en Medical Pharmacology Medical Pharmacology Original Article Original Article <p style="text-align: justify;"><span style="font-size:12px;"><span style="font-family:Tahoma;">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&rsquo;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 <span lang="EN-GB">-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.&nbsp;</span>Renal histological changes were assessed, and markers for inflammation and oxidative stress, including I-&kappa;B&alpha;, p-p38/MAPK, and p-p65NF-&kappa;B 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-&kappa;B&alpha; expression, and inhibited key signaling pathways, specifically p-p38/MAPK and p-p65NF-&kappa;B, 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.</span></span><span style="font-size:10pt"><span new="" roman="" style="font-family:" times=""><span lang="EN-GB" style="font-size:12.0pt"></span></span></span></p> Gambogic acid, Cell inflammation, Diabetic rat, p38/MAPK, NF-κB 448 461 http://ijmcmed.org/browse.php?a_code=A-10-8193-1&slc_lang=en&sid=1 Ruttiya Thongrung ruttiya.t@ubu.ac.th 100319475328460033559 0009-0007-4692-8639 No College of Medicine and Public Health, Ubon Ratchathani University, Warin Chamrap, Ubon Ratchathani, 34190 Thailand. Sarawut Lapmanee lapmanee@tu.ac.th 100319475328460033560 100319475328460033560 No Division of Physiology, Chulabhorn International College of Medicine, Thammasat University, Khlong Luang, Pathum Thani, 12120 Thailand. Penjai Thongnuanjan Bray penjai.bray@hotmail.com 100319475328460033561 100319475328460033561 No Toxicology Graduate Program, Multidisciplinary Unit, Faculty of Science, Mahidol University, Bangkok, 10400 Thailand. Patlada Suthamwong patlada.s@ubu.ac.th 100319475328460033562 100319475328460033562 No Department of Agronomy, Faculty of Agriculture, Ubon Ratchathani University, Warin Chamrap, Ubon Ratchathani, 34190 Thailand. Suwaporn Deandee suwaporn.d@ubu.ac.th 100319475328460033563 100319475328460033563 No College of Medicine and Public Health, Ubon Ratchathani University, Warin Chamrap, Ubon Ratchathani, 34190 Thailand Kanjana Pangjit kanjana.pa@ubu.ac.th 100319475328460033564 100319475328460033564 No College of Medicine and Public Health, Ubon Ratchathani University, Warin Chamrap, Ubon Ratchathani, 34190 Thailand. Chaowalit Yuajit chaowalit.y@ubu.ac.th 100319475328460033565 100319475328460033565 Yes College of Medicine and Public Health, Ubon Ratchathani University, Warin Chamrap, Ubon Ratchathani, 34190 Thailand.