The information was extracted by reading through the entire text. All the texts were written in the vernacular Greek of the respective time, some of them with a Cypriot-Greek coloring. The language is relatively well comprehensible to a reader with knowledge of Modern Greek. When required, specific dictionaries, etymological lexica (Hadjiioannou, 2000; Papangellou, 2001), or glossaries (Myrianthopoulos, 1925; Kostoula, 1991) were consulted. The disorders or symptoms that were mentioned in a recipe were first translated using popular medicinal and medicinal literature or glossaries dealing with the topic of the local nomenclature of diseases (Myrianthopoulos, 1925; Kyriazis, 1926; Chrysanthis, 1944, 1988; Kyprianou, 1987). Ancient names of conditions were cross-checked with their correspondents in the “Deutsches Krankheitsnamen-Buch” (Höfler, 1899). Complementary information including the general medical situation and the diseases prevalent on the island at that time was drawn from books on the local history of medicine (Koureas, 2006; Marangou and Georgiadis, 2006; Stavridis, 2006). Particular care was taken to retain the original wording of a use mentioned in a text. The translated use was then cross-checked with a German edition of “Harrison's principles of internal medicine” (Dietel et al., 2003) or “Health Topics” of the Medline Plus database¹ and if required transcribed into the appropriate clinical term. To accomplish this, a clear understanding of the mentioned condition was essential. However, many of the medicinal uses were ambiguous and sometimes difficult to link to a particular clinical term. For example, the condition “wound on the leg that opens again and again out of its own” can be interpreted as a chronic wound perhaps associated with infection and inflammation or more specifically a venous ulcer.

From the established basic inventory records referring to resin and gum exudates were selected. These also included related products such as volatile oil separated through distillation of the resin or wood tar which usually was obtained through a dry distillation by burning resinous wood in an oven (Blaschek et al., 2007).

By applying linguistic and pharmacognostic criteria a substance was first identified on the basis of the substance name and then assigned to the appropriate botanical source. To establish the identity of a substance the iatrosophia name was cross-referenced with plant or substance names listed in:

After the identity had been established the substance was assigned to the appropriate botanical source based on the information in up-to-date or if necessary also earlier pharmacognostic reference books (Richter, 1827; Tschirch and Stock, 1935/1936; Howes, 1949; Berger, 1964; List et al., 1972; Langenheim, 2003; Blaschek et al., 2007; Nussinovitch, 2010) and other scientific literature. In cases where the respective species can be found in Cyprus this was done using the “Flora of Cyprus” (Meikle, 1977/1985) or other botanical literature on the local flora (Della, 1999; Tsintides et al., 2002; Hadjikyriakou, 2007). All references were cross-checked. Scientific plant names were checked with the Tropicos, Missouri Botanical Garden², or International Plant Name Index³.

Following the approach of Kufer et al. (2005) every use of a substance mentioned in one of the texts was counted as one use report (UR). Records referring to identical uses of a substance within the same text were considered duplicates and removed from the list. Finally, every medicinal use was categorized into 1 of the 12 pre-established medicinal use groups (UGs) largely based on body systems: CA – Cardiovascular and blood, EE – Ears and eyes, DE – Dermatological, FV – Fevers (including malaria), GI – Gastrointesinal and hepatic, GY – Gynecological, HA – Headache and migraine, MS – Musculo-sceletal, OC – Oral cavity, RE – Respiratory tract, UG – Urogenital, VA – Various conditions.

