Novel glycoside from Wedelia calendulacea inhibits diethyl nitrosamine-induced renal cancer via downregulating the COX-2 and PEG2 through nuclear factor-κB pathway

Inflammopharmacology. 2017 Feb;25(1):159-175. doi: 10.1007/s10787-017-0310-y. Epub 2017 Feb 2.

Abstract

A new compound derivative of glycoside 19-α-hydroxy-ursolic acid glucoside (19-α-hydroxyurs-12(13)-ene-28-oic acid-3-O-β-D-glucopyranoside (HEG) was isolated from whole plant of Wedelia calendulacea (Compositae). The structure was elucidated and established by standard spectroscopy approaches. Diethylnitrosamine (DEN) (200 mg/kg) and ferric nitrilotriacetate (Fe-NTA) (9 mg/kg) were used for induction of renal cell carcinoma (RCC) in the rats. The rats were further divided into different groups and were treated with HEG doses for 22 weeks. Anti-cancer effect in RCC by HEG was dose dependent to restrict the macroscopical changes as compared to DEN + Fe-NTA-control animals. Significant alteration in biochemical parameters and dose-dependent alleviation in Phase I and Phase II antioxidant enzymes were responsible for its chemo-protective nature. HEG in dose-dependent manner was significant to alter the elevated levels of pro-inflammatory cytokines and inflammatory mediators during RCC. The histopathological changes were observed in the HEG pre-treated group, which was proof for its safety concern as far as its toxicity is concerned. The isolated compound HEG can impart momentous chemo-protection against experimental RCC by suppressing the cyclooxygenase (COX-2) and prostaglandin E2 (PGE2) expression via nuclear factor-kappa B (NF-κB) pathway.

Keywords: Diethylnitrosamine; Ferric nitrilotriacetate; Inflammation; Pro-inflammatory cytokines; Reactive oxygen species.

MeSH terms

  • Animals
  • Cyclooxygenase 2 / metabolism*
  • Diethylnitrosamine / toxicity
  • Dinoprostone / antagonists & inhibitors
  • Dinoprostone / metabolism*
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects
  • Down-Regulation / physiology
  • Glycosides / isolation & purification
  • Glycosides / pharmacology
  • Glycosides / therapeutic use*
  • Kidney Neoplasms / chemically induced
  • Kidney Neoplasms / metabolism*
  • Kidney Neoplasms / prevention & control
  • Male
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism*
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • Rats
  • Rats, Wistar
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Wedelia*

Substances

  • Glycosides
  • NF-kappa B
  • Plant Extracts
  • Diethylnitrosamine
  • Cyclooxygenase 2
  • Dinoprostone