title: Anti-MMP-2 Activity and Skin-Penetrating Capability of the Chemical Constituents from Rhodiola rosea.
abstract: Based on the significant inhibitory activity toward matrix metalloproteinase-2 and collagenase noticed in preliminary studies, crude extracts of Rhodiola rosea were partitioned and chromatographed sequentially to afford three new compounds, 1,2,3,6-tetra-O-galloyl-4-O-p-hydroxybenzoyl-β-D-glucopyranoside (1), (E)-creoside I (2), and (R,Z)-2-methylhept-2-ene-1,6-diol (3), along with twenty-four known compounds (4-27). Their structures were determined by spectroscopic data analyses. All isolated compounds were subjected to bioactivity assays. In these, 1 specifically inhibited matrix metalloproteinase-2 activity with an IC50 value of 16.3 ± 1.6 µM, while its analogue 1,2,3,6-tetra-O-galloyl-β-D-glucopyranonoside (17) inhibited matrix metalloproteinase-2 with an IC50 value of 23.0 ± 4.8 µM. In the collagenase activity assay, the inhibitory effects of 1 and 17 at concentrations of both 20 and 40 µM were more potent than those of the positive control, 1,10-phenanthroline. In order to realize whether 17 could penetrate from the epidermal layer into the basal and dermal layers of the human skin to inhibit the activity of matrix metalloproteinase-2 and collagenase or not, a transdermal penetration test in nude and white mice skins was performed. Penetration percentages of 17 quantified by LC-MS were 27.8 % and 74.8 % in 24 hours, respectively.
authors.affiliation: Institute of Fisheries Science, National Taiwan University, Taipei, Taiwan.
authors.forename: Tzong-Huei
authors.initials: TH
authors.lastname: Lee
authors.affiliation: Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chieh-Chih
authors.initials: CC
authors.lastname: Hsu
authors.affiliation: Graduate Institute of Medical Science and Department of Pharmacology, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: George
authors.initials: G
authors.lastname: Hsiao
authors.affiliation: Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Kweishan, Taoyuan, Taiwan.
authors.forename: Jia-You
authors.initials: JY
authors.lastname: Fang
authors.affiliation: Department of Obstetrics and Gynecology, Taipei Medical University Hospital, Taipei, Taiwan.
authors.forename: Wei-Min
authors.initials: WM
authors.lastname: Liu
authors.affiliation: Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ching-Kuo
authors.initials: CK
authors.lastname: Lee
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D020778:Matrix Metalloproteinase 2; D061965:Matrix Metalloproteinase Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D029771:Rhodiola / Q000737:chemistry*; D012867:Skin / Q000187:drug effects*
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D010936:Plant Extracts; D020778:Matrix Metalloproteinase 2