Prevention
of the occurrence and development of inflammation is a vital therapeutic
strategy for treating acute lung injury (ALI). Increasing evidence
has shown that a wealth of ingredients from natural foods and plants
have potential anti-inflammatory activity. In the present study, mangiferin,
a natural <i>C</i>-glucosyl xanthone that is primarily obtained
from the peels and kernels of mango fruits and the bark of the Mangifera indica L. tree, alleviated the inflammatory
responses in lipopolysaccharide (LPS)-induced ALI mice. Mangiferin-modified
magnetic microspheres (MMs) were developed on the basis of click chemistry
to capture the target proteins of mangiferin. Mass spectrometry and
molecular docking identified 70 kDa heat-shock protein 5 (Hspa5) and
tyrosine 3-monooxygenase (Ywhae) as mangiferin-binding proteins. Furthermore,
an enzyme-linked immunosorbent assay (ELISA) indicated that mangiferin
exerted its anti-inflammatory effect by binding Hspa5 and Ywhae to
suppress downstream mitogen-activated protein kinase (MAPK) signaling
pathways. Thoroughly revealing the mechanism and function of mangiferin
will contribute to the development and utilization of agricultural
resources from M. indica L