Ginsenoside Rb1 attenuates age-associated vascular impairment by modulating the Gas6 pathway

Abstract

Context

Ginsenoside Rb1 (Rb1) exerts many beneficial effects and protects against cardiovascular disease.

Objective

To investigate whether Rb1 could attenuate age-related vascular impairment and identify the mechanism.

Materials and methods

Female C57BL/6J mice aged 2 and 18 months, randomly assigned to Young, Young + 20 mg/kg Rb1, Old + vehicle, Old + 10 mg/kg Rb1 and Old + 20 mg/kg Rb1 groups, were daily intraperitoneal injected with vehicle or Rb1 for 3 months. The thoracic aorta segments were used to inspect the endothelium-dependent vasorelaxation. Left thoracic aorta tissues were collected for histological or molecular expression analyses, including ageing-related proteins, markers relevant to calcification and fibrosis, and expression of Gas6/Axl.

Results

We found that in Old + vehicle group, the expression of senescence proteins and cellular adhesion molecules were significantly increased, with worse endothelium-dependent thoracic aorta relaxation (58.35% ± 2.50%) than in Young group (88.84% ± 1.20%). However, Rb1 treatment significantly decreased the expression levels of these proteins and preserved endothelium-dependent relaxation in aged mice. Moreover, Rb1 treatment also reduced calcium deposition, collagen deposition, and the protein expression levels of collagen I and collagen III in aged mice. Furthermore, we found that the downregulation of Gas6 protein expression by 41.72% and mRNA expression by 52.73% in aged mice compared with young mice was abrogated by Rb1 treatment. But there was no significant difference on Axl expression among the groups.

Conclusions

Our study confirms that Rb1 could ameliorate vascular injury, suggesting that Rb1 might be a potential anti-ageing related vascular impairment agent.

Keywords:

• Ageing
• vascular calcification
• fibrosis
• growth arrest-specific protein 6 (Gas6)/Axl pathway

Author contributions

SYK, DHL and XXQ contributed to the conception and design of this work. LW, GYS and MW contributed to data analyses. SYK, LW and JMZ wrote the manuscript. All authors read and approved the final version.

Disclosure statement

No potential conflicts of interest were reported by the author(s).

Data availability statement

Data and materials are available upon request to the corresponding author.

Additional information

Funding

This work was supported by grants from the National Natural Science Foundation of China [81370447], the Science and Technology Planning Project of Guangdong Province of China [2016A050502014], the Shenzhen Key Medical Discipline Construction Fund [SZXK002], and the Medical Scientific Research Foundation of Guangdong Province of China [A2019079].