To reveal similarities of the use pattern of a substance, a comparison was conducted between the UGs treated by the uses mentioned in iatrosophia and those mentioned in: (i) Berendes’ (1902) German translation of De Materia Medica of Dioscorides; (ii) Western pharmaceutical books from the era before plant drugs were largely abandoned from mainstream medicine including British Pharmaceutical Codex, 2nd Edition (Council of the Pharmaceutical Society of Great Britain, 1911) and United States Dispensatory (Remington and Woods, 1918). They both were accessed via the online catalog of Henriette's Herbal Homepage; (iii) Authoritative standard texts of phytotherapy in Europe including German Commission E Monographs (BGA, 1978–1994), British Herbal Compendium, Volume 1 (Bradley, 1992), Potter's Herbal Cyclopedia (Williamson, 2003), Hagers Enzyklopädie der Arzneistoffe und Drogen (Blaschek et al., 2007) and ESCOP monographs (ESCOP, 2009). For this purpose, every medicinal use of a substance mentioned in these references was categorized into one of the 12 UGs [see Quantification and Categorization of the use Reports into Use Groups (Steps 5 and 6)]. For each substance the established UGs were then juxtaposed to those in iatrosophia and evaluated based on the number of UGs of the substances the compared texts had in common.

To enable a one-to-one association between the substance and the mentioned use the detailed comparison to reported bioactivity data was conducted involving only simple remedies. These are remedies that include only one active substance, as opposed to compound remedies which contain two or more of them. The method was adopted from the protocol for analyzing historical texts introduced by Buenz et al. (2004, 2005) and included two basic steps, the extrapolation of the pharmacological functions of a substance and the cross-referencing to reported bioactivity data. In a first step the pharmacological therapy required for the treatment of the respective condition was looked up in “Goodman and Gilman's pharmacological basis of therapeutics” (Brunton et al., 2006) or “Health Topics” of the Medline Plus database⁴. The pharmacological properties of the suggested therapy were deduced or, if specified, directly adopted and assigned to the respective substance as presumable pharmacological functions. In doing so, we relatively strictly adhered to the information stated in these references and at the same time disregarded less common causes of a respective disease. The procedure is illustrated by the following example: According to recipe GP PMH 05 crude gum Arabic should be eaten to stop the “flux of the belly,” which according to Höfler (1899, p. 29, “Bauchfluss”) is diarrhea. Most cases of diarrhea are caused by a disturbed intestinal water and electrolyte balance or altered intestinal motility, a medical intervention would include liquid- and electrolyte replacement, bulk-forming agents, motility, or secretory inhibitors. Diarrhea can also be associated with inflammatory bowel disease or microbial infection (Brunton et al., 2006). Assuming that gum Arabic would in fact be able to influence diarrhea bulk-forming, antimotility, antisecretory, anti-inflammatory, or antibiotic effects are likely to be involved in its action. Next, the Web of Knowledge (ISI Web of Knowledge Service for UK Education, Thomson Reuters) and EMBASE (Elsevier Science Publishers) were surveyed for bioactivity data of the respective substance using flexible combinations of substance or species name together with the deduced pharmacological functions as search words. The reported activities were then compared with the associated pharmacological functions and cross-referenced.

The simple remedies in iatrosophia were compared to De Materia Medica of Dioscorides (Berendes, 1902) and “Medical Compendium in Seven Books” of Paulus Aegineta (Adams, 1844/1846/1847). Dioscorides had a distinct influence on the development of the medicinal knowledge in areas from northern Europe to the Indian Ocean (Riddle, 1985, p. xvii). Paulus Aegineta's early Byzantine work is a “distillation of classical drug theory which captured the essence” (Scarborough, 1984, p. 229). As he wrote before the emergence of Arabic/Islamic medicine an influence on his work from this side could be excluded.

In the third recipe on page 14 of the Iatrosophikon of Mitrophanous (recipe IM 14.03) pounded “píssa tou xylalá” is applied on an open fracture of the cranial bone obviously to protect the injury and promote healing. In IM 63.03 the pounded substance is dissolved in rum and then extracted in the sun for 8 days, the resulting “tincture” is drunk as a remedy against podalgia. The name “píssa tou xylalá” can be attributed to all of the above three substances (i, ii, iii).

