Skip to content
2000
image of Mechanistic Insights into the Ferroptosis-Regulating Effects of EF in the Treatment of Chronic Renal Failure

Abstract

Introduction

Chronic Renal Failure (CRF) is a progressive disease that severely affects patients' quality of life, but its current treatment options remain limited. This study explores the potential mechanism of Eriobotryae Folium (EF) in treating CRF by targeting ferroptosis.

Methods

Active compounds and targets of EF were identified through multiple databases (TCMSP, SwissTargetPrediction, UniProt, GeneCards, DrugBank). Using Cytoscape and STRING, both a compound-target network and a PPI network were generated. GO and KEGG analyses were conducted to explore relevant biological functions and pathways. The binding affinity and stability between critical compounds and target proteins were investigated through molecular docking and Molecular Dynamics (MD) simulations.

Results

Eighteen active compounds and 366 targets of EF were identified, along with 1,267 CRF-related and 1,673 ferroptosis-related targets, with 40 overlapping genes. PPI analysis highlighted AKT1, EGFR, HIF1A, SRC, and ESR1 as key targets. The KEGG analysis indicated MAPK and HIF-1 pathways as major regulatory pathways. Molecular docking suggested quercetin, ellagic acid, and oleanolic acid as potential active compounds, with EGFR and SRC as promising targets. MD simulations confirmed strong and stable binding, especially for EGFR-ellagic acid (-21.38 kcal/mol) and EGFR-oleanolic acid (-24.02 kcal/mol).

Discussion

This study suggests that EF treats CRF by targeting ferroptosis-related pathways and key proteins, such as EGFR and AKT1. MAPK and HIF-1 signaling pathways further substantiate its significant role in disease regulation.

Conclusion

EF may regulate ferroptosis through multiple targets and pathways, offering potential therapeutic benefits for CRF. The findings offer foundational insights for subsequent research and therapeutic development.

Loading

Article metrics loading...

/content/journals/cmc/10.2174/0109298673409766250729110405
2025-09-29
2025-11-06
Loading full text...

Full text loading...

