Pharmacological properties of extracts and prenylated isoflavonoids from the fruits of Osage orange (Maclura pomifera (Raf.) C.K.Schneid.).

Osage orange trees (Maclura pomifera (Raf.) C.K.Schneid.) are distributed worldwide, particularly in south-east states of the USA. They produce large quantities of strong yellow fruits, bigger than oranges, but these fruits are inedible, with an acid milky juice which is little consumed by birds and insects. Extracts prepared from Osage orange fruits (hedge apple) have revealed a range of pharmacological properties of interest in human and veterinary medicine. In addition, Osage orange extracts can be used in agriculture and aquaculture, and as dyeing agent for the textile industry. Extracts contain potent antioxidant compounds, notably the isoflavonoids pomiferin and auriculasin, together with other terpenoids and flavonoids. The structural characteristics and pharmacological properties of the major prenylated isoflavones isolated from M. pomifera are discussed here, with a focus on the two phenolic compounds osajin and warangalone, and the two catechol analogues pomiferin and auriculasin. The mechanisms at the origin of their potent antioxidant and anti-inflammatory effects are presented, notably inhibition of xanthine oxidase, phosphodiesterase 5A and kinases such as RKS2 and kRAS. Osajin and auriculasin display marked anticancer properties, owing to their ability to inhibit tumor cell proliferation, migration and tumor angiogenesis. Different molecular mechanisms are discussed, including osajin‑copper complexation and binding to quadruplex DNA. An overview of the mechanism of action of the prenylated isoflavones from Osage orange is presented, with the objective to promote their knowledge and to raise opportunities to better exploit the fruits of Osage orange, abundant but largely neglected at present.