Unequivocal glycyrrhizin isomer determination and comparative in vitro bioactivities of root extracts in four Glycyrrhiza species

Farag, Mohamed A.; Porzel, Andrea; Wessjohann, Ludger A.

To address the issue of potential variation of the anti-inflammatory activity different species and accessions, we measured the ability of methanol extracts from 11 samples to inhibit cyclooxygenase-1 (COX1), an enzyme involved in inflammation processes (Fig. 3 ). G. glabra shows inhibitory effect on COX and LOX products [19] . In this study, extracts prepared from G. glabra and G. uralensis, were among the most effective ones, whereas extracts from G. echinata were the least effective ones tested at doses of 100, 150, and 200 lg/ml. Previous investigations concluded that G is an anti-inflammatory compound in licorice, acting by inhibiting the release of inflammatory mediators [20] . Nevertheless, both b-G and b-GA were found inactive on COX1 in our assay setup up at a dose of 500 lg/ml. In contrast to these results, liquiritin, a major flavonoid in Glycyrrhiza sp. [17] was active in the COX1 assay with an IC 50 value of 96 ± 8 lg/ml. In addition to triterpene saponins, numerous pharmacologically active polyphenols in quantities of 1-5% have been isolated from Glycyrrhiza sp. and might be accountable for its potent anti-inflammatory effect [21] . These findings suggest that with regard to COX1 inhibition enzyme assay, phenylpropanoids constitute an indispensible part of licorice anti-inflammatory efficacy, arguing for a possible (synergistic or at least additive) effect of several secondary metabolites in targeting different enzymes involved in inflammation. A positive relationship appears to exist between the total polyphenols (TP) content and the anti-inflammatory activity for most species, with a potential correlation to phenolic antioxidant activity. Accessions demonstrating the most potent anti-inflammatory effect were enriched in TP, i.e. G. glabra and G. uralensis showed the best effect. A similar trend to the opposite side was observed for species with low TP, i.e. G. echinata (Fig. 3) . Thus, total COX1-inhibitor activity of crude methanol extracts appeared to be dominantly correlated to the (TP) content, which differs across species. It should be noted that no significant difference in TP or anti-inflammatory effect was observed for samples belonging to the same species but coming from different geographical origin. These data support the observation that licorice is an effective COX 1 inhibitor, and provide more insight into the nature of the compounds mediating for such an effect.