title: Matrix metalloproteinase-1 inhibitory activities of Morinda citrifolia seed extract and its constituents in UVA-irradiated human dermal fibroblasts.
abstract: The objective of this study was to examine whether a 50% ethanolic extract (MCS-ext) of the seeds of Morinda citrifolia (noni) and its constituents have matrix metalloproteinase-1 (MMP-1) inhibitory activity in UVA-irradiated normal human dermal fibroblasts (NHDFs). The MCS-ext (10 μg/mL) inhibited MMP-1 secretion from UVA-irradiated NHDFs, without cytotoxic effects, at 48 h after UV exposure. The ethyl acetate-soluble fraction of MCS-ext was the most potent inhibitor of MMP-1 secretion. Among the constituents of the fraction, a lignan, 3,3'-bisdemethylpinoresinol (1), inhibited the MMP-1 secretion at a concentration of 0.3 μM without cytotoxic effects. Furthermore, 1 (0.3 μM) reduced the level of intracellular MMP-1 expression. Other constituents, namely americanin A (2), quercetin (3) and ursolic acid (4), were inactive. To elucidate inhibition mechanisms of MMP-1 expression and secretion, the effect of 1 on mitogen-activated protein kinases (MAPKs) phosphorylation was examined. Western blot analysis revealed that 1 (0.3 μM) reduced the phosphorylations of p38 and c-Jun-N-terminal kinase (JNK). These results suggested that 1 suppresses intracellular MMP-1 expression, and consequent secretion from UVA-irradiated NHDFs, by down-regulation of MAPKs phosphorylation.
authors.affiliation: Faculty of Pharmacy, Kinki University, Osaka, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Masuda
authors.forename: Kazuya
authors.initials: K
authors.lastname: Murata
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Naruto
authors.forename: Akemi
authors.initials: A
authors.lastname: Uwaya
authors.forename: Fumiyuki
authors.initials: F
authors.lastname: Isami
authors.forename: Hideaki
authors.initials: H
authors.lastname: Matsuda
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004147:Dioxins / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D006801:Humans; D007231:Infant, Newborn; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D017705:Lignans / Q000494:pharmacology; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D032066:Morinda; D010936:Plant Extracts / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000494:pharmacology*; D011794:Quercetin / Q000494:pharmacology; D012639:Seeds; D014315:Triterpenes / Q000494:pharmacology; D014466:Ultraviolet Rays; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000097245:Ursolic Acid
chemical_list: D004147:Dioxins; D048031:JNK Mitogen-Activated Protein Kinases; D017705:Lignans; D020781:Matrix Metalloproteinase 1; D061965:Matrix Metalloproteinase Inhibitors; D010936:Plant Extracts; D011480:Protease Inhibitors; D011794:Quercetin; D014315:Triterpenes; D048051:p38 Mitogen-Activated Protein Kinases; D000097245:Ursolic Acid; C055021:americanin A; C522360:MMP1 protein, human