The Quinovic Acid Glycosides Purified Fraction from Uncaria tomentosa Protects against Hemorrhagic Cystitis Induced by Cyclophosphamide in Mice

PLoS One. 2015 Jul 8;10(7):e0131882. doi: 10.1371/journal.pone.0131882. eCollection 2015.

Abstract

Uncaria tomentosa is widely used in folk medicine for the treatment of numerous diseases, such as urinary tract disease. Hemorrhagic cystitis (HE) is an inflammatory condition of the bladder associated with the use of anticancer drugs such as cyclophosphamide (CYP). Sodium 2-mercaptoethanesulfonate (Mesna) has been used to prevent the occurrence of HE, although this compound is not effective in established lesions. It has been demonstrated that the purinergic system is involved in several pathophysiological events. Among purinergic receptors, P2X7 deserves attention because it is involved in HE induced by CYP and, therefore, can be considered a therapeutic target. The objective of this study was to investigate the potential therapeutic effect of the quinovic acid glycosides purified fraction (QAPF) from U. tomentosa in the mouse model of CYP-induced HE. Pretreatment with QAPF not only had a protective effect on HE-induced urothelial damage (edema, hemorrhage and bladder wet weight) but was also able to control visceral pain, decrease IL-1β levels and down-regulates P2X7 receptors, most likely by inhibit the neutrophils migration to the bladder. This research clearly demonstrates the promising anti-inflammatory properties of QAPF, supporting its use as complementary therapy. QAPF represents a promising therapeutic option for this pathological condition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal
  • Cat's Claw / chemistry*
  • Cyclophosphamide / adverse effects*
  • Cystitis / chemically induced
  • Cystitis / complications*
  • Cystitis / drug therapy*
  • Cystitis / physiopathology
  • Glycosides / isolation & purification
  • Glycosides / pharmacology
  • Glycosides / therapeutic use*
  • Hemorrhage / chemically induced
  • Hemorrhage / complications
  • Hemorrhage / drug therapy*
  • Hemorrhage / physiopathology
  • Interleukin-1beta / metabolism
  • Male
  • Mice
  • Nociception / drug effects
  • Peroxidase / metabolism
  • Protective Agents / pharmacology
  • Protective Agents / therapeutic use
  • Receptors, Purinergic P2X7 / metabolism
  • Triterpenes / isolation & purification
  • Triterpenes / pharmacology
  • Triterpenes / therapeutic use*
  • Urinary Bladder / drug effects
  • Viscera / drug effects

Substances

  • Glycosides
  • Interleukin-1beta
  • Protective Agents
  • Receptors, Purinergic P2X7
  • Triterpenes
  • Cyclophosphamide
  • quinovic acid
  • Peroxidase

Grants and funding

This study was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Capes), in addition to a FINEP (Financiadora de Estudos e Projetos) research grant “Implantação, Modernização e Qualificação de Estrutura de Pesquisa da PUCRS” (PUCRSINFRA) #01.11.0014-00. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.