Anti‐Inflammatory Effects of Astragaloside IV–Chitosan Nanoparticles and Associated Anti‐Inflammatory Mechanisms Based on Liquid Chromatography‐Mass Spectrometry Metabolomic Analysis of RAW264.7 Cells

Astragaloside IV (ATS) is an active component of Astragalus membranaceus, which has immune regulation and anti-inflammatory effects. However, owing to its large molecular weight and poor solubility in water, the therapeutic effects of ATS are limited. We aimed to prepare ATS-chitosan (ATS-CS) nanoparticles and determine their anti-inflammatory effect and mechanism of action on RAW264.7 cells using metabolomics. The size of the ATS-CS nanoparticles was 200.3 nm with a zeta potential of 30.5 mV, and the encapsulation rate and drug loading were 69% and 13%, respectively. ATS-CS nanoparticles not only significantly decreased the increase of nitric oxide, interleukin-6, and tumor necrosis factor-α levels induced by lipopolysaccharide, but also exerted an anti-inflammatory effect by acting on arginine and proline, glutathione, sphingolipid, glycerophospholipid, glycine, serine, and threonine metabolism. Our findings confirmed that ATS-CS nanoparticles had good anti-inflammatory activity and showed that the activity of high molecular weight could be increased by producing nanoparticles. Our study paves the way for exploring the mechanism of nanoparticles through metabolomics.