Ginsenoside Rg3 attenuates ovariectomy‐induced osteoporosis via AMPK/mTOR signaling pathway

Abstract

Ginsenoside Rg3, a ginsenoside isolated from Panax ginseng, can regulate autophagy via AMP‐activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) signaling pathway. AMPK/mTOR signaling and autophagy have been reported to be involved in osteogenesis. Here, the effect of Rg3 on ovariectomy (OVX)‐induced osteoporosis is explored. In vivo, rats were treated with 20 mg/kg Rg3 after OVX and the body weight (BW) was monitored. Bone mineral density (BMD), hematoxylin–eosin staining of femur tissues, osteogenesis, autophagy, and AMPK/mTOR signaling were analyzed. In vitro, MC3T3‐E1 cells were treated with 0, 1, 5, 10, 20, and 100 μmol/L Rg3. 10 and 20 μmol/L Rg3, which had no significant effect on cell viability and significantly affected AMPK/mTOR signaling, were chosen for further analysis. Then osteogenic differentiation was induced with Rg3 or/and AMPK inhibitor (Compound C). AMPK/mTOR signaling, autophagy, osteogenic differentiation, and mineralization by Alizarin Red staining were analyzed. The expression or activity of AMPK/mTOR signaling‐related proteins, autophagy markers, and osteogenesis markers was measured by western blotting or commercial kits, and cell viability by cell counting kit‐8 assay kits. Rg3 significantly alleviated OVX‐induced BW increases, BMD declines and histological changes of femur tissues, promoted osteogenesis, autophagy, and AMPK signaling, but inhibited mTOR signaling in vivo. Moreover, Rg3 significantly enhanced AMPK signaling, autophagy, osteogenic differentiation, and mineralization, but suppressed mTOR signaling in vitro. However, Compound C significantly reversed Rg3‐induced alterations in vitro, indicating that Rg3 regulated autophagy, osteogenic differentiation, and mineralization via AMPK/mTOR signaling. Hence, it was speculated that Rg3 might attenuate OVX‐induced osteoporosis via AMPK/mTOR signaling pathway.

Expression Profile Analysis of Long Non-coding RNA in OVX Models-Derived BMSCs for Postmenopausal Osteoporosis by RNA Sequencing and Bioinformatics

“…The KEGG analyses of this subnetwork revealed that the 30 nodes took part in adipogenesis signaling pathways, including adipocytokine signaling pathway, PPAR signaling pathway, AMPK signaling pathway, and apelin signaling pathway. Previous studies have shown that ginsenoside Rg3 reduces osteoporosis caused by ovariectomy through the AMPK/mTOR signaling pathway ( Zhang et al, 2020 ). Exosomes derived from bone marrow mesenchymal stem cells promote the proliferation of osteoblasts through the MAPK pathway to improve osteoporosis ( Zhao et al, 2018 ).…”

Biochemical Targets and Molecular Mechanism of Ginsenoside Compound K for Treating Osteoporosis Based on Network Pharmacology

“…Although these targets have not been obviously reported for other studies about ginsenoside-treated osteoporosis, some of them were veri ed indirectly based on the related-targets in the same pathway. For example, MAP2K1,MAPK12, MAPK14 and MAPK8 were related to MAPKs signaling which was trigged by Rb1 [19] and Rh2 [13], and mTOR was related to mTOR signaling which could be activated by Rg3 [12]. So, this not only implies that GCK has the potential to prevent and treat osteoporosis, but also indicates that there is still large unknowability and necessity for exploring the molecular mechanism of ginsenoside-treated osteoporosis.…”

“…Ginsenosides are the main pharmacologically active compounds in ginseng, pharmacological effects of which include resistance to tumors, inhibition of neurodegeneration in patients with Alzheimer's disease, promotion of brain development and memory improvement, exhibition of anti-in ammatory and antioxidant effects, prevention of diabetes, resistance to fatigue, protection of the heart and antiosteoporosis, etc [11]. Ginsenoside Rb1, Rb2, Rg1, Rg3 and Rh2 can prevent osteoporosis based on in vitro or/and in vivo experiment [10,[12][13][14]. However, the molecular mechanism is not totally understood for ginsenosides to prevent and treat osteoporosis.…”

MiR-27a-3p Targets GLP1R to Regulate Differentiation, Autophagy, and Release of Inflammatory Factors in Pre-Osteoblasts via the AMPK Signaling Pathway

“…Besides, autophagy promotes osteoblast differentiation and exerts a protective effect on osteoblasts ( Li X et al, 2020 ). In addition, studies indicated that activating AMPK induces autophagy and facilitates cellular differentiation ( Ran et al, 2020 ; Zhang et al, 2020 ), whereas inhibiting autophagy reveres the effect of AMPK on osteoblast differentiation ( Li et al, 2018 ). Hence, we speculated that miR-27a-3p is also capable of targeting GLP1R and mediate the AMPK signaling pathway to affect osteoblast autophagy and differentiation, thus influencing bone formation.…”