We have studied the effects of herbal medicine (Kampo formulations) on the prevention and the treatment of diabetes and diabetic complication. Effects of Kampo formulations on the treatment of diabetic neuropathy were investigated.The results obtained suggest that the combination of ten herbal medicines in Goshajinkigan(GJG) may have beneficial effects on metabolic and circulatory disturbances in nerves of diabetic patients. Therefore administration of GJG might be a useful approach for amelioration of the numbness and autonomic dysfunction associated with diabetic neuropathy. Effects of Kampo formulations on in vivo insulin resistance were studied.1.Animal experimental studies. The improvement of insulin resistance in STZ rats by the administration of GJG and Keishikajutsubuto(KJT) and cinnamon might be via NO pathway and due, at least in part, to correction in the abnormal early steps of insulin signaling pathway in skeletal muscle. 2.Clinical Studies.Effects of GJG on insulin resistance in patients with type 2 diabetes were investigated. HOMA-R was significantly decreased after GJG treatment (p=0.019). On the other hand, HOMA-R in the control group did not show significant difference. HOMA-R returned to the pre GJG treatment level 1 month after GJG discontinuation (P=0.018). The high-dose clamp resulted in a significantly increased insulin action (MCR levels) after GJG treatment. These animal experimental and clinical studies suggest that GJG might be effective for improving insulin resistance in patients with type 2 diabetes. In conclusion, Kampo formulations might be useful not only for the prevention and the treatment of diabetic complications but also effective for the prevention and treatment of type 2 diabetes.
Experimental autoimmune encephalomyelitis (EAE) is a prototype experimental model for human multiple sclerosis (MS). This study was conducted to research the effects of Juzentaihoto and Hochuekkito on the onset and development of EAE. Both Juzentaihoto and Hochuekkito suppressed the onset and development of EAE. Suppressive mechanisms of both Kampo medicines are mainly based on the immunosuppressive and anti-inflammatory activity. In addition, Hochuekkito showed immunomodulating activity in the central nervous system. These findings will contribute to consider a new therapy of human MS.
In Japan, Kampo medicines are used for the treatment of menopausal symptoms as an alternative to hormone replacement therapy (HRT). We have previously reported that some Kampo medicines possess estrogen-like activity. However, it is not clear whether these medicines act directly on estrogen receptors (ERs) α and β. Using the Receptor/Coactivator Ligand Assay, we analyzed both the agonistic and antagonistic actions of nine kinds of Kampo medicines, which are used for the treatment of menopausal symptoms, on these receptors. Hachimijiogan (TJ-7), kamishoyosan (TJ-24), keishibukuryogan (TJ-25) and tokakujyokito (TJ-61) acted agonistically on ERβ; however, they had almost no effect on ERα. Kakkonto (TJ-1) acted agonistically on both ERα and ERβ. Tokishakuyakusan (TJ-23) and unkeito (TJ-106) acted antagonistically on ERβ, and orengedokuto (TJ-15) and nyoshinsan (TJ-67) acted antagonistically on both ERα and ERβ. In the present study, we found for the first time that Kampo medicines bind directly on ERα or ERβ as either agonists or antagonists. And all nine Kampo medicines acted on ERβ, suggesting that these medicines may express their pharmacological activities through ERβ.
We examined the preventive effect of the Kampo medicine Juzentaihoto (JTX) on post-partial hepatectomy-induced hyperammonemia, a frequent and potentially fatal consequence of this surgery for resection of hepatocellular carcinomas. In most cases, these liver tumors are associated with pre-existing liver damage such as cirrhosis or chronic hepatitis. Post-surgical hyperammonemia harms further the remaining liver as well brain and other vital functions. With pre-surgical JTX administration, this post-surgical hyperammonemia is suppressed significantly. To explain this phenomenon, we first hypothesized that JTX prevents further damage of the liver, a site of ammonia metabolism. However, post-surgical liver dysfunction is not improved with JTX. Thus we focused on the other source of ammonia, the intestinal microbiota, as the source of the hyperammonemia. To examine the possible effect of JTX on intestinal microbiota, terminal restriction fragment polymorphism (T-RFLP), a culture-independent microbial analysis, was used to document change in the intestinal microbiota with JTX. We documented that partial hepatectomy changed the intestinal microbiota. Then we demonstrated that with oral JTX administration, this post-surgical change of the intestinal microbiota was not observed even after partial hepatectomy. We also showed that the representative ammonia-producing bacteria,Bacteroides, increased with partial hepatectomy and decreased with JTX administration. Cluster analysis of fecal microbiota suggests that JTX administration stabilized the intestinal microbiota and maintained the pre-surgical microbial analysis environment of the gut. This study suggests that JTX is useful to prevent the clinically significant increases in the serum ammonia levels after partial hepatectomy.
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.