An Experimental Analysis of Therapeutic Efefcts of a Chinese Herbal Prescription in Streptozocin-Treated Rats

Abstract

A Chinese herbal prescription, Hachimzjiogan, is one of the traditional Kampo prescriptions in Japan and China, and has been widely used for treatment of several chronic disease including diabetes mellitus. The present study provides experimental evidence for significant lowering of the streptozocin (STZ)-induced increase in plasma glucose level, and for significant recovery to the intact levels of plasma insulin and C-peptide in the STZtreated rats after treatment for four weeks with the prescription. Signs of diabetes mellitus in the STZ-treated rats were also recovered by the treatment with this medicine. These results suggest strongly that Hachimzjiogan has the substantial pharmacological basis of therapeutics on insulin-dependent diabetes mellitus (IDDM).Hachimijiogan. in Japanese (abbreviated as HJ below, Ba-Wei-Di-Huang-Wan. in Chinese) is one of the traditional Chinese herbal prescription and has long been used since Han dynasty in China for diabetes mellitus, chronic nephritis, sterility, and vegetative ataxia (2). The prescription consists of extracts of eight Chinese herbs, seven of which are listed in the official Japanese Pharmacopoeia. In spite of longtime and widespread use of HJ, information as to pharmacological basis for therapeutic effects of this prescription is limited. Intravenous infusion of the water extract of the medicine in the rat tended to suppress the hyperglycemia after oral glucose ingestion, but no effect was noted on the insulin response; the effect on hyperglycemia was enhanced when HJ was administered in combination with adrenaline (7). The effectiveness of the prescription to some of the chronic diabetic complications may be due to the inhibition of aldose reductase activities (1). HJ was found to inhibit the elevation of serum triglyceride, lipid peroxides, and insulin without elevation of serum glucose "Correspondence to: N. Yanaihara at the above address. Tel: (81)-544-2771; Fax: (81)- 544-22-2770 concentration in rats fed a high sugar diet (4).Streptozocin (STZ) has been used to produce experimental diabetes mellitus in laboratory animals. STZ selectively deteriorates the B cells in Langerhans islets, and the STZ-induced diabetes has been regarded as an experimental model of insulindependent diabetes mellitus (IDDM, type I diabetes; 5, 6). In the STZ-induced diabetic rats, Tanaka er al. (8) found significant impairment of the cardiac aladrenoceptor signaling system, and suggested the impairment of 0:1-adrenoceptor signaling associated with the diabetic state. As mentioned above, HJ has long been used not only for diabetes mellitus but also for vegetative ataxia, and its therapeutic effect to inhibit the decreased peripheral utilization of glucose was prominent in the state of adrenergic hyperglycemia. The purpose of the present study was to evaluate the therapeutic effects of this prescription by examining plasma levels of glucose, insulin, and C-peptide in STZ-induced diabetic rats. MATERIALS AND METHODS AnimalsMale Wistar rat (6 week-old, 180-200 g) were pur-

Effects of Hachimi-jio-gan (Ba-Wei-Di-Huang-Wan) on Hyperglycemia in Streptozotocin-Induced Diabetic Rats

“…Therefore, the increases in serum and pancreatic IRI levels due to HJ were attributable to increased insulin synthesis or secretion by residual b cells after STZ administration, but not to differentiation and proliferation of residual pancreatic b cells. In other words, while the present study's results differed in some respects from those of Luo and colleagues, 5) increases in IRI levels by HJ are not due to quantitative changes in pancreatic b cells, and HJ does not repair pancreatic b cells damaged by STZ. The present study clarified that HJ increases IRI levels by elevating insulin synthesis and secretion.…”

“…As to the therapeutic effects of HJ, various human and animal studies have been conducted, [2][3][4][5] most of which examined the effects of HJ on renal damage and the action mechanism for such effects. [6][7][8] Experimentally, HJ has exhibited beneficial effects in patients with diabetes mellitus and in many diabetic animal models, and in particular, it is used in the treatment of dry mouth, thirst, and polyuria associated with diabetes.…”

Effects of Hachimi-jio-gan (Ba-Wei-Di-Huang-Wan) on Intestinal Function in Streptozotocin-induced Diabetic Rats

“…8,9) It is reported that one of the traditional Kampo prescriptions, namely, Hachimi-jio-gan (HJ), has an antidiabetic action that ameliorates hyperglycemia and protects against diabetic nephropathy in experimental diabetic model rats. 10,11) In this study, we examined the eŠects of HJ on intestinal function using streptozotocin (STZ)-induced diabetic model rats. The sucrase and maltase activities in the intestinal mucosa were measured as indices of digestive function measurement, and the mucosal weights, DNA contents and plasma Glucagon-like peptide 2 (GLP-2) levels were measured as indices of intestinal mucosa proliferation.…”