Robinin attenuates cardiac hypertrophy in pulmonary heart disease by modulating SIRT1/NF-κB signaling and inhibiting oxidative stress and the NLRP3 inflammasome.

BackgroundRobinin possesses certain antioxidative and anti-inflammatory properties. However, its mechanisms of action in cardiac hypertrophy (CH) and fibrosis remain inadequately explored.MethodsAn in vitro model of CH was established using angiotensin II-treated rat H9c2 cardiomyocytes treated with escalating concentrations of Robinin. For the in vivo model, pulmonary heart disease-induced CH in rats was induced by chronic hypercapnia and TAC. Myocardial cell markers were evaluated through qRT-PCR, Western blotting, ELISA, cellular immunofluorescence, and HE staining. The role of SIRT1 in Robinin's effects was determined using pharmacological inhibition with SIRT1-IN-1.ResultsIn vitro, Robinin suppressed hypertrophic (ANP, BNP, β-MHC) and fibrotic markers (MyHC, Collagen I, TGF-β1) and reduced NLRP3 components (IL-1β, IL-18, ASC, Caspase-1) and oxidative stress (OS, ↓MDA, ↑SOD/HO-1/Nrf2) in a dose-dependent manner. These effects were mediated by SIRT1 upregulation and NF-κB inactivation. Crucially, SIRT1 inhibition abolished Robinin's protection against hypertrophy and inflammation. In vivo, Robinin attenuated pulmonary heart disease-induced hypertrophy, fibrosis, NLRP3 activation, and OS while restoring SIRT1/NF-κB balance.ConclusionRobinin alleviates CH in pulmonary heart disease by modulating the SIRT1/NF-κB pathway to suppress OS and NLRP3 inflammasome activation, establishing its novel therapeutic potential.