Study on the Mechanism and Dose–Effect Relationship of Flavonoids in Different Extracts of Radix Hedysari Against Gastrointestinal Injury Induced by Chemotherapy

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Publicado en:Pharmaceuticals vol. 18, no. 7 (2025), p. 1072-1102
Autor principal: Zhao Shasha
Otros Autores: Yang, Miaomiao, Yang Zimu, He, Hai, Wang, Ziyang, Zhu, Xinyu, Cui Zhijia, Shao Jing
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022 |a 1424-8247 
024 7 |a 10.3390/ph18071072  |2 doi 
035 |a 3233239449 
045 2 |b d20250101  |b d20251231 
084 |a 231548  |2 nlm 
100 1 |a Zhao Shasha  |u College of Pharmacy, Gansu University of Traditional Chinese Medicine, Lanzhou 730000, China; zhaoshasha1112@163.com (S.Z.); 15294350715@163.com (M.Y.); qitian_122@163.com (Z.Y.); hehai1128@126.com (H.H.); yingtao20@126.com (Z.W.); zhxy19@gszy.edu.cn (X.Z.); zhijiacui@126.com (Z.C.) 
245 1 |a Study on the Mechanism and Dose–Effect Relationship of Flavonoids in Different Extracts of Radix Hedysari Against Gastrointestinal Injury Induced by Chemotherapy 
260 |b MDPI AG  |c 2025 
513 |a Journal Article 
520 3 |a 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–γ, IgG, IL–6, TNF–α 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–κB pathway inhibition, demonstrating significant dose–dependent efficacy. These findings support RH’s potential as a complementary therapy during chemotherapy. 
653 |a Thymus gland 
653 |a Cancer 
653 |a Spleen 
653 |a RNA polymerase 
653 |a Food 
653 |a Traditional Chinese medicine 
653 |a Flavonoids 
653 |a Functional foods & nutraceuticals 
653 |a Reactive oxygen species 
653 |a Ligands 
653 |a Kinases 
653 |a Chemotherapy 
653 |a Drug dosages 
653 |a Transcription factors 
653 |a Proteins 
700 1 |a Yang, Miaomiao  |u College of Pharmacy, Gansu University of Traditional Chinese Medicine, Lanzhou 730000, China; zhaoshasha1112@163.com (S.Z.); 15294350715@163.com (M.Y.); qitian_122@163.com (Z.Y.); hehai1128@126.com (H.H.); yingtao20@126.com (Z.W.); zhxy19@gszy.edu.cn (X.Z.); zhijiacui@126.com (Z.C.) 
700 1 |a Yang Zimu  |u College of Pharmacy, Gansu University of Traditional Chinese Medicine, Lanzhou 730000, China; zhaoshasha1112@163.com (S.Z.); 15294350715@163.com (M.Y.); qitian_122@163.com (Z.Y.); hehai1128@126.com (H.H.); yingtao20@126.com (Z.W.); zhxy19@gszy.edu.cn (X.Z.); zhijiacui@126.com (Z.C.) 
700 1 |a He, Hai  |u College of Pharmacy, Gansu University of Traditional Chinese Medicine, Lanzhou 730000, China; zhaoshasha1112@163.com (S.Z.); 15294350715@163.com (M.Y.); qitian_122@163.com (Z.Y.); hehai1128@126.com (H.H.); yingtao20@126.com (Z.W.); zhxy19@gszy.edu.cn (X.Z.); zhijiacui@126.com (Z.C.) 
700 1 |a Wang, Ziyang  |u College of Pharmacy, Gansu University of Traditional Chinese Medicine, Lanzhou 730000, China; zhaoshasha1112@163.com (S.Z.); 15294350715@163.com (M.Y.); qitian_122@163.com (Z.Y.); hehai1128@126.com (H.H.); yingtao20@126.com (Z.W.); zhxy19@gszy.edu.cn (X.Z.); zhijiacui@126.com (Z.C.) 
700 1 |a Zhu, Xinyu  |u College of Pharmacy, Gansu University of Traditional Chinese Medicine, Lanzhou 730000, China; zhaoshasha1112@163.com (S.Z.); 15294350715@163.com (M.Y.); qitian_122@163.com (Z.Y.); hehai1128@126.com (H.H.); yingtao20@126.com (Z.W.); zhxy19@gszy.edu.cn (X.Z.); zhijiacui@126.com (Z.C.) 
700 1 |a Cui Zhijia  |u College of Pharmacy, Gansu University of Traditional Chinese Medicine, Lanzhou 730000, China; zhaoshasha1112@163.com (S.Z.); 15294350715@163.com (M.Y.); qitian_122@163.com (Z.Y.); hehai1128@126.com (H.H.); yingtao20@126.com (Z.W.); zhxy19@gszy.edu.cn (X.Z.); zhijiacui@126.com (Z.C.) 
700 1 |a Shao Jing  |u College of Pharmacy, Gansu University of Traditional Chinese Medicine, Lanzhou 730000, China; zhaoshasha1112@163.com (S.Z.); 15294350715@163.com (M.Y.); qitian_122@163.com (Z.Y.); hehai1128@126.com (H.H.); yingtao20@126.com (Z.W.); zhxy19@gszy.edu.cn (X.Z.); zhijiacui@126.com (Z.C.) 
773 0 |t Pharmaceuticals  |g vol. 18, no. 7 (2025), p. 1072-1102 
786 0 |d ProQuest  |t Research Library 
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