Cycloastragenol protects against glucocorticoid-induced osteogenic differentiation inhibition by activating telomerase.

Glucocorticoid-induced osteoporosis (GIOP) that is mainly featured as low bone density and increased risk of fracture is prone to occur with the administration of excessive glucocorticoids. Cycloastragenol (CAG) has been verified to be a small molecule that activates telomerase. Studied showed that up-regulated telomerase was associated with promoting osteogeneic differentiation, so we explored whether CAG could promote osteogenic differentiation to protect against GIOP and telomerase would be the target that CAG exerted its function. Our results demonstrated that CAG prominently increased the ALP activity, mineralization, mRNA of runt-related transcription factor 2, osteocalcin, osteopontin, collagen type I in both MC3T3-E1 cells and dexamethasone (DEX)-treated MC3T3-E1 cells. CAG up-regulated telomerase reverse transcriptase and the protective effect of CAG was blocked by telomerase inhibitor TMPyP4. Moreover, CAG improved bone mineralization in DEX-induced bone damage in a zebrafish larvea model. Therefore, the study showed that CAG could alleviate the osteogenic differentiation inhibition induced by DEX in vitro and in vivo, and CAG might be considered as a candidate drug for the treatment of GIOP.

Prediction of the mechanisms of Xiaoai Jiedu Recipe in the treatment of breast cancer: A comprehensive approach study with experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM) holds a great promise for preventing complex chronic diseases through a holistic way. Certain Chinese medicine formulae from TCM are effective for treating and preventing cancer in clinical practice. Xiaoai Jiedu Recipe (XJR) is a Chinese medicine formula that has been used to treat breast cancer (BC). However, its active ingredients and therapeutic mechanisms on tumor are unclear. Therefore, further investigation is necessary. AIM OF THE STUDY: This study aims to elucidate the active compounds of XJR and its molecular mechanisms for the treatment of BC. MATERIALS AND METHODS: A comprehensive approach was used to clarify the pharmacodynamic basis of XJR and its pharmacological mechanism, including the acquisition of differentially expressed genes of BC, screening of active ingredients and their targets, construction of complex internetwork between drugs and diseases, and analysis of the key subnetwork. Finally, these results were validated by in vitro experiments and comparison with literature reviews. RESULTS: By using bioinformatics, 5211 differentially expressed genes of BC were identified, more than half of them had been reported in previous studies. By using network analysis, 113 potential bioactive compounds in the ten component herbs of XJR and 157 BC-related targets were identified, which were significantly enriched in 85 pathways and 1321 GO terms. The in vitro studies showed that quercetin and ursolic acid, the active components of XJR, could effectively inhibit the proliferation of breast cancer cells, and the combination of the two components could significantly decrease the mitochondrial membrane potential and suppress the activation of PI3K-Akt signaling pathway, thus inducing apoptosis of cancer cells. CONCLUSIONS: XJR played an important role in anti-BC through multi-component, multi-target and multi-pathway mechanisms, in which quercetin and ursolic acid may be the key active components. The anticancer effect of multi-component application was better than that of a single component. This study not only deepened our understanding of the role of TCM in the prevention and treatment of diseases, but also provided a reference for the in-depth research, development and application of the ancient medicine.