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

Key words: Eucommia ulmoides Oliv. seed oil; spontaneous hypertension; Toll-like receptor 4/nuclear factor-κB signaling pathway; gut microbiota; organic acids