Preventive effects of Daisaikoto on metabolic disorders in spontaneous obese type Ⅱ diabetes mice

取得学位 : 博士（医学）, 学位授与番号 : 医博甲第1832号, 学位授与年月日 : 平成19年3月22日, 学位授与大学 : 金沢大学, 主査教授 : 宮本 謙一, 副査教授 : 金子 周一, 山本

Preventive effects of Daisaikoto on metabolic disorders in spontaneous obese type II diabetes mice

メタボリックシンドローム(MS)は，生活習慣病の基礎病態として特に注目されている症候群の一つである。近年，肥満人口は増加の一途をたどっているが，内臓脂肪の蓄積はMSの病態基盤として最も重要な危険因子であることが報告されている。本研究においては，MS類似病態を発症する肥満性2型糖尿病モデル動物であるTSODマウスを用い，諸代謝性疾病に対する漢方薬大柴胡湯の効果を検討した。肥満が未発症の４週齢TSODマウスおよび代謝性疾病を発症しないTSNOマウスに大柴胡湯を1％および3％混和させた粉末飼料を2ヶ月間自由摂取させた。その結果，普通食摂餌TSODマウスは，試験開始後より普通食摂餌TSNOマウスに比べ著しい肥満および内臓脂肪の蓄積，血糖値，インスリン値，T-Cho値，TG値およびLDL値の上昇，耐糖能異常などを発症し，さらに高血圧および末梢神経障害が認められた。TSODマウスにおいて，大柴胡湯は投与後期より体重増加や内臓脂肪の蓄積等に対して低下作用を与え，さらに，耐糖能異常，血圧の上昇や末梢神経障害を有意に抑制した。以上より，MS諸症状に対する大柴胡湯の有用性が示唆された。 Metabolic syndrome (MS) is one of the syndromes known as an underlying lifestyle-related diseases. Recently, the number of obese people keeps on increasing, and visceral fat accumulation has been reported as the most important risk factor for the development of MS. In this study, the effects of Daisaikoto, a Kampo preparation, on metabolic disorders were investigated using TSOD mice, an animal model of spontaneous obese type II diabetes. Four-week-old TSOD mice that had not yet developed obesity and TSNO mice that do not develop metabolic disorders were given ad libitum powder feed containing Daisaikoto at a concentration of 1% or 3% for 2 months. After 2 months, the control TSOD mice developed various metabolic disorders such as marked obesity and visceral fat accumulation, increase of the blood glucose level, the insulin level, T-Cho level, TG level and LDL level, abnormal glucose tolerance, hypertension and neuropathy as distinct from the control TSNO mice. In the TSOD mice treated with Daisaikoto, the body weight gain and visceral fat accumulation were suppressed, and the abnormal glucose tolerance, elevation of blood pressure and peripheral neuropathy were also significantly suppressed. On the other hand, in TSNO mice, Daisaikoto showed no noteworthy impacts on most parameters. The above results suggested that Daisaikoto would be effective for the prevention against various symptoms of MS

Inhibitory Effects of Polyacetylene Compounds from Panax ginseng on Neurotrophin Receptor-Mediated Hair Growth

Neurotrophins play an important role in the control of the hair growth cycle. Therefore, neurotrophin receptor antagonists have therapeutic potential for the treatment of hair growth disorders. In this study, we investigated the inhibitory effect of Panax ginseng, a medicinal plant commonly used to treat alopecia, on the binding of neurotrophins to their receptors. In addition, we isolated and characterized the bioactive compounds of P. ginseng extracts. P. ginseng hexane extracts strongly inhibited brain-derived neurotrophic factor (BDNF)-TrkB and β-nerve growth factor (β-NGF)-p75 neurotrophin receptor (p75NTR) binding. Furthermore, we identified the following 6 polyacetylene compounds as the bioactive components in P. ginseng hexane extract: panaxynol (1), panaxydol (2), panaxydol chlorohydrin (3), 1,8-heptadecadiene-4,6-diyne-3,10-diol (4), panaxytriol (5), and dihydropanaxacol (6). In particular, compounds 4, 5, and 6 significantly inhibited BDNF-TrkB binding in a dose-dependent manner. To identify the structural component mediating the inhibitory effect, we investigated the effects of the hydroxyl moiety in these compounds. We found that the inhibitory effect of panaxytriol (5) was strong, whereas the inhibitory effect of Ac-panaxytriol (7) was relatively weak. Our findings suggest that P. ginseng-derived polyacetylenes with a hydroxyl moiety might provide therapeutic benefits to patients with hair growth disorders such as alopecia by inhibiting the binding of neurotrophins to their receptors. Although saponins have been proposed to be the primary mediators of the effects of P. ginseng on hair growth, this study revealed that polyacetylene compounds exert similar effects

A change in bathing style may improve mental fitness

Frequent bathtub bathing (BB) improves the mental health of middle-aged and older Japanese in-dividuals. This study investigated the chronic mental health effects of BB, maintaining warmth using an insulating sheet and sleeping bag after bathtub bathing (BBW), and bathtub bathing with herbal extracts (BBH) in healthy young adults. The study involved healthy young adults who ha-bitually showered, as opposed to bathing. In the first experiment, 18 participants were randomly assigned to either the BB or BBW groups for 14 consecutive nights. After a 2-week washout period, the participants were asked to switch their bathing styles (a cross-over design). In the second ex-periment, 20 participants were randomly assigned to the BB or BBH group. The herbal extracts for the BBH group contained angelicae radix, aurantii nobilis pericarpium, chamomile, and zingiberis rhizoma. After a 2-week washout period, these participants also switched to the other bathing style. The participants’ mental conditions pre- and post-intervention were assessed using the Pro-file of Mood States-Brief Form questionnaire, Japanese version, and were statistically analyzed. The participants’ Anger-Hostility score converged to an average (50 points) in the post-BBW and post-BBH participants, and there were no significant differences in BB. The Confusion change rate was significantly different in the first experiment (BB versus BBW). The Depression-Dejection and Fatigue change rates were significantly different in the second experiment (BB versus BBH). Our findings suggest that changing bathing style from showering to BBW or BBH improves the POMS Anger-Hostility scores of healthy young adults