References

  1. Flythe J.E. Watnick S. Dialysis for chronic kidney failure. JAMA 2024 332 18 1559 1573 10.1001/jama.2024.16338 39356511
    [Google Scholar]
  2. Terzo C. Gembillo G. Cernaro V. Longhitano E. Calabrese V. Casuscelli C. Peritore L. Santoro D. Investigational new drugs for the treatment of chronic renal failure: An overview of the literature. Expert Opin. Investig. Drugs 2024 33 4 319 334 10.1080/13543784.2024.2326624 38429874
    [Google Scholar]
  3. Long D. Mao C. Huang Y. Xu Y. Zhu Y. Ferroptosis in ulcerative colitis: Potential mechanisms and promising therapeutic targets. Biomed. Pharmacother. 2024 175 116722 10.1016/j.biopha.2024.116722 38729051
    [Google Scholar]
  4. Zhou Q. Meng Y. Li D. Yao L. Le J. Liu Y. Sun Y. Zeng F. Chen X. Deng G. Ferroptosis in cancer: From molecular mechanisms to therapeutic strategies. Signal Transduct. Target. Ther. 2024 9 1 55 10.1038/s41392‑024‑01769‑5 38453898
    [Google Scholar]
  5. Liu G. Xie X. Liao W. Chen S. Zhong R. Qin J. He P. Xie J. Ferroptosis in cardiovascular disease. Biomed. Pharmacother. 2024 170 116057 10.1016/j.biopha.2023.116057 38159373
    [Google Scholar]
  6. Wenzel S.E. Tyurina Y.Y. Zhao J. St Croix C.M. Dar H.H. Mao G. Tyurin V.A. Anthonymuthu T.S. Kapralov A.A. Amoscato A.A. Mikulska-Ruminska K. Shrivastava I.H. Kenny E.M. Yang Q. Rosenbaum J.C. Sparvero L.J. Emlet D.R. Wen X. Minami Y. Qu F. Watkins S.C. Holman T.R. VanDemark A.P. Kellum J.A. Bahar I. Bayır H. Kagan V.E. PEBP1 wardens ferroptosis by enabling lipoxygenase generation of lipid death signals. Cell 2017 171 3 628 641.e26 10.1016/j.cell.2017.09.044 29053969
    [Google Scholar]
  7. Jiayi H. Ziyuan T. Tianhua X. Mingyu Z. Yutong M. Jingyu W. Hongli Z. Li S. Copper homeostasis in chronic kidney disease and its crosstalk with ferroptosis. Pharmacol. Res. 2024 202 107139 10.1016/j.phrs.2024.107139 38484857
    [Google Scholar]
  8. Pawłowska A.M. Żurek N. Kapusta I. De Leo M. Braca A. Antioxidant and antiproliferative activities of phenolic extracts of Eriobotrya japonica (Thunb.) Lindl. fruits and leaves. Plants 2023 12 18 3221 10.3390/plants12183221 37765385
    [Google Scholar]
  9. Chen Z. Zhang L. Chen G. Microwave-assisted extraction followed by capillary electrophoresis-amperometric detection for the determination of antioxidant constituents in Folium Eriobotryae. J. Chromatogr. A 2008 1193 1-2 178 181 10.1016/j.chroma.2008.04.032 18462740
    [Google Scholar]
  10. Zhang J. Li Y. Chen S.S. Zhang L. Wang J. Yang Y. Zhang S. Pan Y. Wang Y. Yang L. Systems pharmacology dissection of the anti-inflammatory mechanism for the medicinal herb Folium eriobotryae. Int. J. Mol. Sci. 2015 16 2 2913 2941 10.3390/ijms16022913 25636035
    [Google Scholar]
  11. Jie X.L. Luo Z.R. Yu J. Tong Z.R. Li Q.Q. Wu J.H. Tao Y. Feng P.S. Lan J.P. Wang P. Pi-Pa-Run-Fei-Tang alleviates lung injury by modulating IL-6/JAK2/STAT3/IL-17 and PI3K/AKT/NF-κB signaling pathway and balancing Th17 and Treg in murine model of OVA-induced asthma. J Ethnopharmacol 2023 317 116719 10.1016/j.jep.2023.116719 37268260
    [Google Scholar]
  12. Sarkaki A. Hoseinynejad K. Khombi Shooshtari M. Rashno M. Synaptic plasticity and cognitive impairment consequences to acute kidney injury: Protective role of ellagic acid. Iran. J. Basic Med. Sci. 2022 25 5 621 628 10.22038/IJBMS.2022.62015.13729 35911650
    [Google Scholar]
