Maclurin promotes extracellular matrix formation in osteoblasts via PI3K/Akt pathway activation

Mulberry (Morus nigra L.) is traditionally recognized for its bone-strengthening properties, yet its active constituents and underlying mechanisms remain incompletely understood. This study investigates the effects of maclurin, a key flavonoid from mulberry, on extracellular matrix (ECM) deposition and bone formation. In vitro, maclurin (5-20 μM) treatment enhanced ECM protein expression, including fibronectin (FN), laminin subunit gamma-2, and collagen alpha-1(I) chain (Col I) in MC3T3-E1 osteoblasts in a dose-dependent manner. Transcriptomic analysis suggested the involvement of PI3K/Akt signalling pathway, which was subsequently validated by increased Akt phosphorylation that was reversed by siAkt and PI3K inhibitor LY294002. In a subcutaneous ectopic bone formation model, oral maclurin administration (0.5-2.0 mg/kg) promoted Col I and FN expressions, improved collagen fibre organization, and increased calcium deposition in newly formed bone tissues. These results provide experimental evidence for osteogenic activity of maclurin and enhance our understanding of the bone-health benefits associated with mulberry.