New and known iridoid- and phenylethanoid glycosides from Harpagophytum procumbens and their in vitro inhibition of human leukocyte elastase.
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, [alpha]). 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 IC (50) of 542 microg/mL was determined for the aqueous extract of H. procumbens, but 1012 microg/mL for that of H. zeyheri. 6'- O-Acetylacteoside (8), that is not present in H. zeyheri, inhibited the enzyme with an IC (50) of 47 microg/mL (70 microM), compound 7 with 179 microg/mL (286 microM), 2 with 179 microg/mL (331 microM), 5 with 154 microg/mL (260 microM) and 10, which was also used as reference compound, with an IC (50) of 86 microg/mL (475 microM). The IC (50) values of acteoside, harpagoside, cinnamic acid and stachyose were higher than 300 microg/mL and thus not further determined.
Institut für Pharmazeutische Biologie und Phytochemie, Westfälische Wilhelms-Universität, Hittorstrasse 56, 48149 Münster, Germany.
Kerstin
K
Boje
Matthias
M
Lechtenberg
Adolf
A
Nahrstedt
D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006027:Glycosides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D031684:Harpagophytum; D006801:Humans; D020128:Inhibitory Concentration 50; D039823:Iridoids / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors*; D009682:Magnetic Resonance Spectroscopy; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D018517:Plant Roots
D004791:Enzyme Inhibitors; D006027:Glycosides; D039823:Iridoids; D010936:Plant Extracts; D019272:Leukocyte Elastase