Morinda officinalis Oligosaccharides Protect Against LPS-Induced Uterine Damage and Endometrial Inflammation in Mice and Bovine Endometrial Epithelial Cells

Abstract

Endometritis poses a significant challenge to the dairy industry, impairing bovine reproductive performance and causing substantial economic losses. Although Morinda officinalis oligosaccharides (MOO) exhibit anti-inflammatory properties, their therapeutic potential against endometritis remains unclear. This study investigated MOO’s protective effects against LPS-induced uterine injury in mice and inflammation in bovine endometrial epithelial cells (BENDs), and explored the underlying mechanisms. In mice, MOO attenuated uterine inflammation by improving histopathology, reducing pro-inflammatory cytokines and decreasing oxidative stress. In BEND cells, MOO alleviated LPS-induced inflammation, oxidative stress, and apoptosis via downregulating pro-inflammatory mediators (IL-1β, IL-6, TNF-α, IL-8, TLR4, RELA), restoring antioxidant enzymes (HMOX1, NQO1, Nrf2, NOX4), and modulating apoptosis markers (BAX, cleaved CASP3, CASP9, BCL2). MOO reduced ROS accumulation, preserved mitochondrial membrane potential, and inhibited calcium influx. Critically, the calcium channel agonist Bay K 8644 reversed MOO’s protective effects, confirming calcium signaling modulation as a key mechanism. This study provides the first evidence that MOO mitigates LPS-induced uterine damage and BENDs inflammation through calcium signaling regulation, suggesting its potential for treating inflammation-related reproductive disorders in livestock.