文献类型：期刊文献

英文题名：Guiqi Baizhu prescription attenuates 5-FU-induced intestinal mucositis by targeting IKKβ to inhibit M1 macrophage polarization

作者：Zhou, Yu-Cen[1,2];Li, Ya-Ling[1,2];Ma, Jing[2];Li, Junjie[2];Si, Qi[2];Wang, Shunzhi[2];Huang, Dan[2];Wa, Xiao-Xia[2];Cai, Hui[1];Liu, Yong-Qi[2,3]

第一作者：Zhou, Yu-Cen

通信作者：Cai, H[1];Liu, YQ[2];Liu, YQ[3]

机构：[1]Gansu Prov Hosp, NHC Key Lab Diag & Therapy Gastrointestinal Tumor, Lanzhou 730000, Gansu, Peoples R China;[2]Gansu Univ Chinese Med, Key Lab Dun Huang Med & Transformat, Minist Educ Peoples Republ China, Lanzhou 730000, Gansu, Peoples R China;[3]Gansu Univ Chinese Med, Gansu Univ, Key Lab Mol Med & Chinese Med Prevent & Treatment, Lanzhou 730000, Gansu, Peoples R China

第一机构：Gansu Prov Hosp, NHC Key Lab Diag & Therapy Gastrointestinal Tumor, Lanzhou 730000, Gansu, Peoples R China

通信机构：[1]corresponding author), Gansu Prov Hosp, NHC Key Lab Diag & Therapy Gastrointestinal Tumor, Lanzhou 730000, Gansu, Peoples R China;[2]corresponding author), Gansu Univ Chinese Med, Key Lab Dun Huang Med & Transformat, Minist Educ Peoples Republ China, Lanzhou 730000, Gansu, Peoples R China;[3]corresponding author), Gansu Univ Chinese Med, Gansu Univ, Key Lab Mol Med & Chinese Med Prevent & Treatment, Lanzhou 730000, Gansu, Peoples R China.|[10735]甘肃中医药大学;

年份：2026

卷号：21

期号：1

外文期刊名：CHINESE MEDICINE

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001822320400001)】；

基金：This study was supported by the National Natural Science Foundation of China (No. 8226150235, No. 82405224), NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor (No. NHCDP2022009), Gansu Province Youth Talent Project (No. 2025NQTD11), Foundation of Gansu Postdoctoral Fund (Li Ya-Ling).

语种：英文

外文关键词：Guiqi Baizhu prescription; Chemotherapy-induced intestinal mucositis; Macrophages polarization; IKK beta; NF-kappa B

摘要：Background Chemotherapy-induced intestinal mucositis (CIM), particularly that induced by agents such as 5-fluorouracil (5-FU), frequently leads to chemotherapy discontinuation. However, effective treatment options remain limited. Guiqi Baizhu prescription (GQBZP), a traditional Chinese medicine formula, has been reported to possess anticancer, analgesic, and anti-inflammatory activities.Purpose This study aimed to evaluate the therapeutic efficacy of GQBZP against 5-FU-induced intestinal mucositis (IM) and to clarify its underlying molecular mechanisms and material basis.Methods The protective effects and mechanistic actions of GQBZP were investigated using a murine model of 5-FU-induced IM. Potential IKK beta-targeting compounds within GQBZP were screened through virtual docking combined with CCK-8 assays and subsequently evaluated in 5-FU-stimulated human intestinal epithelial cells (HIECs) and lipopolysaccharide/interferon-gamma (LPS/IFN-gamma)-stimulated THP-1 macrophages. Target specificity and binding characteristics were further validated by molecular dynamics (MD) simulations, surface plasmon resonance (SPR) analysis, and experiments using IKK beta-overexpressing HEK293T cells.Results In vivo experiments demonstrated that GQBZP significantly alleviated 5-FU-induced IM by suppressing M1 macrophage polarization within intestinal tissues and restoring intestinal barrier integrity, effects closely associated with modulation of the IKK beta/NF-kappa B signaling pathway. Virtual screening and CCK-8 assays identified five IKK beta-targeting compounds in GQBZP: Rhamnocitrin, Toralactone, Naringenin, Liquiritigenin, and Carvacrol. These compounds markedly reduced apoptosis and pro-inflammatory cytokine production in 5-FU-treated HIECs. In addition, they inhibited M1 macrophage polarization and cytokine release in LPS/IFN-gamma-stimulated THP-1 cells, accompanied by attenuation of IKK beta/NF-kappa B pathway activation. MD simulations, SPR assays, and functional studies in IKK beta-overexpressing HEK293T cells further confirmed that Toralactone directly binds to and suppresses IKK beta activation, whereas Rhamnocitrin modulates IKK beta activity through an indirect regulatory mechanism.Conclusion GQBZP alleviates 5-FU-induced IM by promoting recovery of the intestinal epithelial barrier and inhibiting M1 macrophage polarization through an IKK beta/NF-kappa B-dependent mechanism, thereby exerting synergistic anti-inflammatory effects. Toralactone was identified as a key active constituent responsible for direct inhibition of IKK beta-mediated M1 polarization. These findings suggest that targeting IKK beta to regulate macrophage polarization represents a promising therapeutic strategy for the management of CIM.