Astragalus (Astragalus mongholicus) Improves Ventricular Remodeling via ESR1 Downregulation RhoA/ROCK Pathway

Astragalus (Astragalus mongholicus) alleviates myocardial remodeling caused by hypertension. However, the detailed molecular mechanism is unclear.This study aims to investigate the effect of Astragalus on ventricular remodeling in ovariectomized sponta-neous hypertensive rats (OVX-SHR).Female SHR/NCrl rats were subjected to bilateral ovariectomy to establish the OVX-SHR model and treated with Astragalus extract by gavage. The hemodynamics and cardiac function parameters were measured. HE and Masson staining were used to detect the pathological structure of myocardial remodeling and observe the hyperplasia of myocardial collagen fibers. The immunohistochemistry tested the level of alpha-SMA. The ex-pression levels of inflammatory cytokines, I kappa B, p65, Cleaved-Caspase3, RhoA, and ROCK1/2 were detected us-ing Western blot. The method of qRT-PCR measured the expression of matrix metalloproteinase (MMP-2 and MMP-9).Hemodynamic and cardiac function parameters were significantly improved after a high dose of Astragalus extract and Valsartan treatment. The myocardial integrity of the model group was significantly reduced, ar-ranged loosely, and disordered, while the expression of alpha-SMA was increased. However, Astragalus extract and Valsartan treatments significantly reduced the pathological damage and alpha-SMA. The levels of TNF-alpha, IL-1(3, IL-6, TGF-(3, MMP-2, and MMP-9 in the model group were increased but decreased after Astragalus extract treatment. Adding an ESR1 inhibitor attenuated the improvement effect of Astragalus extract on myocardial re-modeling and restored the expression of RhoA and ROCK1/2. Astragalus extract attenuates the cardiac damage in OVX-SHR by downregulating the RhoA/ROCK path-ESR1.