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.
Highlights
Erefore, screening and validating chemical reagents or plant natural products targeting profibrotic TGF-β/Smad signaling might be an effective strategy to alleviate the progression of kidney fibrosis [9]
We explored the efficacy of oleanolic acid in a ureteral obstruction (UUO) rat model and identified the critical role of the TGF-β/Smad pathway mediating the protective efficacy of oleanolic acid
Antibodies including anti-TGF-β, anti-TGF-β receptor I (TβRI), anti-TGF-β receptor II (TβRII), antiphosphorylated Smad2, anti-β-actin, and horseradish peroxidase (HRP)-labeled goat anti-rabbit or anti-mouse IgG were purchased from Cell Signaling Technology (Danvers, MA)
Summary
Erefore, screening and validating chemical reagents or plant natural products targeting profibrotic TGF-β/Smad signaling might be an effective strategy to alleviate the progression of kidney fibrosis [9]. Oleanolic acid is a natural triterpenoid in plant kingdom, medicinal herbs, and is an integral part of the human diet. Several pharmacological attributes of oleanolic acid, such as antiviral, antiinflammatory, antiangiogenic, antiapoptotic, and antitumor activities, have been reported in both in vitro and in vivo researches [10, 11]. By employing unilateral ureteral obstruction (UUO) and nephrectomy models, oleanolic acid was shown to attenuate renal fibrosis in one previous study [12], but the underlying mechanism was remained unknown. We explored the efficacy of oleanolic acid in a UUO rat model and identified the critical role of the TGF-β/Smad pathway mediating the protective efficacy of oleanolic acid
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