Kampo medicine, Stephania tetrandra Radix (Stephania) in Boi-ogi-to increases the blood insulin level and falls the blood glucose level in streptozotocin (STZ)-diabetic ddY mice. These actions of Stephania are potentiated by Astragalus membranaceus Bunge Radix (Astragali) in Boi-ogi-to (Liu et al., J. Traditional Med., 17, 253-260, 2000). In the present study, actions of bis-benzylisoquinoline alkaloids isolated from Stephania were investigated in the hyperglycemia of STZ-diabetic mice. A main bis-benzylisoquinoline alkaloid, fangchinoline (0.3-3 mg/kg) significantly fell the blood glucose level of the diabetic mice in a dose-dependent manner. The effect of fangchinoline was 3.9-fold greater than that of water extract of Stephania. However, another main compound, tetrandrine (1-100 mg/kg) did not have any effect. The water extract of Astragali did not affect singly but potentiated the anti-hyperglycemic action of fangchinoline (0.3 mg/kg). Out of used compounds (1 mg/kg) isolated from Stephania, fangchinoline, fangchinoline 2'-N-alpha-oxide and 2'-N-norfangchinoline, which are substituted with 7-hydroxy side chain for 7-O-methyl side chain, decreased to near 50% of high blood glucose level. In addition, tetrandrine 2'-N-beta-oxide, tetrandrine 2'-N-alpha-oxide, tetrandrine 2-N-beta-oxide, fangchinoline 2'-N-alpha-oxide, which are added to 2- or 2'-N-oxide side chain, also decreased to near 50% of the high blood glucose level. In conclusion, fangchinoline but not tetrandrine from Stephania shows the anti-hyperglycemic action in the STZ-diabetic mice. The demethylation of 7-O-position and/or addition of 2- or 2'-N-oxide side chain in bis-benzylisoquinoline compounds in Stephania have a role for the induction of the anti-hyperglycemic actions.
The hypoglycemic effects of Fun-boi (Stephania Radix, SR), Boi (Sinomeni Cauli set Rhizoma, SCR) and Boi-Ogi-to (Fang-ji-huang-qi-tang, FJHQ) were investigated in streptozotocin (STZ)-diabetic ddY mice, a non-insulin-dependent diabetes mellitus model. The STZ-diabetic mice were prepared by a bolus treatment with 150mg/kg STZ into a tail vein. Blood glucose levels of 14-hour-food-deprived mice were determined before, and 4 and 6 hours after, intraperitoneal administration of these drugs by the glucose oxidase method. SR and FJHQ containing SR (FJHQ-SR) significantly reduced blood glucose levels of STZ-diabetic mice. FJHQ-SR also reduced blood glucose levels of age-matched normal mice. However, SCR and FJHQ containing SCR (FJHQ-SCR) have a tendency to reduce blood glucose levels of STZ-mice. Glibenclamide, a positive control, had a greater antihyperglycemic action than FJHQ-SR, but the induction time of its action was delayed more than that of FJHQ-SR. These results demonstrated that FJHQ-SR improved the hyperglycemic state of the diabetic mice, providing an experimental basis for its use as a clinical treatment for patients with diabetes mellitus.
The protective effect of a Japanese herbal medicine, Toki-Shakuyaku-San extract (TJ-23) was investigated on β-Amyloid protein (β40)-induced apoptosis in PC12 cells. TJ-23 has been reported to activate cholinergic neurons in the brain, and to aid in the recovery from the spatial cognition disorder induced by scopolamine in rats. The association between neuron death in Alzheimer's disease (AD) and apoptosis has attracted attention, and studies in cultured cells have suggested that β-Amyloid protein induces cell death by apoptosis. The pathway for the induction of apoptosis is caspase cascade activation. In addition, caspase-3 activation due to β-induced injury in PC12 cells has been reported. We evaluated the caspase-3 activity of TJ-23 on β-induced apoptosis in PC12 cells using a fluorophotometer. In our study, TJ-23 significantly inhibited the increase in lactate dehydrogenase (LDH) release following β40-induced cell injury and significantly increased 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction, significantly increasing the cell survival rate. These results suggested the protective effects of TJ-23. In addition, the inhibition of β40-induced cell injury and the significant increase in the cell survival rate by TJ-23 were continuous, suggesting continuous protective effects. TJ-23 significantly inhibited caspase-3 activation due to β40-induced cell injury. These results suggest that a pathway via caspase-3 activation is one of the mechanisms of the protective effects of TJ-23.
clinically used in the treatment of arthritis and edema in both Japan and China. Since FJHQ(SCR) has been reported to inhibit the elevation of serum cholesterol and decrease the ratio of visceral fat to somatic fat in diabetic patients with obesity, 1) it is possible that FJHQ(SR) has a similar or more beneficial effect in improving diabetes.Streptozotocin (STZ)-induced diabetes mellitus has been widely accepted as a model of insulin-dependent diabetes mellitus.2) However, STZ-diabetic rodents still have low insulin levels and survive for some months. Recently, several investigators have reported that a single treatment of low doses of STZ induces a non-insulin-dependent diabetes mellitus (NIDDM)-like hyperglycemic state in both neonatal and adult rodents. [3][4][5] This diabetic model characteristically shows mild hyperglycemia and impaired pancreatic function, accompanied by insulin resistance. In addition, the oral administration of antidiabetic drugs such as tolbutamide and glibenclamide improves hyperglycemia and increases the blood insulin level in STZ-diabetic rodents.6-8) These characteristics of STZ-diabetic mice are very similar to those of NIDDM.The chronic complications of diabetes, including retinopathy, neuropathy and nephropathy, 9) are the major causes of morbidity and mortality associated with the disease. It has been shown that diabetic complications may result from damage of cellular function caused by abnormal polyol metabolism. [10][11][12][13] In other words, the complications in poorly controlled diabetes would be ultimately caused by abnormal polyol metabolism 14) as well as glycation of proteins, 15,16) because the modification of nucleic acids and proteins by polyol can be due to activation of the hyperglycemia-induced polyol pathway. 17)In our previous studies, it was found that high blood glucose is reduced, whereas blood immunoreactive insulin is elevated in STZ-diabetic mice after
The relative proportions (% of total fatty acids) of odd chain (15:0-29:0) and long-chain (22:0-30:0) saturated fatty acids in phospholipids of biotin-deficient rat lymphocytes were significantly in creased as compared with biotin-supplemented rats, and the ratio of unsaturated fatty acids to saturated fatty acids in the former was signifi cantly decreased mainly due to the reduced composition of poly unsaturated fatty acids in the ƒÖ-3, ƒÖ-6, and ƒÖ-9 pathway. The ratio of cis-vaccenic acid to palmitoleic acid in biotin-deficient rats was signifi cantly lower than that in control rats, and was thought to be another important, but previously unreported indicator of biotin deficiency. These changes imply that the elongation and desaturation of unsaturated fatty
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