Ginsenoside Rb1 ameliorates CKD-associated vascular calcification by inhibiting the Wnt/β-catenin pathway

Area of Science:

• Cardiovascular Biology
• Nephrology
• Pharmacology

Background:

• Vascular calcification (VC) is a major contributor to cardiovascular disease morbidity and mortality.
• Chronic kidney disease (CKD) is frequently associated with VC, highlighting the need for therapeutic targets.
• The cardiovascular protective effects of Ginsenoside Rb1 (Rb1) are known, but its role in VC remains unexplored.

Purpose of the Study:

• To investigate the therapeutic potential of Ginsenoside Rb1 (Rb1) in mitigating vascular calcification (VC).
• To elucidate the underlying molecular mechanisms of Rb1's action in VC, particularly its interaction with the Wnt/β-catenin pathway.

Main Methods:

• Established in vivo (CKD-associated VC rat model) and in vitro (β-glycerophosphate-induced VSMC calcification) models.
• Administered Rb1 and assessed its effects on calcium deposition and VSMC osteogenic transdifferentiation.
• Utilized confocal microscopy to observe β-catenin nuclear translocation and employed pathway modulators (SKL2001, GW9662) to confirm mechanisms.

Main Results:

• Rb1 significantly ameliorated calcium deposition and prevented VSMC osteogenic transdifferentiation in both experimental models.
• Rb1 activated peroxisome proliferator-activated receptor-γ (PPAR-γ), which subsequently inhibited the Wnt/β-catenin pathway by preventing β-catenin nuclear translocation.
• Pharmacological inhibition of Wnt/β-catenin (SKL2001) diminished Rb1's protective effects, while PPAR-γ antagonism (GW9662) reversed Rb1's inhibition of β-catenin.

Conclusions:

• Ginsenoside Rb1 (Rb1) demonstrates significant anticalcific properties in the context of chronic kidney disease-associated vascular calcification.
• Rb1 exerts its protective effects by activating PPAR-γ, leading to the inhibition of the Wnt/β-catenin signaling pathway.
• The findings suggest that the PPAR-γ/Wnt/β-catenin axis is a key mediator of Rb1's therapeutic action, offering new avenues for VC treatment.