  13. Tu H. Ma D. Luo Y. Tang S. Li Y. Chen G. Wang L. Hou Z. Shen C. Lu H. Zhuang X. Zhang L. Quercetin alleviates chronic renal failure by targeting the PI3k/Akt pathway. Bioengineered 2021 12 1 6538 6558 10.1080/21655979.2021.1973877 34528858
    [Google Scholar]
  14. Kasuno K. Yodoi J. Iwano M. Urinary thioredoxin as a biomarker of renal redox dysregulation and a companion diagnostic to identify responders to redox-modulating therapeutics. Antioxid. Redox Signal. 2022 36 13-15 1051 1065 10.1089/ars.2021.0194 34541903
    [Google Scholar]
  15. Fu H. Li W. Liu J. Tang Q. Weng Z. Zhu L. Ding B. Ellagic acid inhibits dihydrotestosterone-induced ferroptosis and promotes hair regeneration by activating the wnt/β-catenin signaling pathway. J. Ethnopharmacol. 2024 330 118227 10.1016/j.jep.2024.118227 38685364
    [Google Scholar]
  16. Xie R. Zhao W. Lowe S. Bentley R. Hu G. Mei H. Jiang X. Sun C. Wu Y. Yueying liu Quercetin alleviates kainic acid-induced seizure by inhibiting the Nrf2-mediated ferroptosis pathway. Free Radic. Biol. Med. 2022 191 212 226 10.1016/j.freeradbiomed.2022.09.001 36087883
    [Google Scholar]
  17. Zhang J. Xu H.Y. Wu Y.J. Zhang X. Zhang L.Q. Li Y.M. Neutrophil elastase inhibitory effects of pentacyclic triterpenoids from Eriobotrya japonica (loquat leaves). J. Ethnopharmacol. 2019 242 111713 10.1016/j.jep.2019.01.037 30703491
    [Google Scholar]
  18. Elshafei S.O. Mahmoud N.A. Almofti Y.A. Immunoinformatics, molecular docking and dynamics simulation approaches unveil a multi epitope-based potent peptide vaccine candidate against avian leukosis virus. Sci. Rep. 2024 14 1 2870 10.1038/s41598‑024‑53048‑6 38311642
    [Google Scholar]
  19. Nada H. Lee K. Gotina L. Pae A.N. Elkamhawy A. Identification of novel discoidin domain receptor 1 (DDR1) inhibitors using E-pharmacophore modeling, structure-based virtual screening, molecular dynamics simulation and MM-GBSA approaches. Comput. Biol. Med. 2022 142 105217 10.1016/j.compbiomed.2022.105217 35032738
    [Google Scholar]
  20. Gao W.C. Wang X.P. He L.S. Quality evaluation of crude drug and different processed products of Eriobotryae Folium. China Pharmacy 2022 196 202 10.6039/j.issn.1001‑0408.2022.02.12
    [Google Scholar]
  21. Ioutsi A. Sarnitskaya A. Sumtsov M. Simultaneous determination of general active ingredients in topical formulations by gas chromatography with flame ionization detection (GC-FID). J. Chromatogr. Sci. 2023 62 7 bmad086 10.1093/chromsci/bmad086 37965747
    [Google Scholar]
  22. Greytak A.B. Abiodun S.L. Burrell J.M. Cook E.N. Jayaweera N.P. Islam M.M. Shaker A.E. Thermodynamics of nanocrystal–ligand binding through isothermal titration calorimetry. Chem. Commun. 2022 58 94 13037 13058 10.1039/D2CC05012A 36353927
    [Google Scholar]
  23. Kim S. Chen J. Cheng T. Gindulyte A. He J. He S. Li Q. Shoemaker B.A. Thiessen P.A. Yu B. Zaslavsky L. Zhang J. Bolton E.E. PubChem 2023 update. Nucleic Acids Res. 2023 51 D1 D1373 D1380 10.1093/nar/gkac956 36305812
    [Google Scholar]
  24. Berman H.M. Westbrook J. Feng Z. Gilliland G. Bhat T.N. Weissig H. Shindyalov I.N. Bourne P.E. The protein data bank. Nucleic Acids Res. 2000 28 1 235 242 10.1093/nar/28.1.235 10592235
    [Google Scholar]
  25. Al-Farraj E.S. Younis A.M. El-Reash G.M.I.A. Synthesis, characterization, biological potency, and molecular docking of Co 2+ , Ni 2+ and Cu 2+ complexes of a benzoyl isothiocyanate based ligand. Sci. Rep. 2024 14 1 10032 10.1038/s41598‑024‑58108‑5 38693156
    [Google Scholar]
