Ellagic Acid Displays a Protective Effect on Red Blood Cell Membrane During Aging in Humans

Ellagic acid (EA) is an antioxidant and anti-inflammatory compound primarily found in pomegranates and berries. It is a dimer of gallic acid and has been shown to have health advantages. We assessed the protective effect of EA against oxidative stress caused by tert-butyl hydroperoxide (t-BHP) on erythrocyte cell membrane indicators during the aging process in humans. In control and oxidative stress caused by t-BHP in human subjects' erythrocytes of both sexes (n = 80), we evaluated the in vitro effect of EA on Na⁺, H⁺ exchanger (NHE), Na⁺, K⁺ ATPase, Ca²⁺ ATPase, protein carbonyl group content and osmotic fragility. We note that the NHE activity increases relative to their respective controls in the young, middle, and old subjects. Stress-inducing t-BHP significantly increases (p < 0.001) NHE activity in all age groups compared to the respective control. NHE activity is further reduced by EA treatment. In middle-aged and older human participants, erythrocyte membrane Na⁺, K⁺, and Ca²⁺ ATPase activity was considerably (p < 0.001) lower than in younger subjects in the control group. In all age groups, there was a noteworthy reduction (p < 0.001) in Na⁺, K⁺, and Ca²⁺ ATPase activity in the membrane of t-BHP-induced erythrocytes compared to their corresponding controls. Administration of different concentrations of EA (10^-5-10^-7 M) decreases carbonyl group content significantly compared to their respective control in each age group in a concentration-dependent manner. When the erythrocytes were induced with stress using t-BHP, the lysis % increased, and after the treatment of EA, the lysis % was found to decrease in all the age groups. The activity of membrane-bound enzymes is markedly increased when EA is applied to these erythrocyte membranes. Through the modulation of membrane transporters, the study sheds light on the beneficial health advantages of EA.