Ursolic acid improves survival and attenuates lung injury in septic rats induced by cecal ligation and puncture

J Surg Res. 2015 Apr;194(2):528-536. doi: 10.1016/j.jss.2014.10.027. Epub 2014 Oct 22.

Abstract

Background: Sepsis is characterized as a systemic inflammatory response syndrome during infection, which can result in multiple organ dysfunction and death. Ursolic acid (UA), a pentacyclic triterpene acid, has been reported to have potent anti-inflammatory and antioxidant properties. The aim of this study was to detect the possible protective effects of UA on sepsis-evoked acute lung injury.

Materials and methods: A rat model of sepsis induced by cecal ligation and puncture (CLP) was used. Rats were injected intraperitoneally with UA (10 mg/kg) after CLP, and then the survival was determined twice a day for 4 d. The protective effects of UA on CLP-induced acute lung injury were assayed at 24 h after CLP.

Results: The results revealed that UA treatment markedly improved the survival of septic rats, and attenuated CLP-induced lung injury, including reduction of lung wet/dry weight ratio, infiltration of leukocytes and proteins, myeloperoxidase activity, and malondialdehyde content. In addition, UA significantly decreased the serum levels of tumor necrosis factor-α, interleukin-6, and interleukin-1β, inhibited the expression of inducible nitric oxide synthase and cyclooxygenase-2 in the lung, which are involved in the productions of nitric oxide and prostaglandin E2.

Conclusions: These findings indicate that UA exerts protective effects on CLP-induced septic rats. UA may be a potential therapeutic agent against sepsis.

Keywords: Acute lung injury; Inflammatory mediator; Sepsis; Survival; Ursolic acid.

MeSH terms

  • Acute Lung Injury / etiology
  • Acute Lung Injury / prevention & control*
  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Biomarkers / metabolism*
  • Cyclooxygenase 2 / metabolism
  • Cytokines / blood
  • Dinoprostone / metabolism
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Lung / drug effects
  • Lung / metabolism
  • Male
  • Malondialdehyde / metabolism
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Peroxidase / metabolism
  • Phytotherapy
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • Random Allocation
  • Rats, Sprague-Dawley
  • Sepsis / complications
  • Sepsis / drug therapy*
  • Sepsis / mortality
  • Triterpenes / pharmacology
  • Triterpenes / therapeutic use*
  • Ursolic Acid

Substances

  • Antineoplastic Agents, Phytogenic
  • Biomarkers
  • Cytokines
  • Plant Extracts
  • Triterpenes
  • Nitric Oxide
  • Malondialdehyde
  • Peroxidase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat
  • Cyclooxygenase 2
  • Ptgs2 protein, rat
  • Dinoprostone