古来より婦人科領域で用いられている処方の 1 つ 「当帰芍薬散 （TS）」 は， 治療薬として評価を得ているが， 体内の標的など未解明な点が数多く残されている。 そこで TS のターゲット， E2 との作用差， リスクの有無について検証した。 まずTS はコレステロールから女性ホルモンが生成される過程にある StAR をターゲットとすることが明らかとなった。 次に TS の成分が直接エストロゲン受容体 （ER） へ作用するか否かを調べたところ， E2 には作用が認められたが， TS は作用を示さなかった。 一方視床下部でホルモン生合成に重要なPACAP は， TS を投与した OVX， 下垂体摘出 （HPX） ラット視床下部において mRNA 発現量促進が認められたが， E2投与ラットでは発現促進が見られなかった。 さらに HPX ラット卵巣では， E2+P4 より TS の方が強い卵胞発達促進を認めた。 最後に， 臨床で婦人科癌マーカーとして用いられる ER, PR の発現を OVX ラット子宮で観察したところ， TS 投与による両者の発現は認められなかったが， E2 投与では両者の顕著な発現が認められた。 以上の結果より， TS は StAR, PACAP をターゲットとし， E2 とは異なる経路で作用することが明らかとなった。 さらに TS は乳癌・子宮癌に対するリスクの低い処方であることも証明された。

抄録全体を表示

Natural products effective on in vitro calcium phosphate precipitation are classified into two groups, i.e. stimulators and inhibitors. Stimulators were found to be gelatin, agarose, starch and plant oil, while inhibitors were Kampo medicines, herbs, polyphenols, gelatin-soluble tannins, tannin-saliva complex, teas and honeybee products. These are possible sources of oral calcification agents (remineralization and anticalculus), which may be effective with few or no side effects.

抄録全体を表示

The dried roots of Angelica acutiloba (Yamato-toki in Japanese) are an important crude drug component of traditional Chinese prescriptions used to improve menopausal symptoms. The improvement in blood circulation by Yamato-toki was revealed by the oral administration of (Z)-ligustilide, a major ingredient of Yamato-toki, which showed significant shortening of euglobulin lysis time. This is the first report to reveal fibrinolytic activity of (Z)-ligustilide. Furthermore, ferulic acid and adenosine were two active ingredients with antiplatelet, antierythrocyte aggregation, and fibrinolytic activities. A. acutiloba roots are processed into Yamato-toki by Yumomi treatment, which is a traditional processing procedure involving blanching in hot water. Methanol extracts of A. acutiloba roots with or without Yumomi treatment showed similar dose-dependent and significant antierythrocyte aggregation activities. There was no discernable difference in the (Z)-ligustilide, ferulic acid, and adenosine contents between A. acutiloba roots with or without Yumomi treatment. Sugar analysis results indicated that Yumomi processing increases the monosaccharide content, which enhances sweetness. The results showed that (Z)-ligustilide was a fibrinolytic activator. However, there was no enhancement of biological activity following Yumomi treatment. Thus, Yumomi is utilized mainly to improve appearance and quality, as evaluated by sensory tests, and to enhance sweetness and brownish color rather than raising the contents of ingredients.

抄録全体を表示

Traditional medicines, including Chinese prescriptions, have attracted much attention due to their extensive and unique biological activities without toxic and/or side effects. We evaluated the effects of hachimijiogan and identified its active compound ameliorating diabetic renal damage using a type 1 diabetic nephropathy rat model which underwent a subtotal nephrectomy plus streptozotocin injection, and Otsuka Long-Evans Tokushima Fatty rats as a model of human type 2 diabetes and its complications. Hachimijiogan treatment decreased the levels of glucose-induced oxidative stress, advanced glycation endproduct formation, renal protein overexpression, and proteinuria. These results indicate that hachimijiogan is a potential therapeutic agent in the development of type 1 and 2 diabetic nephropathy. Furthermore, according to the identification of the active component of the crude drug, Corni Fructus, 7-O-galloyl-D-sedoheptulose is considered to be the most important contributor to prevent and/or delay the onset of diabetic renal damage. 7-O-Galloyl-D-sedoheptulose is expected to provide a novel therapeutic strategy against the development of diabetic nephropathy.

抄録全体を表示

Chronic glomerulonephritis and nephrosclerosis are major causes of the renal failure after diabetic nephropathy. Steroids and immunosuppressants are often used to the patients with active type of glomerulonephritis; however, long term-use of these drugs occasionally induces undesirable side effects. It is generally accepted that angiotensin converting enzyme inhibitors and angiotensin II receptor blockers are beneficial to protect renal injury in CKD. The availability of recent evaluation methods in basic study and clinical practice has revealed the efficacy and usefulness of traditional Kampo medicines for CKD. The Kampo formula saireito ameliorated proteinuria, mesangial proloferation, and extracellular matrix accumulation in experimental rat mesangioproliferative glomerulonephritis (MsPGN). Perilla suppressed proteinuria, proliferation of glomerular cells, serum levels of IgA, glomerular IgA and IgG depositions in HIGA mice. Uninephrectomized rats with anti-Thy-1 nephritis, an irreversible MsPGN model, shichimotsukokato suppressed elevation of systolic blood pressure and glomerular hypertrophy. Saireito has been applied to nephrotic syndrome, and occasionally induces rapid response to the therapy. Saireito has been reported to be effective in reducing proteinuria in IgA nephropathy with focal mesangial proliferation in a prospective controlled study. In a retrospective clinical evaluation, saibokuto reduced proteinuria and hematuria as well as an anti-platelet agent dilazep in mildly active IgA nephropathy accompanied with frequent episodes of upper respiratory infection. Recently, re-evaluation and application of shichimotsukokato in CKD has begun. In CKD patients of nephrosclerosis, with elevated creatinine levels, treatment of shichimotsukokato following angiotensin II receptor blockers furthermore reduced blood pressure, and induced reduction of serum creatinine levels. Kampo medicines may have the potential to improve CKD, when added to the standard treatment. The challenges that remain are to identify the subset of CKD conditions with good response to Kampo medicines.

抄録全体を表示