Ginsenoside Re Ameliorates Cardiac Hypertrophy by Regulating CaSR-Mediated Signaling Pathway

Article Ginsenoside Re Ameliorates Cardiac Hypertrophy by Regulating CaSR-Mediated Signaling Pathway Panpan Chen 1,2,3, Mubo Liu 1,2,3,4, Hong Xiao 1,2,4, Ting Luo 1,2,4, Hong Ling 1,2,4, Xiaoyan Chen 5, Zongli Li 4, Shangfu Xu 1,2, Zheng Li 1,2,4 and Jiang Deng 1,2,4,* 1 Key Laboratory of Basic Pharmacology of Ministry of Education, Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563000, China 2 Key Laboratory of Basic Pharmacology of Guizhou Province, Zunyi Medical University, Zunyi 563000, China. 3 The Affiliated Aerospace Hospital of Zunyi Medical University, Guizhou Aerospace Hospital, Zunyi 563000, China 4 Department of Pharmacology, School of Pharmacy, Zunyi Medical University, Zunyi 563000, China 5 Department of Pathophysiology, Zunyi Medical University, Zunyi 563000, China * Correspondence: [email protected]; Tel.: +86-851-2864-3411; Fax: +86-851-2864-2406 Received: 31 August 2024; Revised: 17 September 2024; Accepted: 19 September 2024; Published: 5 March 2025 Abstract: Cardiac hypertrophy is a compensatory response to pathological stimuli. Recent studies have suggested that calcium-sensing receptor (CaSR) plays an important role in the development of cardiac hypertrophy. Ginsenoside Re (Re) is a monoconstituent of the ginseng plant. Many studies have shown that Re has various beneficial pharmacological effects on the cardiovascular system. It remains uncertain if Re have an anti-cardiac hypertrophic effect through the modulation of the CaSR-mediated signaling pathway. In this research, we employed a rat model of cardiac hypertrophy to investigate the relationship between Re and CaSR. Significant reductions in blood pressure, left ventricle hypertrophic indexes, cross-sectional area of cardiomyocytes, and levels of the β-myosin heavy chain and atrial natriuretic peptide were observed in spontaneously hypertensive rats (SHR) after Re administration. In addition, Re improved cardiac structure and function in SHR. Furthermore, Re inhibited CaSR, calcineurin (CaN), nuclear factor of activated T cells 3 (NFAT3), phosphorylated zinc finger transcription factor 4 (p-GATA4), protein kinase C-β (PKC-β), rapidly accelerated fibrosarcoma-1 (Raf-1), and phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2). It also increased the expression of p-NFAT3 and mitogen-activated protein kinase phosphatase-1 (MKP-1). These findings suggest that Re has beneficial effects on cardiac hypertrophy in SHR. The mechanisms underlying these effects are the regulation of the PKC-MAPK axis and the CaSR-mediated signaling pathway.