Salidroside attenuates the osteoblastic differentiation of vascular smooth muscle cells via AMPK/AKT signaling pathway.

Salidroside (SAL), a major bioactive compound derived from Rhodiola rosea L., exhibits diverse pharmacological activities, including anti-tumor, anti-inflammatory and cardiovascular protective effects. Arterial calcification is a prevalent vascular pathology characterized by the osteogenic differentiation of vascular smooth muscle cells (VSMCs). However, the potential role of SAL in arterial calcification and its underlying molecular mechanisms remain to be elucidated. An in vitro arterial calcification model was established by stimulating VSMCs with β-glycerophosphate (β-GP). This model was utilized to investigate the effect of SAL on osteogenic differentiation, using alkaline phosphatase activity and Runx2 expression as key markers. To detemine the specific signaling mechanisms, the AMPK inhibitor Compound C and the AKT inhibitor LY294002 were employed. Furthermore, the in vivo efficacy of SAL in mitigating arterial calcification was evaluated using a vitamin D(3)-induced arterial calcification model in C57BL/6 J mice. Our study demonstrates that SAL effectively attenuates β-GP-induced osteogenic differentiation of VSMCs in vitro and suppresses arterial calcification in vivo. Mechanistically, SAL treatment resulted in the activation of both AMPK and AKT signaling pathways. Notably, pharmacological inhibition of either AMPK or AKT significantly abolished the protective effects of SAL against osteogenic differentiation of VSMCs, indicating that the anti-calcific activity of SAL in VSMCs is mediated via the AMPK/AKT axis. Collectively, our findings suggest that SAL ameliorates arterial calcification by suppressing the osteogenic differentiation of VSMCs via activation of the AMPK/AKT signaling pathway.