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Transcriptomic Exploration of Tetrahydrocurcumin Effects in Chronic Kidney Disease
Alyssa Mariana Alvarez1,2, Winston Hibler2, Su Mi Lee2,3
1Department of Biomedical Engineering, University of California, Irvine, CA 92697, USA.
Biomedicines
|July 28, 2026
Summary
Tetrahydrocurcumin (THCu) shows promise in treating chronic kidney disease (CKD) by reducing fibrosis and inflammation. This study found THCu modulated key gene pathways, offering potential therapeutic benefits for kidney damage.
Area of Science:
- Biochemistry
- Pharmacology
- Genomics
Background:
- Chronic kidney disease (CKD) is characterized by progressive renal function loss, oxidative stress, and kidney fibrosis.
- Tetrahydrocurcumin (THCu), a curcumin metabolite, exhibits potential antioxidant properties relevant to CKD.
- The 5/6 nephrectomy rat model is utilized to study CKD progression and therapeutic interventions.
Purpose of the Study:
- To evaluate the therapeutic potential and transcriptomic effects of THCu in a rat model of CKD.
- To investigate THCu's impact on kidney damage, fibrosis, and associated gene expression patterns.
- To assess the antioxidant and anti-fibrotic mechanisms of THCu in the context of CKD.
Main Methods:
- Rats with 5/6 nephrectomy-induced CKD were treated with varying doses of liposomal THCu (100, 300, 500 mg/kg) orally for 4 weeks.
- Serum creatinine, proteinuria, and kidney fibrosis (histology) were assessed.
- Total RNA sequencing was performed on kidney lysates to analyze differential gene expression and pathway enrichment.
Main Results:
- CKD rats exhibited increased serum creatinine, proteinuria, and upregulation of genes related to immune activation, kidney injury, inflammation, and oxidative stress.
- THCu treatment downregulated immune cell activation markers and kidney injury marker (Kim1), and decreased fibrosis markers (Col1a1, Col3a1).
- High-dose THCu upregulated cellular detoxification (Abcb11, Gls2) and antioxidant (Gpx1) genes, restoring metabolic and signaling pathways disrupted by renal fibrosis.
Conclusions:
- Oral THCu administration demonstrated significant transcriptomic modulation of antioxidant and anti-fibrotic pathways in a rat CKD model.
- THCu therapy reduced proteinuria and showed promising gene expression changes related to kidney protection.
- Further protein-level studies are warranted to confirm the functional benefits of THCu on kidney function in CKD.
