Proteomics reveals the role of Eucommia ulmoides-Tribulus terrestris in the central regulation of antihypertension by improving the hypothalamus in spontaneously hypertensive rats

BACKGROUND: In this study, the combination of Eucommia ulmoides-Tribulus terrestris (EU-TT) was used to intervene in aging spontaneously hypertensive rats (SHRs). Quantitative proteomics sequencing was performed to screen the targets of EU-TT, so as to provide data support for the clinical application of EU-TT. METHODS: Eighteen-month-old SHRs were administered EU-TT (5.53 g/kg/day) intragastrically for 8 weeks. Blood pressure was recorded to evaluate the efficacy of EU-TT in vivo. Transmission electron microscopy (TEM) and hematoxylin-eosin (HE) staining were used to assess the morphology of the hypothalamus. The label free proteomics assay was performed to screen the targets of EU-TT in hypertensive hypothalami. ERK, JNK, and p38 were chosen for Reverse Transcription-quantitative Polymerase Chain Reaction (RT-qPCR) and Western blot. RESULTS: After 8 weeks of treatment, EU-TT effectively decreased systolic blood pressure (SBP) by 19.2 mmHg and diastolic blood pressure (DBP) by 8.6 mmHg (P<0.05), and improved the hypothalamus morphology of aging SHRs. Label free proteomics identified 248 differentially expressed (DE) proteins (157 were upregulated and 91 were downregulated) in the hypothalamus after EU-TT treatment. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis suggested that EU-TT regulated the MAPK signal transduction pathway, which was also confirmed by RT-qPCR and Western blot. CONCLUSIONS: EU-TT steadily decreased the SBP and DBP of aging SHRs, and improved the morphology of the hypothalamus, which was pharmacologically related to the MAPK signaling pathway. KEYWORDS: Aging spontaneously hypertensive rats (SHRs); Eucommia ulmoides-Tribulus terrestris (EU-TT); hypothalamus; label free proteomics; MAPK signaling pathway