Antidepressant-like activity of a Kampo (Japanese herbal) medicine, Koso-san (Xiang-Su-San), and its mode of action via the hypothalamic-pituitary-adrenal axis.
Koso-san (Xiang-Su-San in Chinese), a Kampo (Japanese herbal) medicine, is used clinically in East Asia for the treatment of depression-like symptoms associated with the initial stage of the common cold, allergic urticaria due to food ingestion, irritable bowel syndrome, chronic fatigue syndrome, insomnia, and autonomic imbalance. However, the antidepressant-like activity of Koso-san has never been evaluated scientifically. In this study, ddY mice subjected to a combination of forced swimming and chronic mild stresses were termed depression-like model mice. The degree of the depression-like state was measured by the animal's duration of immobility using the forced swimming test (FST). Oral administration of Koso-san (1.0 g/kg/body wt./day, 9 days) significantly shortened the duration of immobility of the depression-like model mice in the FST; however, locomotor activity was not affected. Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis plays an important role in the pathophysiology of depression. Levels of corticotropin-releasing hormone mRNA expression in the hypothalamus and proopiomelanocortin mRNA expression in the pituitary were significantly increased, and glucocorticoid receptor protein expression in the hypothalamus paraventricular nucleus was downregulated in the depression-like model mice. However, Koso-san ameliorated these alterations to the normal conditions. The results of this study suggest that Koso-san shows the antidepressant-like effect through suppressing the hyperactivity of the HPA axis in depression-like model mice.
Ito
N
N
Kitasato Institute for Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
Nagai
T
T
Yabe
T
T
Nunome
S
S
Hanawa
T
T
Yamada
H
H
D000818:Animals; D000928:Antidepressive Agents / Q000032:analysis / Q000494:pharmacology*; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000187:drug effects; D003975:Diazepam / Q000494:pharmacology; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D007031:Hypothalamus / Q000187:drug effects; D046353:Immobility Response, Tonic / Q000187:drug effects; D008297:Male; D020835:Medicine, Kampo; D051379:Mice; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects; D010902:Pituitary Gland / Q000187:drug effects; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D011333:Pro-Opiomelanocortin / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects; D011965:Receptors, Glucocorticoid / Q000187:drug effects; D013550:Swimming
D000928:Antidepressive Agents; D004365:Drugs, Chinese Herbal; D006993:Hypnotics and Sedatives; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; C400346:koso-san; D011333:Pro-Opiomelanocortin; D003346:Corticotropin-Releasing Hormone; D003975:Diazepam; D003345:Corticosterone