According to recipe PME 01 in the Geoponikon (GP PME 01) drinking every morning cherry gum dissolved in water should relieve cough, improve liver health and vision as well as “make the face look bright.” While in GP PME 02 the gum dissolved in wine is recommended in stones. Looking at Dioscorides’ account on the gum (Berendes, 1902, 1.157) reveals that the iatrosophia appear to have borrowed from this reference. Paulus Aegineta, too, mentioned the above recipe for stone affections and the gum's ability to ease “asperities of the trachea” (Adams, 1844/1846/1847, 7.3, 167).

The symptoms listed in GP PME 01 could be related to a defined disease of some specific organ or, in their entirety, a complex systemic disease or even intoxication. While cherry gum can hardly boast of bioactivity data, another natural gum typically composed of sugar polymers is comparatively well explored. Namely, for gum Arabic a number of the actions have been suggested which are related to some of the pharmacological functions deduced from the above recipes. In Sudan, the gum is prescribed in chronic renal failure (CRF) due to its ability to decrease uremia levels or reduce the frequency of dialysis. In a preliminary study involving 36 CRF patients, a significant improvement of the metabolic profile could be observed in the groups receiving 50 g gum Arabic daily in comparison to baseline and control (Ali et al., 2008). Although gum Arabic seems to lack a direct hepatoprotective action, 100 mg administered intraperitoneally suppressed macrophage activation and attenuated the extent of liver injury in a rat model of induced hepatic necrosis (Mochida et al., 1996).

In recipe GP PΞΓ 02 an ointment containing frankincense, pig fat, and egg white was prepared for the topical treatment of “every kind of rheumatism.” The Roman encyclopedist Celsus (ca. 25 BCE – 50 CE), wrote that frankincense was beneficial in the treatment of gout (Martinez et al., 1989) and Paulus Aegineta applied it in a powder-mix for the same condition (Adams, 1844/1846/1847, 7.13, 539).

The majority of studies conducted with Boswellia resins refer to Indian frankincense from B. serrata, which according to the ESCOP monographis indicated for “relief of painful osteoarthritis” or “treatment of inflammatory bowel disease.” Numerous studies have been conducted both with the resin and its constituents, they suggest among others anti-inflammatory and immunomodulatory activities (ESCOP, 2009). Some of these data are based on boswellic acids. These pentacyclic triterpenic acids are characteristic for Boswellia resins including those from African or Arabian species and, therefore, relevant in the context of the above iatrosophia remedy. In fact, studies reviewed by Moussaieff and Mechoulam (2009) showed the potential of these compounds in animal models of arthritic conditions.

However, studies actually conducted with the resin of African or Arabian Boswellia species are limited. One of these studies investigated the anti-inflammatory activity of extract fractions and triterpene acids isolated from the resin of B. carteri in TPA-induced ear edema in mice. Topically applied hexane- and EtOAc-soluble fractions (1.0 mg/ear) exhibited potent inhibitory activities (91–94% inhibition, p < 0.01 significant from control). Isolated di- and triterpenes, with the exception of incensole acetate, exhibited marked anti-inflammatory activities (ID₅₀ values of 0.05–0.49 mg/ear). Some of the compounds were equally or more active than the positive controls hydrocortisone (ID₅₀ 0.03 mg/ear) or indomethacine (ID₅₀ 0.3 mg/ear) respectively (Banno et al., 2006). The resin of B. carteri (B. carterii) was also investigated for its potential to influence adjuvant-induced arthritis in rats. The tested acetone extract administered intragastrally at a dose of 0.9 g/kg (average body weight: 224.63 g) significantly suppressed arthritic scores, attenuated paw edema and decreased cytokine levels (TNF-α, IL-1 β), compared to control (Fan et al., 2005).

In an in vitro model of osteoarthritis, 100 μg/ml of an absolute ethanol extract from the resin of B. frereana (the dose was selected as a result of a dose response study on isolated articular chondrocytes) showed a protective effect against cartilage loss by inhibiting breakdown of the collagenous matrix mainly through inhibition of pro-inflammatory mediators (Blain et al., 2010).

