17βH-Neriifolin Improves Cardiac Remodeling Through Modulation of Calcium Handling Proteins in the Heart Failure Rat Model

Abstract

Background: Cardiac glycosides such as digoxin have been commonly used for patients with heart failure; however, their toxicity remains a main concern. 17βH-neriifolin (SNA209), a cardiac glycoside compound, has been recently isolated from Ceberra odollum Gaertn and was shown to improve the heart’s pumping ability in failing hearts ex vivo. Thus, this study aimed to investigate the potential use of SNA209 as a treatment for isoprenaline (ISO)-induced heart failure in rats. Methods: Forty male Wistar rats were randomly divided into five groups. Heart failure was induced by isoprenaline (ISO, 10 mg/kg/s.c) for 14 days daily, followed by SNA209 treatment (5 mg/kg; p.o) for another 14 days daily. Control rats were given saline as a vehicle for ISO and DMSO as a vehicle for SNA209. Results: Systolic and diastolic blood pressure (SBP and DBP) in all ISO-treated groups were significantly increased compared to the control group (p < 0.05), and SNA209 treatment managed to reduce the SBP and DBP. Additionally, SNA209 treatment significantly increased the heart rate and normalized the ECG parameters in ISO-treated rats. Pro-B-type natriuretic peptide and troponin T level, a cardiac injury markers, was remarkably reduced by SNA209 in the ISO-treated group. Cardiac hypertrophy was evident in increased cardiomyocyte size in ISO groups; however, SNA reduced the cardiomyocyte size. The left ventricular developed pressure (LVDP) in ISO treated with SNA209 was significantly raised, indicating a chronotropic effect. Cardiac Na⁺/K⁺-ATPase expression of the α1 subunit, sarcoplasmic/endoplasmic reticulum Ca²⁺ ATPase 2a (SERCA2a), and sodium–calcium exchanger subunit were significantly increased in the SNA treatment groups. Conclusions: The SNA 209 treatment improved cardiac function and structure, likely via modulating intracellular calcium management, so underscoring its potential as an adjuvant therapy for heart failure.