Oncotarget

Research Papers:

Asiatic acid attenuates lipopolysaccharide-induced injury by suppressing activation of the Notch signaling pathway

Xiong Yuyun _, Cheng Xi, Yin Qing, Xia Lin, Rui Ke and Sun Bingwei

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Oncotarget. 2018; 9:15036-15046. https://doi.org/10.18632/oncotarget.24542

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Abstract

Xiong Yuyun1,*, Cheng Xi2,*, Yin Qing1, Xia Lin1, Rui Ke1 and Sun Bingwei3

1Department of Clinical Laboratory, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China

2Atom Bioscience and Pharmaceutical Co., Ltd., Zhenjiang, Jiangsu 212001, P.R. China

3Department of Burn and Plastic Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China

*These authors contributed equally to this work

Correspondence to:

Xiong Yuyun, email: 191853184@qq.com

Keywords: asiatic acid; lipopolysaccharide; Notch; sepsis

Received: September 01, 2017     Accepted: November 14, 2017     Epub: January 23, 2018     Published: March 13, 2018

ABSTRACT

Sepsis is a severe multisystem disease with high mortality rates and limited treatment options. However, advances during the last decade have opened opportunities to develop novel therapeutic strategies. The Notch signaling pathway plays a critical role in inflammation, and its inhibition offers an avenue to treat inflammatory diseases, such as sepsis. Asiatic acid (AA), a triterpenoid isolated from Centella asiatica, reportedly exerts anti-oxidant, anti-tumor, and anti-inflammatory effects, but its mechanisms remain unclear. In our study, we found that AA decreased levels of interleukin-1β (IL-1β), IL-6, alanine aminotransferase and blood urea nitrogen in serum; attenuated liver, lung and kidney damage; and improved the survival among mice with experimental sepsis. AA also reduced lipopolysaccharide-stimulated expression of proinflammatory mediators, including nitric oxide, IL-1β and IL-6 in RAW 264.7 macrophages. Notably, we demonstrated for the first time that AA is a novel small molecule inhibitor of the Notch signaling pathway. Its effects include upregulation of Notch receptor (Notch3) and delta-like ligand (DLL4), inhibition of Notch3 binding to the IL-6 promoter and regulation of mitochondrial function. These novel effects of AA may provide new approaches and strategies for the treatment of inflammatory disorders.


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