内质网
细胞凋亡
细胞生物学
氧化应激
未折叠蛋白反应
p38丝裂原活化蛋白激酶
化学
药理学
信号转导
生物
生物化学
MAPK/ERK通路
作者
Junjie Zhang,Shuang Wang,Xu-fei Gao,Yun‐yi Hou,Jun‐nan Hu,Jingtian Zhang,Jingang Hou,Zi Wang,Xia Li,Wei Li
标识
DOI:10.1016/j.ijbiomac.2022.04.068
摘要
Many dietary polysaccharides have been shown to protect against various harmful external stimuli by protecting the integrity of the intestinal barrier. Arabinogalactan (AG) is a high molecular weight polysaccharide composed of arabinose and galactose, which has good immunomodulatory, antioxidant and intestinal conditioning activities. Gastrointestinal injury caused by cisplatin (CP) is an inevitable damage during CP chemotherapy. This research explored the ameliorative effect of AG on cisplatin-induced intestinal toxicity and its possible molecular targets and mechanisms. The results showed that AG (200, 400 mg/kg) could significantly reverse the intestinal histopathological changes and oxidative stress injury caused by CP. Meantime, AG could target the IRE1α/JNK axis to inhibit the expression of apoptosis-related proteins and block the apoptotic cascade, thus reducing intestinal damage. In vitro, AG (10, 20, and 40 μg/mL) could regulate the IRE1α/JNK axis, inhibit apoptosis, and restore the antioxidant defense system damaged by CP to play a protective role in the intestine. In addition, 4-phenylbutyrate (4-PBA), a specific inhibitor of endoplasmic reticulum stress, was used to verify that AG also affected protein expression levels by regulating the IRE1α/JNK pathway-mediated endoplasmic reticulum stress signaling pathway, thereby alleviating CP-induced gastrointestinal dysfunction. Therefore, AG may be a potential drug to prevent CP-induced intestinal damage.
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