Abstract: FR-PO0316
Role of Total Flavonoids of Abelmoschus manihot (L) Medic in Improving Renal Fibrosis in Diabetic Kidney Disease via O-GlcNAcylation and Fatty Acid Oxidation Pathway
Session Information
- Diabetic Kidney Disease: Basic and Translational Science Advances - 1
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 701 Diabetic Kidney Disease: Basic
Authors
- Weilong, Xu, Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu, China
- Ochi, Akinobu, Osaka Koritsu Daigaku, Osaka, Osaka Prefecture, Japan
- Shan, Chuchu, Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu, China
- Liu, Zihui, Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu, China
- Zhou, Xiqiao, Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu, China
- Yu, Jiangyi, Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu, China
Background
Diabetic kidney disease (DKD) progression is driven by 'metabolic memory', where early hyperglycemic injury leads to persistent cellular dysfunction. O-GlcNAcylation plays a key role by activating HIF-1α, impairing fatty acid oxidation (FAO), and promoting fibrosis. Using LC-MS, we profiled the active flavonoids of Abelmoschus manihot (TFA). RNAseq and molecular docking identified glycosylation-related pathways as potential TFA targets. OGT-mediated glycosylation emerged as a pivotal node in this network. This study aimed to elucidate how TFA modulates the O-GlcNAc–HIF-1α–FAO axis to alleviate DKD.
Methods
A db/db mouse model was treated with TFA (97.5–390 mg/kg/day) for 14 weeks. HK-2 cells under high glucose were used for in vitro assays. RNAseq guided downstream validation. O-GlcNAc levels were visualized using HaloTag probes. HIF-1α was modulated via LV. ChIP-qPCR evaluated HIF-1α–CPT1A interaction. Mitochondrial function was assessed by TEM, JC-1, Seahorse, and 14C-palmitate oxidation (Figure attached).
Results
TFA suppressed O-GlcNAcylation/HIF-1α axis and restored FAO.TEM and JC-1 staining showed improved mitochondrial integrity. Seahorse and 14C oxidation assays confirmed FAO recovery, while JC-1 staining revealed restored mitochondrial membrane potential. SPR/ITS validated TFA–OGT interaction. ChIP-qPCR revealed reduced HIF-1α binding to the CPT1A promoter. These effects aligned with reduced fibrosis markers and improved renal metabolism (Figure attached).
Conclusion
TFA alleviates DKD by targeting the O-GlcNAc–HIF-1α–FAO pathway. The integrative evidence supports its druggability and clinical translation potential. These findings establish a rationale for developing TFA into a standardized botanical drug for metabolic complications.
Funding
- Government Support – Non-U.S.