Preliminary Evaluation on the Anti‐Osteoporosis Mechanism of Sojae Semen Germinatum Based on Network Pharmacology and Germination‐Improved Bioavailability

ABSTRACT Sojae Semen Germinatum is a processed soybean product germinated using mature seeds of Glycine max (L.) Merr. with therapeutic benefits for osteoporosis. However, its action mechanism and related chemical components are unclear. Therefore, hypothesis‐generating methods of network pharmacology and molecular docking were adopted to initially predict the potential mechanism of SSG in treating osteoporosis. Subsequently, experimental validation was performed using mesenchymal stem cell (MSC) proliferation assays to verify the hypothesis. The MSC proliferation‐promoting activity of soybean isoflavone aglycones was greater than that of soybean isoflavone glycosides ( p < 0.05). Additionally, an LC–ESI–MS/MS method was investigated to confirm the bioavailability of those chemical components after oral administration of SSG and soybean to rats. Only small amounts of free daidzein, glycitein, and genistein were detected in rat plasma, while large amounts of them were detected after being hydrolyzed by β–glucosidase, indicating the main forms of isoflavones were their corresponding phase II metabolites. The bioavailability of total daidzein, glycitein, and genistein increased during soybean germination, reaching 143 ± 30%, 184 ± 32%, and 130 ± 24%, respectively. Soybeans are processed into SSG through germination, which increases the contents of soy isoflavone aglycones, thereby improving their bioavailability and enhancing their therapeutic effect on osteoporosis.