Metabolite profiling of polyphenols in a Terminalia chebula Retzius ayurvedic decoction and evaluation of its chemopreventive activity

Ethnopharmacological relevance: The decoction of Terminalia chebula fruit is an ayurvedic remedy whose prolonged or aladministration is prized as a generic intestinal and hepatic detoxifying agent. Its administration is suggested also under the perspective of a reduced risk of cancer, metabolic and cardiovascular diseases. Aim of the study: To evaluate the phytochemical profile and the chemopreventive potential of Terminalia chebula fruit decoction prepared according to the ayurvedic decoction recipe. Materials and methods: The quali-and quantitative metabolite profiling o fpolyphenols was obtained using HPLC–UV/DAD and HPLC-ESI-MS. The crude decoction and purified compounds were tested for their capability to interact with the EphA2-ephrin-A1 system and for their antimutagenic properties against dietary and environmental mutagens (AA, 2-NF, NaN3, and heterocyclic amines IQ, MeIQ, MeIQx, Glu-P1,Glu-P2) in the Ames–Salmonella/microsome assay, with and without enzymatic induction. Results: The decoction was found to contain 3,4,6-tri-O-galloyl-D-glucose (55.87 mg/g), chebulic acid (54.03 mg/g), β-punicalagin (41.25mg/g), corilagin (40.31mg/g), α-punicalagin (35.55 mg/g), chebulagic acid (29.09 mg/g), gallic acid (27.96 mg/g), 1,3,4,6-tri-O-galloyl-β-D-glucose (24.25 mg/g), chebulinic acid (20.23 mg/g), 1,2,3,4,6-penta-O-galloyl-D-glucose (13.53 mg/g), ellagic acid (8.00 mg/g), 1,6-di-O-galloyl-D-glucose (4.16 mg/g). An inhibitory effect was recorded in both Salmonella typhimurium TA98 and TA100 strains against the mutagenic activity of heterocyclic amines (22–61%), promutagenAA (91–97%) and directly actingmutagen 2-NF (52%) with but not against NaN3 (7%). Galloyl derivatives allowed an inhibition of mutagenicity induced by MeIQ above 80% at 0.01mol/plate. Both decoction and purified compounds were able to modulate the EphA2-ephrin A1 system,suggesting a potential multiple chemopreventive mechanism. Conclusions: The traditional ayurvedic decoction of Terminalia chebula may harbour a potential as a safe and low-costchemopreventive agent at the intestinal level, if administered according to the ayurvedic specifications. Moreover,its recourse may enhance the presence of some polyphenolic constituents.