Schisandra chinensis-Derived Bioactive Constituents Loaded in pH-ROS Dual-Responsive Polysaccharide Nanoparticles for Atherosclerosis Treatment

Background Atherosclerosis (As) is a chronic vascular inflammatory disease, which has become a major global public health challenge. Therefore, it is urgent to find natural anti-As active ingredients with high efficacy and low toxicity and develop a suitable delivery system to prevent and treat AS. Schisandra chinensis (Sch) has attracted much attention because of its rich anti-inflammatory active compounds, but its targeted delivery and bioavailability in vivo are still problems to be solved urgently. Objective The purpose of this study is to screen the effective components of Sch with significant therapeutic effect on AS, and to construct a dual-response nano-carrier of pH‑ROS to realize accurate drug release and targeted therapy. Methods The experimental research design was employed by integrating network pharmacological prediction, molecular docking verification, in vitro cell model and in vivo animal model. Results Through network pharmacology and molecular docking technology, we first identified schizandrol A (Sch A) as the main active ingredient against As. Under the condition of a feed ratio of 6:4, the double-response nanoparticles showed excellent physical and chemical properties: the average particle size was 234.9 nm, the drug loading was 19.88%, and the encapsulation efficiency was 62.06%. In vitro biological evaluation demonstrated that the nanoparticles loaded with Sch A exerted a strong anti‑steatosis effect by inhibiting the PI3K/AKT/SREBP-1 signaling pathway, thus reducing intracellular lipid synthesis and inflammatory responses. In vivo experiments revealed that the nanoparticles displayed good biocompatibility and targeting ability, effectively reducing plaque area in the aorta, enhancing plaque stability, and significantly lowering blood lipid levels in mice. Conclusions In summary, Sch A is an effective component for anti-As, and the constructed pH-ROS dual-responsive nanoparticles demonstrate good biological safety and targeting both in vitro and in vivo , indicating their potential application in the treatment of As.