Safety and Efficacy of Dietary Epigallocatechin Gallate Supplementation in Attenuating Hypertension via Its Modulatory Activities on the Intrarenal Renin–Angiotensin System in Spontaneously Hypertensive Rats

This study aimed to identify the no-observed-adverse-effect level (NOAEL) of dietary epigallocatechin gallate (EGCG) supplementation and its possible antihypertensive and nutrigenomics effects in modulating intrarenal renin-angiotensin system (RAS) gene expression in spontaneously hypertensive rats (SHR). EGCG (50, 250, 500 or 1000 mg/kg b.w. i.g., once daily) was administered to SHR for 28 days. All the SHR survived with no signs of systemic toxicity. Increased alanine aminotransferase (ALT), aspartate aminotransferase (AST) and thiobarbituric acid reactive substances (TBARS) were evident in SHR supplemented with 500 and 1000 mg/kg b.w. but not in those supplemented with lower doses of EGCG. Subsequently, the NOAEL of EGCG was established at 250 mg/kg b.w., and the same protocol was replicated to assess its effects on blood pressure and renal RAS-related genes in SHR. The systolic blood pressure (SBP) of the EGCG group was consistently lower than the control group. The mRNA levels of cortical <i>Agtr2</i> and <i>Ace2</i> and medullary <i>Agtr2, Ace and Mas1</i> were upregulated while medullary <i>Ren</i> was downregulated in EGCG group. Statistical analysis showed that SBP reduction was associated with the changes in medullary <i>Agtr2</i>, <i>Ace</i>, and <i>Ren</i>. Dietary EGCG supplementation exhibits antihypertensive and nutrigenomics effects through activation of intrarenal <i>Ace</i> and <i>Agtr2</i> and suppression of <i>Ren</i> mediators, while a high dose of EGCG induced liver damage in SHR. In future clinical studies, liver damage biomarkers should be closely monitored to further establish the safety of the long-term use of EGCG.