Cycloastragenol (CAG) is a triterpenoid saponin compound and a hydrolysis product of the main active ingredient in Astragalus membranaceus (Fisch.) Bunge. An increasing body of evidence has indicated that CAG has a wide spectrum of pharmacological functions, which are attracting attention in the research community. The aim of the present review paper was to review and elucidate the advanced study of CAG. The focus was on advanced studies of CAG in English and Chinese databases; the literature was collected and reviewed to summarize the latest efficacy, pharmacokinetics and adverse reactions of CAG. Extensive pharmacological effects have been attributed to CAG, including telomerase activation, telomere elongation, anti-inflammatory and anti-oxidative properties; CAG has also been reported to improve lipid metabolism. Clinical research has demonstrated that CAG activates telomerase in humans and ameliorates various biomarkers. CAG is absorbed through the intestinal epithelium via passive diffusion and undergoes first-pass hepatic metabolism. Within a certain dose range, oral CAG is relatively safe; however, underlying mechanisms associated with CAG are not clear, and thus, we should be aware of potential adverse reactions associated with CAG. According to existing studies and clinical trials, CAG is safe and has broad application prospects. However, further studies are required to fully understand its efficacy and potential adverse reactions, and to ensure the proper use of CAG is applied to treat diseases clinically.

Glucocorticoid (GC)-induced osteoporosis (GIO) is characterized by impaired bone formation, which can be alleviated by tanshinol, an aqueous polyphenol isolated from Salvia miltiorrhiza Bunge. In this study we investigated the molecular mechanisms underlying GC-induced modulation of osteogenesis as well as the possibility of using tanshinol to interfere with GIO. Female SD rats aged 4 months were orally administered distilled water (Con), prednisone (GC, 5 mg·kg·d), GC plus tanshinol (Tan, 16 mg·kg·d) or GC plus resveratrol (Res, 5 mg·kg·d) for 14 weeks. After the rats were sacrificed, samples of bone tissues were collected. The changes in bone formation were assessed using Micro-CT, histomorphometry, and biomechanical assays. Expression of Kruppel-like factor 15 (KLF15), peroxisome proliferator-activated receptor γ 2 (PPARγ 2) and other signaling proteins in skeletal tissue was measured with Western blotting and quantitative RT-PCR. GC treatment markedly increased the expression of KLF15, PPARγ2, C/EBPα and aP2, which were related to adipogenesis, upregulated FoxO3a pathway proteins (FoxO3a and Gadd45a), and suppressed the canonical Wnt signaling (β-catenin and Axin2), which was required for osteogenesis. Thus, GC significantly decreased bone mass and bone quality. Co-treatment with Tan or Res effectively counteracted GC-impaired bone formation, suppressed GC-induced adipogenesis, and restored abnormal expression of the signaling molecules in GIO rats. We conclude that tanshinol counteracts GC-decreased bone formation by inhibiting marrow adiposity via the KLF15/PPARγ2/FoxO3a/Wnt pathway.

Resveratrol (Res) is a multi-functional polyphenol compound that has protective functions in cardiovascular and neurodegenerative diseases. This study aimed to determine the effect of Res on osteogenic differentiation and bone mineralization in zebrafish ( Danio rerio ) with dexamethasone (Dex)-induced bone damage. Our results showed that Dex exposure (15 μmol/l) decreased the green fluorescence areas and the integrated optic density (IOD) values in the skull bones of zebrafish larvae of the TG(SP7:EGFP) strain in a dose-dependent manner ( p < 0.01). Furthermore, Dex exposure decreased the alizarin red S-stained areas (bone mineralization area) in the skeleton and spinal bones of zebrafish larvae of the AB strain in a dose-dependent manner ( p < 0.01). By contrast, Res treatment (150 μmol/l) significantly increased both the green fluorescence and bone mineralization area in Dex-exposed zebrafish larvae. Thus, our data show that Res improves bone mineralization after glucocorticoid-induced bone damage in a zebrafish model. Res may be a candidate drug for the prevention of osteoporosis.

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Polygonum multiflorum Thunb. is a traditional Chinese medicinal herb that has been widely used to treat age-associated diseases. Tetrahydroxystilbene glucoside (TSG), also known as 2,3,5,4-tetrahydroxystilbene-2-O-β-D-glucoside, is a major component of this herb. The present study was designed to investigate the osteogenic differentiation promoting activity of TSG in rat mesenchymal stem cells (MSCs) and in zebrafish. Preliminary experiments using MTT assay and ALP methods indicate that the high potential activity for promoting osteogenic differentiation was observed when 50% ethanol eluate was used. Further isolation and purification of TSG from the 50% ethanol eluate was performed by bioassay-guided fractionation, and its structure was confirmed using nuclear magnetic resonance and mass spectrometry analyses. In addition, the relative content of TSG with the highest potential activity in the promotion of osteogenic differentiation was identified as 14.34% by reversed-phase high performance liquid chromatography. Subsequently, the osteogenic differentiation promoting abilities of TSG in MSCs were examined. The results demonstrated that TSG promoted the alkaline phosphatase activity at concentrations of 1.56–25 µg/ml, while it increased the content of osteocalcin 7 days after treatment with 6.25–25 µg/ml in MSCs. Furthermore, experiments in zebrafish indicated that different concentrations of TSG (3.12–12.5 µg/ml) protected against further bone loss induced by 10 µmol/l dexamethasone (Dex), simulating an osteoporosis (OP) model. TSG treatment (12.5 µg/ml) in Dex-induced zebrafish significantly increased the area of nodules by 50.14% compared with the untreated model group. In conclusion, TSG, as a major component of P. multiflorum Thunb. exhibited an osteogenic promoting activity in MSCs and in zebrafish. The results provided scientific evidence to support the potential use of TSG for protecting the bone in degenerative diseases, such as OP.