AbstractThe long-lasting discussion, why plants produce secondary metabolites, which are pharmacologically and toxicologically active towards mammals traces back to the eminent role of medicinal plants in the millennia-old history of manhood. In recent years, the concept of an animal plant warfare emerged, which focused on the co-evolution between plants and herbivores. As a reaction to herbivory, plants developed mechanical defenses such as thorns and hard shells, which paved the way for adapted animal physiques. Plants evolved further defense systems by producing chemicals that exert toxic effects on the animals that ingest them. As a result of this selective pressure, animals developed special enzymes, e.g. cytochrome P450 monooxigenases (CYP450) that metabolize xenobiotic phytochemicals. As a next step in the evolutionary competition between plants and animals, plants evolved to produce non-toxic pro-drugs, which become toxic only after ingestion by animals through metabolization by enzymes such as CYP450. Because these sequestered evolutionary developments call to mind an arms race, the term animal plant warfare has been coined. The evolutionary competition between plants and animals may help to better understand the modes of action of medicinal plants and to foster the efficient and safe use of phytotherapy nowadays.Graphical abstract
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