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Oxidative Medicine and Cellular Longevity

Oxidative Medicine and Cellular Longevity

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Ruscogenins Improve CD-Like Enteritis by Inhibiting Apoptosis of Intestinal Epithelial Cells and Activating Nrf2/NQO1 Pathway.

Published:10 March 2022 DOI: 10.1155/2022/4877275
H. Wen,?Xiaofeng Zhang,?Qingqing Li,?Ju Huang,?Guangyong Liu,?Jingyue Zhao,?Yiran Liu,?L. Shen,?Yuyang Li,?Kun Yang,?L. Zuo,?Jing Li,?Jing Nian,?P. Xiang,?Hao Zhao,?Liangzu Yu,?Mulin Liu,?Z. Geng,?Xue Song

Abstract

Interaction of intestinal barrier dysfunction and intestinal inflammation promotes the progression of Crohn's disease (CD). A more recent study has suggested that ruscogenins (RUS) can exert anti-inflammatory effects through activation of the Nrf2/NQO1 pathway. The current study is aimed at determining the functionalization of RUS on CD-like colitis. Wild-type (WT) mice induced with trinitrobenzene sulfonic acid (TNBS) exhibit a significant inflammation in their colon and are hence widely used for CD models. In the current study, the mice were treated with the Nrf-2 antagonist (ML385) or ruscogenin (RUS) whereas normal WT mice were kept as the negative control. Comparative analysis was then performed on the inflammation and barrier function of the colons. In vitro analysis of mouse colonic organoid systems revealed the influence of RUS on LPS-induced apoptosis, cytokine, and chemokine expressions in the intestinal epithelium. It was found that RUS ameliorates murine colitis through activation of the Nrf2/NQO1 pathway which was presented as a decrease in inflammation score and downregulated levels of cytokine and chemokine synthesis, as well as increased intestinal permeability. Further, it was noted that RUS alleviated LPS-induced apoptosis in the intestinal epithelium cells through upregulation of the Nrf2/NQO1 signaling pathway in the mouse colonic organoids. In addition, ruscogenin (RUS) attenuated the levels of Bax and C-caspase-3 through activation of the Nrf2/HO1 signaling pathway both in vivo and in vitro. Therefore, it was evident that RUS can be applied as a potential alternative therapeutic agent in CD based on its protective effects on the barrier function and anti-inflammatory activity.

Substances (3)

Materials Related products
Procduct Name CAS Molecular Formula Supplier Price
ML385 846557-71-9 C29H25N3O4S 157 suppliers $18.00-$2646.00
ML385 846557-71-9 C29H25N3O4S 157 suppliers $18.00-$2646.00

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