Hypotensive Effect of Eucommia ulmoides Oliv. Seed Oil: Insights from the Perspectives of TLR4/NF-κB Signaling Pathway and Gut Microbiota

To investigate the antihypertensive effect of Eucommia ulmoides Oliv. seed oil on spontaneously hypertensive rats (SHR) and its potential molecular mechanisms.

SHR were randomly grouped and orally administered with the seed oil for 8 weeks. Changes in blood pressure and body weight were monitored. Vascular morphology and collagen deposition were observed using hematoxylin-eosin staining and Masson’s trichrome staining.Employing immunohistochemistry, enzyme-linked immunosorbent assay, Western blot, polymerase chain reaction, 16S rRNA sequencing, and high performance liquid chromatography, we detected vascular inflammatory factors, oxidative stress markers, vasoactive substances (angiotensin Ⅱ, big endothelin-1, and NO), the expression of key molecules in the Toll-like receptor 4/myeloid differentiation primary response 88/nuclear factor-κB (TLR4/MyD88/NF-κB) signaling pathway, gut microbiota structure, and organic acid (e.g., acetate) content, and we also analyzed the correlations among these indicators.

The oil significantly reduced blood pressure in SHR, alleviated vascular fibrosis and collagen deposition, down-regulated inflammatory factors and malondialdehyde levels, enhanced superoxide dismutase activity, inhibited TLR4/MyD88/NF-κB signaling pathway activation, regulated gut microbiota homeostasis, and increased the abundance of beneficial bacteria and acetate production. These indicators showed significant correlations with inflammation levels.

E. ulmoides Oliv. seed oil likely exerts its antihypertensive effects by regulating the gut microbiota-organic acid metabolism axis, suppressing inflammatory responses, and protecting vascular endothelial function. This finding provides theoretical support for its development and application as a functional food ingredient.