Schisandrin B regulates the SIRT1/PI3K/Akt signaling pathway to ameliorate Ang II-infused cardiac fibrosis

Abstract

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 (2.0 mg/kg/day, HY-13948, MedChemExpress) was administered subcutaneously to male C57BL/6 mice aged between 8 and 10 weeks. SchB (30 mg/kg/day, HY-N0089, MedChemExpress) was given via intraperitoneal injection two hours before Ang II infusion for 28 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 1 (SIRT1) expression while reducing α-SMA, TGF-β1, collagen I, collagen III, and CTGF in vivo. Furthermore, SchB inhibited the migration of Ang II-infused rat cardiac fibroblasts. SchB increased SIRT1 expression while decreasing TGF-β1, α-SMA, collagen I, and collagen III, whereas EX-527, an inhibitor of SIRT1, recovered their activities in vitro. Furthermore, SchB elevated SIRT1 expression while lowering the expressions of p-PI3K (p85, Tyr458) and p-Akt (Ser473) proteins.Conclusion: Our results suggest that SchB regulates the SIRT1/PI3K/Akt pathway to prevent Ang II-infused cardiac fibrosis.