title: Anti-apoptotic and anti-glycative effects of asiatic acid in the brain of D-galactose treated mice.
abstract: Protection of asiatic acid (AA) in mice brain against D-galactose (DG) induced aging was examined. AA at 5, 10 or 20 mg kg(-1) per day was supplied to DG treated mice for 8 weeks. AA intake at 10 or 20 mg kg(-1) per day increased its deposit in brain. DG treatment increased Bax, cleaved caspase-3 protein expression and decreased Bcl-2 expression. AA intake at 10 and 20 mg kg(-1) per day declined Bax, cleaved caspase-3 expression, and retained Bcl-2 expression. DG treatment decreased brain glutathione content and glutathione peroxidase activity; increased brain reactive oxygen species and protein carbonyl levels, and enhanced NAPDH oxidase expression. AA intake at test doses reversed these changes. DG treatment up-regulated the expression of advanced glycation end product (AGE), carboxymethyllysine, receptor of AGE (RAGE), mitogen-activated protein kinases and CD11b as well as increasing the interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha release in the brain. AA intake at 5, 10 and 20 mg kg(-1) per day lowered AGE and carboxymethyllysine expression, and at 10 and 20 mg kg(-1) per day reduced RAGE production. AA intake dose-dependently suppressed p-p38 expression and lowered IL-6 and TNF-alpha levels, and at 10 and 20 mg kg(-1) per day down-regulated p-JNK and CD11b expression. DG treatment declined brain-derived neurotropic factor (BDNF) expression and raised glial fibrillary acidic protein (GFAP) expression. AA intake at 20 mg kg(-1) per day retained BDNF expression and at 10 and 20 mg kg(-1) per day reduced GFAP expression. These findings indicated that the supplement of asiatic acid might be beneficial to the prevention or alleviation of brain aging.
authors.affiliation: School of Health Diet and Industry Management, Chung Shan Medical University, Taichung City, Taiwan.
authors.forename: Pei-chun
authors.initials: PC
authors.lastname: Chao
authors.forename: Mei-chin
authors.initials: MC
authors.lastname: Yin
authors.forename: Mei-chin
authors.initials: MC
authors.lastname: Mong
mesh_terms: D000375:Aging / Q000187:drug effects*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005690:Galactose / Q000009:adverse effects*; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008239:Lysine / Q000031:analogs & derivatives / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D053978:Pentacyclic Triterpenes / Q000494:pharmacology*; D050050:Protein Carbonylation; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: C494827:Bax protein, mouse; D005904:Glial Fibrillary Acidic Protein; D017127:Glycation End Products, Advanced; D015850:Interleukin-6; D053978:Pentacyclic Triterpenes; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; C048496:N(6)-carboxymethyllysine; C017032:asiatic acid; D005979:Glutathione Peroxidase; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C505409:Casp3 protein, mouse; D053148:Caspase 3; D005978:Glutathione; D008239:Lysine; D005690:Galactose