Senkyunolide H Affects Cerebral Ischemic Injury through Regulation on Autophagy of Neuronal Cells via P13K/AKT/mTOR Signaling Pathway

Abstract

Cerebral ischemia (CI) is associated with high global incidence and risk; therefore, its rapid and reliable therapeutic management is essential for protecting patients’ lives and improving health. Senkyunolide H (SH) is remarkably effective against phlebosclerosis, oxidation, and apoptosis. Blood-brain barrier is the main obstacle impeding the delivery of drugs and xenobiotics to brain areas. Drugs’ loading in nanoparticles can overcome the blood-brain barrier obstacle and thus directly and completely act on brain tissue, and such a loading can also change the half-life of drugs in vivo and lower the dosage requirement of drugs. In this study, we loaded the SH in lipid nanoparticles to improve its delivery to the brain for the therapy of CI. Thus, this study preliminarily analyzed the mechanism of SH-loaded nanoparticles in CI. The SH-loaded lipid nanoparticles were prepared and characterized with electron microscopy and PS potentiometery. The SH-loaded nanoparticles were intraperitoneally administered to CI-induced rats and brain tissue water content, and neuronal apoptosis and autophagy-associated proteins were determined. Our assays revealed SH-loaded nanoparticle’s ability to reduce nerve injury and brain tissue water content in rats with CI and inhibit the apoptosis and autophagy of their neuronal cells (NCs). Additionally, under intervention with SH-loaded nanoparticles, P13K/AKT/mTOR pathway-associated proteins in brain tissue of rats decreased. As the assay results showed, SH-loaded nanoparticles can suppress the autophagy of NCs through medicating P13K/AKT/mTOR pathway and lower apoptosis, thus delivering the effect of treating CI. Results of this study indicate SH-loaded nanoparticles as promising strategy for delivery SH to brain areas for treating CI.