Schisandrin B regulates the SIRT۱/PI۳K/Akt signaling pathway to ameliorate Ang II-infused cardiac fibrosis

Objective(s): Schisandrin B (SchB), extracted from Schisandra chinensis, has antimicrobial and anti-inflammatory effects. The study aimed to investigate SchB’s possible defense against angiotensin II (Ang II)-infused cardiac fibrosis and its molecular processes.Materials and Methods: An equivalent volume of saline or Ang II (۲.۰ mg/kg/day, HY-۱۳۹۴۸, MedChemExpress) was administered subcutaneously to male C۵۷BL/۶ mice aged between ۸ and ۱۰ weeks. SchB (۳۰ mg/kg/day, HY-N۰۰۸۹, MedChemExpress) was given via intraperitoneal injection two hours before Ang II infusion for ۲۸ days. Comprehensive morphological, histological, and biochemical analyses were conducted. We evaluated the mRNA and protein expression levels using western blot and RT-qPCR techniques.Results: SchB treatment improves heart disease in Ang II-induced mice. SchB markedly lowered serum levels of cardiac fibrosis-related markers, including cTnI, cTnT, ANP, and BNP. In addition, SchB elevated sirtuin ۱ (SIRT۱) expression while reducing α-SMA, TGF-β۱, collagen I, collagen III, and CTGF in vivo. Furthermore, SchB inhibited the migration of Ang II-infused rat cardiac fibroblasts. SchB increased SIRT۱ expression while decreasing TGF-β۱, α-SMA, collagen I, and collagen III, whereas EX-۵۲۷, an inhibitor of SIRT۱, recovered their activities in vitro. Furthermore, SchB elevated SIRT۱ expression while lowering the expressions of p-PI۳K (p۸۵, Tyr۴۵۸) and p-Akt (Ser۴۷۳) proteins.Conclusion: Our results suggest that SchB regulates the SIRT۱/PI۳K/Akt pathway to prevent Ang II-infused cardiac fibrosis.

کلیدواژه ها:

Angiotensin II ، PI۳K/Akt ، Sirtuin ۱ ، α-SMA ، Collagen I ، Collagen III