According to recipe IM 134.05 drinking pounded galbanum in water will expel a dead embryo/fetus. The same use was mentioned by the authors of “On the Diseases of Women,” one of the Hippocratic treatises (Riddle, 1992), by Dioscorides (Berendes, 1902: 3.87(97)) as well as by Paulus Aegineta (Adams, 1844/1846/1847, 3.61, 611).

The use of uterine stimulating herbs during pregnancy is regarded as a potential risk factor for a spontaneous abortion (Johns and Sibeko, 2003). Although the ancient use might suggest to place galbanum among these herbs, no studies reporting contractile effects on the uterus are available. Based on its traditional use in the treatment of diarrhea, Sadraei et al. (2001) instead investigated the spasmolytic effects of essential oil and extracts of the gum resin from Ferula gummosa on the contraction of isolated rat ileum. Ether, petrol and methanol extracts inhibited the contractions induced by 80 mM KCl most potently (IC₅₀ values: 0.55, 1.4, and 7.5 μg/ml, respectively). Etheric or petrolic extracts attenuated the maximum attainable response of ACh with IC₅₀ values of 10 or 5.1 μg/ml, respectively. The authors argued that at least part of the inhibitory effect was due to α- and β-pinene, two common constituents of the essential oil, ether, and petrol extracts. As shown in a study with the essential oil of Bupleurum fruticosum L., another Apiaceae, fractions containing substantial amounts of these two monoterpenes are able to exert antispasmodic effects on the uterus of the rat (Lorente et al., 1989). While this points to some possibly relevant effects, no direct evidence for the induction of labor or abortion exists for galbanum. Perhaps the iatrosophia use of galbanum should not be linked to a later stage of pregnancy as purported by the wording of the above recipe but rather to earlier stages or fertility control in general. Rosemary (Rosmarinus officinalis L., Lamiaceae), for example, has known antispasmodic in vivo effects on the uterus and is used in tea mixtures for fertility control in Central America (Lemonica et al. (1996).

The gum ingested with old wine and some food is said to be a remedy in diarrhea (GP PMH 05). Dioscorides in discussing akakia, used the juice of the pods to “bind a loose belly” and was also acquainted with the astringent properties of the gum (Berendes, 1902, 1.133). Paulus Aegineta was mixing akakia with other herbs for the treatment of dysentery (Adams, 1844/1846/1847, 7.12, 530–531, 534–535). Finally, the gum has been reported as a dysentery remedy from Senegal (Watt and Breyer-Brandwijk, 1962, cited in Maiga et al., 2005).

Published studies on biological effects of the gum have been reviewed in detail by Ali et al. (2009). In particular the effects on the gastrointestinal tract were rated positively; Gum Arabic improved small intestinal absorption of sodium and water in two rat models of induced diarrhea (Wapnir et al., 1997; Codipilly et al., 2006). Other rats recovering from diarrhea induced by cathartic agents gained more weight and had lower fecal output when additionally supplemented with the gum (Teichberg et al., 1999). In general, the in vivo data suggest a potential benefit of gum Arabic in the context of diarrhea and malabsorption caused by infection or intestinal dysfunction.

In a multicenter randomized placebo controlled study 144 boys aged 1–36 months suffering from diarrhea received an oral rehydration solution with or without a mixture containing 9% gum Arabic in addition to other non-digestible carbohydrates. However, since no significant group differences in stool volume, duration of diarrhea, duration of hospital stay and need of intravenous rehydration could be observed, the mixture was considered ineffective (Hoekstra et al., 2004).

