Panax quinquefolium saponin attenuates cardiac remodeling induced by simulated microgravity

Abstract

Background: Cardiac atrophy and reduced cardiac distensibility have been reported following space flight. Cardiac function is correspondingly regulated in response to changes in loading conditions. Panax quinquefolium saponin (PQS) improves ventricular remodeling after acute myocardial infarction by alleviating endoplasmic reticulum stress and Ca²⁺overload. However, whether PQS can ameliorate cardiac atrophy following exposure to simulated microgravity remains unknown.

Purpose: To explore the protective role of PQS in cardiac remodeling under unloading conditions and its underlying mechanisms.

Methods: Hindlimb unloading (HU) model was used to simulate unloading induced cardiac remodeling. Forty-eight male rats were randomly assigned to four groups, including control, PQS, HU and HU + PQS. At 8 weeks after the experiment, cardiac structure and function, serum levels of Creatine Kinase-MB (CK-MB), Cardiactroponin T (cTnT), ischemia modified albumin (IMA), and cardiomyocyte apoptosis were measured. Network pharmacology analysis was used to predict the targets of the six major constituents of PQS, and the signaling pathways they involved in were analyzed by bioinformatics methods. Changes in the key proteins involved in the protective effects of PQS were further confirmed by Western Blot.

Results: Simulated microgravity led to increases in serum levels of CK-MB, cTnT and IMA, remodeling of cardiac structure, impairment of cardiac function, and increased cardiomyocyte apoptosis as compared with control. PQS treatment significantly reduced serum levels of CK-MB, cTnT and IMA, improved the impaired cardiac structure and function, and decreased cardiomyocyte apoptosis induced by unloading. The activation of AMPK and inhibition of Erk1/2 and CaMKII/HDAC4 were demonstrated in the cardiocytes of HU rats after PQS treatment.

Conclusion: PQS provides protection against cardiac remodeling induced by simulated microgravity, partly resulting from changes in the signaling pathways related to energy metabolism reduction, calcium overloading and cell apoptosis.

Keywords: Cardiac remodeling; Cardiac remodeling pathways; Mechanism; Panax quinquefolium saponin; Simulated microgravity; Unloading.