Construction of Co-assembled Oleanolic Acid-betulinic Acid Nanoparticles and Clarification of Their Protective Effect on LPS-induced Acute Lung Injury

ZHANG Juan; ZHANG Ling; WANG Jiacheng; LI Guocai

doi:10.13982/j.mfst.1673-9078.2025.5.0384

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 OA-BA 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.