chebulagic-acid and 1-1-diphenyl-2-picrylhydrazyl

The aqueous extract of galls from Terminalia chebula Retz. (Combretaceae) was fractionated on Diaion and refractionated on octadecyl silica column. Six phenolic compounds were isolated and identified as gallic acid (1), punicalagin (2), isoterchebulin (3), 1,3,6-tri-O-galloyl-β-D-glucopyranose (4), chebulagic acid (5) and chebulinic acid (6). All of the compounds showed stronger 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and melanin inhibitory activities than ascorbic acid, butylated hydroxytoluene, α-tocopherol, arbutin and kojic acid, the reference compounds. Gallic acid (1) exhibited inhibitory activity against nitric oxide production in lipopolysaccharide-activated macrophages. However, all isolated compounds exhibited less activity than the reference compounds in mushroom tyrosinase inhibition and human tumour cytotoxicity assays. This study has demonstrated that the phenolic compounds isolated from galls of T. chebula might contribute significantly due to their antioxidant and whitening activities.

Topics: Analysis of Variance; Animals; Benzopyrans; Biphenyl Compounds; Cell Line, Tumor; Cell Proliferation; Chemical Fractionation; Free Radical Scavengers; Gallic Acid; Glucosides; Humans; Hydrolyzable Tannins; Melanins; Mice; Molecular Structure; Nitric Oxide; Phenols; Picrates; Plant Extracts; Plant Tumors; Terminalia

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

Topics: Antioxidants; Apoptosis; Arachidonate 5-Lipoxygenase; Benzopyrans; Biphenyl Compounds; Blotting, Western; Cell Line, Tumor; Cell Proliferation; Chromatography, High Pressure Liquid; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; DNA Fragmentation; Flow Cytometry; Free Radical Scavengers; Free Radicals; Fruit; Glucosides; Humans; Indicators and Reagents; Lipoxygenase Inhibitors; Magnetic Resonance Spectroscopy; Mass Spectrometry; Picrates; Spectrophotometry, Infrared; Terminalia