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Original Article

Korean J Physiol Pharmacol 2024; 28(6): 503-513

Published online November 1, 2024 https://doi.org/10.4196/kjpp.2024.28.6.503

Copyright © Korean J Physiol Pharmacol.

Protective effect of 6′-Sialyllactose on LPS-induced macrophage inflammation via regulating Nrf2-mediated oxidative stress and inflammatory signaling pathways

Hami Yu1,#, Yujin Jin1,#, Hyesu Jeon3, Lila Kim2, and Kyung-Sun Heo1,*

1College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon 34134, 2GeneChem Inc., Daejeon 34025, 3Department of Cancer AI & Digital Health, National Cancer Center, Goyang 10408, Korea

Correspondence to:Kyung-Sun Heo
E-mail: kheo@cnu.ac.kr

#These authors contributed equally to this work.

Author contributions: H.Y., Y.J., and K.S.H. contributed to study concepts and design. H.Y., Y.J., and H.J. were involved in experimental studies and data acquisition. H.Y., Y.J., H.J., and L.K. conducted data analysis and statistical analysis. H.Y. and Y.J. were wrote manuscript draft and K.S.H. was responsible for finalizing manuscript. All authors read and approved the final manuscript.

Received: March 19, 2024; Revised: June 3, 2024; Accepted: June 21, 2024

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: Acute inflammation, Oxidative stress, 6’-sialyllactose