Potential Renoprotective Effects of <i>Physalis angulata</i> L. Active Fraction on Podocytopathy, Inflammation, Tubular Injury, and Fibrosis in a Diabetic Nephropathy Rat Model

Diabetic nephropathy (DN), a major complication of diabetes mellitus, is driven by chronic hyperglycemia that induces podocyte injury, inflammation, and oxidative stress, leading to tubular damage and renal fibrosis. Physalis angulata L. (PA) is a medicinal plant with antidiabetic, vasoprotective, antioxidative, and anti-inflammatory activities. This study investigated the effects of the PA active fraction on DN-related renal alterations, particularly podocytopathy, glomerulosclerosis, tubular injury, and fibrosis. Male Wistar rats (200–250 g) were induced with diabetes using streptozotocin (60 mg/kg, i.p.) and divided into control, diabetic, and PA-treated diabetic groups receiving 8.5, 34, or 136 mg/kg of the PA active fraction. Blood glucose was monitored biweekly, while 24-h urinary parameters and creatinine clearance were assessed to evaluate renal function. Renal injury and fibrosis were examined using periodic acid-Schiff and Sirius Red staining. Antioxidative, inflammatory, podocyte, and epithelial-mesenchymal transition, fibrotic markers were analyzed by polymerase chain reaction. Myofibroblast activation was evaluated by immunohistochemistry and Western blot. PA treatment did not significantly affect glycemia, microalbuminuria, or creatinine clearance, but reduced urine albumin-to-creatinine ratio, decreased the expression of transforming growth factor-beta (TGF-β), vimentin, and tumor necrosis factor-alpha, increased nephrin and superoxide dismutase 1/2 expression, and reduced alpha-smooth muscle actin and platelet-derived growth factor receptor beta expression. Histological analysis also showed lower glomerulosclerosis and reduced interstitial fibroblast/myofibroblast expansion in PA-treated diabetic rats. Taken together, the PA active fraction showed potential renoprotective effects against DN-related histological and molecular alterations, while definitive improvement in renal function and direct TGF-β/Smad pathway inhibition remain to be demonstrated in future studies.