Ginsenoside Rg1 attenuates mechanical stress-induced cardiac injury via calcium sensing receptor-related pathway

Abstract

Background Ginsenoside Rg1 (Rg1) has been well documented to be effective against various cardiovascular disease. The aim of this study is to evaluate the effect of Rg1 on mechanical stress-induced cardiac injury and its possible mechanism with a focus on the calcium sensing receptor (CaSR) signaling pathway. Methods Mechanical stress was implemented on rats through abdominal aortic constriction (AAC) procedure and on cardiomyocytes and cardiac fibroblasts by mechanical stretching with Bioflex Collagen I plates. The effects of Rg1 on cell hypertrophy, fibrosis, cardiac function, [Ca 2+ ] i , and the expression of CaSR and calcineurin (CaN) were assayed both on rat and cellular level. Results Rg1 alleviated cardiac hypertrophy and fibrosis, and improved cardiac decompensation induced by AAC in rat myocardial tissue and cultured cardiomyocytes and cardiac fibroblasts. Importantly, Rg1 treatment inhibited CaSR expression and increase of [Ca 2+ ] i , which similar to the CaSR inhibitor NPS2143. In addition, Rg1 treatment inhibited CaN and TGF-β1 pathways activation. Mechanistic analysis showed that the CaSR agonist GdCl 3 could not further increase the [Ca 2+ ] i and CaN pathway related protein expression induced by mechanical stretching in cultured cardiomyocytes. CsA, an inhibitor of CaN, inhibited cardiac hypertrophy, cardiac fibrosis, [Ca 2+ ] i and CaN signaling but had no effect on CaSR expression. Conclusion The activation of CaN pathway and the increase of [Ca 2+ ] i mediated by CaSR are involved in cardiac hypertrophy and fibrosis, that may be the target of cardioprotection of Rg1 against myocardial injury.

Pinoresinol diglucoside alleviates pressure overload-induced cardiac injury via the AMPK/SIRT3/RIG-1 pathway

“…In vitro, cell models of pressure overload were established by inducing NRVFs with PE (50µM) for 48h. Consistent with the previous studies, the relative mRNA levels of Col I and Col III [31] were increased after PE treatment, as well as the periostin [32] and α-SMA [33] expression. The mRNA expression levels of these brotic biomarkers were signi cantly reduced by high dosage of PDG treatment (7.5 ug/ml) (Fig.…”

Comparison between the Biological Active Compounds in Plants with Adaptogenic Properties (Rhaponticum carthamoides, Lepidium meyenii, Eleutherococcus senticosus and Panax ginseng)

“…According to data obtained from animal studies, ginsenosides have great potential to be used for the treatment of cardiovascular diseases, hepatic disorders and obesity [ 227 , 228 , 229 , 230 , 231 , 232 , 233 ]. According to data obtained from cell culture studies, ginsenosides have great potential to be used for the treatment cardiovascular diseases, hypercholesterolemia, and some types of cancer [ 234 , 235 , 236 , 237 ].…”

Progress on the Elucidation of the Antinociceptive Effect of Ginseng and Ginsenosides in Chronic Pain

“…Protopanaxadiol mainly includes the ginsenosides Rb1, Rb2, Rb3, Rc, Rd, Rg3, and Rh2 and compound K, whereas protopanaxatriol is mainly composed of the ginsenosides Re, Rg1, Rg2, and Rh1. These types of ginsenosides have different biological activity and different clinical effects, such as regulation of the central nervous system ( Chen et al, 2019 ; Park et al, 2012b ; Wu et al, 2018 ), promoting learning and memory ability ( Chen et al, 2018 ; Jiang et al, 2021 ), improving heart function ( Li X. et al, 2020 ; Lu M. et al, 2021 ), hypoglycemic effects ( Tabandeh et al, 2015 ; Meng et al, 2017 ), improving resistance to stress ( Chen et al, 2016 ; Li c. w. et al, 2020), and modulating the immune response ( Park et al, 2015 ). Based on various clinical studies, the pharmacokinetics of the different types of ginsenosides remain unclear because of their heterogeneous chemical structures ( Qi et al, 2011 ).…”