文献类型：期刊文献

英文题名：Study on the Mechanism and Dose-Effect Relationship of Flavonoids in Different Extracts of Radix Hedysari Against Gastrointestinal Injury Induced by Chemotherapy

作者：Zhao, Shasha[1,2,3];Yang, Miaomiao[1];Yang, Zimu[1];He, Hai[1];Wang, Ziyang[1];Zhu, Xinyu[1];Cui, Zhijia[1];Shao, Jing[1,2,3]

第一作者：Zhao, Shasha

通信作者：Shao, J[1];Shao, J[2];Shao, J[3]

机构：[1]Gansu Univ Tradit Chinese Med, Coll Pharm, Lanzhou 730000, Peoples R China;[2]Key Lab Tradit Chinese Med Chem, State Adm Tradit Chinese Med Class 3 Lab, Lanzhou 730000, Peoples R China;[3]Northwest China Tibet Med Collaborat Innovat Ctr, Lanzhou 730000, Peoples R China

第一机构：甘肃中医药大学药学院（西北中藏药协同创新中心办公室）

通信机构：[1]corresponding author), Gansu Univ Tradit Chinese Med, Coll Pharm, Lanzhou 730000, Peoples R China;[2]corresponding author), Key Lab Tradit Chinese Med Chem, State Adm Tradit Chinese Med Class 3 Lab, Lanzhou 730000, Peoples R China;[3]corresponding author), Northwest China Tibet Med Collaborat Innovat Ctr, Lanzhou 730000, Peoples R China.|[1073501e14fb35863569f]甘肃中医药大学药学院（西北中藏药协同创新中心办公室）;[10735]甘肃中医药大学;

年份：2025

卷号：18

期号：7

外文期刊名：PHARMACEUTICALS

收录：;Scopus(收录号：2-s2.0-105011615775);WOS:【SCI-EXPANDED(收录号:WOS:001541077100001)】；

基金：This studied was funded by: 1. Gansu Province Science and Technology Program Joint Research Fund Project (25JRRA1175), 2025. 2. Technology Support Special Project of the Third Batch of Lanzhou Science and Technology Program Projects (2024-3-35), 2024. 3. Natural Science Foundation of Gansu Province (Grant No. 21JR11RA136). 4. Gansu Province Science and Technology Plan East-West Cooperation Project (22CX8NA068). 5. Regional Science Foundation Project of National Natural Science Foundation of China (Grant No. 82060914). 6. Double First-Class Major Scientific Research Project of Gansu Provincial Department of Education (GSSYLXM-05).

语种：英文

外文关键词：Radix Hedysari; chemotherapy; gastrointestinal injury; mechanism of action; flavonoids; correlation

摘要：Background: Previous studies have shown Radix Hedysari (RH)'s gastroprotective potential, but its active components and mechanisms remain uncharacterized. This study aimed to identify RH's bioactive fractions, elucidate protection mechanisms, establish flavonoid dose-effect relationships, and determine the pharmacodynamic basis. Methods: Chemical profiling quantified eight flavonoids via HPLC. Network pharmacology screened targets/pathways using TCMSP, GeneCards databases. In vivo validation employed cisplatin-induced injury models in Wistar rats (n = 10/group). Assessments included: behavioral monitoring; organ indices; ELISA (MTL, VIP, IFN-gamma, IgG, IL-6, TNF-alpha etc.); H & E; and Western blot:(SCF, c-Kit, p65). Dose-effect correlations were analyzed by PLS-DA. Results: Content determination indicated that Calycosin-7-glucoside and Ononin were notably enriched on both the n-BuOH part and the EtOAc part. Network pharmacology identified 5 core flavonoids and 8 targets enriched in IL-17/TNF signaling pathways. n-BuOH treatment minimized weight loss vs. MCG, increased spleen/thymus indices. n-BuOH and HPS normalized gastrointestinal, immune, inflammatory biomarkers (p < 0.01 vs. MCG). Histopathology confirmed superior mucosal protection in n-BuOH group vs. MCG. Western blot revealed n-BuOH significantly downregulated SCF, c-kit, and p65 expressions in both gastric and intestinal tissues (p < 0.001 vs. MCG). PLS-DA demonstrated Calycosin-7-glucoside had the strongest dose-effect correlation (VIP > 1) with protective outcomes. Conclusions: The n-BuOH fraction of RH is the primary bioactive component against chemotherapy-induced gastrointestinal injury, with Calycosin-7-glucoside as its key effector. Protection is mediated through SCF/c-Kit/NF-kappa B pathway inhibition, demonstrating significant dose-dependent efficacy. These findings support RH's potential as a complementary therapy during chemotherapy.