Gallic Acid Alleviates Diabetic Glomerulopathy in Diabetic Mice through Suppression of p47phox and TGF-β1

Pimsiri  Buahombura; Panitta  Wongyai; Kitsada  Sertjantuk; Weerapon Sanggartit

Authors

Pimsiri Buahombura Department of Physiology, Faculty of Medicine, Khon Kaen University, Thailand https://orcid.org/0009-0003-7372-6128
Panitta Wongyai Department of Physiology, Faculty of Medicine, Khon Kaen University, Thailand https://orcid.org/0009-0000-4803-1824
Kitsada Sertjantuk Department of Physiology, Faculty of Medicine, Khon Kaen University, Thailand https://orcid.org/0009-0009-6711-5914
Weerapon Sanggartit Department of Physiology, Faculty of Medicine, Khon Kaen University, Thailand https://orcid.org/0000-0002-5058-2294

Keywords:

gallic acid, diabetic glomerulopathy, , type 2 diabetic mice, oxidative stress

Abstract

Objective This study aims to evaluate whether gallic acid (GA) alleviates diabetic glomerulopathy in a type 2 diabetic mouse model.

Methods ICR mice were fed a high-fat diet (60% fat) and providing a 25% (w/v) fructose solution for 10 weeks and given multiple intraperitoneal injections of streptozotocin (STZ) (35 mg/kg) to induce type 2 diabetes (T2D) and kidney injury. After diabetes onset, mice were treated with GA at 30 or 60 mg/kg/day for four weeks. Fasting
glucose levels, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), renal malondialdehyde (MDA) levels, renal superoxide anion radicals (O₂^•–) formation, glomerular histology, and the expression of p47phox, a key regulator of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and transforming growth factor beta 1 (TGF-β1), were assessed.

Results Diabetic mice exhibited marked hyperglycemia, increased HOMA-IR, and elevated renal oxidative stress, as demonstrated by higher MDA levels, enhanced O₂^•–, and increased p47phox expression (p < 0.05 vs. controls). Histological analysis showed glomerular hypertrophy, enlarged glomerular volume, expanded Bowman’s space, thickening of the glomerular basement membrane, and raised TGF-β expression (p < 0.05 vs. controls). Notably, GA treatment significantly reduced these pathological changes, with the 60 mg/kg/day dose being more effective than the 30 mg/kg/day dose.

Conclusion GA effectively reduces oxidative stress and mitigates structural kidney alterations in a diabetic mouse model, highlighting its potential as an adjunct therapy for diabetes-induced kidney injury.

Keywords gallic acid, diabetic glomerulopathy, type 2 diabetic mice, oxidative stress

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