Salidroside improves hypoxia-induced milk synthesis disorder and endoplasmic reticulum stress via AKT/mTOR signaling in bovine mammary epithelial cells.

Abstract

Ethnopharmacological relevance: Rhodiola crenulata, a distinctive medicinal herb in Tibetan medicine, has been utilized for thousands of years to treat physical weakness, chest tightness, difficulty breathing, and discomfort caused by high-altitude environments. Salidroside is one of the most potent bioactive ingredients of the genus Rhodiola.

Aim of study: This study investigated the protective effect of salidroside in hypoxia-induced milk biosynthesis impairment using bovine mammary epithelial cells (MAC-T), elucidating its underlying molecular mechanism.

Materials and methods: Cells with or without salidroside were exposed to hypoxia, with milk biosynthesis quantitatively assessed via using immunofluorescence, biochemical assays, Western blot, and Quantitative real-time PCR (QRT-PCR), alongside parallel evaluation of endoplasmic reticulum (ER) and mitochondrial functions.

Results: Results demonstrated that hypoxia inhibited cell proliferation, downregulated mRNA/protein expression of milk synthesis factors (α-casein, β-casein, SREBP1, and FASN), and concurrently triggered ER stress and mitochondrial dysfunction. Conversely, salidroside alleviated hypoxia-induced milk biosynthesis disorder through inhibiting ER stress. Additionally, hypoxia treatment decreased the expression of phosphorylated protein kinase B (AKT) and mammalian target of rapamycin (mTOR) levels, whereas salidroside blocked the decrease in p-AKT and p-mTOR levels. Targeted activation of AKT/mTOR signaling using SC79 (an AKT activator) or L-leucine (a mTOR activator) mimicked salidroside's protective effects, rescuing ER homeostasis, and milk synthesis capacity in hypoxia-treated cells.

Conclusions: The AKT/mTOR signaling is involved in the protective effect of salidroside on hypoxia-induced milk biosynthesis disorder. These findings provide promising evidence for the therapeutic potential of salidroside against hypoxia-induced cellular damage and milk biosynthesis impairment in MAC-T cells.