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

Abstract

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 IC50 values of 15 ± 0.288, 0.92 ± 0.011 and 2.1 ± 0.057 μM 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. © 2009 Elsevier Ireland Ltd. All rights reserved.