Glycyrrhizae Radix Inhibits Osteoclast Differentiation by Inhibiting c-Fos-Dependent NFATc1 Expression

Abstract

Osteoporosis results from imbalance between new bone formation and bone resorption leading to bone loss and is especially troublesome for postmenopausal women who suffer from estrogen deficiency. The ability of new therapeutic agents to treat this bone disease with minimal side effects has been extensively reported on and is continuously being sought out by researchers in this field. Thus, the purpose of this study was to investigate a natural herb that was already being used as a new treatment for osteoporosis. Here we found that water extract of Glycyrrhizae radix (GR) inhibits receptor activator of nuclear factor-[Formula: see text]B ligand (RANKL)-induced osteoclast differentiation in a dose-dependent manner without causing cytotoxicity. The mRNA expression of c-Fos, nuclear factor of activated T cells cytoplasmic 1 (NFATc1), tartrate-resistant acid phosphatase (TRAP), and osteoclast-associated receptor (OSCAR) was considerably inhibited by GR treatment. GR inhibited RANKL-mediated c-Fos and NFATc1 expression in a dose-dependent manner. GR inhibited the degradation of I-[Formula: see text]B in RANKL-stimulated BMMs. However, GR-mediated inhibition of osteoclast differentiation and osteoclast-specific gene expression, including NFATc1, was reversed by ectopic expression of c-Fos. Also, GR significantly inhibited osteoclast formation in mouse calvariae in the presence of IL-1 and prostaglandin E2 (PGE2). Taken together, these results suggest that GR inhibited osteoclast differentiation, raising the possibility that GR may serve as a useful drug for osteoporosis.

Poligoni�Multiflori Radix enhances osteoblast formation and reduces osteoclast differentiation

“…Bone marrow cells (BMCs) were obtained by flushing the femurs and tibiae of 5-week-old ICR mice as described previously ( 14 ). To obtain BMMs, BMCs were seeded on culture dishes in α-MEM supplemented with 10% FBS and M-CSF (10 ng/ml) and cultured for 1 day.…”

Corilagin suppresses RANKL‐induced osteoclastogenesis and inhibits oestrogen deficiency‐induced bone loss via the NF‐κB and PI3K/AKT signalling pathways

“…14 RANKL binds to RANK and recruits TNF receptor-associated adaptor molecules, activating the expression of osteoclast-related genes and causing excessive osteoclastogenesis and bone destruction. 15,16 Considering that only osteoclasts mediate bone resorption, inhibition of osteoclastogenesis shows promising as a therapeutic strategy for osteoporosis. 17,18 Corilagin (C 27 H 22 O 18 , β-1-O-galloyl-3,6-(R)-hexahydroxydiphenoyl-d-glucose), a natural compound of medicinal herbaceous plants such as Caesalpinia coriaria, has anti-inflammatory, 19,20 antioxidant, 21 hepatoprotective, 22 anti-brain injury, 23 antimicrobial 24 and anti-gastric lesion activities 25 ; it also alleviated Parkinson's disease in a rat model.…”

Isoliquiritin Apioside Suppresses in vitro Invasiveness and Angiogenesis of Cancer Cells and Endothelial Cells

“…Glycyrrhizae radix et rhizoma (GR), which is the root of Glycyrrhiza uralensis , has been used as a traditional Chinese medicine in clinical practice mainly to treat hepatitis, bowel diseases, cough, and pulmonary and skin diseases because of its ability to replenish the deficiencies in “Gi and Blood” (Jiang, 2005; Sekine-Osajima et al, 2009). Pharmacological studies have demonstrated antioxidant, anti-tumor, antitussive, anti-inflammatory, antiosteoporosis, anti-ulcerative colitis, detoxification, and neuroprotective activities of GR (Lee et al, 2012; Shi et al, 2014; Jeon et al, 2016; Rho et al, 2017). Several chemical components isolated from GR, including glycyrrhizin, liquiritigenin, and liquiritin, have been reported to possess anti-cancer activities that induce apoptosis and inhibit invasion (Huang et al, 2014; Wei et al, 2017; He et al, 2017; Meng and Lin, 2018).…”