Effect of Zuoguiwan on osteoporosis in ovariectomized rats through RANKL/OPG pathway mediated by β2AR

Liu, Feixiang; Tan, Feng; Tong, Wei-Wei; Fan, Qing; Ye, Sumin; Shen, Lu; Teng, Zhan-Li; Han, Miaomiao; Zhang, Mingyue; Chai, Yi

doi:10.1016/j.biopha.2018.04.102

Cited by 21 publications

(17 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In OVX‐induced osteoporosis model, femoral BMD was significantly decreased in this study, indicating that OVX led to bone loss of femur. Furthermore, OVX resulted in abnormalities of trabeculae, which was in accordance with previous reports (Liu et al, 2018; Rajfer et al, 2019). As expected, Rg3 prevented OVX‐induced declines in BMD and improved abnormalities of trabeculae, indicating that Rg3 exhibited a protective effect on femur in OVX‐induced osteoporosis.…”

Section: Discussionsupporting

confidence: 92%

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

Zhang

Huang

Chen

et al. 2020

Drug Development Research

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 92%

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

Zhang

Huang

Chen

et al. 2020

Drug Development Research

View full text Add to dashboard Cite

show abstract

“…The dose selection of ZGW was based on the recommended daily dose for humans (18 g/kg), and the equivalent conversion between animals and humans was based on the body surface area. This method of calculating the rat oral administration dose is similar to previous studies ( 9 , 20 ).…”

Section: Methodsmentioning

confidence: 60%

“…As a well-known TCM for treating GIOP, Zuo-Gui-Wan (ZGW) comprises eight herbal medicines: Radix Rehmanniae, Semen Cuscutae, Radix Achyranthis Bidentatae, Carapax et Plastrum Testudinis, Cornu Cervi Pantotrichum, Rhizoma Dioscoreae, Fructus Corni, and Fructus Lycii. Recent research has found that ZGW can treat ovariectomy-induced osteopenia by regulating the Th17/Treg or RANKL/OPG signal transduction pathway ( 6 – 9 ). Moreover, our previous studies have demonstrated that extracts from plastrum testudinis, one of the major active ingredients of ZGW, may ameliorate GIOP via regulating OPG, Runx2, and CTSK expressions ( 10 , 11 ).…”

Section: Introductionmentioning

confidence: 99%

Zuo-Gui-Wan Aqueous Extract Ameliorates Glucocorticoid-Induced Spinal Osteoporosis of Rats by Regulating let-7f and Autophagy

et al. 2022

View full text Add to dashboard Cite

ObjectiveThis study proposes to explore the protective effect of Zuo-Gui-Wan (ZGW) aqueous extract on spinal glucocorticoid-induced osteoporosis (GIOP) in vivo and in vitro, and the underlying mechanisms of ZGW in GIOP and osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) were conducted.MethodsIn vivo, SD rats were randomly divided into three groups: control group (CON), dexamethasone (DEXM) group, and ZGW group, which were given vehicle, DEXM injection, and ZGW intragastric administration at the same time. Vertebral bone microarchitecture, biomechanics, histomorphology, serum AKP activity, and the autophagosome of osteoblasts were examined. The mRNA expressions of let-7f, autophagy-associated genes (mTORC1, Beclin-1, ATG12, ATG5, and LC3), Runx2, and CTSK were examined. In vitro, the let-7f overexpression/silencing vector was constructed and transfected to evaluate the osteogenic differentiation of BMSCs. Western blot was employed to detect the expression of autophagy-associated proteins (ULK2, ATG5, ATG12, Beclin-1, LC3).ResultsIn vivo, ZGW promoted the bone quantity, quality, and strength; alleviated histological damage; increased the serum AKP activity; and reduced the autophagosome number in osteoblasts. Moreover, ZGW increased the let-7f, mTORC1, and Runx2 mRNA expressions and reduced the Beclin-1, ATG12, ATG5, LC3, and CTSK mRNA expressions. In vitro, bioinformatics prediction and dual luciferase reporter gene assay verified that let-7f targeted the binding to ULK2 and negatively regulated the ULK2 expression. Furthermore, by let-7f overexpression/silencing, ZGW may promote osteoblast differentiation of BMSCs by regulating let-7f and autophagy as evidenced by Western blot (ULK2, ATG5, ATG12, Beclin-1, LC3).ConclusionsZGW may ameliorate GC-induced spinal osteoporosis by promoting osteoblast differentiation of BMSCs by activation of let-7f and suppression of autophagy.

show abstract

“…The structure of trabecular bone of the femur was determined by micro‐CT (Skyscan 1176). According to the protocol reported in the previous literature, the CT scan parameters were set as follows: resolution 9 μm, voltage 65 kV and current 384 mA; a 1‐mm filter was used. After the scan was completed, a uniform region of interest (ROI), namely, a section of cancellous bone with a length of 3 mm located approximately 0.5 mm from the intercondylar fossa growth plate, was selected for each specimen and reconstructed using the system's built‐in CTAn 1.14 software.…”

Section: Methodsmentioning

confidence: 99%

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

Wang

Zheng

Huang

et al. 2020

J Cellular Molecular Medi

View full text Add to dashboard Cite

Osthole (OST), a derivative of Fructus Cnidii, has been proved to have potential antiosteoporosis effects in our recent studies. However, its pharmacological effects are limited in the human body because of poor solubility and bioavailability. Under the guidance of the classical theory of Chinese medicine, Osthole-loaded N-octyl-O-sulfonyl chitosan micelles (NSC-OST), which has not previously been reported in the literature, was synthesized in order to overcome the defects and obtain better efficacy. In this study, we found that NSC-OST inhibited on the formation and resorption activity of osteoclasts through using a bone marrow macrophage (BMM)derived osteoclast culture system in vitro, rather than affecting the viability of cells.We also found that NSC-OST inhibited osteoclast formation, hydroxyapatite resorption and RANKL-induced osteoclast marker protein expression. In terms of mechanism, NSC-OST suppressed the NFATc1 transcriptional activity and the activation of NF-κB signalling pathway. In vivo, ovariectomized (OVX) rat models were established for further research. We found that NSC-OST can attenuate bone loss in OVX rats through inhibiting osteoclastogenesis. Consistent with our hypothesis, NSC-OST is more effective than OST in parts of the results. Taken together, our findings suggest that NSC-OST can suppress RANKL-induced osteoclastogenesis and prevents ovariectomy-induced bone loss in rats and could be considered a safe and more effective anti-osteoporosis drug than OST. K E Y W O R D Shomology of medicine and food, mutual promotion, NFATc1, NSC-OST, osteoclasts, osteoporosis

show abstract

Effect of Zuoguiwan on osteoporosis in ovariectomized rats through RANKL/OPG pathway mediated by β2AR

Cited by 21 publications

References 34 publications

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

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

Zuo-Gui-Wan Aqueous Extract Ameliorates Glucocorticoid-Induced Spinal Osteoporosis of Rats by Regulating let-7f and Autophagy

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

Contact Info

Product

Resources

About