Baicalein (BN) is an active ingredient naturally present in Chinese herbs such as Scutellaria baicalein, Coptis coptis and Dendrobium officinale. It has a variety of pharmacological activities, including antioxidant, anti-inflammatory and antibacterial effects. Therefore, Baicalein (BN) is widely used in the field of medicine and is considered as a potential natural medicine. At the same time, osteoporosis (OP) is a bone metabolic disease characterized by decreased bone mineral density and bone structure destruction, which is mainly caused by decreased bone formation and increased bone resorption. With the continuous development of molecular biology, the signaling pathways and gene targets of bone metabolism are also expanding. Recent studies have shown that baicalein may affect the function of osteoblasts, osteoclasts and bone marrow mesenchymal stem cells through MAPK/ERK, MAPKs/NF-κB signaling pathways, so as to have a therapeutic effect on OP. However, the specific mechanism of baicalein in the treatment of OP is still unclear. This article reviews the literature, analyzes and summarizes the mechanism of baicalein, and discusses its potential in the prevention and treatment of OP, so as to provide a basis for the clinical application of baicalein.

Postmenopausal osteoporosis (PMOP) is a prevalent skeletal disorder associated with the aging population. Traditional Chinese Medicine (TCM) natural products have been clinically used for centuries to effectively treat PMOP. Kuntai Capsule (KTC), an herbal formula, has been proven to be an efficacious PMOP treatment in China, although its pharmacological mechanisms remain elusive. Herein, we elucidated the underlying mechanisms of KTC against PMOP through the utilization of a network pharmacology strategy and molecular docking analysis, combined with in vitro experimental validation. The network pharmacology analysis outcomes demonstrated the retrieval of a total of 30 active constituents and 112 intersecting targets of KTC associated with PMOP from the corresponding databases, thereby constructing an intricate ingredient-target-disease network. The analysis of protein-protein interactions identified 112 core targets, encompassing JUN, AKT1, TP53, MYC, FOS, etc., which served as pivotal targets. Then, functional enrichment analyses revealed significant enrichments of the PI3K-Akt and cell apoptosis signaling pathways mediated by these targets, consequently establishing them as the targets for subsequent molecular docking and experimental validation. Importantly, the docking results substantiated the robust binding activities of the principal active compounds in KTC with the enriched genes in the PI3K-Akt1 and cell apoptosis signaling pathways. Furthermore, in vitro experiments employing a mouse osteoblasts cell line (MC3T3) demonstrated that KTC not only facilitated the phosphorylation of PI3K and Akt1 but also suppressed cell apoptosis by inhibiting the cleavage of Caspase-3 and expression of Bax, while simultaneously augmenting the expression of Bcl2, thereby promoting osteogenesis. Collectively, our findings demonstrate the potential pharmacological mechanisms of KTC against PMOP, encompassing a multitude of ingredients, targets, and signaling pathways, with particular emphasis on the activation of the PI3K-Akt pathway and the inhibition of the apoptosis signaling pathway.