Gambogic Acid Mitigates Nephropathy by Inhibiting Oxidative Stressand Inflammation in Diabetic Rats

Document Type : Original Article

Authors
Ruttiya Thongrung 1
Sarawut Lapmanee 2
Penjai Thongnuanjan Bray 3
Patlada Suthamwong 4
Suwaporn Deandee 1
Kanjana Pangjit 1 , 5
Chaowalit Yuajit 1 , 5
1 College of Medicine and Public Health, Ubon Ratchathani University, Warin Chamrap, Ubon Ratchathani, 34190 Thailand.
2 Division of Physiology, Chulabhorn International College of Medicine, Thammasat University, Khlong Luang, Pathum Thani, 12120 Thailand.
3 Toxicology Graduate Program, Multidisciplinary Unit, Faculty of Science, Mahidol University, Bangkok, 10400 Thailand.
4 Department of Agronomy, Faculty of Agriculture, Ubon Ratchathani University, Warin Chamrap, Ubon Ratchathani, 34190 Thailand.
5 Research Group for Biomedical Research and Innovative Development (RG-BRID), College of Medicine and Public Health, Ubon Ratchathani University, Warin Chamrap, Ubon Ratcha.thani, 34190 Thailand.
10.22088/IJMCM.BUMS.14.1.448
Abstract
Diabetic nephropathy is a leading cause of end-stage renal disease globally, with limited treatment
options to prevent its progression. Gambogic acid (GA), a xanthone isolated from Garcinia hanburyi,
has shown notable anti-oxidative, anti-inflammatory, and anti-proliferative properties. This study
aimed to assess GA’s renoprotective effects in a model of diabetic nephropathy mediated by low dose
streptozotocin (STZ) combined with a high-fat diet, focusing on its potential to reduce oxidative stress
and inflammation. Control-treated vehicle and STZ/high-fat diet-mediated diabetic rats were
administered either the vehicle or 3 or 6 mg/kg of GA to assess its effects on renal inflammation,
fibrosis, and oxidative stress. Renal histological changes were assessed, and markers for inflammation
and oxidative stress, including I-κBα, p-p38/MAPK, and p-p65NF-κB pathways, were measured to
explore the mechanisms of GA. Diabetic rats showed significant renal dysfunction, structural damage,
and increased inflammation and fibrosis. Treatment with GA markedly improved renal structure and
function. GA also reduced oxidative stress, increased I-κBα expression, and inhibited key signaling
pathways, specifically p-p38/MAPK and p-p65NF-κB, involved in cellular inflammation. GA exhibits
promising renoprotective effects in diabetic nephropathy by reducing oxidative stress and
inflammation, supporting its potential as a natural therapeutic agent for diabetic renal disease.
Keywords
Gambogic acid, Cell inflammation, Diabetic rat, p38/MAPK, NF-κB