Tianma Gouteng Decoction regulates oxidative stress and inflammation in AngII-induced hypertensive mice via transcription factor EB to exert anti-hypertension effect

Hypertension is one of the important causes of cardiovascular diseases, and the imbalance of vascular homeostasis caused by oxidative stress and endothelial inflammation occurs throughout hypertension pathogenesis. Therefore, inhibiting oxidative stress and endothelial inflammation is important for treating hypertension. Tianma Gouteng Decoction (TGD) is a Chinese herbal medicine that is commonly used to treat hypertension in China, and demonstrates clinically effective antihypertensive effects. However, its blood pressure reduction mechanism remains unclear. In this study, we further determined the antihypertensive effects of TGD and revealed its underlying mechanism. We established an AngII-induced hypertension mice model, which was treated with TGD for six weeks. We monitored blood pressure, heart rate, and body weight every week. After six weeks, we detected changes in the structure and function of the heart, the structure of blood vessels, and vasomotor factors. We also detected the expression of oxidative stress and inflammation-related genes. We found that TGD can significantly reduce blood pressure, improve cardiac structure and function, and reverse vascular remodeling, which could be due to the inhibition of oxidative stress and inflammation. We also found that the effect of inhibiting oxidative stress and inflammation could be related to the up-regulation of transcription factor EB (TFEB) expression by TGD. Therefore, we used AAV9 to knock down TFEB and observe the role of TFEB in TGD's antihypertensive and cardiovascular protection properties. We found that after TFEB knockdown, the protective effect of TGD on blood pressure and cardiovascular remodeling in AngII-induced hypertensive mice was inhibited, and that it was unable to inhibit oxidative stress and inflammation. Therefore, our study demonstrated for the first time that TGD could exert anti-oxidative stress and anti-inflammatory effects through TFEB and reverse the cardiovascular remodeling caused by hypertension.