title: Dietary phytophenols curcumin, naringenin and apigenin reduce infection-induced inflammatory and contractile pathways in human placenta, foetal membranes and myometrium.
abstract: A tenet of contemporary obstetrics is that a significant proportion of preterm births involve bacterial infection. Bacterial endotoxin induces pro-inflammatory cytokines, prostaglandins and proteases via the pro-inflammatory pathway nuclear factor-κB (NF-κB), which plays a key role in initiating uterine contractions and rupture of foetal membranes. In non-gestational tissues, the phytophenols curcumin, naringenin and apigenin exert anti-inflammatory properties via inhibition of NF-κB. The aim of this study was to determine whether these treatments regulate pro-inflammatory and pro-labour mediators in human gestational tissues. Placenta, foetal membranes and myometrium were treated with curcumin, naringenin and apigenin in the presence of lipopolysaccharide (LPS) or interleukin (IL)-1β. In placenta and foetal membranes, all treatments significantly reduced LPS-stimulated release and gene expression of pro-inflammatory cytokines IL-6 and IL-8; placenta decreased cyclooxygenase (COX-2) mRNA expression, subsequent release of prostaglandins PGE2 and PGF2α and expression and activity of matrix-degrading enzyme matrix metalloproteinase (MMP)-9. In myometrial cells, all treatments attenuated IL-1β-induced COX-2 expression, release of PGE2 and PGF2α and expression and activity of MMP-9. Although naringenin significantly attenuated IL-1β-induced IL-6 and IL-8 mRNA expression and release, there was no effect of curcumin and apigenin. LPS-stimulated release of 8-isoprostane, a marker of oxidative stress, was attenuated by all treatments. NF-κB p65 DNA-binding activity was also decreased using these treatments. In conclusion, curcumin, naringenin and apigenin exert anti-inflammatory properties in human gestational tissues by inhibiting the transcriptional activity of NF-κB. Further studies should be undertaken to define a possible implication of these natural spices in the management of preterm labour and delivery.
authors.affiliation: Department of Obstetrics and Gynaecology, University of Melbourne, Mercy Hospital for Women, Level 4/163 Studley Road, Heidelberg, Victoria 3084, Australia.
authors.forename: Ratana
authors.initials: R
authors.lastname: Lim
authors.forename: Gillian
authors.initials: G
authors.lastname: Barker
authors.forename: Courtney A
authors.initials: CA
authors.lastname: Wall
authors.forename: Martha
authors.initials: M
authors.lastname: Lappas
mesh_terms: D047310:Apigenin / Q000494:pharmacology*; D002478:Cells, Cultured; D003474:Curcumin / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D019587:Dietary Supplements; D005321:Extraembryonic Membranes / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D044950:Flavanones / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D009215:Myometrium / Q000187:drug effects* / Q000378:metabolism; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D047928:Premature Birth / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D044950:Flavanones; D015850:Interleukin-6; D016209:Interleukin-8; D051996:Transcription Factor RelA; D047310:Apigenin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C005273:naringenin; D003474:Curcumin
keywords: inflammation; phytophenol; preterm birth