Current Protein and Peptide Science - Online First

Baicalein (BN), a potent flavonoid derived from scutellaria scutellaria, exhibits an array of noteworthy attributes, such as anti-inflammatory, antibacterial, and antipyretic properties. Furthermore, its potential in treating osteoporosis has been highlighted. Nonetheless, the exact modes of action responsible for its therapeutic effects remain obscure. Hence, this study aims to elucidate the improvement effect of BN on OVX rats and explore its potential mechanism of action in treating osteoporosis through a comprehensive strategy that integrates network pharmacology and rigorous animal experiments.

The potential protein targets and OP disease targets in BN are analyzed using the protein database. The protein interaction diagram is constructed by Cytoscape3.7.2 software, and binding energy is used to evaluate the binding activity between BN and core targets, and some key genes are verified by protein experiments.

Topology analysis and prediction reveal that osteoporosis (OP) is associated with more than ten core target proteins. Notably, NAD-dependent deacetylase sirtuin 1 (SIRT1), Androgen Receptor (AR), Estrogen Receptor beta (ESR1), and Cyclooxygenase-2 (PTGS2) emerge as pivotal proteins in the treatment of osteoporosis with BN. The biological process underlying BN treatment of osteoporosis primarily involves the regulation of sex hormone levels, autophagy, inflammatory response, and reactive oxygen metabolism. Moreover, the signaling pathways involved are predominantly the PI3K-Akt pathway, AMPK pathway, and estrogen signaling pathway. Subsequent animal experiments corroborate these findings by demonstrating that BN significantly enhances the expression levels of SIRT1, AR, and ESR1 in tissues, while concurrently reducing the protein expression of PTGS2. This multifaceted approach ultimately achieves the desired therapeutic outcome of osteoporosis treatment.

In summary, this study has validated the therapeutic effect of BN on OP and analyzed multiple potential therapeutic targets of BN for osteoporosis, which provides new ideas for further clinical treatment and experimental research of BN.