Nobiletin suppresses MMP-9 expression through modulation of p38 MAPK activity in human dermal fibrobalsts.

Abstract:

:We aimed to identify a novel flavonoid from the in-house natural products to suppress matrix metalloproteases (MMPs), which is responsible for degradation of collagen and other extracellular matrix proteins. Total eight natural products were screened for identification of a novel MMP-9 suppressor using MMP-9 reporter system, where the prompt initial screening with multiple samples is readily examined. Among the extracts used in the present study, one extract (Citrus unshiu) was found active in this assay system. Furthermore, three representative flavonoids in this active extract of Citrus unshiu peel were tested in MMP-9 reporter system. Nobiletin (NB) of the tested flavonoids suppressed MMP-9 expression without cytotoxicity, which was validated by both real-time polymerase chain reaction (PCR) and zymography analyses. Sustained p38 mitogen activated protein kinase (MAPK) activity, closely associated with induction of MMP-9 under stress condition, was markedly reduced by NB treatment, which implies that modulation of p38MAPK by nobiletin is responsible for reduction of MMP9 expression. Hence, nobiletin, identified from MMP-9 reporter system based screening, may be further applied for the purpose of delaying collagen degradation in skin fibroblasts.

journal_name

Biol Pharm Bull

authors

Kim JJ,Korm S,Kim WS,Kim OS,Lee JS,Min HG,Chin YW,Cha HJ

doi

10.1248/bpb.b13-00534

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

158-63

issue

1

eissn

0918-6158

issn

1347-5215

pii

DN/JST.JSTAGE/bpb/b13-00534

journal_volume

37

pub_type

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