title: In Vitro Bioaccessibility, Human Gut Microbiota Metabolites and Hepatoprotective Potential of Chebulic Ellagitannins: A Case of Padma Hepaten® Formulation.
abstract: Chebulic ellagitannins (ChET) are plant-derived polyphenols containing chebulic acid subunits, possessing a wide spectrum of biological activities that might contribute to health benefits in humans. The herbal formulation Padma Hepaten containing ChETs as the main phenolics, is used as a hepatoprotective remedy. In the present study, an in vitro dynamic model simulating gastrointestinal digestion, including dialysability, was applied to estimate the bioaccessibility of the main phenolics of Padma Hepaten. Results indicated that phenolic release was mainly achieved during the gastric phase (recovery 59.38%-97.04%), with a slight further release during intestinal digestion. Dialysis experiments showed that dialysable phenolics were 64.11% and 22.93%-26.05% of their native concentrations, respectively, for gallic acid/simple gallate esters and ellagitanins/ellagic acid, in contrast to 20.67% and 28.37%-55.35% for the same groups in the non-dialyzed part of the intestinal media. Investigation of human gut microbiota metabolites of Padma Hepaten and pure ChETs (chebulinic, chebulagic acids) established the formation of bioactive urolithins (A, B, C, D, M5). The fact of urolithin formation during microbial transformation from ChETs and ChET-containing plant material was revealed for the first time. Evaluation of the protective effect of ChETs colonic metabolites and urolithins on tert-butyl hydroperoxide (t-BHP)-induced oxidative injury in cultured rat primary hepatocytes demonstrated their significant reversion of the t-BHP-induced cell cytotoxicity, malonic dialdehyde production and lactate dehydrogenase leakage. The most potent compound was urolithin C with close values of hepatoprotection to gallic acid. The data obtained indicate that in the case of Padma Hepaten, we speculate that urolithins have the potential to play a role in the hepatic prevention against oxidative damage.
authors.affiliation: Laboratory of Medical and Biological Research, Institute of General and Experimental Biology, Siberian Division, Russian Academy of Science, Sakh'yanovoy Street 6, Ulan-Ude 670-047, Russia. olennikovdn@mail.ru.
authors.forename: Daniil N
authors.initials: DN
authors.lastname: Olennikov
authors.affiliation: Laboratory of Medical and Biological Research, Institute of General and Experimental Biology, Siberian Division, Russian Academy of Science, Sakh'yanovoy Street 6, Ulan-Ude 670-047, Russia. ninkk@mail.ru.
authors.forename: Nina I
authors.initials: NI
authors.lastname: Kashchenko
authors.affiliation: Department of Biochemistry and Biotechnology, North-Eastern Federal University, 58 Belinsky Street, Yakutsk 677-027, Russian. hofnung@mail.ru.
authors.forename: Nadezhda K
authors.initials: NK
authors.lastname: Chirikova
mesh_terms: D000818:Animals; D001578:Benzopyrans / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001682:Biological Availability; D002470:Cell Survival; D002478:Cells, Cultured; D003374:Coumarins / Q000008:administration & dosage / Q000378:metabolism; D004063:Digestion; D000069196:Gastrointestinal Microbiome / Q000502:physiology*; D041981:Gastrointestinal Tract / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects; D006801:Humans; D047348:Hydrolyzable Tannins / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D008107:Liver Diseases / Q000517:prevention & control*; D010084:Oxidation-Reduction; D010936:Plant Extracts / Q000032:analysis / Q000378:metabolism / Q000493:pharmacokinetics*; D051381:Rats; D020122:tert-Butylhydroperoxide / Q000633:toxicity
chemical_list: D001578:Benzopyrans; D003374:Coumarins; D047348:Hydrolyzable Tannins; C543472:Padma Hepaten; D010936:Plant Extracts; C572649:chebulic acid; C000595064:urolithin B; C588364:urolithin C; C000595063:urolithin D; C026423:3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one; D020122:tert-Butylhydroperoxide
keywords: Bras Bu; Padma Hepaten; Tibetan medicine; Triphala; bioaccessibility; chebulic ellagitannins; hepatoprotective activity; human gut microbiota; urolithins