Abstract
Semen Vaccariae, the seed of Vaccaria segetalis, is traditionally used in East Asian countries for the treatment of breast milk deficiency, but the underlying molecular mechanism has not been discovered yet. The present study assessed the stimulatory effect of vaccarin, one of the major constituents of Semen Vaccariae, on proliferation of and milk synthesis in bovine mammary epithelial cells (BMECs) and explored the corresponding molecular mechanism. Vaccarin affected cell proliferation and milk fat and protein synthesis in a concentration-dependent manner, with the best stimulatory effects at 0.5 μg/ml concentration. Vaccarin (0.5 μg/ml) had the similar effects as prolactin (Prl, 0.5 μg/ml) on cell proliferation, milk fat and protein synthesis, expression of Cyclin D1, phosphorylation of mechanistic target of rapamycin (mTOR), and expression and maturation of sterol regulatory element binding protein 1c (SREBP-1c). Vaccarin stimulated these signaling pathways via the Prl receptor-phosphatidyl inositol 3-kinase (PI3K) signaling. Vaccarin also concentration-dependently stimulated expression of the Prl receptor, with the best effects at 0.5 μg/ml concentration. In summary, we demonstrate that vaccarin promotes proliferation of and milk synthesis in BMECs through the Prl receptor-PI3K signaling, suggesting that vaccarin might be the main active component promoting milk production of BMECs in Semen Vaccariae.