Qian Yang Yu Yin Granule ameliorates hypertension-induced renal injury through the modulation of oxidative stress via Sestrin2 signaling pathway

Abstract Objective This study investigated the protective mechanisms of Qian Yang Yu Yin Granule (QYYYG) against hypertensive renal injury. Methods A hypertensive renal injury model was established in Spontaneous hypertensive rat (SHR) rats using angiotensin II infusion combined with unilateral nephrectomy. Rats were assigned to model, valsartan, and high-/low-dose QYYYG groups and treated for 8 weeks. Blood pressure (BP), blood urea nitrogen (BUN), renal histopathology, and related biochemical indicators were evaluated. In vitro, HK-2 cells pretreated with QYYYG or valsartan were subjected to hypoxic conditions. The expression levels of HIF-1α, NOX4, HO-1, Nrf2, and SESN2 were quantified. Key findings QYYYG markedly reduced BP and BUN levels and ameliorated renal histopathological damage. It upregulated SESN2, activated AMPKα, inhibited mTOR phosphorylation, and suppressed NOX4 expression, thereby reducing HIF-1α accumulation. QYYYG also enhanced the expression of SESN2, Nrf2, and HO-1. Consistently, in vitro, QYYYG significantly increased SESN2, Nrf2, and HO-1 expression while reducing NOX4 and HIF-1α levels. Conclusion QYYYG alleviates hypertensive renal injury by regulating the Sestrin2 signaling pathway and improving local oxidative stress responses.