To heal hemorrhoids accompanied by an anal eczema, 10 dr (drámi) ladanum were heated in 4 dr olive oil, spread on a piece of cloth and applied as a poultice on the affected area. This treatment should be continued for 8 days (IM 48.02). According to recipe IM 128.03 exposing the scalp to smoke of ladanum would stop hair loss. In fact, Ladanum was used to treat hair loss by Dioscorides (Berendes, 1902, 1.128) as well as by Paulus Aegineta (Adams, 1844/1846/1847, 3.1.5/8, 339 and 7.3.11, 208). While both of them knew of its applications in liniments or plasters (Adams, 1844/1846/1847, 7.18.8, 578; Berendes, 1902, 1.128), in particular the latter author made specific reference to abscesses, furuncles, or ulcers (Adams, 1844/1846/1847, 4.34.2, 94–95 and 4.39.1, 103). (for synonyms see Inventory of Resins and Gums and Table 3)

While no data are available regarding alopecia, a number of studies investigated potential actions of the Cistus resinor its compounds that could be of relevance in the treatment of hemorrhoids or eczema. Ladanum from C. creticus subsp. creticus exerted only a weak antibacterial activity against Staphylococcus aureus, S. epidermidis, and S. hominis (MIC 2 mg/ml; Demetzos et al., 1999), although its chloroform–methanolic extract showed some inhibitory activity against several bacteria (Acinetobacter anitratus, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, S. aureus; Kalpoutzakis et al., 1998). Isolated sclareol and another labdane type diterpene inhibited the growth of the three tested Staphylococcus germs with a MIC of 0.1 mg/ml which is 100-fold lower than streptomycin (Demetzos et al., 1999).

Because ladanum is exuded from the glandular hairs of stem and leaf (Hadjikyriakou, 2007, p. 174), bioactivity data on lipophilic compounds of the leaves or corresponding lipophilic extracts should not be disregarded; Pure ethanolic extracts of C. incanus subsp. tauricus and C. aff. creticus at a dose of 10 μg/ml showed an antioxidant effects with TEAC values of 3.6 and 2.5, respectively (Trolox: IC₅₀ = 0.63 ± 0.02 μg/ml). However, no significant inhibition of the tested inflammatory parameters (IL-6, IL-1β, TNF-α, PGE₂, NF-κB) could be shown (Taila et al., 2008). Similarly, in an anti-inflammatory model, no significant effect on the skin barrier repair could be observed with two labdane diterpenes from the leaves of C. creticus subsp. eriocephalus (Viv.) Greuter and Burdet which were applied on the back of hairless mice (5% solution, 25 μl/cm³) previously exposed to UV-B irradiation (Demetzos et al., 2001).

For the therapy of rheumatic conditions and podalgia a poultice is prepared using píssa mávri (IM 64.2). This name denotes cooked resin known as resina nigra (Table 2), the dark-colored quality of rosin (Richter, 1827). The pounded substance is dissolved in hot barley gruel, the mass is then spread on a piece of cloth of the size of the affected area be it the knee, ankle, or hand. Dioscorides mentioned that one of the properties common to all resins was their warming effect (1.91), in particular “burnt” resin was used in plasters or ointments (1.93; Berendes, 1902). Paulus Aegineta mentioned poultices containing “turpentine” for the treatment of rheumatic diseases and gout (Adams, 1844/1846/1847, 3.78, 663, 665). Arnold-Apostolides (1985) recorded several medicinal uses of topical applications of resin and tar from P. brutia, P. nigra ssp. pallasiana, and P. halepensis from various places in Cyprus. Similar uses and applications were also reported in another ethnobotanical study conducted in western Anatolia (Turkey) for the resin from P. nigra ssp. pallasiana and P. brutia (Honda et al., 1996).

