Premium
Securinine suppresses osteoclastogenesis and ameliorates inflammatory bone loss
Author(s) -
Kwak Sung Chul,
Jeong Da Hye,
Cheon YoonHee,
Lee Chang Hoon,
Yoon KwonHa,
Kim JuYoung,
Lee Myeung Su
Publication year - 2020
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.6735
Subject(s) - osteoclast , rankl , chemistry , in vivo , bone resorption , protein kinase b , nf κb , osteoporosis , pharmacology , monocyte , bone remodeling , cancer research , microbiology and biotechnology , receptor , endocrinology , medicine , signal transduction , biology , biochemistry , activator (genetics)
Abstract Securinine (Sec) is a naturally derived compound separated from the roots of Securinega suffruticosa , which has long been used as a herbal medicine. Sec is widely known as a GABA receptor antagonist, it is also known as an innate immune cell agonist and has been reported to increase macrophage activity and promote monocyte maturation. On the basis of these studies, we investigated the effect of Sec on osteoclast differentiation and bone resorbing function. We have found that Sec inhibits RANKL‐induced osteoclast differentiation, fusion, actin ring formation, and bone resorbing function by the inhibition of gene expression associated with each stage. Moreover, Sec significantly suppressed osteoclastogenesis by decreasing the phosphorylation of p38, Akt, JNK, IκB, and PLCγ2, in pathways involved in early osteoclastogenesis as well as through the subsequent suppression of c‐Fos and NFATc1. Finally, Sec effectively protected bone loss induced by the excessive inflammatory responses and activity of osteoclasts in vivo by a micro‐CT and histological analysis. In conclusion, our findings suggest that Sec may be a promising drug for bone metabolic diseases such as osteoporosis, which is associated with the excessive activity of osteoclasts.