016

ARTICLE INFO

Article history:

Received 30 April 2016

Revised 9 June 2016

Accepted 21 June 2016

Conflict of interest

The authors declare to have no conflict of interest.

Acknowledgments

This project has received funding from the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement no. 606895.

Supplementary materials

Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j.phymed.2016.06.016.

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P.O. Staub (a), L. Casu (b), M. Leonti (a), *

(a) Department of Biomedical Sciences, University of Cagliari, via Ospedale 72, 09124 Cagliari, Italy

(b) Department of Life and Environmental Sciences, University of Cagliari, via Ospedale 72, Cagliari, Italy

Abbreviations: CE, common era; Chap., chapter; It., Italian; Lat., Latin; Spp., species pluralis.

* Corresponding author. Tel.: +390706758712, Fax: +390706758553.

E-mail address: marcoleonti@netscape.net, mleonti@unica.it (M. Leonti).

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Author:Staub, P.O.; Casu, L.; Leonti, M.
Publication:Phytomedicine: International Journal of Phytotherapy & Phytopharmacology
Article Type:Survey
Geographic Code:1USA
Date:Sep 15, 2016
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