Acteoside Suppresses RANKL-Mediated Osteoclastogenesis by Inhibiting c-Fos Induction and NF-κB Pathway and Attenuating ROS Production

Abstract

Numerous studies have reported that inflammatory cytokines are important mediators for osteoclastogenesis, thereby causing excessive bone resorption and osteoporosis. Acteoside, the main active compound of Rehmannia glutinosa, which is used widely in traditional Oriental medicine, has anti-inflammatory and antioxidant potentials. In this study, we found that acteoside markedly inhibited osteoclast differentiation and formation from bone marrow macrophages (BMMs) and RAW264.7 macrophages stimulated by the receptor activator of nuclear factor-kappaB (NF-κB) ligand (RANKL). Acteoside pretreatment also prevented bone resorption by mature osteoclasts in a dose-dependent manner. Acteoside (10 µM) attenuated RANKL-stimulated activation of p38 kinase, extracellular signal-regulated kinases, and c-Jun N-terminal kinase, and also suppressed NF-κB activation by inhibiting phosphorylation of the p65 subunit and the inhibitor κBα. In addition, RANKL-mediated increases in the expression of c-Fos and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) and in the production of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 were apparently inhibited by acteoside pretreatment. Further, oral acteoside reduced ovariectomy-induced bone loss and inflammatory cytokine production to control levels. Our data suggest that acteoside inhibits osteoclast differentiation and maturation from osteoclastic precursors by suppressing RANKL-induced activation of mitogen-activated protein kinases and transcription factors such as NF-κB, c-Fos, and NFATc1. Collectively, these results suggest that acteoside may act as an anti-resorptive agent to reduce bone loss by blocking osteoclast activation.

Bu-Shen-Ning-Xin decoction suppresses osteoclastogenesis <i>via </i>increasing dehydroepiandrosterone to prevent postmenopausal osteoporosis

“…Catalpol is considered to be a potential therapy for treatment of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease (55). Acteosides suppress RANKL-mediated osteoclastogenesis by inhibiting c-Fos induction and the NF-κB pathway and by attenuating ROS production (29).…”

“…the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway and attenuating the production of reactive oxygen species (ROS) (29). An extract of common Anemarrhena rhizome has antitumor, anti-inflammatory, and antioxidant action (56).…”

“…Acteoside in dried Rehmannia root suppresses RANKL-mediated osteoclastogenesis by inhibiting c-Fos induction and the NF-κB pathway and by attenuating ROS production (29). Flavonoids in Shorthorned Epimedium delayed bone loss without affecting the uterus in OVX mice (45), and icariin inhibited osteoclastogenesis in vitro (44).…”

Isopsoralen regulates PPAR‑γ/WNT to inhibit oxidative stress in osteoporosis

“…In the present study, it was found that isopsoralen Bone cells are a type of long-life cell, which is more susceptible to oxidative stress than osteoblasts and osteoclasts (20). Several experiments on rodents and humans have indicated that under oxidative stress induced by aging of the body, the number of bone cells gradually decreases, with weakened viability (21). The extracellular matrix in tissue is comprised of organic and inorganic components; the organic components are predominantly composed of a variety of collagens, whereas the inorganic components are hydroxyapatite crystals (5).…”

Metabolites of Rehmannia glutinosa Libosch extract by intestinal bacteria from normal and chronic kidney disease rats in vitro

“…11 Previous phytochemical investigations on Rehmannia glutinosa Libosch led to the isolation of diverse biologically active compounds, and the majority of them are iridoids. [15][16][17][18] Most herbal medicines are administrated orally, so their components are inevitably in contact with microorganisms in the gut. 12 Catalpol exhibits a verity of pharmacological actions, such as anti-brain ischemia, anti-senile dementia, promoting neuro-remodeling, and reducing capillary permeability.…”