2-Methoxystypandrone, a natural product isolated and purified from the roots of Polygonum cuspidatum, displays an immunomodulatory effect in a cellular model, specifically inhibits JAK and IKKβ kinase activities, blocks inflammatory responses by impairing NF-κB signaling to limit the inflammation and oxidative stress for preservation of BBB integrity, concomitantly promotes neurodevelopmental protein expression and endogenous neurogenesis through inactivation of GSK3β to enhance β-catenin signaling for upexpression of neuroprotective genes and proteins, and has anti-osteoclastogenic effect, could reflect the block of RANKL-induced association of TRAF6-TAK1 complexes with consequent decrease of IkappaB-mediated NF-kappaB and mitogen-activated protein kinases-mediated c-Fos activation pathways and suppression of NFATc1 and other gene expression, essential for bone resorption.