文献类型：期刊文献

英文题名：Astragaloside IV alleviates cytarabine-induced intestinal mucositis by remodeling macrophage polarization through AKT signaling

作者：Li, Jun-Jie[1];Li, Ya-Ling[1];Chu, Wei[1];Li, Gao-Qin[1];Zhang, Min[3];Dong, Juan-Juan[1];Li, Ling[1];Li, Cheng-Hao[1];Zhang, Jin-Bao[1,3];Li, Jia-Wei[1];Jin, Xiao-Jie[1,3];Liu, Yong-Qi[1,2,4]

第一作者：李金娟

通信作者：Liu, YQ[1]

机构：[1]Gansu Univ Chinese Med, Gansu Univ Key Lab Mol Med & Chinese Med Prevent &, Lanzhou, Peoples R China;[2]Gansu Univ Chinese Med, Key Lab Dun Huang Med & Transformat, Minist Educ Peoples Republ China, Lanzhou, Peoples R China;[3]Gansu Univ Chinese Med, Coll Pharm, Lanzhou, Peoples R China;[4]Gansu Univ Chinese Med, 35 Dingxi East Rd, Lanzhou 730000, Peoples R China

第一机构：甘肃中医药大学

通信机构：[1]corresponding author), Gansu Univ Chinese Med, 35 Dingxi East Rd, Lanzhou 730000, Peoples R China.|[10735]甘肃中医药大学;

年份：2023

卷号：109

外文期刊名：PHYTOMEDICINE

收录：;Scopus(收录号：2-s2.0-85144471992);WOS:【SCI-EXPANDED(收录号:WOS:000923455500001)】；

基金：This study was supported by Basic Research Innovation Group in Gansu (20JR10RA332) , Young Doctoral Fund Project of Gansu Province Colleges and Universities (2021QB-076) , National Natural Science Foundation of China (82260927) and Youth Science and Technology Fund in Gansu (21JR11RA149) .

语种：英文

外文关键词：Cytarabine; Intestinal mucositis; Macrophage polarization; Astragaloside IV; AKT

摘要：Background: Intestinal mucositis (IM) is one of the common side effects of chemotherapy with Cytarabine (Ara-C) and contributes to the major dose-limiting factor of chemotherapy, while the effective drug for IM is little. Astragalus, one of the main active components extrated from the roots of Astragalus membranaceus (AS-IV), is a common Chinese herbal medicine used in gastrointestinal diseases. However, the effect and mechanism of AS-IV on IM is unclear. Accumulating evidence suggests that M1 macrophages play a pivotal role in IM progression. Purpose: The purpose of the study was to explore the protection of AS-IV and its potential molecular mechanism on intestinal mucositis injury induced by Ara-C. Method: The protective effect of AS-IV was investigated in LPS-induced macrophages and Ara-C-induced intes-tinal mucositis mouse model. H&E, immunofluorescence and western blotting were used to evaluate the damage in different doses of Ara-C. Silencing AKT targeted by siRNA was performed to explore the potential mechanisms regulating macrophage polarization effect of Ara-C, which was investigated by CCK-8, immunofluorescence and western blotting. Flow cytometry, immunofluorescence and Western blotting were used to detect macrophage surface marker proteins and inflammatory genes to explore the potential molecular mechanism of AS-IV regu-lating macrophage polarization. Results: The Cytarabine intervention at dose of 100mg/kg significantly induced IM in mice, with the ileum the most obvious site of injury, accompanied by decreased intestinal barrier, intestinal macrophage polarization to M1 and inflammation response. The administration of AS-IV improved weight loss, food intake, ileal morpho-logical damage, intestinal barrier destruction and inflammatory factor release in mice induced by Ara-c, and also suppressed macrophage polarization to M1, regulating in phenotypic changes in macrophages. In vitro, the expression of M1 macrophage surface marker protein was markedly decreased in LPS-induced macrophages after silencing AKT. Similarly, the western blotting of intestinal tissues and molecular docking indicated that the key mechanisms of AS-IV were remodel AKT signaling, and finally regulating M1 macrophages and decrease inflammation response. Conclusion: Our study highlights that AS-IV exerts protective effect in Ara-C-induced IM through inhibit polar-ization to M1 macrophages based on AKT, and AS-IV may serve as a novel AKT inhibitor to counteract the in-testinal adverse effects of chemotherapeutic agents. [GRAPHICS] .