Oleanolic Acid Attenuates Renal Fibrosis through TGF-β/Smad Pathway in a Rat Model of Unilateral Ureteral Obstruction

Abstract

Renal fibrosis is a common final pathological process in the progression of kidney disease. Oleanolic acid is a bioactive pentacyclic triterpenoid and is widely found in medicinal herbs around the world. In this study, we explored the effect of oleanolic acid on renal fibrosis and the underlying molecular mechanisms by using a rat model of unilateral ureteral obstruction (UUO). Male Sprague-Dawley rats were orally administered with oleanolic acid (6 mg/kg/d) or vehicle (olive oil) for 21 days after the UUO surgery. Upon termination, urine and blood were collected for renal function analysis, and kidneys were harvested for pathological analysis by using hematoxylin-eosin and Masson trichrome staining. Changes of extracellular matrix mRNA expressions and TGF-β/Smad signaling in the kidneys were also determined. As a result, oleanolic acid significantly reduced the kidney index, the level of serum creatinine and blood urea nitrogen, and the urinary level of microalbumin, α1-microglobulin, and N-acetyl-β-glucosaminidase. Masson trichrome staining showed significantly less collagen deposition in the UUO rats with oleanolic acid treatment. Diminished mRNA expressions of collagen I, collagen III, fibronectin, and α-SMA in the kidney tissues were observed after the treatment. Oleanolic acid led to decreased protein expressions of TGF-β, TGF-β receptor I, and TGF-β receptor II, as well as the phosphorylation of Smad2. Our current study suggested that oleanolic acid could be a complementary and alternative therapy for renal fibrosis potentially by targeting the TGF-β/Smad pathway.