  26. Ni B. Wang H. Khalaf H.K.S. Blay V. Houston D.R. AutoDock-SS: AutoDock for multiconformational ligand-based virtual screening. J. Chem. Inf. Model. 2024 64 9 3779 3789 10.1021/acs.jcim.4c00136 38624083
    [Google Scholar]
  27. Tang S. Ding J. Zhu X. Wang Z. Zhao H. Wu J. Vina-GPU 2.1: Towards further optimizing docking speed and precision of AutoDock Vina and its derivatives. IEEE/ACM Trans. Comput. Biol. Bioinformatics 2024 21 6 2382 2393 10.1109/TCBB.2024.3467127 39320991
    [Google Scholar]
  28. Oanca G. van der Ent F. Åqvist J. Efficient empirical valence bond simulations with GROMACS. J. Chem. Theory Comput. 2023 19 17 6037 6045 10.1021/acs.jctc.3c00714 37623818
    [Google Scholar]
  29. Bhadra P. Siu S.W.I. Refined empirical force field to model protein–self-assembled monolayer interactions based on AMBER14 and GAFF. Langmuir 2019 35 29 9622 9633 10.1021/acs.langmuir.9b01367 31246036
    [Google Scholar]
  30. Luedemann M. Stadler D. Cheng C.C. Protzer U. Knolle P.A. Donakonda S. Montelukast is a dual-purpose inhibitor of SARS-CoV-2 infection and virus-induced IL-6 expression identified by structure-based drug repurposing. Comput. Struct. Biotechnol. J. 2022 20 799 811 10.1016/j.csbj.2022.01.024 35126884
    [Google Scholar]
  31. Saini R.S. Binduhayyim R.I.H. Gurumurthy V. Alshadidi A.A.F. Aldosari L.I.N. Okshah A. Kuruniyan M.S. Dermawan D. Avetisyan A. Mosaddad S.A. Heboyan A. Dental biomaterials redefined: Molecular docking and dynamics-driven dental resin composite optimization. BMC Oral Health 2024 24 1 557 10.1186/s12903‑024‑04343‑1 38735940
    [Google Scholar]
  32. Bettadj F.Z.Y. Benchouk W. Guendouzi A. Computational exploration of novel ketoprofen derivatives: Molecular dynamics simulations and MM-PBSA calculations for COX-2 inhibition as promising anti-inflammatory drugs. Comput. Biol. Med. 2024 183 109203 10.1016/j.compbiomed.2024.109203 39395347
    [Google Scholar]
  33. Zhang C. Li X. Gao D. Zhu H. Wang S. Tan B. Yang A. Network pharmacology and experimental validation of the anti-inflammatory effect of Tingli Dazao Xiefei decoction in acute lung injury treatment. J Inflamm Res 2023 16 6195 6209 10.2147/JIR.S433840 38145012
    [Google Scholar]
  34. Hollingsworth S.A. Dror R.O. Molecular dynamics simulation for all. Neuron 2018 99 6 1129 1143 10.1016/j.neuron.2018.08.011 30236283
    [Google Scholar]
  35. Coutsias E.A. Wester M.J. RMSD and Symmetry. J. Comput. Chem. 2019 40 15 1496 1508 10.1002/jcc.25802 30828834
    [Google Scholar]
  36. Zhao Y. Zhang J. Zhang H. Gu S. Deng Y. Tu Y. Hou T. Kang Y. Sigmoid accelerated molecular dynamics: An efficient enhanced sampling method for biosystems. J. Phys. Chem. Lett. 2023 14 4 1103 1112 10.1021/acs.jpclett.2c03688 36700836
    [Google Scholar]
  37. Ma X. Neek-Amal M. Sun C. Advances in two-dimensional ion-selective membranes: Bridging nanoscale insights to industrial-scale salinity gradient energy harvesting. ACS Nano 2024 18 20 12610 12638 10.1021/acsnano.3c11646 38733357
    [Google Scholar]
  38. Al Khzem A.H. Shoaib T.H. Mukhtar R.M. Alturki M.S. Gomaa M.S. Hussein D. Tawfeeq N. Bano M. Sarafroz M. Alzahrani R. Alghamdi H. Rants’o T.A. Repurposing FDA-approved agents to develop a prototype Helicobacter pylori shikimate kinase (HPSK) inhibitor: A computational approach using virtual screening, MM-GBSA calculations, MD simulations, and DFT analysis. Pharmaceuticals 2025 18 2 174 10.3390/ph18020174 40005988
    [Google Scholar]
  39. Wang Y. Yang J. Zhang Y. Zhou J. Focus on mitochondrial respiratory chain: Potential therapeutic target for chronic renal failure. Int. J. Mol. Sci. 2024 25 2 949 10.3390/ijms25020949 38256023
