Ageratina adenophora

2014

The family Asteraceae comprises some 20,000 species and is the second largest family of higher plants. Considering the size of this family it is interesting to note that relatively few species are commercially exploited as food plants, whereas a comparatively large number is known to accumulate poisonous natural products such as sesquiterpene lactones that are cytotoxic or elicit contact allergy or liver toxic pyrrolizidine alkaloids. In evolutionary terms, the Asteraceae is still a young plant family that has nevertheless successfully spread worldwide. There is now increasing evidence suggesting that the accumulation of toxic natural products forms a major ecological contribution to the successful radiation of the Asteraceae as well as of other families, enabling plants to fight off herbivors or pathogenic microorganisms. In search of new sources of potentially useful natural products that may become important as key structures for designing new drugs or agrochemicals, it is appropriate to focus on those species that are the most vigorous and have successfully adapted to different habitats, since they can be expected to contain an effective arsenal of interesting biologically active compounds.

A representative of this former group of promising species from the Asteraceae is Ageratina adenophora (Spreng.) K. & R. (tribe Eupatorieae) (common name “jediondo” or “hierba negra” in Spanish). Whereas the core of Ageratina is restricted to the western parts of the Americas, A. adenophora is widely adventive in many tropical and subtropical parts of the world. The weedy character, vigorous growth, and dispersal of this species cause problems, for example on several of the Canary islands, where this species had been introduced in the last century and now represents a threat to several of the autochtonous species.

Previously we could show that seedlings of A. adenophora accumulate several chromene derivatives but no benzofurans. Chromenes as well as structurally related benzofurans are frequently encountered in species of the Asteraceae especially from the tribes Astereae, Eupatorieae, Heliantheae, Inuleae, or Senecioneae. Most of the compounds known so far have been isolated from species that grow under arid or semi-arid conditions like A. adenophora. Encecalin, as well as demethoxyencecalin, is toxic to an array of insects (including for example the migratory grasshopper Melanoplus sanguinipes, the variegated cutworm Peridroma saucia, or the milkweed bug Oncopeltus fasciatus), and they are assumed to have evolved as an effective chemical defense of plants against herbivorous insects. The toxicity of chromenes is not restricted to insects only, since encecalin, for example, was also shown to be phototoxic to several bacteria and yeasts in longwave UV light. In comparison to chromenes like encecalin, the structurally related benzofurans seem devoid of insecticidal activity. Several benzofurans, however, have been reported to be bacteriostatic, toxic in a goldfish bioassay, phototoxic to several bacteria and yeasts, or to exhibit antitumor activity. Chromenes and benzofurans thus represent a group of natural products exhibiting a wide array of interesting biological activities. Very little, however, is known of the physiology and biochemistry of chromenes and benzofurans in plants. This may be partly due to problems arising in cultivating suitable plants under experimental conditions. We have now established and studied cell suspension cultures of A. adenophora as a model in vitro system to gain insight into the metabolism of chromenes and benzofurans and into processes leading to the induction of chromene and benzofuran accumulation.

Chromenes and benzofurans exhibit a plethora of biological activities and seem to be of importance for the chemical defense of plants. Studies on the biosynthesis and on the metabolism of chromenes and benzofurans in differentiated plants have so far been hampered by the fact that most of these compounds accumulate in species that grow under arid or semi-arid conditions, and are difficult to germinate and to grow in a greenhouse or phytotron. As shown here for Ageratina adenophora, cell suspension cultures offer an alternative and easily accessible experimental approach to study metabolic processes related to the biosynthesis, biotransformation, and induction of chromenes and benzofurans. However, several of the data achieved in this study seem to apply only to cell suspension culture of A. adenophora and do not reflect the metabolism in differentiated plants of this species. Benzofurans, for example, that are among the prominent natural products of cell suspension cultures following treatment of the cultures either with encecalin or with yeast extract are not detected in plants of A. adenophora and can therefore be regarded as cell culture metabolites only. The increased accumulation of benzofurans in cell suspension cultures following addition of encecalin or of yeast extract offers an interesting experimental system to study biochemical processes related to the induction of an enhanced natural product accumulation. In the case of yeast extract our data indicate an elicitation of the biosynthesis leading to an increased level of constitutively present natural products. In the case of encecalin no final explanations can be given at present. A modulation of the balance between benzofuran synthesis and degradation seems possible.

Medicinal and Aromatic Plants III (1991)