## 5 Bioactivity of Secondary Metabolites in the _Leontopodium_ Taxa
### Anti-Neurodegenerative Activity  
Aging is commonly associated with an increased incidence of cognitive impairment, the most common being Alzheimer's disease, Parkinson's disease and others [123]. Although few studies exist on this subject, several _Leontopodium_ species have been tested, which led to the discovery of secondary metabolites that could easily pass the blood-brain barrier and either increase acetylcholinesteraseic (ACh) levels or inhibit the expression of acetylcholinesteraseic (AChE) in the brains of affected individuals (Table 5).  
The crude dichloromethane extract of _L. alpinum_ roots inhibited ex vitro AChE activity and promoted an increase in the ACh level in an animal model [9]. A concentration of 1 mg/mL inhibited 78.79 \(\pm\) 2.59% of the enzyme's activity, while the application of an extract injection in the nucleus accumbens of rats caused a high increase in extracellular ACh by 2.5-3-times over the basal level. Further, this root extract was fractioned, and the effects of the obtained subfractions were determined on the brain ACh level and on the ability to memorize and learn in rats. The most potent compound proved to be isocompene, which caused an increase in extracellular ACh at a low concentration (2 umol/dose) and had a generally positive effect on learning and memory in normal and impaired rats.  
\begin{table}
\begin{tabular}{l l l l l} \hline \hline
**Taxon/Extract/Bioactive** & \multicolumn{2}{c}{**Experimental Model**} & \multicolumn{2}{c}{**Effects/Applied Tests**} & \multicolumn{1}{c}{**Ref.**} \\ \hline \multicolumn{4}{l}{Anti-neurodegenerative activity} \\ \hline \multicolumn{4}{l}{_L. alpinum_} & - & enhanced the cholinergic & \\ - & roots extract & & transmission activity by increasing & \\ - & isocompene & Sprague-Dawley rats & ACh level, & \\ - & isocompene & & - & positive effect on memorizing & \\ \multicolumn{4}{l}{_L. dedekensii_} \\ \multicolumn{4}{l}{_L. subulatum_} \\ \multicolumn{4}{l}{_L. franchetti_} & \multicolumn{2}{c}{Ex vitro assay of AChE activity} & \multicolumn{1}{c}{-} & inhibition of AChE & [124] \\ - & methanolic extracts & & & \\ - & sesquiterpene & & & \\ \hline \multicolumn{4}{l}{Anti-tumoral activity} \\ \hline \multicolumn{4}{l}{_L. longifolium_} \\ - & roots extract & SMMC-7721 and HL-60 & - & a moderate cytotoxic effect on the & \\ - & bisabolene sesquiterpenes & & lines & HL-60 cell line (MTT test) & [38] \\ \hline - & longifolactone & HepG2 and HeLa lines & - & weak effect & [36] \\ \hline \multicolumn{4}{l}{_L. leontopodioides_} \\ - & aerial parts extract & & & & \\ - & essential oils & & & \\ \hline \hline \end{tabular}
\end{table}
Table 5: Other bioactivities exhibited by different types of _Leontopodium_ taxa extracts and/or bioactive compounds.  
The anti-neurodegenerative potential of dried roots and aerial parts of several _Leontopodium_ taxa has also been tested. Greater AChE inhibition was exhibited by the methanolic extracts, in comparison to dichloromethane extracts, with _L. dedekensii_ showing the best inhibition (55.5 \(\pm\) 15.2%), followed by _Leontopodium subultum_ [PERSON]. (39.4 \(\pm\) 10.5%) and _L. franchetti_ (37.4 \(\pm\) 9.5%). In another in vitro AChE inhibition test, the most potent metabolite was a sesquiterpene, which inhibited 61.8% of the enzyme activity at a 100 \(\upmu\)M concentration [124].