Aqueous Extract of Syringa oblata Lindl. Alleviates Murine Endometritis by Modulating TLR4/MyD88 Signaling and Macrophage Polarization.

Syringa oblata Lindl. (SOL) has long been used in traditional medicine for inflammatory disorders, yet its molecular actions in reproductive tract inflammation remain poorly defined. This study investigated the phytochemical composition and anti-inflammatory mechanisms of an aqueous SOL leaf extract using murine and cellular models of endometritis. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis revealed major constituents including rutin, salidroside, and esculetin. In a murine model of bacterial endometritis induced by Escherichia coli and Staphylococcus aureus, SOL markedly attenuated uterine edema, epithelial disruption, leukocyte infiltration, and bacterial burden. Mechanistic analyses demonstrated that SOL suppressed the Toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MyD88) axis and decreased the uterine expression of interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). In lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages, SOL and its principal monomers significantly reduced nitric oxide (NO) and reactive oxygen species (ROS) production both in the presence and absence of the TLR4 inhibitor TAK-242, suggesting additional modulation of redox-responsive pathways beyond canonical TLR4 signaling. Moreover, SOL selectively decreased the M1 macrophage marker CD86 in uterine tissue without altering CD163, consistent with partial inhibition of pro-inflammatory macrophage polarization. Collectively, these findings indicate that SOL exerts potent antimicrobial, anti-inflammatory, and antioxidative effects through coordinated regulation of innate immune signaling and macrophage activation, supporting its potential as a natural therapeutic candidate for inflammation-associated reproductive disorders.