Mechanism of Green Tea Peptides in Lowering Blood Pressure and Alleviating Renal Injury Induced by Hypertension Through the Ang II/TGF-β1/SMAD Signaling Pathway

<b>Background/Objectives:</b> The kidney plays a crucial role in regulating normal blood pressure and is one of the major organs affected by hypertension. The present study aimed to investigate the hypotensive and renoprotective effects of four specific green tea peptides extracted from green tea dregs on spontaneously hypertensive rats (SHRs) and to investigate the underlying mechanisms. <b>Methods:</b> Four specific green tea peptides (40 mg/kg) were gavaged to SHRs for 4 weeks, and blood pressure, renal function, renal pathological changes, renal tissue fibrosis indexes, and inflammation indexes were examined in SHRs to analyze the role of the four green tea peptides in alleviating hypertension and its renal injury. <b>Results:</b> The results showed that the four TPs significantly reduced systolic and diastolic blood pressure (20-24% and 18-28%) in SHR compared to the model group. Meanwhile, gene levels and protein expression of renal fibrosis-related targets such as phospho-Smad2/3 (<i>p</i>-Smad2/3) (26-47%), Sma- and Mad-related proteins 2/3 (Smad2/3) (19-38%), transforming growth factor-β1 (TGF-β1) (36-63%), and alpha-smooth muscle actin (alpha-SMA) (58-86%) were also significantly reduced. In addition, the reduced expression levels of medullary differentiation factor 88 (MyD88) (14-36%), inducible nitric oxide synthase (iNOS) (58-73%), and nuclear factor-κB p65 (NF-kB p65) (35-78%) in kidneys also confirmed that TPs attenuated renal inflammation in SHR. Therefore, green tea peptides could attenuate the fibrosis and inflammatory responses occurring in hypertensive kidneys by inhibiting the Ang II/TGF-β1/SMAD signaling pathway and MyD88/NF-κB p65/iNOS signaling pathway. <b>Conclusions:</b> The results showed that green tea peptides may be effective candidates for lowering blood pressure and attenuating kidney injury.