Ursolic acid improves diabetic nephropathy via suppression of oxidative stress and inflammation in streptozotocin-induced rats

Biomed Pharmacother. 2018 Sep:105:915-921. doi: 10.1016/j.biopha.2018.06.055. Epub 2018 Jun 19.

Abstract

Inflammation plays a pivotal role in the pathogenesis of diabetic nephropathy (DN). Overexpression of inflammatory chemokine and cytokines is involved in the development of DN. Ursolic acid (UA), a common pentacyclic triterpenoid compound, has been reported to have myriad benefits and medicinal properties. However, its protective effects against renal injury in streptozotocin (STZ)-induced diabetic rats have not been firmly established. In the current report, we investigated whether UA inhibits oxidative stress and inflammation in the kidneys of STZ-induced diabetic rats. Diabetes mellitus (DM) was induced by STZ (40 mg/ kg, i.v.). Animals were randomly divided into control group (normal saline, i.g.), DN group (normal saline, i.g.), DN + UA group (35 mg/kg UA + normal saline, i.g.) and DN + telmisartan group (12 mg/kg telmisartan + normal saline, i.g.). Fasting blood glucose (FBG) levels were monitored at regular intervals. The administration of compounds started at 5th week and lasted for 8 weeks. At the beginning of 13th week, rats were humanely euthanized, KW/BW, BUN, SCr, SOD and MDA were measured. Histopathological changes in renal tissue were observed after hematoxylin-eosin (HE) staining. Furthermore, the expressions of TNF-α, MCP-1 and IL-1β in kidney were determined by immunohistochemistry and western blot. Our results showed that UA significantly lowered the levels of FBG, KW/BW, BUN, SCr and MDA in diabetic rats. Additionally, the SOD activity in UA treated group was higher than that in DN group. Furthermore, renal structural abnormalities and the elevation of TNF-α, MCP-1 and IL-1β expression level were blocked by the administration of UA. In conclusion, our data demonstrate that UA could be well used as a protective agent to counter renal dysfunction - through antioxidant and anti-inflammatory effects.

Keywords: Diabetic nephropathy; Inflammation; Oxidative stress; Ursolic acid.

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetic Nephropathies / chemically induced
  • Diabetic Nephropathies / drug therapy*
  • Diabetic Nephropathies / metabolism
  • Inflammation / chemically induced
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Inflammation Mediators / antagonists & inhibitors*
  • Inflammation Mediators / metabolism
  • Kidney / drug effects
  • Kidney / metabolism
  • Male
  • Oxidative Stress / drug effects*
  • Oxidative Stress / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Streptozocin / toxicity
  • Triterpenes / pharmacology
  • Triterpenes / therapeutic use*
  • Ursolic Acid

Substances

  • Inflammation Mediators
  • Triterpenes
  • Streptozocin