Ptelea trifoliata L. (Rutaceae) is a bush of North American origin that has been cultivated in Europe since the eighteenth century. Pharmacological properties (particularly bacteriocidal and cytotoxic activities) are due to the presence of coumarins and quinoline alkaloids.
Botany and Distribution
Ptelea trifoliata’s common names include: quinine tree, potato chip tree, and hop tree (the latter being the most widely used today); in Spanish, Cola de Zorillo; in French Ptelea a 3 feuilles, trefle de Virginie, Orme de Samarie – this last name was first used in France around 1800 and is still widely used ().
Ptelea trifoliata L., described by Linnaeus in 1753, is extremely variable in its morphology and chemical composition. This explains the description of numerous varieties which have often been raised to the rank of species. The most recent revision of the genus Ptelea is by Bailey () who recognizes only three species: Ptelea trifoliata L., Ptelea crenulata Greene, and Ptelea aptera Parry, although he subdivides P. trifoliata into five subspecies and ten varieties.
The Ptelea species are deciduous bushes, 3-4 m tall, with trifoliate aromatic leaves (). A large number of detailed descriptions exist (). There have been many studies of the floral morphology, most recently that of Ambrose et al. () which clearly confirms the dioecious nature of this species, with only 2% of otherwise male plants producing a few hermaphrodite flowers and fruits. These fruits are two-celled samaras (). The seeds germinate weakly; this is certainly linked to the presence of inhibitors in this species ().
The present habitat of Ptelea trifoliata is central and southern parts of North America, where it is often localized, and hence designated as “rare” or “endangered” in Ontario and in four states of America ().Ptelea trifoliata seems to have originated in southern Mexico where certain populations have persisted in the earliest colonized areas, while others have migrated toward the north in the soils made available after glacial retreat (). Geological and climatic fluctuations since the tertiary era account for the great number of varieties and forms, more or less linked by hybridization. In a chemotaxonomic study on the genera Ptelea, Bailey et al. () used the coumarin and alkaloid patterns of 150 specimens as a means of determining the relationship between different subspecies and varieties. We recently analyzed the dihydrofuro[2,3-b]quinolinium alkaloid patterns of trees belonging to natural populations in Ontario. They were sometimes quite different: studying these patterns alongside morphology would possibly yield a better characterization of these populations ().
Pharmaceutical uses of Ptelea have been known through the reports of an English army doctor, Schoepf, who noted that the Canadian populations used the leaves as a antihelminthic and for healing of wounds ().
The most frequently reported medicinal properties concern the tonic, stomachic, and aperitive effects of the root bark, which is more active in this respect than flowers, fruit, or leaves (). The antipyretic properties of root bark, used in Louisiana before the introduction of quinine, account for the common name of “quinine tree”. Spencer et al. () found that this root bark also showed weak antimalarial properties, but trials using material from our collection – trees growing in the Botanical Garden in Tours – showed no antimalarial activity although antipyretic activity was observed ().
The antimicrobial and tuberculostatic properties reported by King and Lloyd (1886) have been confirmed by more recent studies: various alkaloids and coumarins with bacteriocidal properties have been isolated, in particular quaternary alkaloids such as pteleatinium () and ptelefolonium ().
Other physiological properties of coumarins and alkaloids are listed in Table “Physiological activities of some coumarins and alkaloids”. The plant possesses toxicity proportional to the alkaloid content of its organs, stem bark being the most toxic and seeds the least (). Also, dermatitis has been reported after contact with the leaves and this reaction is almost certainly linked to the presence of coumarins and some alkaloids ().
Ptelea trifoliata is currently used in treatment of gastric disorders due to its spasmolytic activity: it is included, for this reason, in some French homoeopathic preparations (). It was listed in the American Pharmacopoeia from 1878 to 1941. It remains a folk remedy in many Eastern European countries and in India.
