Hawthorn leaves flavonoids attenuate cardiac remodeling induced by simulated microgravity

Context Hawthorn leaves are a kind of widely used medicinal plant in China. The major ingredient, hawthorn leaves flavonoids (HLF), have cardiotonic, cardioprotective, and vascular protective effects. Objective The study evaluated the protective role of HLF in cardiac remodelling and the underlying mechanisms under simulated microgravity by hindlimb unloading rats. Materials and methods Adult male Sprague-Dawley rats were divided into control, HLF, HU (hindlimb unloading) and HU + HLF groups (n = 8). After HU and daily intragastric administration at the dose of 100 mg/kg/d for 8 weeks, cardiac function and structure were evaluated by biochemical indices and histopathology. We identified the main active compounds and mechanisms involved in the cardioprotective effects of HLF via bioinformatics and molecular docking analysis, and relative signalling pathway activity was verified by Western blot. Results HLF treatment could reverse the HU-induced decline in LV-EF (HU, 55.13% +/- 0.98% vs. HU + HLF, 71.16% +/- 5.08%), LV-FS (HU, 29.44% +/- 0.67% vs. HU + HLF, 41.62% +/- 4.34%) and LV mass (HU, 667.99 +/- 65.69 mg vs. HU + HLF, 840.02 +/- 73.00 mg). Furthermore, HLF treatment significantly increased NPRA expression by 135.39%, PKG by 51.27%, decreased PDE5A by 20.03%, NFATc1 by 41.68% and Rcan1.4 by 54.22%. Conclusions HLF plays a protective effect on HU-induced cardiac remodelling by enhancing NPRA-cGMP-PKG pathway and suppressing the calcineurin-NFAT pathway, which provides a theoretical basis for use in clinical therapies.