Tokishakuyakusan (TS) is one of the prescriptions used for the treatment of female hormonal imbalances in China and Japan. However, its effectiveness and safety are not yet fully understood. This paper reports new observations on the targets of TS, the differences between TS and estrogen, and the potential risks of TS treatment both in vitro and in vivo. Steroidogenic acute regulatory protein (StAR) and pituitary adenylate cyclase-activating polypeptide (PACAP) were targeted by TS in uterus and pituitary of ovariectomized (OVX) rats. TS had estrogenic activity, but a yeast two-hybrid assay showed that TS did not bind to estrogen receptor α (ERα) and ERβ, whereas 17β-estradiol (E2) did. However, administration of TS to OVX and hypophysectomized (HPX) rats promoted the expression of PACAP mRNA, whereas E2 did not. In addition, histological observations showed that administration of TS promoted development of ovary in HPX rat more effectively than administration of E2+progesterone. Finally, expression of ERα and the progesterone receptor (PR), which is used as a clinical gynecological cancer marker, was tested in the uterus of OVX rats. Administration of TS did not increase expression of ERα and PR, whereas E2 did. These results indicate that TS targets the expression of StAR and PACAP through different pathways than E2, and it is effective and safe for the treatment of menopausal syndrome in women.
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.
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.
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.
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.