Estrogenic, Osteogenic, and Anti-Osteoclastogenic Effects of Ixeridium dentatum Ethanol Extract on Bone Remodeling in Postmenopausal Osteoporosis

Abstract

Osteoporosis, a metabolic bone disorder, is a major concern in postmenopausal women due to the 40% increased fracture risk, which is associated with estrogen deficiency, because estrogen promotes bone formation by osteoblasts and suppresses bone resorption by osteoclast. Current postmenopausal osteoporosis therapies have severe side effects under their long-term treatment, necessitating safe alternatives from natural products. Ixeridium dentatum (Thunb.) Tzvelev is an edible medicinal plant with neuroprotective, anti-diabetic, anti-allergic, and anti-inflammatory activities. However, the effects of this plant on bone metabolism have been not studied until now. Here, osteogenic potential of Ixeridium dentatum ethanol extract (IDEE) was evaluated. 25-100 μg·mL-1 of IDEE promoted osteoblast differentiation and mineralization by activating all three major osteogenic signaling pathways (BMP2, TGFβ, and Wnt) on pre-osteoblastic cell line MC3T3-E1. It also showed estrogenic activity in the MCF-7 breast cancer cell line, as determined by ERE-Luc activity assay. In ovariectomized mice, 40-100 mg·kg IDEE administration improved bone health parameters and serum Gla-type osteocalcin level. In primary cells isolated from ovariectomized mice, IDEE increased osteoblast population and osteogenic signaling, and inhibited osteoclast population and osteoclast-related marker expression. IDEE also suppressed osteoclastogenesis in macrophage cell line RAW264.7. These results demonstrate that IDEE improves bone remodeling by estrogenic properties, enhancing osteoblast differentiation and suppressing osteoclast formation, which makes it a promising candidate for postmenopausal osteoporosis prevention.