Abstract
Ginsenoside is widely used in China for therapeutic and healthcare practice. Ginsenoside-Rb2 shows the antiosteoporosis effects in ovariectomized rodents. However, the protective effects on osteoporosis induced by ketogenic diet (KD) remain unknown. Therefore, this study aimed at evaluating the effects of ginsenoside-Rb2 on KD-induced osteoporosis. Thirty mice were randomly divided into three groups: sham, KD, and KD + Rb2. Bone microstructures, biomechanical properties, concentrations of serum bone alkaline phosphatase (BALP) and tartrate-resistant acid phosphatase (TRACP), and protein expression of osteocalcin (OCN), peroxisome proliferation-activated receptor γ (PPAR-γ), cathepsin K, and TRAP were evaluated after a 12-week intervention. The results show that KD induced significant bone loss and biomechanical impairment. Ginsenoside-Rb2 attenuated significant bone loss and maintained biomechanics in cancellous bone. The bone volume fraction increased from 2.3 to 6.0% in the KD + Rb2 group than that in the KD group. Meanwhile, ginsenoside-Rb2 effectively maintained biomechanical strengths in cancellous bone, increased serum BALP and decreased TRACP, and upregulated OCN and downregulated TRAP, PPAR-γ, and cathepsin K in the KD mice. This study demonstrated that ginsenoside-Rb2 retards bone loss and maintains biomechanics with KD. The underlying mechanism might be that ginsenoside-Rb2 inhibits bone resorption process and induces osteogenic differentiation, providing evidence for ginsenoside as being an alternative option for osteoporosis induced by KD.
Highlights
Osteoporosis is a common disease, especially in the aged, which is manifested as deteriorated bone microarchitectures and weakening biomechanical strengths, fragile bone and a higher risk of fracture (Zhang et al, 2020)
ELISA results showed that the bone alkaline phosphatase (BALP) concentration was obviously lower and the tartrate-resistant acid phosphatase (TRACP) concentration was remarkably higher in the ketogenic diet (KD) group than those in the sham group (KD vs. Sham: 7.70 mg/ml vs. 12.49 mg/ml and 63.37 U/L vs. 38.73 U/L in BALP and TRACP, respectively)
After the intervention of ginsenosideRb2, the BALP concentration was significantly upregulated and the TRACP concentration was significantly downregulated in the KD + Rb2 group than those in the KD group, and it showed no difference between the sham group and the KD + Rb2 group (Figure 2B)
Summary
Osteoporosis is a common disease, especially in the aged, which is manifested as deteriorated bone microarchitectures and weakening biomechanical strengths, fragile bone and a higher risk of fracture (Zhang et al, 2020). Osteoporosis is mainly caused by imbalance of bone metabolism, which might be affected by physical activities, diet intervention, hormonal and clinical status (Lelovas et al, 2008). A new concept was introduced that osteoporosis (impaired microarchitecture of the skeletons) can be caused by certain unhealthy lifestyles, diseases, or medications. It is commonly accepted that high-fat diet can be used for obesity in rodents, which weakens the activity of osteoblasts, aggravates bone loss, and decreases bone strength in rats (Wang et al, 2017). Our previous studies further confirmed that KD compromises bone mass and weakens biomechanical strengths by reducing BMSCs osteogenic capability (Wu et al, 2017; Xu et al, 2019)
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