Tannic acid fortifies extracellular matrix against dicarbonyl stress

Abstract Methylglyoxal (MGO), a highly reactive dicarbonyl metabolite that accumulates in diabetes and aging, causes tissue dyshomeostasis, for which therapeutic interventions are limited. Herein, we investigate the potential of tannic acid (TA) in fortifying organ and organismal health against MGO. Anatomical disruption in vivo of hydra bodies and ex vivo decellularization of murine mesenteries with MGO suggested an impaired interaction between cells and their extracellular matrix (ECM); however, pretreatment of these systems with TA reversed this effect. We confirmed this through subsequent exposure of control and TA-pretreated mammalian cell-secreted endogenous matrix, Collagen I, and basement membrane matrix to MGO. TA prevented loss of ECM biochemical characteristics and restored perturbed cell adhesion and spreading on these substrata induced by MGO. NMR titrations confirmed TA-bound MGO in a 1:5 stoichiometry, potentially quenching its electrophilic properties. Our study posits TA as a novel candidate for protecting organ and organismal architectures against the histopathological effects of dicarbonyl stress.