These poultices act as a rubefacients, irritants, and counter-irritants. They certainly will achieve an increase of blood flow in the area of application, which may favor the absorption of anti-inflammatory secondary metabolites. In this context, an ethyl alcohol extract of turpentine (crude pine resin) from Pinus nigra ssp. pallasiana showed an in vivo anti-nociceptive effect when administered internally thus supporting the existence of such active principles. The extract revealed a dose-dependent analgesic effect in a writhing response in mice induced by acetic acid at a dose of 25 mg/kg. Metamizol at 200 mg/kg and the resin extract at 50 mg/kg showed a comparable effect (Gülçin et al., 2003). However, the pharmacological effects of topically applied preparations can only be of any relevance in arthritic inflammations if the active principle is able to penetrate the skin. In fact, certain of the possibly involved compounds show a topical bioavailability and suggest direct anti-inflammatory effects. The diterpene abietic acid, for example, is one of the major compounds in the non-volatile fraction of the resin of P. brutia (Gören et al., 2010). In a TPA-induced mouse ear edema model topically applied abietic acid inhibited the development of swelling in a significant and dose-dependent manner. The highest dose (1 mg/ear) showed an inhibitory effect of 74.8% being in the similar range as the effect of indomethacin (0.5 mg/ear, inhibitory effect approx. 90%; Fernández et al., 2001).

Another study investigated the in vivo anti-inflammatory activity of an ethyl-acetate extract from the bark of P. brutia in comparison to Pycnogenol^®, a standardized bark extract of French maritime pine Pinus maritima Lam. In the carrageenan induced rat paw edema model the intraperitoneal administration of each of the preparations inhibited paw-swelling dose-dependently exhibiting significant anti-inflammatory activities at doses of 75 and 100 mg/kg. At these doses P. brutia extract also showed a significantly stronger activity than 10 mg/kg of indomethacin (Ince et al., 2009).

According to GP PKΘ 06 drinking plum gum dissolved in red wine also dissolves the “stones of dysuria.” This recipe, obviously related to the doctrine of signatures and an alternative of GP PME 02 (cf. 3.4.2), was already mentioned by Dioscorides (Berendes, 1902, 1.175) and again by Paulus Aegineta (Adams, 1844/1846/1847, 7.3, 180). From the villages of Cyprus plum gum was reported as a tonic, laxative, and vermifuge in substitution of more expensive gums (Arnold-Apostolides, 1985). No bioactivity data were available for this exudate.

In IM 41.05 a drink is prepared by mixing 1/3 dr scammony and 1 dr of sugar in some water. This remedy would purge easily expelling all “depositions and poisons.” Repeating the therapy after 1 month would keep off “fevers, shivers, and quartan fevers” (malaria caused by Plasmodium malariae) for the rest of the year. Although Dioscorides was well acquainted with the purgative effects of scammony [Berendes, 1902, 1.168(171)] and Paulus Aegineta applied the drug in numerous simple and compound remedies for this purpose (Adams, 1844/1846/1847, 7.3, 341 and 7.4, 481), neither of them mentioned fever or malaria. Unlike these two, the physician Alexander of Tralles from Lydia in Asia Minor, who wrote in the sixth century, highlighted the usefulness of scammony in “quartan” and other fevers linking their cause to excessive “bile and phlegm” (Puschmann, 1878/1879, p. 1.384).

Beside Convolvulus scammonia, several other species of the Apocynaceae and Convolvulaceae provide some sort of scammony, the resinous exudates obtained from the root. Mexican scammony, for example, is obtained from Ipomoea orizabensis (G. Pelletin) Ledeb. ex Steud., Convolvulaceae. This and the former species are recognized to act as laxatives or drastic purgatives due to the resin glycosides present in the exudate (Williamson, 2003; Blaschek et al., 2007). A number of these resin glycosides including scammonins isolated from Ipomoea tricolor and I. orizabensis were tested against different S. aureus strains. Synergistic effects between these compounds were observed, revealing direct bactericidal (MIC values 4–32 μg/ml compared to 0.25 and 64 μg/ml for tetracyclin), resistance disabling or antibiotic potentiating effects (Pereda-Miranda et al., 2006). However, studies investigating the potential of scammony or its compounds against malaria causing pathogens (Plasmodium spp.) are lacking.

