Aims: The antihypertensive mechanism (s) of the epigallocatechin-3-gallate (EGCG), a major effective component in green tea, might associate with microRNAs (miRNAs). Here, we aimed to investigate which microRNA in aorta of spontaneously hypertensive rats (SHRs) were modulated by administration of EGCG and its mechanism.
Main methods: The pharmacokinetic behaviors of EGCG and epigallocatechin (EGC) in Sprague-Dawley rats were analyzed by HPLC and DRUG AND STATISTICS software. Blood pressure of SHRs was monitored by the tail-cuff method, the miRNomes of aorta from SHRs was analyzed with deep sequencing, and expression of hypertension-associated miRNAs with significant change and their host genes and target genes were validated by real-time PCR and Western blot.
Key findings: The plasma deposition of EGCG and EGC best fitted a mono-compartmental model with maximum plasma concentration post-dose (Cmax, 6.65 vs 4.45 μg/ml) and the corresponding time (Tmax, 15 vs 10 min). Systolic blood pressure (SBP) of SHRs decreased to the lowest point by 34.04 mmHg and recovered by 23.39 mmHg after 15 and 30 min of administration at dose of 300 mg/kg BW EGCG, respectively, and it decreased again at 60 min and recovered at time 2 h. Total 35 upregulated and 18 downregulated miRNAs were identified compared to the control group (p < .01) after EGCG administration. Expression of hypertension-associated miRNA-126a-3p and miRNA-150-5p were further validated. In turn, their host gene and target genes were up-regulated and down-regulated, respectively.
Significance: Our results indicated that miRNA-150-5p might be involved in the antihypertensive effect of EGCG through SP1/AT1R pathway.
Keywords: Antihypertensive; EGCG; Pharmacokinetic; miRNomes.
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