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

Pharm Biol. 2021 Dec;59(1):1369-1377. doi: 10.1080/13880209.2021.1986076.

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; fibrosis; growth arrest-specific protein 6 (Gas6)/Axl pathway; vascular calcification.

MeSH terms

  • Age Factors
  • Aging / drug effects*
  • Aging / pathology
  • Animals
  • Aorta, Thoracic / drug effects
  • Aorta, Thoracic / metabolism
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • Female
  • Gene Expression Regulation / drug effects
  • Ginsenosides / administration & dosage
  • Ginsenosides / pharmacology*
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Mice
  • Mice, Inbred C57BL
  • RNA, Messenger / metabolism
  • Vascular Diseases / prevention & control*
  • Vasodilation / drug effects

Substances

  • Ginsenosides
  • Intercellular Signaling Peptides and Proteins
  • RNA, Messenger
  • growth arrest-specific protein 6
  • ginsenoside Rb1

Grants and 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].