Orcinol Glucoside Improves Senile Osteoporosis through Attenuating Oxidative Stress and Autophagy of Osteoclast via Activating Nrf2/Keap1 and mTOR Signaling Pathway

Abstract

Oxidative stress and autophagy play essential roles in the development of senile osteoporosis which is characterized by disrupted osteoclastic bone resorption and osteoblastic bone formation. Orcinol glucoside (OG), a phenolic glycoside isolated from Curculigo orchioides Gaertn, possesses antiosteoporotic properties. This study examined the protective effects of OG on bone loss in SAMP6 mice and explored the underlying mechanisms. The osteoporotic SAMP6 mice were treated with OG oral administration. RAW264.7 cells were induced to differentiate into osteoclast by RANKL and H2O2 in vitro and received OG treatment. The results demonstrated that OG attenuated bone loss in SAMP6 mice and inhibited the formation and bone resorption activities of osteoclast and reduced levels of oxidative stress in bone tissue of SAMP6 mice and osteoclast. Furthermore, OG activated Nrf2/Keap1 signaling pathway and enhanced the phosphorylation of mTOR and p70S6K which are consequently suppressing autophagy. Of note, the effect of OG on Nrf2/Keap1 signaling was neutralized by the mTOR inhibitor rapamycin. Meanwhile, the inhibitory effect of OG on autophagy was reversed by the Nrf2 inhibitor ML385.Conclusively, OG attenuated bone loss by inhibiting formation, differentiation, and bone resorption activities of osteoclast. Regulation of Nrf2/Keap1 and mTOR signals is a possible mechanism by which OG suppressed oxidative and autophagy of osteoclasts. Thus, OG prevented senile osteoporosis through attenuating oxidative stress and autophagy of osteoclast via activating Nrf2/Keap1 and mTOR signaling pathway.

Osteoclasts and osteoarthritis: Novel intervention targets and therapeutic potentials during aging

“…In addition, p70S6K has been identified as an inhibitor for autophagy, working downstream of the mTORC1 complex. Activation of the mTOR‐p70S6K signaling pathway by orcinol glucoside suppresses autophagy and osteoclast differentiation (Gong et al., 2022 ).…”

Plant molecules reinforce bone repair: Novel insights into phenol-modified bone tissue engineering scaffolds for the treatment of bone defects

“…These two activated pathways synergistically facilitated the osteogenic progress. In terms of the autophagy of osteoclasts, Wan Gong et al employed a phenolic glycoside named orcinol glucoside (OG) to increase the production of Nrf-2 in osteoclast precursors to phosphorylate the mTOR signaling, resulting in the blockage of ROS-induced autophagy [ 69 ]. Another study regarding three phenolic acids (tannic acid (TA), gallic acid (GA) and ellagic acid) also confirmed their negative effects on the autophagy of osteoclasts via decreasing ROS, intracellular Ca 2+ content and mitochondrial membrane potentials [ 70 ].…”

The Potential of Natural Compounds Regulating Autophagy in the Treatment of Osteoporosis

“… 156 Orcinol glucoside (OG), a naturally occurring phenolic glycoside derived from Curculigo curculigo, exhibits a multitude of beneficial properties, including antioxidative, anxiolytic, neuroprotective, and anti-osteoporotic activities. 157 , 158 Senile OP is associated with oxidative stress, Gong et al have reported that OG holds the potential to mitigate oxidative stress and curb OCs autophagy by activating the Nrf2/Keap1 and mTOR signaling pathways. Additionally, OG exerts a down-regulatory effect on OCs differentiation and function, thereby presenting a preventive approach against senile OP.…”

“…Additionally, OG exerts a down-regulatory effect on OCs differentiation and function, thereby presenting a preventive approach against senile OP. 158 Lycorine is an alkaloid isolated from Lycoraceae plants, which has anti-inflammatory and antioxidant effects. 159 Notably, lycorine exhibits the ability to diminish the production of mROS, modulate the triggering signal for autophagy via the mROS/TRPML1/TFEB axis, and mitigate lipopolysaccharide-induced OCs autophagy, as well as suppress OCs activity and abundance.…”