The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Protective effect of 6'-Sialyllactose on LPS-induced macrophage inflammation via regulating Nrf2-mediated oxidative stress and inflammatory signaling pathways

  • Hami Yu (College of Pharmacy and Institute of Drug Research and Development, Chungnam National University) ;
  • Yujin Jin (College of Pharmacy and Institute of Drug Research and Development, Chungnam National University) ;
  • Hyesu Jeon (Department of Cancer AI & Digital Health, National Cancer Center) ;
  • Lila Kim (GeneChem Inc.) ;
  • Kyung-Sun Heo (College of Pharmacy and Institute of Drug Research and Development, Chungnam National University)
  • Received : 2024.03.19
  • Accepted : 2024.06.21
  • Published : 2024.11.01
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Abstract

Macrophages play a central role in cardiovascular diseases, like atherosclerosis, by accumulating in vessel walls and inducing sustained local inflammation marked by the release of chemokines, cytokines, and matrix-degrading enzymes. Recent studies indicate that 6'-sialyllactose (6'-SL) may mitigate inflammation by modulating the immune system. Here, we examined the impact of 6'-SL on lipopolysaccharide (LPS)-induced acute inflammation using RAW 264.7 cells and a mouse model. In vivo, ICR mice received pretreatment with 100 mg/kg 6'-SL for 2 h, followed by intraperitoneal LPS injection (10 mg/kg) for 6 h. In vitro, RAW 264.7 cells were preincubated with 6'-SL before LPS stimulation. Mechanistic insights were gained though Western blotting, qRT-PCR, and immunofluorescence analysis, while reactive oxygen species (ROS) production was assessed via DHE assay. 6'-SL effectively attenuated LPS-induced p38 MAPK and Akt phosphorylation, as well as p65 nuclear translocation. Additionally, 6'-SL inhibited LPS-induced expression of tissue damage marker MMP9, IL-1β, and MCP-1 by modulating NF-κB activation. It also reduced ROS levels, mediated by p38 MAPK and Akt pathways. Moreover, 6'-SL restored LPS-suppressed Nrf2 and HO-1 akin to specific inhibitors SB203580 and LY294002. Consistent with in vitro results, 6'-SL decreased oxidative stress, MMP9, and MCP-1 expression in mouse endothelium following LPS-induced macrophage activation. In summary, our findings suggest that 6'-SL holds promise in mitigating atherosclerosis by dampening LPS-induced acute macrophage inflammation.

Keywords

Acknowledgement

This work was supported by National Research Foundation of Korea (KNRF-2022R1A2C40017761231482092640102).

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