Abstract: TH-PO0838
Isovitexin, a Naturally Occurring Molecule, Alleviates Kidney Tubulointerstitial Fibrosis by Mediating Epithelial-to-Mesenchymal Transition, Inflammation, Oxidative Stress, and Ferroptotic Pathways
Session Information
- Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
- 1900 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
Authors
- Huang, Po-Yu, Division of Nephrology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
- Tsai, Jen-Pi, Division of Nephrology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
- Hsieh, Yi-Hsien, Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
Background
Kidney tubulointerstitial fibrosis is predictive of chronic kidney dysfunction and kidney failure. Indoxyl sulfate (IS), a gut-derived uremic retention molecule, contributes to kidney disease progression. Isovitexin, a naturally occurring flavonoid derivative, plays a pivotal role in organ protection through antifibrotic, anti-inflammatory, and antioxidant effects. The present investigation hypothesizes that isovitexin protects the kidneys from fibrotic damage.
Methods
We generated the unilateral ureteral obstruction (UUO) mice model in vivo and treated the mice with various doses of isovitexin. Regarding the in vitro study, we utilized NRK52E rat proximal tubular epithelial cell lines which were co-administered with IS and isovitexin. We explored the mechanisms of action by which isovitexin mediates kidney fibrosis, and the markers of interest were measured via histology, immunohistochemical staining, Western blotting, immunofluorescence, and RT-qPCR. RNA sequencing was adopted to identify the genes regulated by isovitexin within the IS-treated NRK52E cells.
Results
In mice undergoing UUO, isovitexin feeding resulted in regression of collagen deposition and less severe tubular atrophy in the renal tubulointerstitium. Isovitexin decreased the mRNA and protein expression of EMT and fibrotic markers induced by IS within the NRK52E cells. Isovitexin diminished protein expression of NLRP3, cleaved caspase-1, and cleaved interleukin-1β, which are markers of NLRP3 inflammasome activation. Isovitexin reduced the generation of reactive oxygen species and modulated the Nrf2/HO-1 axis. Isovitexin inhibited ferroptosis in the NRK52E cells treated with IS by decreasing intracellular ferrous accumulation and restoring GPX4 expression. RNA sequencing revealed that interleukin-7 gene expression upregulated after IS was inhibited by isovitexin.
Conclusion
Isovitexin lessens the severity of kidney TIF through the modulation of multiple pathways.