In recipes KI 9.01/10.01 and IM 89.03 terebinth resin was pounded, mixed with egg yolk and used as a ointment or applied in a poultice for the treatment of infected, ulcerative, or malignant wounds and deep cuts. To ease urination problems the pounded resin was spread on a piece of bread and eaten (IM 149.03). The latter use could be related to bladder stones, some infection, prostate hyperplasia or cancer. Dioscorides in referring to all resins highlighted their diuretic properties, their use in leprosy or in plasters, poultices, and ointments (Berendes, 1902, 1.91). Paulus of Aegina was making copious use of (rētinē) terebinthinē in topical applications such as plasters or ointments for abscesses, swellings, foul, and spreading ulcers or phagedena (Adams, 1844/1846/1847, 4.41, 4.44, 7.17–7.20). Several references from the Roman Antiquity and the European Renaissance to early modern periods mention the use of the terebinth resin to treat various cancers, tumors, carcinomas and indurations (Hartwell, 1967). Recent accounts on the use of resin from P. atlantica are equally limited as such for P. terebinthus. One report from Iraq documents that resin from Pistacia trees (P. atlantica Desf. and P. khinjuk Stocks in Hook.) was applied as an antiseptic to wounds by local inhabitants (Guest and Al-Rawi, 1966, p. 107). Another recipe (IM 137.05) recommends exposing an infant to the smoke of terebinth resin to stop diarrhea. Medicinal smokes are popular in many cultures; the treatment of diarrhea by smoke inhalation has also been reported from Guyana and North America for leaves and stems of two members of the Lauraceae but the understanding of the pharmacodynamics of medicinal smokes is limited (Ben Amar, 2006).

Bioactivity studies investigating the resin of P. atlantica are lacking and quantitative analytical data are restricted to the volatile fraction. The crude oleo resin is rich in essential oil, 32.6% were measured in samples from Morocco with α-pinene accounting for 42.9% (Barrero et al., 2005). Corresponding figures for the variety P. atlantica var. mutica were 22.0 and 70.0%, respectively (Delazar et al., 2004). Different qualities of essential oil of the resin from P. atlantica were tested for their antimicrobial potential against seven bacteria (E. coli, E. cloacae, K. pneumoniae, Xanthomonas maltophilia, P. aeruginosa, Enterococcus faecalis, S. aureus) and three different strains of C. albicans. The MIC for the Gram-positive and Gram-negative bacteria were ≤10 and 10² μg/ml, respectively, and for C. albicans between 10³ and 1 mg/ml (Benabderrahmane et al., 2009).

Alpha-pinene isolated from the turpentine oil of Pinus pinaster Aiton exhibited a distinctive bioactivity against various isolates of Actinomadura madurae with MICs ranging between 3.3 and 5.0 μl/ml (positive control streptomycin: 29.8–50.0 μl/ml) and a minimum microbicidal concentration (MMC) of 10.0 μl/ml (streptomycin: 50.0–75.0 μl/ml). This pathogen is the main cause of actinomycetoma, an infectious skin disease which is able to eventually form a tumor and cause problematic secondary infections (Stojkovic et al., 2008). The same monoterpene compound isolated from the essential oil of Ugni myricoides (Kunth) O. Berg, Myrtaceae, was investigated for its anti-hypernociceptive potential in a model of neuropathic pain of the sciatic nerve in mice. Alpha-pinene orally applied at doses of 25 and 50 mg/kg was capable of abolishing the hypernociceptive response with inhibitions of 64 and 89%, respectively. This effect was comparable to gabapentin, a drug clinically used to treat neuropathic pain (70 mg/kg, orally applied: inhibition of 88%; Quintão et al., 2010).

