Abstract | ETHNOPHARMACOLOGICAL RELEVANCE: AIM OF STUDY: In this study, we aimed to investigate the protective effects of PUR on type 2 diabetic nephropathy in vivo, in silico and in vitro, as well as unveil the underlying mechanism through inhibiting ferroptosis. MATERIALS AND METHODS: In vivo, blood glucose and lipid, renal function, kidney histology and immunohistochemistry analysis were used to vindicate the protective effects of PUR on diabetic nephropathy in type 2 DN rat model. In silico, pharmacophore matching and enrichment analysis were adopted to predict the potential mechanism of PUR on DN. In vitro, we utilized high glucose stress to induce impairment in glomerular mesangial cells (GMCs) as diabetic nephropathy cell model. Cell count kit-8 (CCK-8) was used to observe cell viability. qPCR, Western blot, immunofluorescence staining and flow cytometry were used to evaluate the effect of PUR on the generation of extracellular matrix (ECM), ferroptosis and iron homeostasis in vitro and in vivo. RESULTS: PUR markedly improved glucose and lipid metabolism, as well as alleviated renal dysfunction in diabetic nephropathy rats. Pharmacophore matching and enrichment analysis predicted the anti-DN effect of PUR may correlate with ECM. Experimental validation suggested that PUR treatment could inhibit the generation of ECM to alleviate high- glucose-induced cell impairments, suppressing ROS production and excessive collagen fiber accumulation in GMSs, and reduce mesangial matrix expansion and renal fibrosis in type 2 DN rats. Further study suggested that PUR protected GMCs against ferroptosis via reducing LDH release and GSH disruption, suppressing key regulators of two pathways for ferroptosis execution. Moreover, PUR also maintained iron metabolism hemostasis by regulating iron transportation proteins, iron exporter proteins, and iron storage proteins and reducing intracellular iron in type 2 DN rats. CONCLUSION:
|
Authors | Biyu Hou, Peng Ma, Xinyu Yang, Xiaoyue Zhao, Li Zhang, Yuerong Zhao, Ping He, Li Zhang, Guanhua Du, Guifen Qiang |
Journal | Journal of ethnopharmacology
(J Ethnopharmacol)
Vol. 319
Issue Pt 2
Pg. 117281
(Jan 30 2024)
ISSN: 1872-7573 [Electronic] Ireland |
PMID | 37797872
(Publication Type: Journal Article)
|
Copyright | Copyright © 2023 Elsevier B.V. All rights reserved. |
Chemical References |
|
Topics |
- Rats
- Animals
- Diabetic Nephropathies
(pathology)
- Ferroptosis
- Extracellular Matrix
(metabolism)
- Mesangial Cells
- Glucose
(metabolism)
- Diabetes Mellitus, Type 2
(complications, drug therapy, metabolism)
- Iron
(metabolism)
|