Asaronic Acid Attenuates Macrophage Activation toward M1 Phenotype through Inhibition of NF-κB Pathway and JAK-STAT Signaling in Glucose-Loaded Murine Macrophages

• DOI: 10.1021/acs.jafc.9b03926
• Publication Date: 2019-08-17T19:49:31Z
• Authors: Hyeongjoo Oh; Sin-Hye Park; Min-Kyung Kang; Yun-Ho Kim; Eun-Jung Lee; Dong Yeon Kim; Soo-Il Kim; SuYeon Oh; Soon Sung Lim; Young-Hee Kang
• Keywords: Proinflammatory cytokine; Macrophage polarization

Macrophage polarization has been implicated in the pathogenesis of obesity and type 2 diabetes, which are recognized as chronic proinflammatory diseases. This study investigated that high level glucose, similar to lipopolysaccharide (LPS), activated macrophages toward M1 phenotypes 1–20 μM asaronic acid (AA) counteracted diabetic macrophage activation. AA reduced LPS-promoted secretion interleukin (IL)-6 monocyte chemoattractant protein-1. The LPS markedly elevated induction markers Toll-like receptor 4 (TLR4), CD36, CD68, was attenuated by AA. Also, significantly enhanced nuclear factor (NF)-κB transactivation, signal transducers, activators transcription 1 (STAT1)/STAT3 activation suppressor cytokine signaling 3 (SOCS3) macrophages. However, highly suppressed aforementioned effects LPS. Glucose-stimulated expressed advanced glycation end products (AGEs) for AGE (RAGE). Administration 20 partly but such (1.65 ± 0.12 vs 0.95 0.25 times glucose control AGE; 2.33 0.31 1.40 0.22 RAGE). Furthermore, TLR4 inducible nitric oxide synthase IL-6 production, while it demoted production anti-inflammatory arginase-1 IL-10. In contrast, reversed these glucose-loaded dose-dependently encumbered NF-κB Janus kinase (JAK2) STAT1/STAT3 activation, SOCS3 upregulated glucose-supplemented These results demonstrated first time may limit phenotype through inhibition TLR4-/IL-6-mediated NF-κB/JAK2-STAT entailing AGE–RAGE interaction.