Rosmarinic acid from Perillae Herba produces an antidepressant-like effect in mice through cell proliferation in the hippocampus.
Rosmarinic acid (RA) is one of major polyphenolic ingredients of Perillae Herba (a leaf of Perilla frutescens), and has an antidepressant-like property in animal models of depression. However, the mechanism(s) underlying this activity are unknown. Recent studies have reported that regulation of hippocampal neurogenesis is associated with the pathogenesis of depression. To elucidate the mode of action of RA-induced antidepressant-like activity, proliferative effect of RA on newborn cells in the dentate gyrus of mouse hippocampus was investigated using immunohistochemical analysis with bromodeoxyuridine (BrdU), a marker of proliferating cells. RA treatment for 7 or 14 d significantly increased in the number of BrdU-positive cells in inverse correlation with significant reductions in immobility in a forced swimming test, an animal model of depression, in a dose-dependent manner. However, locomotor activities were not affected. These results suggest that RA produces an antidepressant-like effect at least in part via the proliferation of newborn cells in the dentate gyrus of the hippocampus.
Ito
Naoki
N
Department of Clinical Research, Oriental Medicine Research Center, Kitasato University, Tokyo, Japan.
Yabe
Takeshi
T
Gamo
Yuji
Y
Nagai
Takayuki
T
Oikawa
Tetsuro
T
Yamada
Haruki
H
Hanawa
Toshihiko
T
D000818:Animals; D000928:Antidepressive Agents; D000963:Antimetabolites; D001973:Bromodeoxyuridine; D049109:Cell Proliferation / Q000187:drug effects*; D002934:Cinnamates / Q000302:isolation & purification / Q000494:pharmacology*; D053630:Depsides / Q000302:isolation & purification / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000737:chemistry / Q000378:metabolism; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism; D064231:Nestin; D009474:Neurons / Q000187:drug effects; D031343:Perilla / Q000737:chemistry*; D018515:Plant Leaves / Q000737:chemistry; D013550:Swimming / Q000523:psychology; D000097123:Rosmarinic Acid
D000928:Antidepressive Agents; D000963:Antimetabolites; D001973:Bromodeoxyuridine; D002934:Cinnamates; D053630:Depsides; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; D064231:Nestin; D000097123:Rosmarinic Acid; C577485:Nes protein, mouse