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Inflamm Res. 2019 Jun;68(6):471-479. doi: 10.1007/s00011-019-01232-0. Epub 2019 Mar 29.

α-Mangostin suppresses NLRP3 inflammasome activation via promoting autophagy in LPS-stimulated murine macrophages and protects against CLP-induced sepsis in mice.

Author information

1
Department of General Intensive Care Unit, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310052, China.
2
Department of General Intensive Care Unit, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310052, China. 20130505@zju.edu.cn.

Abstract

BACKGROUND:

The major mechanism of sepsis is immunosuppression caused by host response dysfunction. It has been found that α-Mangostin (α-M) is a potential candidate as a treatment for multiple inflammatory and immune disorders. To date, the role of α-M in host response during sepsis remains unexplored.

METHODS AND RESULTS:

Herein, we examined the effect of α-M on macrophages-mediated host response in the presence of lipopolysaccharide (LPS), and the vital organ function, inflammatory response, and survival rate in septic mice. In murine peritoneal macrophages, α-M induced autophagy and then inhibited LPS-stimulated NLRP3 inflammasome activation, as well as interleukin-1β (IL-1β) production. Moreover, α-M improved phagocytosis and killing of macrophages, and increased M2 macrophages numbers after LPS stimulation. Furthermore, in vivo experiment suggested that α-M reduced serum levels of tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), IL-1β, alanine transaminase (ALT), aspartate transaminase (AST), and creatinine (Cr), whilst increased that of interleukin-10 (IL-10) in caecal ligation and puncture (CLP) mice.

CONCLUSION:

Taken together, these findings showed that α-M-mediated macrophages autophagy contributed to NLRP3 inflammasome inactivation and α-M exerted organ protection in septic mice.

KEYWORDS:

Autophagy; Macrophages; NLRP3 inflammasome; Sepsis; α-Mangostin

PMID:
30927050
DOI:
10.1007/s00011-019-01232-0

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