Nguyen-Ngo Caitlyn, Willcox Jane C, Lappas Martha
Obstetrics, Nutrition and Endocrinology Group, Department of Obstetrics and Gynaecology, University of Melbourne, Heidelberg, Victoria, Australia; Mercy Perinatal Research Centre, Mercy Hospital for Women, Heidelberg, Victoria, Australia.
Dietetics and Human Nutrition, School of Allied Health, Human Services and Sport, La Trobe University, Bundoora, Victoria, Australia.
Placenta. 2020 Oct;100:1-12. doi: 10.1016/j.placenta.2020.08.002. Epub 2020 Aug 10.
The world is witnessing a steady rise in the prevalence of gestational diabetes mellitus (GDM), correlated with the current obesity epidemic. Both GDM and obesity negatively impact both the health of women but also that of the next generation. GDM and maternal obesity are associated with increased maternal and fetal inflammation and oxidative stress. A safe and effective intervention that can prevent these pathological features, and reduce the intergenerational burden, is required. Phenolic acids, such as punicalagin and curcumin, possess anti-inflammatory and antioxidant properties. Thus, the aim of this study was to examine the effects of punicalagin and curcumin on pro-inflammatory cytokines and chemokines, and antioxidant expression in an in vitro model of inflammation.
Human placenta, visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) explants were obtained at term elective Caesarean section and stimulated with TNF alpha (TNF).
We found that punicalagin and curcumin significantly supressed TNF-induced pro-inflammatory cytokine (IL1A, IL1B, and IL6) and chemokine (CCL2-4, CXCL1, CXCL5 and CXCL8) expression in human placenta, VAT and SAT. Anti-inflammatory cytokine IL4 and IL13 mRNA expression was also upregulated by punicalagin and curcumin treatment in placenta, VAT and SAT. Punicalagin and curcumin also altered antioxidant (SOD2 and catalase) mRNA expression in placenta, VAT and SAT, with minimal effect on hydrogen peroxide concentrations in tissue lysates.
These findings suggest that the phenolic acids punicalagin and curcumin possess potent anti-inflammatory capabilities in in vitro human models of inflammation. Further studies are warranted to determine their suitability as therapeutic interventions for pro-inflammatory gestational complications, including GDM and maternal obesity.
随着当前肥胖症的流行，全球妊娠期糖尿病（GDM）的患病率正在稳步上升。GDM和肥胖症对女性健康以及下一代健康均产生负面影响。GDM和母体肥胖与母体和胎儿炎症及氧化应激增加有关。需要一种安全有效的干预措施来预防这些病理特征，并减轻代际负担。诸如石榴皮素和姜黄素之类的酚酸具有抗炎和抗氧化特性。因此，本研究的目的是在体外炎症模型中研究石榴皮素和姜黄素对促炎细胞因子和趋化因子以及抗氧化剂表达的影响。
在择期剖宫产足月时获取人胎盘、内脏脂肪组织（VAT）和皮下脂肪组织（SAT）外植体，并用肿瘤坏死因子α（TNF）进行刺激。
我们发现石榴皮素和姜黄素可显著抑制TNF诱导的人胎盘、VAT和SAT中促炎细胞因子（IL1A、IL1B和IL6）和趋化因子（CCL2 - 4、CXCL1、CXCL5和CXCL8）的表达。在胎盘、VAT和SAT中，石榴皮素和姜黄素处理还上调了抗炎细胞因子IL4和IL13的mRNA表达。石榴皮素和姜黄素还改变了胎盘、VAT和SAT中抗氧化剂（SOD2和过氧化氢酶）的mRNA表达，对组织裂解物中过氧化氢浓度的影响最小。
这些发现表明，酚酸石榴皮素和姜黄素在体外人类炎症模型中具有强大的抗炎能力。有必要进一步研究以确定它们作为治疗包括GDM和母体肥胖在内的促炎性妊娠并发症的治疗干预措施的适用性。
