Hawthorn leaves flavonoids attenuate cardiac remodeling induced by simulated microgravity

Abstract

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.

Keywords:

• Hindlimb unloading
• molecular docking
• NPRA-cGMP-PKG pathway
• calcineurin-NFAT pathway

Author contribution

Tian Liu and Yuqi Ma analyzed and wrote the manuscript. Hui Zhao revised the manuscript. Xi Shen and Yan Niu treated data curation and visualization. Pengli Wang, Yuehuan Hu and Bing Yan interpreted data and prepared figures. Mingxia Zhang analyzed data. Jun Yu conceived and designed research. All authors have participated sufficiently in the study and approved the final version.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (Grant No. 81870172), Natural Science Basic Research Program of Shaanxi (Grant Nos. 2021JQ-938, 2022JQ-805) and the Foundation of Xi’an International Medical Center Hospital (Grant Nos. 2020QN023, 2021QN020).