title: Potential of Horse Apple Isoflavones in Targeting Inflammation and Tau Protein Fibrillization.
abstract: 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 vitro for 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 pg/mL (1.5-1.8 fold increase) and inhibiting iNOS and NF-κB activity with IC50 values in the range of 6-13 µg/mL. Pomiferin also inhibited intracellular oxidative stress with IC50 of 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.
authors.forename: Ehab A
authors.initials: EA
authors.lastname: Abourashed
authors.forename: Aida
authors.initials: A
authors.lastname: Abraha
authors.forename: Shabana I
authors.initials: SI
authors.lastname: Khan
authors.forename: Tanika
authors.initials: T
authors.lastname: McCants
authors.forename: Saad
authors.initials: S
authors.lastname: Awan
mesh_terms: D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D005638:Fruit / Q000737:chemistry; D005786:Gene Expression Regulation / Q000187:drug effects; D055436:Growth Differentiation Factor 15 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D007529:Isoflavones / Q000737:chemistry / Q000494:pharmacology*; D031624:Maclura / Q000737:chemistry*; D015394:Molecular Structure; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors; D016875:tau Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000975:Antioxidants; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D007529:Isoflavones; D016875:tau Proteins; D052247:Nitric Oxide Synthase Type II