    [Google Scholar]
  40. Bayır H. Dixon S.J. Tyurina Y.Y. Kellum J.A. Kagan V.E. Ferroptotic mechanisms and therapeutic targeting of iron metabolism and lipid peroxidation in the kidney. Nat. Rev. Nephrol. 2023 19 5 315 336 10.1038/s41581‑023‑00689‑x 36922653
    [Google Scholar]
  41. Jin L. Yu B. Wang H. Shi L. Yang J. Wu L. Gao C. Pan H. Han F. Lin W. Lai E.Y. Wang Y.F. Yang Y. STING promotes ferroptosis through NCOA4-dependent ferritinophagy in acute kidney injury. Free Radic. Biol. Med. 2023 208 348 360 10.1016/j.freeradbiomed.2023.08.025 37634745
    [Google Scholar]
  42. Chen W. Wang B. Liang S. Zheng L. Fang H. Xu S. Zhang T. Wang M. He X. Feng W. Fullerenols as efficient ferroptosis inhibitor by targeting lipid peroxidation for preventing drug-induced acute kidney injury. J Colloid Interface Sci 2025 680 Pt A 261 273 10.1016/j.jcis.2024.10.198 39509775
    [Google Scholar]
  43. Guo R. Duan J. Pan S. Cheng F. Qiao Y. Feng Q. Liu D. Liu Z. The road from AKI to CKD: Molecular mechanisms and therapeutic targets of ferroptosis. Cell Death Dis. 2023 14 7 426 10.1038/s41419‑023‑05969‑9 37443140
    [Google Scholar]
  44. Li S. Han Q. Liu C. Wang Y. Liu F. Pan S. Zuo L. Gao D. Chen K. Feng Q. Liu Z. Liu D. Role of ferroptosis in chronic kidney disease. Cell Commun. Signal. 2024 22 1 113 10.1186/s12964‑023‑01422‑8 38347570
    [Google Scholar]
  45. Zhu Y. Yu C. Zhuang S. Protein arginine methyltransferase 1 mediates renal fibroblast activation and fibrogenesis through activation of Smad3 signaling. Am. J. Physiol. Renal Physiol. 2020 318 2 F375 F387 10.1152/ajprenal.00487.2019 31813251
    [Google Scholar]
  46. Huang X. Hou R. Pan W. Wu D. Zhao W. Li Q. A functional polysaccharide from Eriobotrya japonica relieves myocardial ischemia injury via anti-oxidative and anti-inflammatory effects. Food Funct. 2022 13 1 113 120 10.1039/D1FO03208A 34878451
    [Google Scholar]
  47. Khouya T. Ramchoun M. Elbouny H. Hmidani A. Bouhlali E.T. Alem C. Loquat ( Eriobotrya japonica (Thunb) Lindl.): Evaluation of nutritional value, polyphenol composition, antidiabetic effect, and toxicity of leaf aqueous extract. J. Ethnopharmacol. 2022 296 115473 10.1016/j.jep.2022.115473 35718052
    [Google Scholar]
  48. Jian T. Zhou L. Chen Y. Tian Y. Wu R. Tong B. Niu G. Gai Y. Li W. Chen J. Total sesquiterpenoids of loquat leaves alleviated high-fat diet-induced obesity by targeting fecal metabolic profiling and gut microbiota composition. J. Agric. Food Chem. 2022 70 41 13279 13288 10.1021/acs.jafc.2c04900 36198678
    [Google Scholar]
  49. Hajiluian G. Karegar S.J. Shidfar F. Aryaeian N. Salehi M. Lotfi T. Farhangnia P. Heshmati J. Delbandi A.A. The effects of Ellagic acid supplementation on neurotrophic, inflammation, and oxidative stress factors, and indoleamine 2, 3-dioxygenase gene expression in multiple sclerosis patients with mild to moderate depressive symptoms: A randomized, triple-blind, placebo-controlled trial. Phytomedicine 2023 121 155094 10.1016/j.phymed.2023.155094 37806153
    [Google Scholar]
  50. Kontoghiorghes G.J. The importance and essentiality of natural and synthetic chelators in medicine: Increased prospects for the effective treatment of iron overload and iron deficiency. Int. J. Mol. Sci. 2024 25 9 4654 10.3390/ijms25094654 38731873
    [Google Scholar]
