Valerenic acid and iridoid derivatives from the roots of Valeriana officinalis L.

Valeriana officinalis L. is a widely spread representative of the Eurasian flora. Preparations based on valerian extracts are recognized as sedatives, antidepressants and anxiolytics by both traditional and modern medicine. Despite the extremely high interest in the biological and pharmacological properties of valerian extracts, the composition of biologically active substances and specific activities of their components are still not completely studied. Therefore, here we address the metabolic profiles of the valerian plants with a special emphasis on their major root constituents with pronounced neuroprotective activity. The following phytochemical analysis of the V. officinalis L. roots led to isolation of nine compounds, including two previously undescribed iridoids – isovaltrate isovaleroyloxyisohydrin (1) and isovaltrate α-(isovaleroxy)isovaleroxyhydrin (2) together with one previously undescribed valerenic acid derivative – 2-oxovalerenic acid (3). Three previously described iridoids – iridoidvol A (4), isovaltrate isovaleroyloxyhydrin (5) and valtrate hydrine B1 (6), along with valerenic acid (7) and its metabolites - hydroxyvalerenic (8) and acetoxyvalerenic acids (9) were isolated. Functional assays accomplished with the isolated compounds revealed moderate antioxidant activity characteristic for all of them. Moreover, high neuroprotective potential was observed for the compound 3 (and to less extent of 8). This potential was manifested by a pronounced antineurodegenerative effect in the model of Aβ25-35 induced cytotoxicity. In respect of thrombin-induced platelet aggregation, compounds 1, 4 and 7 demonstrated pronounced inducing and compounds 2, 5 and 6 showed clear potentiating activity. Valerenic acid showed activity on TRPV1 ion channels, manifested by both channel activation and potentiation of the capsaicin response in CHO cells expressing TRPV1. Moderate antioxidant activity was characteristic of all compounds.