title: Aluminum ammonium sulfate dodecahydrate purified from traditional Chinese medicinal herb Korean monkshood root is a potent matrix metalloproteinase inhibitor.
abstract: Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases and key regulators for many physiological and pathological functions. The MMP inhibitors have been shown to modulate diseases such as cancer, inflammation, and cardiovascular diseases. In this paper we tracked the MMP inhibitory activities of the traditional Chinese medicinal herb Korean Monkshood Root. The purified active ingredient was identified by the elemental analysis, infrared spectrum (IR) and X-ray diffraction as aluminum ammonium sulfate dodecahydrate. This inorganic compound showed inhibitory activities toward a number of MMP family members. In particular, it has a strong inhibitory effect toward MMP-2 and MMP-9, with IC50 values of 0.54 and 0.50 μM, respectively. Further analysis suggested that the MMP inhibitory activity is mainly due to Al(3+). Cell viability assays using human fibrosarcoma HT1080 cells showed aluminum ammonium sulfate had minimal cyto-toxicity with a concentration up to 500 μM. However, within 50 μM, it exhibited significant inhibition of cell invasion. To our knowledge, there has been no previous report of inorganic form of the MMP inhibitor with strong inhibitory activity. Our results for the first time showed that aluminum ammonium sulfate is an inorganic form of MMP inhibitor with high potency, and can be used to interfere with MMP related cellular processes.
authors.affiliation: Biotechnology Center, School of Pharmacy, Fourth Military Medical University, Xi'an, Shaanxi, 710069, People's Republic of China.
authors.forename: Yehua
authors.initials: Y
authors.lastname: Shen
authors.forename: Sen
authors.initials: S
authors.lastname: Liu
authors.forename: Fenghai
authors.initials: F
authors.lastname: Jin
authors.forename: Tianyang
authors.initials: T
authors.lastname: Mu
authors.forename: Cong
authors.initials: C
authors.lastname: Li
authors.forename: Kun
authors.initials: K
authors.lastname: Jiang
authors.forename: Weihua
authors.initials: W
authors.lastname: Tian
authors.forename: Dahai
authors.initials: D
authors.lastname: Yu
authors.forename: Yingqi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xuexun
authors.initials: X
authors.lastname: Fang
mesh_terms: D000534:Alum Compounds / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000737:chemistry* / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D010946:Plants, Medicinal / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D000534:Alum Compounds; D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; C059726:aluminum ammonium sulfate