Anti-inflammatory effects of phenolic acids punicalagin and curcumin in human placenta and adipose tissue

Introduction: 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. Methods: 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). Results: 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. Conclusion: 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.