Inhibition of lipopolysaccharide‐induced inflammatory responses by 1′‐acetoxychavicol acetate. (8th May 2022)

• Record Type: Journal Article
• Authors: Ong, Guang Han; Ori, Daisuke; Kawasaki, Takumi; Kawai, Taro
• Is Part Of: Genes to cells. Volume 27:Number 7(2022)
• Page Start: 482
• Page End: 492
• Publication Date: 2022-05-08
• Subjects: 1′‐acetoxychavicol acetate -- cytokine -- inflammation -- innate immunity -- TLR4; Cytogenetics -- Periodicals; Cells -- Mechanical properties -- Periodicals; Molecular genetics -- Periodicals; Genes -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Biomechanics -- Periodicals; 571.6
• DOI: 10.1111/gtc.12943
• Languages: English
• ISSNs: 1356-9597

Abstract

Abstract: Lipopolysaccharide on gram negative bacteria can be detected by Toll‐like receptor 4 (TLR4) to elicit a series of innate immune responses, leading to inflammation to eliminate the targeted pathogen. However, dysregulation in the responses results in excessive inflammation. The 1′‐acetoxychavicol acetate (ACA) is a bioactive compound originated from Alpinia species known to have anti‐inflammatory and apoptosis‐inducing properties. Here, we found that ACA inhibits lipopolysaccharide‐induced expression and production of proinflammatory cytokines such as interleukin 6 and TNFα by macrophages. ACA suppresses the activation of NF‐κB and MAP kinases in TLR4 signaling. Moreover, ACA also inhibits TLR4‐mediated induction of type I interferon by suppressing IRF3 activation. In lipopolysaccharide‐challenged mice, ACA treatment successfully increased the survival of mice and alleviated inflammation in the lung. Thus, ACA is a potential anti‐inflammatory agent to regulate excessive inflammation. Abstract : In this study, ACA treatment inhibited the production of lipopolysaccharide (LPS)‐induced pro‐inflammatory cytokines by suppressing the activation of NF‐κB, MAP kinases and IRF3 pathway. ACA treatment also rescued mice from lethal dose LPS injection and alleviated lung inflammation in the LPS‐challenged mice. This showed that ACA is a potential anti‐inflammation agent.