  51. Yang X. Chu F. Jiao Z. Yu H. Yang W. Li Y. Lu C. Ma H. Wang S. Liu Z. Qin S. Sun H. Ellagic acid ameliorates arsenic-induced neuronal ferroptosis and cognitive impairment via Nrf2/GPX4 signaling pathway. Ecotoxicol. Environ. Saf. 2024 283 116833 10.1016/j.ecoenv.2024.116833 39128446
    [Google Scholar]
  52. Chen S. Zhou M. Ying X. Zhou C. Ellagic acid protects rats from chronic renal failure via MiR-182/FOXO3a axis. Mol. Immunol. 2021 138 150 160 10.1016/j.molimm.2021.08.007 34428620
    [Google Scholar]
  53. Feng Q. Yang Y. Qiao Y. Zheng Y. Yu X. Liu F. Wang H. Zheng B. Pan S. Ren K. Liu D. Liu Z. Quercetin ameliorates diabetic kidney injury by inhibiting ferroptosis via activating Nrf2/HO-1 signaling pathway. Am. J. Chin. Med. 2023 51 4 997 1018 10.1142/S0192415X23500465 37046368
    [Google Scholar]
  54. Wang Y. Quan F. Cao Q. Lin Y. Yue C. Bi R. Cui X. Yang H. Yang Y. Birnbaumer L. Li X. Gao X. Quercetin alleviates acute kidney injury by inhibiting ferroptosis. J. Adv. Res. 2021 28 231 243 10.1016/j.jare.2020.07.007 33364059
    [Google Scholar]
  55. Chen J. Zhang H. Yang Y. Chen B. Quercetin regulates vascular endothelium function in chronic renal failure via modulation of Eph/Cav-1 signaling. Drug Dev. Res. 2022 83 5 1167 1175 10.1002/ddr.21940 35470469
    [Google Scholar]
  56. Liu Y. Li T. Bai J. Liu W. Wang Z. Feng C. Pu L. Wang X. Liu H. Isoquercitrin attenuates the osteoclast-mediated bone loss in rheumatoid arthritis via the Nrf2/ROS/NF-κB pathway. Biochim. Biophys. Acta Mol. Basis Dis. 2024 1870 2 166977 10.1016/j.bbadis.2023.166977 38065271
    [Google Scholar]
  57. Ru Y. Luo Y. Liu D. Huang Q. Zhou X. Linghu M. Luo X. Lv Z. Wu Y. Zhang H. Huang Y. Isorhamnetin alleviates ferroptosis-mediated colitis by activating the NRF2/HO-1 pathway and chelating iron. Int. Immunopharmacol. 2024 135 112318 10.1016/j.intimp.2024.112318 38795598
    [Google Scholar]
  58. Kong X. Zhao L. Huang H. Kang Q. Lu J. Zhu J. Isorhamnetin ameliorates hyperuricemia by regulating uric acid metabolism and alleviates renal inflammation through the PI3K/AKT/NF-κB signaling pathway. Food Funct. 2025 16 7 2840 2856 10.1039/D4FO04867A 40111208
    [Google Scholar]
  59. Castellano J.M. Ramos-Romero S. Perona J.S. Oleanolic acid: Extraction, characterization and biological activity. Nutrients 2022 14 3 623 10.3390/nu14030623 35276982
    [Google Scholar]
  60. Xia X. Liu H. Lv H. Zhang J. Zhou J. Zhao Z. Preparation, characterization, and in vitro/vivo studies of oleanolic acid-loaded lactoferrin nanoparticles. Drug Des. Devel. Ther. 2017 11 1417 1427 10.2147/DDDT.S133997 28533680
    [Google Scholar]
  61. Sun H. Peng G. Chen K. Xiong Z. Zhuang Y. Liu M. Ning X. Yang H. Deng J. Identification of EGFR as an essential regulator in chondrocytes ferroptosis of osteoarthritis using bioinformatics, in vivo , and in vitro study. Heliyon 2023 9 9 e19975 10.1016/j.heliyon.2023.e19975 37810027
    [Google Scholar]
  62. Lv D. Zhong C. Dixit D. Yang K. Wu Q. Godugu B. Prager B.C. Zhao G. Wang X. Xie Q. Bao S. He C. Heiland D.H. Rosenfeld M.G. Rich J.N. EGFR promotes ALKBH5 nuclear retention to attenuate N6-methyladenosine and protect against ferroptosis in glioblastoma. Mol. Cell 2023 83 23 4334 4351.e7 10.1016/j.molcel.2023.10.025 37979586
    [Google Scholar]
  63. Shi Z. Yuan H. Cao L. Lin Y. AKT1 participates in ferroptosis vulnerability by driving autophagic degradation of FTH1 in cisplatin-resistant ovarian cancer. Biochem. Cell Biol. 2023 101 5 422 431 10.1139/bcb‑2022‑0361 37011414
    [Google Scholar]
