Dietary phytophenols curcumin, naringenin and apigenin reduce infection-induced inflammatory and contractile pathways in human placenta, foetal membranes and myometrium

• Published in: Molecular human reproduction 2013-07, Vol.19 (7), p.451-462
• Main Authors: Lim, Ratana, Barker, Gillian, Wall, Courtney A, Lappas, Martha
• Format: Article
• Language: English
• Subjects: Apigenin - pharmacology; Cells, Cultured; Curcumin - pharmacology; Cyclooxygenase 2 - metabolism; Dietary Supplements; Extraembryonic Membranes - drug effects; Extraembryonic Membranes - metabolism; Female; Flavanones - pharmacology; Humans; In Vitro Techniques; Inflammation; Interleukin-6 - metabolism; Interleukin-8 - metabolism; Myometrium - drug effects; Myometrium - metabolism; Placenta - drug effects; Placenta - metabolism; Pregnancy; Premature Birth - metabolism; Reverse Transcriptase Polymerase Chain Reaction; Transcription Factor RelA - metabolism
• ISSN: 1360-9947; 1460-2407
• DOI: 10.1093/molehr/gat015

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.