Background: The aim of this study was to investigate anti-apoptotic effects of luteolin on
angiotensin II-stimulated murine peritoneal macrophages and to explore its mechanisms.
Methods and Results: The viability and cytotoxicity of murine peritoneal macrophages were assessed
using the Cell Counting Kit-8 assay and measuring lactate dehydrogenase levels, respectively. Apoptotic
rates were determined using Annexin V/propidium iodide staining. Protein expression was examined
by western blotting, and markers of macrophage phenotypes were analyzed by flow cytometry
and ELISA. Luteolin decreased the apoptotic rate of angiotensin II-stimulated macrophages. This effect
was associated with increased Bcl-2 and caspase-3 levels as well as decreased Bax and cleaved
caspase-3 levels. Additionally, luteolin reduced the expression of M1 macrophage phenotype markers
(IL-6, TNF-α, iNOS, CD16/32) and increased the expression of M2 macrophage phenotype markers
(Dectin-1, IL-10, Arg-1, CD206). Moreover, luteolin blocked Akt phosphorylation on residues 308 and
473, which were up-regulated in presence of angiotensin II. The effects of luteolin were similar to
those of LY294002, a specific PI3K/Akt pathway inhibitor.
Conclusions: These results indicated that luteolin has anti-apoptotic effects on angiotensin II-stimulated
macrophages via macrophage polarization, which might be associated with PI3K/Akt signaling.