  64. Liu Y. Gong S. Li K. Wu G. Zheng X. Zheng J. Lu X. Zhang L. Li J. Su Z. Liu Y. Xie J. Chen J. Li Y. Coptisine protects against hyperuricemic nephropathy through alleviating inflammation, oxidative stress and mitochondrial apoptosis via PI3K/Akt signaling pathway. Biomed. Pharmacother. 2022 156 113941 10.1016/j.biopha.2022.113941 36411660
    [Google Scholar]
  65. Gong R. Rifai A. Dworkin L.D. Activation of PI3K–Akt–GSK3β pathway mediates hepatocyte growth factor inhibition of RANTES expression in renal tubular epithelial cells. Biochem. Biophys. Res. Commun. 2005 330 1 27 33 10.1016/j.bbrc.2005.02.122 15781227
    [Google Scholar]
  66. Li Y. Wan C. Li F. Xin G. Wang T. Zhou Q. Wen T. Li S. Chen X. Huang W. Indirubin attenuates sepsis by targeting the EGFR/SRC/PI3K and NF-κB/MAPK signaling pathways in macrophages. Front. Pharmacol. 2025 16 1542061 10.3389/fphar.2025.1542061 40144662
    [Google Scholar]
  67. Zheng X.J. Chen Y. Yao L. Li X.L. Sun D. Li Y.Q. Identification of new hub- ferroptosis-related genes in Lupus Nephritis. Autoimmunity 2024 57 1 2319204 10.1080/08916934.2024.2319204 38409788
    [Google Scholar]
  68. Zhao W.M. Wang Z.J. Shi R. Zhu Y. Li X.L. Wang D.G. Analysis of the potential biological mechanisms of diosmin against renal fibrosis based on network pharmacology and molecular docking approach. BMC Complement. Med. Ther. 2023 23 1 157 10.1186/s12906‑023‑03976‑z 37179298
    [Google Scholar]
  69. Xu M. Trung T.S. Zhu Z. Li S. Gong S. Cheng N. Zhou P. Wang S. ESR1-dependent suppression of LCN2 transcription reverses autophagy-linked ferroptosis and enhances sorafenib sensitivity in hepatocellular carcinoma. J. Physiol. Biochem. 2025 81 2 299 312 10.1007/s13105‑025‑01073‑y 40126852
    [Google Scholar]
  70. Xue Q. Kang R. Klionsky D.J. Tang D. Liu J. Chen X. Copper metabolism in cell death and autophagy. Autophagy 2023 19 8 2175 2195 10.1080/15548627.2023.2200554 37055935
    [Google Scholar]
  71. del Balzo U. Signore P.E. Walkinshaw G. Seeley T.W. Brenner M.C. Wang Q. Guo G. Arend M.P. Flippin L.A. Chow F.A. Gervasi D.C. Kjaergaard C.H. Langsetmo I. Guenzler V. Liu D.Y. Klaus S.J. Lin A. Neff T.B. Nonclinical characterization of the hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat, a novel treatment of anemia of chronic kidney disease. J. Pharmacol. Exp. Ther. 2020 374 2 342 353 10.1124/jpet.120.265181 32487538
    [Google Scholar]
  72. Chang W.T. Bow Y.D. Fu P.J. Li C.Y. Wu C.Y. Chang Y.H. Teng Y.N. Li R.N. Lu M.C. Liu Y.C. Chiu C.C. A marine terpenoid, heteronemin, induces both the apoptosis and ferroptosis of hepatocellular carcinoma cells and involves the ROS and MAPK pathways. Oxid. Med. Cell. Longev. 2021 2021 1 7689045 10.1155/2021/7689045 33488943
    [Google Scholar]
  73. Ye Q. Zeng C. Luo C. Wu Y. Ferrostatin-1 mitigates cognitive impairment of epileptic rats by inhibiting P38 MAPK activation. Epilepsy Behav 2020 103 Pt A 106670 10.1016/j.yebeh.2019.106670 31864943
    [Google Scholar]
  74. Xu Z. Zhang M. Wang W. Zhou S. Yu M. Qiu X. Jiang S. Wang X. Tang C. Li S. Wang C.H. Zhu R. Peng W.X. Zhao L. Fu X. Patzak A. Persson P.B. Zhao L. Mao J. Shu Q. Lai E.Y. Zhang G. Dihydromyricetin attenuates cisplatin-induced acute kidney injury by reducing oxidative stress, inflammation and ferroptosis. Toxicol. Appl. Pharmacol. 2023 473 116595 10.1016/j.taap.2023.116595 37328118
    [Google Scholar]
  75. Ye Y. Chen Y. Wu H. Fu Y. Sun Y. Wang X. Li P. Wu Z. Wang J. Yang Z. Zhou E. Investigations into ferroptosis in methylmercury-induced acute kidney injury in mice. Environ. Toxicol. 2023 38 6 1372 1383 10.1002/tox.23770 36880449
