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.

越橘种子，越橘种子，在东亚国家传统上用于治疗母乳缺乏症，但尚未发现潜在的分子机制。本研究评估了牛痘疫苗的主要成分之一牛痘菌素对牛乳腺上皮细胞（BMECs）的增殖和乳汁合成的刺激作用，并探讨了相应的分子机制。Vaccarin以浓度依赖的方式影响细胞增殖以及乳脂和蛋白质的合成，在0.5μg/ ml的浓度下具有最佳的刺激作用。Vaccarin（0.5μg/ ml）与催乳素（Prl，0.5μg/ ml）对细胞增殖，乳脂和蛋白质合成，Cyclin D1的表达，雷帕霉素（mTOR）的机械靶磷酸化，固醇调节元件结合蛋白1c（SREBP-1c）的表达和成熟。Vaccarin通过Prl受体-磷脂酰肌醇3-激酶（PI3K）信号传导刺激这些信号传导途径。Vaccarin还可以浓度依赖性地刺激Prl受体的表达，在0.5μg/ ml的浓度下效果最佳。总之，我们证明痘苗蛋白通过Prl受体-PI3K信号传导促进BMEC的增殖和乳汁合成，这表明痘苗蛋白可能是促进精液中BMECs乳汁产生的主要活性成分。