Botanical drugs, synergy, and network pharmacology: forth and back to intelligent mixtures

For centuries the science of pharmacognosy has dominated rational drug development until it was gradually substituted by target-based drug discovery in the last fifty years. Pharmacognosy stems from the different systems of traditional herbal medicine and its "reverse pharmacology" approach has led to the discovery of numerous pharmacologically active molecules and drug leads for humankind. But do botanical drugs also provide effective mixtures? Nature has evolved distinct strategies to modulate biological processes, either by selectively targeting biological macromolecules or by creating molecular promiscuity or polypharmacology (one molecule binds to different targets). Widely claimed to be superior over monosubstances, mixtures of bioactive compounds in botanical drugs allegedly exert synergistic therapeutic effects. Despite evolutionary clues to molecular synergism in nature, sound experimental data are still widely lacking to support this assumption. In this short review, the emerging concept of network pharmacology is highlighted, and the importance of studying ligand-target networks for botanical drugs is emphasized. Furthermore, problems associated with studying mixtures of molecules with distinctly different pharmacodynamic properties are addressed. It is concluded that a better understanding of the polypharmacology and potential network pharmacology of botanical drugs is fundamental in the ongoing rationalization of phytotherapy.

[In Medea's gardens--two tales of colchicine]

Colchicine is a highly active alkaloid used in the treatment of acute inflammatory syndromes such as Mediterranean fever, M. Behçet or gouty arthritis. The two cases we present here illustrate exemplarily the pros and contras of colchicine therapy. In the first case, colchicine was successfully given for recurrent febrile attacks due to acute rheumatic fever. The second patient unfortunately had a fatal colchicine intoxication. The pharmacology of colchicine, the clinical features associated with overdose and the options for treatment are discussed. Colchicine should not be given in combination with macrolides, especially in patients with renal insufficiency.

Non-naturalized alien plants receive fewer flower visits than naturalized and native plants in a Swiss botanical garden

Many animal-pollinated plant species have been introduced to non-native regions without their usual pollinators. Nevertheless, some of these alien species managed to establish reproducing naturalized populations, which might negatively affect native plants. Recent studies have shown that many naturalized alien species can readily attract native pollinators. However, it is not known whether alien species that have not established naturalized populations are less successful in attracting pollinators. Therefore, we tested whether flower-visitation rates are lower for non-naturalized aliens than for naturalized alien and native species. We conducted a comparative study on flower visitation of 185 native, 37 naturalized alien and 224 non-naturalized alien plant species in the Botanical Garden of Bern, Switzerland. Our phylogenetically corrected analyses showed that non-naturalized alien species received fewer flower visitors than both naturalized alien and native species. Native, naturalized alien and non-naturalized alien species were visited by similar flower-visitor communities. Furthermore, among the naturalized alien species, the ones with a broader distribution range in Switzerland received a more diverse set of flower visitors. Although it has been suggested that most alien plants can readily integrate into native plant–pollinator networks, we show evidence that the capacity to attract flower visitors in non-native regions is different for naturalized and non-naturalized alien plants. Therefore, we conclude that successful naturalization of alien plants may be related to flower visitation.

Variation in life-history traits and their plasticities to elevational transplantation among seed families suggests potential for adaptative evolution of 15 tropical plant species to climate change

• Premise of the study: Because not all plant species will be able to move in response to global warming, adaptive evolution matters largely for plant persistence. As prerequisites for adaptive evolution, genetic variation in and selection on phenotypic traits are needed, but these aspects have not been studied in tropical species. We studied how plants respond to transplantation to different elevations on Mt. Kilimanjaro, Tanzania, and whether there is quantitative genetic (among-seed family) variation in and selection on life-history traits and their phenotypic plasticity to the different environments. • Methods: We reciprocally transplanted seed families of 15 common tropical, herbaceous species of the montane and savanna vegetation zone at Mt. Kilimanjaro to a watered experimental garden in the montane (1450 m) and in the savanna (880 m) zone at the mountain’s slope and measured performance, reproductive, and phenological traits. • Results: Plants generally performed worse in the savanna garden, indicating that the savanna climate was more stressful and thus that plants may suffer from future climate warming. We found significant quantitative genetic variation in all measured performance and reproductive traits in both gardens and for several measures of phenotypic plasticity in response to elevational transplantation. Moreover, we found positive selection on traits at low and intermediate trait values levelling to neutral or negative selection at high values. • Conclusions: We conclude that common plants at Mt. Kilimanjaro express quantitative genetic variation in fitness-relevant traits and in their plasticities, suggesting potential to adapt evolutionarily to future climate warming and increased temperature variability.