Structure‐activity relationship of anthocyanidins as an inhibitory effect on inflammatory bone resorption

Abstract

Delphinidin, cyanidin and pelargonidin (anthocyanidins) are the group of aglycons of anthocyanins that are the natural compounds derived from reddish vegetables and fruits. Anthocyanidins exhibit various biological activities including anti-oxidative effects; however, their activity of anti-bone resorption was still not known. We have reported that anthocyanidins showed bone protective effects through the inhibition of osteoclast differentiation. Anthocyanidins inhibited IL (interleukin)-1 and LPS (lipopolysaccharide)-induced osteoclast differentiation and bone-resorbing activity in mouse calvarial organ cultures. In osteoblasts, anthocyanidin suppressed PG (prostaglandin) E₂ production through the downregulation of Ptges (membrane-bound prostaglandin E synthase) expression that resulted in Rankl (receptor activator of NF-κB ligand) suppression. In osteoclasts, anthocyanidins inhibited RANKL-induced osteoclast differentiation by downregulated the osteoclast functional genes such as Nfatc1 (nuclear factor of activated T cells, cytoplasmic 1), Ctsk (cathepsin K) and Acp5 (acid phosphatase 5, tartrate resistant).

We further demonstrated that delphinidin directly suppressed IKK (inhibitor of NF-κB kinase) activity in vitro assay. Besides, in silico assay indicated that delphinidin binds to the ATP binding pocket of IKK protein. These data suggest that anthocyanidins attenuate IKK-NF-κB signaling via the direct inhibition of IKK activity, resulting in inhibiting PGE2-mediated osteoclast differentiation. The effects of anthocyanidins depended on the number and the position of hydroxyl groups and methoxy groups of the B ring. This review described that the function of the anthocyanidins for the anti-bone resorptive effects. The utilization of anthocyanidins as the functional food with compounds for maintaining bone health contributes to promote human locomotive activity in current super-aged society.