AUTHOR=Liu Qi , Zhou Jian , Yang Zhou , Xie Chuhai , Huang Yan , Ling Long , Cao Yanming , Hu Hailan , Hua Yue TITLE=The Ginsenoside Exhibits Antiosteoporosis Effects in Ketogenic-Diet-Induced Osteoporosis via Rebalancing Bone Turnover JOURNAL=Frontiers in Pharmacology VOLUME=Volume 11 - 2020 YEAR=2021 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2020.593820 DOI=10.3389/fphar.2020.593820 ISSN=1663-9812 ABSTRACT=Purpose: The ginsenoside is wildly used in the China for therapeutic and healthcare applications. Ginsenoside-Rb2 has shown the anti-osteoporosis effects in ovariectomized rats. However, the protective effects on osteoporosis induced by ketogenic diet(KD) is unknown. Therefore, this study was aimed to evaluate the effects of ginsenoside-Rb2 on KD-induced osteoporosis. Methods: Thirty mice were randomly divided into three groups: the sham, KD, and KD+Rb2 groups. The bone micro-structures, the biomechanical properties, the concentrations of serum bone alkaline phosphatase (BALP) and tartrate-resistant acid phosphatase (TRACP), as well as the protein expression of osteocalcin (OCN), peroxisome proliferation-activated receptor γ (PPAR-γ) and TRACP, were evaluated after 12 weeks intervention. Results: The results showed that the KD significantly induced bone loss and impaired biomechanics. Ginsenoside-Rb2 significant attenuate bone loss and maintained biomechanics in the cancellous bone. The bone volume fraction was increased from 2.3 to 6.0% in the KD+Rb2 group than that in KD group. Meanwhile, the ginsenoside-Rb2 maintained the biomechanical strengths in the cancellous bone. Ginsenoside-Rb2 effectively increased serum BALP and decreased TRACP, and up-regulated OCN and down-regulated TRAP, PPAR-γ and cathepsin K in KD mice. Conclusions: This study demonstrated that ginsenoside-Rb2 retarded bone loss and maintained the biomechanics under KD. The underlying mechanism might that the ginsenoside-Rb2 inhibited bone resorption process and induced osteogenic differentiation, which providing evidence for ginsenoside as an alternative option for osteoporosis induced by KD.