Inhibition of secretory sphingomyelinase by epicatechin-3-O-gallate and other antioxidants

Objective Secretory sphingomyelinase (sSMase) is one of the key enzymes involved in oxidative stress-related diseases [Biol. Pharm. Bull, 2013]. The elevation of its activity resulted in an increase of ceramide that is the bioactive lipid inducing cellular apoptosis, proliferation, and differentiation. In this study, we searched for novel sSMase inhibitors during some antioxidants which are expected to ameliorate oxidative stress-related diseases. Methods Each of several antioxidants was incubated with and sSMase derived from rats in the assay mixture (pH 5.0) and analyzed their inhibitory activity by using HPLC. Results Epicatechin 3-O-gallate (ECg) significantly inhibited sSMase activity as compared with non-gallate type catechins. In addition, Anti-Oxidant Biofactor (AOB) extract that is the mixture of fermented grain foods and catechins, markedly inhibited sSMase activity. Conclusion ECg and some gallate type catechins had a strong inhibitory effect on sSMase in a physiological plasma concentration (IC50=1.7–25.7 µM). This inhibition may be due to their specific structures such as galloyl residue, and it depends on the reducing activity. Moreover, antioxidant mixture such as AOB might inhibit synergistically sSMase. It will be further discussed.