## 4 Secondary Metabolites Identified in the _Leontopodium_ Taxa
The major components of essential oil from aerial parts of _L. leontopodioides_ were palmitic acid, n-pentadecanal, linalool, \(\beta\)-ionone, hexahydrofearnesyl acetone, bisabolone and \(\beta\)-caryophyllene [36], while the same type of essential oil extracted from _L. longifolium_ had, as predominant compounds, \(\alpha\)-bisabolol and \(\alpha\)-bisabolol oxide [31]. The main classes of metabolites identified in _Leontopodium_ sp. were terpenes and phenylpropanol compounds (Supplementary Material S2). Among the terpenes, tricyclic sesquiterpenes and bisabolene sesquiterpenes, but also dicterpenes, monoterpenes or sterols, were isolated, mostly present at the root level, with the exception of two _ent_-kaureneoic derivatives reported in the extracts from the aerial parts [78]. Among the identified phenylpropanol compounds, the phenolic acids were found mainly in the aerial parts or in extracts from in vitro cultures, flavonoids in extracts from aerial parts, infloreserences or whole extracts; coumarins were reported exclusively in the roots, while lignans and benzofuran in both the aerial and underground parts. In _L. alpinum_, these two types of metabolites were extracted exclusively from the root level [4; 11; 33], while in _L. leontopodioides_, they were reported in the aerial parts [13; 78; 79]. Other studies which investigated the metabolic fingerprint in _Leontopodium_ sp. and phylogenetic relationships between the species of this genus showed a species-specific occurrence of some metabolites. The European _L. alpinum_ and eight Asian _Leontopodium_ species showed significant differences in the bisabolenes and coumarins patterns in the root extracts. For example, _Leontopodium franchetti_ [PERSON] and _Leontopodium sinensis_ [PERSON]. contained none of the known bisabolene derivatives [81], while the known lignan derivative occurred in all investigated species. Root extracts of _L. alpinum_, _Leontopodium campestre_ ([PERSON].) Hand.-Mazz. and _L. leontopodioides_, three closely related species, showed a similar secondary metabolites pattern. The analysis of the aerial parts revealed no significant differences between the investigated species, leontopodic acids being present in all investigated samples [82]. Another study showed that among 11 different _Leontopodium_ species, two species groups were distinguished, the first group having as discriminators fatty acids and sucrose and the second group differing from the first based on the content of _ent_-kaureneoic acids and their derivatives [33]. The authors identified two bisabolene derivatives responsible for the discrimination of different Asian _Leontopodium_ taxa and one _ent_-kaureneoic acid derivative, which could divide the two taxa from the second group _L. franchetti_ and _L. sinense_. Additionally, two morphologically related species, _Leontopodiumdedekensii_ [PERSON] and _L. sinense_, could be distinguished based on \({}^{1}\)H NMR and LC-MS metabolic fingerprinting [33]. The peculiarities of the species, especially that concerning the content of secondary metabolites, which belong to diverse classes of compounds, explain the multitude of the extracts' bioactivities. Sesquiterpenes could be involved in the anti-inflammatory activity through bisabolene and tricyclic sesquiterpene derivatives, having anti-oedematous effects [3] or by inhibiting the synthesis of leukotrienes [4]. Ester, tricyclic and bisabolene sesquiterpenes could have antimicrobial activity; however, the most potent activity was manifested by linoleic and linolenic fatty acids [8]. The anti-neurodegenerative activity is due to another sesquiterpene, isocompene, which inhibits acetylcholinesterasecholinesteraseerase activity [9]. Diterpene, _ent_-kaurenoic derivatives, have anti-inflammatory activity by decreasing NO levels [4] and inhibiting cyclooxygenaseenases [35].