Patterns of Genetic Variation of <i>Nepeta nuda</i> L. from the Central Balkans: Understanding Drivers of Chemical Diversity

<i>Nepeta nuda</i> L., a notable medicinal species in the tradition of the Balkan region, is a rich source of bioactive iridoids and phenolics previously described as high-resolution taxonomical classifiers for the genus <i>Nepeta</i>. However, their potential in investigating intra-species differentiation is here described for the first time. The aim was to recognize the sources of natural chemical diversity and their association with the genetic variability both within and among <i>N. nuda</i> populations in the Central Balkans. Chemical diversity was assessed from methanol extracts and essential oils through untargeted and targeted metabolomics using state-of-the-art analytical tools, covering a broad spectrum of compounds that represent the <i>N. nuda</i> metabolome. We found that chemodiversity primarily resides within populations of <i>N. nuda</i>, and similar results were obtained at the DNA level using microsatellite markers. The low genetic and chemical differentiation of the studied <i>N. nuda</i> populations implies that their metabolomic profiles may be less influenced by geographic distance and variable environmental conditions within the Central Balkans, as they are under the pivotal control of their genetic backgrounds. Screening the distribution of the major bioactive compounds belonging to phenolics (phenolic acids and flavonoids) and iridoids (both aglycones and glycosylated forms), within and among <i>N. nuda</i> populations, is able to guarantee mass spectrometry-based tools for the selection of elite representative genotypes with practical importance. The knowledge acquired will allow us to delve deeper into the molecular background of <i>N. nuda</i> chemical diversity, which is the course of our further work.