Potential of Horse Apple Isoflavones in Targeting Inflammation and Tau Protein Fibrillization

In our ongoing search for anti-inflammatory and neuroprotective agents of natural origin, the total methanolic extract (MPE) of horse apple (Maclura pomifera)and its two major prenylated isoflavones, osajin (OSA) and pomiferin (POM), were evaluated in vitrofor their ability to affect four mediators of inflammation and to inhibit tau protein fibrillization. The two isoflavones were effective in enhancing the activity of NSAID activated gene (NAG-1) at 2.5 μg/mL (1.5 – 1.8 fold increase) and inhibiting iNOS and NF-κB activity with IC50values in the range of 6 – 13 μg/mL. Pomiferin also inhibited intracellular oxidative stress with IC50of 3.3 μg/mL, while osajin did not show any effect. The extract activated NAG-1 and inhibited iNOS and oxidative stress without affecting NF-κB. As observed by transmission electron microscopy (TEM), MPE, OSA and POM also inhibited arachidonic acid-induced tau fibrillization in a concentration-dependent manner.