The potential of resin extracts from P. terebinthus L. var. chia to protect LDL from oxidation was dependent on the polarity of the solvent and ranged between 27.0 and 49.5%. A corresponding extract from Chios mastic gum (P. lentiscus L. var. chia) showed a distinctly higher protection rate sometimes more than doubling the one achieved with the terebinth resin (Andrikopoulos et al., 2003).

Anti-inflammatory and anti-phospholipase A₂ activities of a methanolic extract from P. terebinthus L. galls were investigated in a number of animal models. In TPA- or EEP-induced mouse ear edema models topically applied extract (1 mg/ear) revealed a 58 or 44%, respectively, inhibition of chronic inflammatory swelling. Orally applied extract (200 mg/kg) inhibited paw edema induced by PLA₂ from two different types of venoms by 48–67% (Giner-Larza et al., 2000). In partially identical mouse models the same group tested four different triterpenes from P. terebinthus L. galls administered in concentrations between 0.3 and 1 mg/kg topically and 30 mg/kg intraperitoneally (Giner-Larza et al., 2001 and 2002). Two isoforms, masticadienonic acid and masticadienolic acid, were also found in turpentine resin (Blaschek et al., 2007). They both showed significant inhibitory activities in ear and paw edemas. The latter additionally inhibited leukotriene B₄ production in rat polymorphonuclear leukocytes with an IC₅₀ of 16.6 μM (apigenin IC₅₀ of 13 μM; Giner-Larza et al., 2002).

Altogether 28 studies were included in this comparison (Table 6). Although several further studies were found in the literature search, the unusual high concentrations of the test samples applied in the respective assays eventually questioned the significance of the suggested biological activities and made us abstain from including them. Similar observations were made by Adams et al. (2009) when discussing the results of bioscientific studies in relationship to the uses described in the European Renaissance herbals. This problem was addressed by Gertsch (2009) in a commentary regarding the interpretation of molecular pharmacological data in ethnopharmacological publications. The author argued that much of the problem is related to a misemployment of the concentration-effect paradigm and the overinterpretation of in vitro data.

The comparison of the deduced pharmacological functions with matching biological activities reported in the literature revealed an overall fragmentary picture in terms of the available data (Table 6). While for cherry gum (Prunus avium) no matching data were found, plum gum (Prunus domestica), solid storax (S. officinalis) and, apart from its essential oil, terebinth resin from P. atlantica do not appear to have been explored at all. For the remaining 9 of the 12 substances, which to a certain extent have been the subject of medicinal or pharmacological research, one or more studies were available that reported some sort of matching effects. Frankincese, gum Arabic and pine resin had corresponding bioactivity data for at least half of the deduced pharmacological functions. The majority of the associated data were linked to studies including mainly in vitro (11) and animal models (14) only two studies included data from patients. In several of these models, however, isolated compounds, extracts from other plant parts or compound preparations and not the substance mixture were tested. Some of the studies referring to gum Arabic, ladanum, and turpentine resin also reported inactivity, weak, or non-significant effects. Nevertheless, in the great majority of the cases the available studies reported positive results. At least four cases have appropriate data available which allows to draw direct conclusions on the putative pharmacological effectiveness of the respective substance, because the associated in vivo studies were actually conducted with the plant exudate or its full extract and showed meaningful results; For the iatrosophia use of pine resin in rheumatic conditions and podalgia corresponding evidence is available demonstrating the analgesic potential of a crude resin extract from P. nigra subsp. pallasiana. Moreover, both from other historical texts as well as ethnobotanical studies various topical applications of pine resins were reported. Overlapping uses with ethnobotanical data “can lend strength and credibility to a lead which originated from a historical text” (Hunt, 1996, p. 92). Ethnomedical uses supporting the findings of animal studies were reported too for applications of gum Arabic as a diarrhea remedy, frankincense from Boswellia carteri in the treatment of rheumatic diseases and Sumatra or Siam benzoin as an antiseptic agent.