Abstract:Oleanolic acid (OA) and betulinic acid (BA) are common bioactive substances in various fruits and vegetables. In this study, pure natural OA-BA nanoparticles (NPs) were prepared using OA and BA as raw materials through a supramolecular assembly strategy. The microstructure, hydrophilicity-hydrophobicity balance, particle size distribution, and sustained release capability of OA-BA NPs were characterized. The protective effect of OA-BA NPs on the inflammatory response induced by lipopolysaccharide (LPS) in RAW264.7 cells was clarified, as well as its protective effect on LPS induced acute lung injury in ICR mice. The results indicated that OA-BA NPs exhibited a sickle-shaped structure, a water contact angle of 36.6°, a hydrophilic diameter of approximately 360 nm, and an accumulated release of approximately 80% in a pH 7.4 medium over 48 hours. In vitro experiments demonstrated that treatment with OA-BA NPs significantly reduced the expression of cytokines TNF-α and IL-6 and significantly increased the expression of IL-10. Tail intravenous injection of OABA NPs effectively reduced LPS-induced acute lung injury in mice. Compared with the model group, the expression of p-PI3K, p-PDK1, p-AKT, and p-GSK-3β proteins in lung tissues of the OA-BA NPs treatment group significantly decreased. In conclusion, OA-BA NPs exhibit favorable dispersion, stability, and sustained release properties. They demonstrate the ability to modulate the LPS-induced release of inflammatory factors and effectively ameliorate LPS-induced inflammatory lung injury. The underlying mechanism is potentially associated with the activation of the PI3K/AKT/GSK-3β signaling pathway. The successful development of this nanopreparation presents a novel approach for managing sepsis-induced inflammatory injury in early clinical intervention.
