Salidroside impedes Ang II-infused myocardial fibrosis by activating the SIRT۱-Nrf۲ pathway

Objective(s): This research examined the protective function of salidroside (SAL) against angiotensin II (Ang II)-infused myocardial fibrosis and its associated mechanism.Materials and Methods: The C۵۷BL/۶ male murine models (n=۲۴) received either saline solution or Ang II (۱۵۰۰ ng/kg/day) subcutaneously and an oral dosage of SAL (۵۰ mg/kg/day) once daily for ۲۸ days. Newborn Sprague-Dawley (SD) rats were used to isolate atrial fibroblasts.Results: The fibrotic region was raised by Ang II infusion, while SAL treatment inhibited it. Collagen I and III expression was raised by Ang II induction, but SAL therapy reduced their expression. SAL therapy also decreased the expression of other fibroblast differentiation-related markers induced by Ang II infusion. It elevated SIRT۱, Nrf۲, and HO-۱ levels in atrial fibroblasts. Additionally, SAL significantly inhibited atrial fibroblasts, whereas EX۵۲۷, an inhibitor of SIRT۱, noticeably increased the migration ability. Furthermore, SAL suppressed intracellular ROS production and oxidative stress in Ang II-infused atrial fibroblasts. Conclusion: SAL protects against myocardial fibrosis infused by Ang II by activating the SIRT۱-Nrf۲ pathway.

Keywords:

Angiotensin II , Oxidative stress , Reactive Oxygen Species , Salidroside , SIRT۱