Platycodin D Inhibits Osteoclastogenesis by Repressing the NFATc1 and MAPK Signaling Pathway

Abstract

Platycodon grandiflorum root-derived saponins (Changkil saponins, CKS) are reported to have many pharmacological activities. In our latest research, CKS was proven to have a significant osteogenic effect. However, the detail molecular mechanism of CKS on osteoclastic differentiation has not been fully investigated. Administration of CKS considerably reduced OVX-induced bone loss, and ameliorated the reduction in plasma levels of alkaline phosphatase, calcium, and phosphorus observed in OVX mice. CKS also repressed the deterioration of bone trabecular microarchitecture. Interestingly, platycodin D, the most abundant and major pharmacological constituent of triterpenoid CKS, inhibited receptor activator of NF-κB ligand (RANKL)-induced activation of NF-κB, and ERK and p38 MAPK, ultimately repressing osteoclast differentiation. OVX-induced bone turnover was attenuated by CKS, possibly via repression of osteoclast differentiation by platycodin D, the active component of CKS. Platycodin D can be regarded as an antiosteoporotic candidate for treatment of osteoporosis diseases. J. Cell. Biochem. 118: 860-868, 2017. © 2016 Wiley Periodicals, Inc.

Platyconic Acid A, Platycodi Radix-Derived Saponin, Suppresses TGF-β1-Induced Activation of Hepatic Stellate Cells via Blocking SMAD and Activating the PPARγ Signaling Pathway

“…Recently, Platycodi radix, which contains various nutrients (amino acids, trace elements, and unsaturated fatty acids such as linoleic acid), has been considered to be a food source [15]. Our previous studies have reported that aqueous extract and saponin derived from Platycodi radix has protective effects on atopic dermatitis-like skin diseases, airway inflammation, osteoporosis, and metastasis [16][17][18][19][20][21][22]. Importantly, we reported that an aqueous extract from Platycodi radix and Platycodi radix-derived saponin inhibited various hepatic toxicant-induced liver diseases via numerous biological and pharmacological effects.…”

Osthole‐loaded N‐octyl‐O‐sulfonyl chitosan micelles (NSC‐OST) inhibits RANKL‐induced osteoclastogenesis and prevents ovariectomy‐induced bone loss in rats

“…It is well known that osteoporosis is a chronic metabolic bone disease that is characterized by decreased bone mass and degeneration of the bone microstructure. Micro‐CT, HE staining and biomechanical assays have been widely used to assess bone mass and quality . The results of all three types of assays showed that oral administration of NSC‐OST significantly inhibited bone loss in the OVX rats and improved bone microstructure to a certain extent.…”

Betulinic Acid Protects From Bone Loss in Ovariectomized Mice and Suppresses RANKL-Associated Osteoclastogenesis by Inhibiting the MAPK and NFATc1 Pathways

“…Here, we observed no marked suppressive effects of BA on IκBα degradation or p65 phosphorylation, indicating the anti-osteoclastic effects of BA are not caused by NF-κB inactivation. Therefore, we hypothesized that another pathway, MAPK signaling, which encompasses JNK, p38, and ERK, is also induced by phosphorylation and in combination with NF-κB modulates the transcription of genes that initiate osteoclast formation ( Choi et al., 2017 ). In pre-osteoclasts, ERK (ERK 1 and 2) and JNK (JNK1, 2 and 3) isoforms mostly control cell proliferation and apoptosis, respectively ( Boyle et al., 2003 ; Ikeda et al., 2008 ; Lee et al., 2016 ).…”