title: Enzymatic modification enhances the protective activity of citrus flavonoids against alcohol-induced liver disease.
abstract: Alcoholic liver disease (ALD) can be developed by a prolonged or large intake of alcohol in a short period of time. ALD is considered as a leading cause for a liver injury in modern dietary life. This study was aimed to investigate the effects of orally administrated citrus flavonoids (CFs) and their enzymatically modified ones (EM-CFs) to prevent ALD. Hesperidin and narirutin were extracted from peels of Citrus unshiu by ultra-sonication and purified further. These CFs were modified enzymatically through glycosylation and de-rhamnosylation by the actions of cyclodextrin glucanotransferase (CGTase) and hesperidinase, respectively. CFs and EM-CFs were fed to ICR mouse along with ethanol for 8 weeks, and changes in lipid contents, lipid peroxidation, GSH, antioxidant enzymes activity and proinflammatory cytokines in hepatic tissues were observed. Administration of CFs and EM-CFs along with alcohol significantly suppressed increases in prognostic parameters of a hepatocellular injury. Especially, EM-CFs fed groups maintained malondialdehyde, GSH levels and catalase activity in hepatic tissues close to those of the normal diet fed group. Abrupt increases in proinflammatory cytokines such as IκB-α, TNF-α, IL-1β and IL-6 in hepatocytes due to a chronic alcohol uptake were significantly suppressed by co-administration of EM-CFs. These results indicate that although the administration of CFs can alleviate ALD through preventing excessive lipid formation, protecting the antioxidant system and suppressing induction of inflammation in hepatocytes, their effectiveness can be further improved by glycosylation and de-rhamnosylation.
authors.affiliation: Functional Materials Research Group, Korea Food Research Institute, Gyeonggi 463-746, Republic of Korea.
authors.forename: Ho-Young
authors.initials: HY
authors.lastname: Park
authors.forename: Hee-Don
authors.initials: HD
authors.lastname: Choi
authors.forename: Hyojin
authors.initials: H
authors.lastname: Eom
authors.forename: Inwook
authors.initials: I
authors.lastname: Choi
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry; D002957:Citrus / Q000737:chemistry*; D005419:Flavonoids / Q000008:administration & dosage* / Q000737:chemistry; D005656:Fungal Proteins / Q000737:chemistry; D005964:Glucosyltransferases / Q000737:chemistry; D005978:Glutathione / Q000378:metabolism; D006026:Glycoside Hydrolases / Q000737:chemistry; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008108:Liver Diseases, Alcoholic / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D015394:Molecular Structure; D010407:Penicillium / Q000201:enzymology; D020011:Protective Agents / Q000008:administration & dosage* / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D046968:Thermoanaerobacter / Q000201:enzymology
chemical_list: D001426:Bacterial Proteins; D005419:Flavonoids; D005656:Fungal Proteins; D020011:Protective Agents; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D005964:Glucosyltransferases; C019963:cyclomaltodextrin glucanotransferase; D006026:Glycoside Hydrolases; C023307:hesperidinase; D005978:Glutathione