    [Google Scholar]
  76. Su L. Jiang X. Yang C. Zhang J. Chen B. Li Y. Yao S. Xie Q. Gomez H. Murugan R. Peng Z. Pannexin 1 mediates ferroptosis that contributes to renal ischemia/reperfusion injury. J. Biol. Chem. 2019 294 50 19395 19404 10.1074/jbc.RA119.010949 31694915
    [Google Scholar]
  77. Li D. Xie X. Zhan Z. Li N. Yin N. Yang S. Liu J. Wang J. Li Z. Yi B. Zhang H. Zhang W. HIF-1 induced tiRNA-Lys-CTT-003 is protective against cisplatin induced ferroptosis of renal tubular cells in mouse AKI model. Biochim. Biophys. Acta Mol. Basis Dis. 2024 1870 7 167277 10.1016/j.bbadis.2024.167277 38871033
    [Google Scholar]
  78. McGettrick A.F. O’Neill L.A.J. The role of HIF in immunity and inflammation. Cell Metab. 2020 32 4 524 536 10.1016/j.cmet.2020.08.002 32853548
    [Google Scholar]
  79. Dudowicz J. Freed K.F. Douglas J.F. Lattice cluster theory of associating polymers. II. Enthalpy and entropy of self-assembly and Flory-Huggins interaction parameter χ for solutions of telechelic molecules. J. Chem. Phys. 2012 136 6 064903 10.1063/1.3681256 22360220
    [Google Scholar]
  80. Rainio O. Teuho J. Klén R. Evaluation metrics and statistical tests for machine learning. Sci. Rep. 2024 14 1 6086 10.1038/s41598‑024‑56706‑x 38480847
    [Google Scholar]
  81. Chen J. Qiu C. Li H. Zheng X. Role of molecular packing in solvent-mediated ellagic acid·phenazine co-crystals toward biological activity enhancement and rational drug design. Cryst. Growth Des. 2024 24 21 8829 8837 10.1021/acs.cgd.4c00805
    [Google Scholar]
  82. Chen C. Ai Q. Shi A. Wang N. Wang L. Wei Y. Oleanolic acid and ursolic acid: Therapeutic potential in neurodegenerative diseases, neuropsychiatric diseases and other brain disorders. Nutr. Neurosci. 2023 26 5 414 428 10.1080/1028415X.2022.2051957 35311613
    [Google Scholar]
  83. Crespo I. García-Mediavilla M.V. Gutiérrez B. Sánchez-Campos S. Tuñón M.J. González-Gallego J. A comparison of the effects of kaempferol and quercetin on cytokine-induced pro-inflammatory status of cultured human endothelial cells – CORRIGENDUM. Br. J. Nutr. 2023 129 9 1656 10.1017/S0007114522003725 36876716
    [Google Scholar]
  84. Speisky H. Arias-Santé M.F. Fuentes J. Oxidation of quercetin and kaempferol markedly amplifies their antioxidant, cytoprotective, and anti-inflammatory properties. Antioxidants 2023 12 1 155 10.3390/antiox12010155 36671017
    [Google Scholar]
  85. Lin B Liu L Lu Y Zhang DW Clinical study of Shenqi Dihuang Decoction and Xiaochengqi Decoction combined with hemodialysis in the treatment of the patients with CKD stage 5 and Qi and Yin deficiency and turbid poison inherent pattern. Int J Tradit Chin Med 2023 807 812 10.3760/cma.j.cn115398‑20210719‑00180
    [Google Scholar]
  86. Jin Z. Wang X. Traditional Chinese medicine and plant-derived natural products in regulating triglyceride metabolism: Mechanisms and therapeutic potential. Pharmacol. Res. 2024 208 107387 10.1016/j.phrs.2024.107387 39216839
    [Google Scholar]
  87. von Samson-Himmelstjerna F.A. Kolbrink B. Riebeling T. Kunzendorf U. Krautwald S. Progress and setbacks in translating a decade of ferroptosis research into clinical practice. Cells 2022 11 14 2134 10.3390/cells11142134 35883577
    [Google Scholar]
/content/journals/cmc/10.2174/0109298673409766250729110405
Loading
/content/journals/cmc/10.2174/0109298673409766250729110405
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test