Regulatory effects of Dieckol on inflammatory cytokines and Osteoclastogenesis in Ovariectomized mouse model

Dieckol, a major bioactive compound of Ecklonia cava, exhibits antiosteoporosis, anti-inflammatory, antioxidant, and muscle atrophy attenuation properties. This study investigated its effects on IL-6 signaling suppression, estrogen activity, and osteoclastogenesis inhibition. Dieckol inhibited IL-6-induced p-STAT3 activity and downstream signaling molecules like STAT3 and ERK, suppressing the expression of genes such as CRP, IL-1β, SOCS3, and ICAM-1. It attenuated M-CSF/RANKL-induced osteoclastogenesis in mouse bone marrow macrophages and prevented bone loss in an ovariectomized mouse model by improving bone mineral density and microarchitecture. Dieckol also enhanced estrogen receptor activity, upregulating ESR2 while downregulating ESR1, and increased serotonin and norepinephrine levels, potentially alleviating mood disturbances. The doses used were within the safe range in animal studies, and available data indicate good tolerability in humans. These findings suggest dieckol as a promising therapeutic agent for IL-6-mediated or estrogen deficiency-related osteoporosis and associated mood disorders. • Dieckol inhibits IL-6 signaling pathway and related inflammatory marker genes. • Dieckol inhibits RANKL-induced osteoclastogenesis and bone loss in mice. • Dieckol activates estradiol and mimics its effect on estrogen receptor expression. • Brain neurotransmitters are restored in OVX mice by dieckol.