New and Known Iridoid- and Phenylethanoid Glycosides from Harpagophytum procumbens and their in vitro Inhibition of Human Leukocyte Elastase

Abstract

Ten compounds, harpagoside (1), 8-p-coumaroylharpagide (2), 8-feruloylharpagide (3), 8-cinnamoylmyoporoside (4), pagoside (5), acteoside (6), isoacteoside (7), 6′-O-acetylacteoside (8), cinnamic acid (9) and caffeic acid (10) were isolated from the storage roots of Harpagophytum procumbens, Pedaliaceae. Compounds 1, 2, 6, 7 and 9 are known for H. procumbens; 3 and 10 were isolated the first time from H. procumbens; compounds 4, 5 and 8 are new natural products. Their structures were elucidated using spectroscopic data (NMR, with NOE, COSY and HMBC experiments, UV, [α]). The inhibitory activity of aqueous extracts of the roots of H. procumbens and H. zeyheri as well as the main compounds isolated from H. procumbens was tested on human neutrophile elastase. Although inhibition was comparatively weak a dose-dependence was observed. An IC₅₀ of 542 μg/mL was determined for the aqueous extract of H. procumbens, but 1012 μg/mL for that of H. zeyheri. 6′-O-Acetylacteoside (8), that is not present in H. zeyheri, inhibited the enzyme with an IC₅₀ of 47 μg/mL (70 μM), compound 7 with 179 μg/mL (286 μM), 2 with 179 μg/mL (331 μM), 5 with 154 μg/mL (260 μM) and 10, which was also used as reference compound, with an IC₅₀ of 86 μg/mL (475 μM). The IC₅₀ values of acteoside, harpagoside, cinnamic acid and stachyose were higher than 300 μg/mL and thus not further determined.

Key words

Harpagophytum procumbens - Haryagophytum zeyheri - Pedaliaceae - iridoids - 8-cinnamoylmyoporoside - pagoside - phenylethanoid glycosides - 6′-O-acetylacteoside - elastase-inhibiting activity

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