Vaccarin treats lactation insufficiency through the ALKBH5-SFRP2-Wnt/β-catenin signaling pathway

• Published in: Journal of ethnopharmacology Vol. 348; p. 119898
• Main Authors: Xue, Qiuyun, Li, Hui, Liu, Guosheng, Xiong, Youyi, Zhou, Guoliang, Xu, Pengfei, He, Juan, Wang, Xiaomei, Miao, Chenggui
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 28.05.2025
• Subjects: AlkB Homolog 5, RNA Demethylase - genetics; AlkB Homolog 5, RNA Demethylase - metabolism; alkylation; Alkylation repair homolog protein 5; Animals; beta Catenin - metabolism; Cells, Cultured; childbirth; Epithelial Cells - drug effects; Epithelial Cells - metabolism; epithelium; Female; flavonoids; Flavonoids - pharmacology; Flavonoids - therapeutic use; fluorescent antibody technique; glycosides; Glycosides - pharmacology; Glycosides - therapeutic use; Gypsophila; lactation; Lactation - drug effects; Lactation Disorders - drug therapy; Lactation Disorders - metabolism; Lactation insufficiency; mammary glands; Mammary Glands, Animal - drug effects; Mammary Glands, Animal - metabolism; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; milk production; milk secretion; precipitin tests; prolactin; prolactin receptors; Rats; Rats, Sprague-Dawley; RNA; SFRP2; traditional medicine; Vaccaria; Vaccarin; Western blotting; Wnt Signaling Pathway - drug effects; Wnt/β-catenin signaling pathway; Wnt/β-catenin signaling pathway; MT; Alkylation repair homolog protein 5; mRNA; PRL; WB; BMECs; MECs; PRLR; CK18; ALKBH5; Vaccarin; SFRP2; CCND1; RIP; Vac; RMECs; Lactation insufficiency
• ISSN: 0378-8741; 1872-7573; 1872-7573
• DOI: 10.1016/j.jep.2025.119898

Vaccarin, a natural small molecule extracted from Gypsophila vaccaria (L.) Sm., is an active flavonoid glycoside. Lactation insufficiency refers to insufficient milk secretion in women after childbirth, which affects the feeding of infants and even their development. Our preliminary experiments showed that alkylation repair homolog protein 5 (ALKBH5) was abnormally overexpressed in mammary tissue of lactation deficiency model rats, which played an important role in regulating milk secretion, but the mechanism was not clear, and no research reports were reported in this aspect. The aim of this study was to investigate whether Vaccarin (Vac) treated lactation insufficiency through the ALKBH5-SFRP2-Wnt/β-catenin signaling pathway. The lactation insufficiency model rats and primary cultured rat mammary epithelial cells (RMECs) were used as experimental subjects. RT-qPCR, Western blot, RNA Immunoprecipitation, immunofluorescence and related methods were used to study the mechanism of Vac treatment for lactation insufficiency. Vac effectively increased the milk production, significantly improved the thickness and density of mammary ducts and follicles, and promoted the prolactin (PRL) secretion and the prolactin receptor (PRLR) expression in lactation insufficiency model rats. Vac significantly promoted the expression of FASN, CSN2, and GLUT1. ALKBH5 was upregulated in the mammary gland of model mice, promoting SFRP2 expression and inhibiting the Wnt/β-catenin signaling pathway and the expression of FASN, CSN2 and GLUT1. Furthermore, Vac inhibited the expression of SFRP2 by targeting the ALKBH5, and subsequently activated the Wnt/β-catenin signaling pathway to promote milk secretion in the lactation insufficiency model rats. Vac promoted milk secretion and improved lactation insufficiency through the ALKBH5-SFRP2-Wnt/β-catenin signaling pathway. [Display omitted] •Vaccarin increases lactation in model rats.•Vaccarin promotes PRL secretion in model rats.•Vaccarin promotes lactose, milk fat, and milk protein expression by activating Wnt/β-catenin signaling pathway.•Vaccarin improves postpartum hypogalactia through ALKBH5-SFRP2-Wnt/β-catenin pathway.