Chebulagic acid, a COX-LOX dual inhibitor isolated from the fruits of Terminalia chebula Retz., induces apoptosis in COLO-205 cell line

J Ethnopharmacol. 2009 Jul 30;124(3):506-12. doi: 10.1016/j.jep.2009.05.022. Epub 2009 May 28.


Ethnopharmacological relevance: Terminalia chebula has an esteemed origin in Indian mythology; its fruits are used to treat many diseases such as digestive, diabetes, colic pain, chronic cough, sore throat, asthma, etc.

Aim of the study: The water or ethanolic extracts of the fruits were reported to have anti-oxidant, anti-inflammatory, anti-cancer and radio-protector properties. The present study is to isolate and identify the compounds that inhibit COX and 5-LOX, the key enzymes involved in inflammation and carcinogenesis.

Materials and methods: The ethanolic extract of the fruits was fractionated by RP-HPLC and fractions were tested for enzyme inhibition activity against COX and 5-LOX. One of the fractionated compounds showed potent dual inhibition against COX and 5-LOX. It was identified as chebulagic acid by LC-MS, NMR and IR analyses. The chebulagic acid was also tested for anti-proliferative activity.

Results: Chebulagic acid showed potent COX-LOX dual inhibition activity with IC(50) values of 15+/-0.288, 0.92+/-0.011 and 2.1+/-0.057 microM for COX-1, COX-2 and 5-LOX respectively. It also showed anti-proliferative activity against HCT-15, COLO-205, MDA-MB-231, DU-145 and K562 cell lines. Further mechanistic studies on COLO-205 cells revealed induction of apoptosis by chebulagic acid.

Conclusions: Chebulagic acid, a COX-2 and 5-LOX dual inhibitor isolated from the fruits of Terminalia chebula, induces apoptosis in COLO-205 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / pharmacology
  • Apoptosis / drug effects*
  • Arachidonate 5-Lipoxygenase / isolation & purification
  • Benzopyrans / pharmacology*
  • Biphenyl Compounds / chemistry
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Chromatography, High Pressure Liquid
  • Cyclooxygenase 2 Inhibitors / pharmacology
  • Cyclooxygenase Inhibitors / pharmacology*
  • DNA Fragmentation / drug effects
  • Flow Cytometry
  • Free Radical Scavengers / chemistry
  • Free Radicals / chemistry
  • Fruit / chemistry
  • Glucosides / pharmacology*
  • Humans
  • Indicators and Reagents
  • Lipoxygenase Inhibitors / pharmacology*
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Picrates / chemistry
  • Spectrophotometry, Infrared
  • Terminalia / chemistry*


  • Antioxidants
  • Benzopyrans
  • Biphenyl Compounds
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Free Radical Scavengers
  • Free Radicals
  • Glucosides
  • Indicators and Reagents
  • Lipoxygenase Inhibitors
  • Picrates
  • chebulagic acid
  • 1,1-diphenyl-2-picrylhydrazyl
  • Arachidonate 5-Lipoxygenase