Conventional Practices for the Preparation. Production of Medicinal Compounds
Acclimatized in Europe very early, Ptelea trifoliata is now cultivated throughout the world. Cultivation is possible under all conditions of soil and exposure, and sowing is carried out directly after harvest, the dormant seeds needing 2-4 months at 1 °C (). Other cultivation methods used include layering and grafting under frames on young seedlings.
The Hungarian team of Reisch, Szendrei and Novak, known for their work on Ruta graveolens (), began the analysis of Ptelea trifoliata in 1969, resulting in the identification of a large number of alkaloids and coumarins responsible for the majority of the biological activities. Parallel research on antimicrobial substances by Mitscher et al. () and that on plant growth inhibitors by Garestier and Rideau () have resulted in the isolation of many alkaloids, particularly quaternary ones. Some of them (ptelefolonium and hydroxyluninium) have a prominent cytotoxic effect both on KB tumorous cells and Wi 38 human cells (). More recently, our group isolated two new dihydrofuro[2,3-b]quinolinium alkaloids: ptelecultinium and ptelefolidonium (). Various flavonoids () and essential oils () were also obtained.
The chemical variability encountered in parallel with the morphological variations most likely explains the differences observed in pharmacological activity between extracts prepared from different sources of Ptelea trifoliata. In fact, two of the alkaloids reported to be responsible for the major physiological properties of the extracts, ptelefolonium and kokusaginine, are completely absent in some samples.
Biogenetically, furoquinolines are derived from anthranilic acid. Key intermediates are 2,4-dihydroxyquinoline and 3-dimethylaIlyl-4 methoxy-2 quinolone. Recently, it was found that an S-adenosyl L-methionine-anthranilic acid N-methyl transferase and an N-methyl anthranilic acid “activating” enzyme are involved in the first steps of quinoline alkaloid biosynthesis in Rutaceae (). Only one study of the dimerization of the pyranoquinoline, N-methylflindersine, has been conducted on Ptelea trifoliata (). It may be of interest to note that coumarins and quinolines both derived biogenetically from anthranilic acid.
In Vitro Culture of Ptelea Is Possible But Difficult
Most of the stem explants developed primary callus. This required the addition of coconut milk to the culture media. However, it was not possible to obtain cell lines from all the trees. Certain trees are better suited to in vitro culture than others. Thus, the importance of the genotype of origin for in vitro is shown for Ptelea trifoliata. This observation should be considered in conjunction with the difficulty in obtaining cell lines from Ptelea trifoliata protoplasts.
Dihydro [2,3-b] Quinolinium Is Accumulated in Ptelea trifoliata Tissue Cultures
The different cell lines and protoclones showed important genotypic variations in growth, pigmentation, friability as well as in alkaloid content. A new alkaloid, ptelecultinium, was present in all cell cultures, irrespective of the tree of origin: although absent in stems, it accumulated rapidly in the primary explants, while the other quaternary alkaloids which were present in the explant progressively decreased. It appears, therefore, that alkaloid metabolism can change very rapidly once the explant is no longer under the regulatory control of the whole plant. Ptelecultinium was mostly dominant in the in vitro cultures often associated with ptelefolonium. This alkaloid pattern is similar to that of roots and cotyledons where ptelecultinium has been isolated (). This correlation in chemical composition between in vitro cultures and roots has been observed in two members of Rutaceae, Choisya ternata and Ruta graveolens (unpublished) and also by Wink ().
Apparently, the in vitro Ptelea trifoliata cultures are unable to reach the level of chemical differentiation of the cells of stems or flowers, and therefore offer a choice of material for the analysis of the early stages of metabolite biogenesis.
Future developments are possible in several directions:
- Further knowledge of the quinoline alkaloid biogenesis pathway;
- Optimization of the production of quinoline alkaloids by the use of elicitors;
- Search of new dihydrofuroquinoline alkaloids by the use of somatic fusions between protoplasts obtained from different genotypes;
- Further knowledge of pharmacological properties of the isolated dihydro-furoquinolinium alkaloids.
Selections from the book: “Medicinal and Aromatic Plants IV”, 1993.