Anti-inflammatory Effects of Astragaloside IV–chitosan Nanoparticles and Associated Anti-inflammatory Mechanisms Based on LC-MS 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 astragaloside IV-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 NO, IL-6 and TNF-α levels induced by LPS, but also exerted an anti-inflammatory effect by acting on arginine and proline, glutathione, sphingolipid, glycerophospholipid, and glycine, serine, and threonine metabolism. Our findings confirmed that ATS-CS nanoparticles have good anti-inflammatory activity and showed that the activity of high molecular weight can be increased by producing nanoparticles. Our study paves the way for exploring the mechanism of nanoparticles through metabolomics.