A folk prescription consisting of Alnus hirsuta, Rosa davurica, Acanthopanax senticosus and Panax schinseng has been used in the treatment of diabetes mellitus. The aim of the present investigation was to evaluate the antidiabetic effects of the herb formula extract (HFE) composed of Alnus hirsuta, Rosa davurica, Acanthopanax senticosus and Panax schinseng in the streptozotocin (STZ)-induced diabetic rats. The HFE was mixed in the food supply of the healthy and STZ-induced diabetic male Sprague-Dawley rats, and its effects on the body weight, water and food intake, hyperglycemia, hypolipidemic and islet structure were studied. The treatment of the rats with STZ for 6 weeks resulted in marasmus, polydipsia, polyphagia, hyperglycemia and hypoinsulinemia. In addition, the diabetic rats showed an apparent decrease in the insulin immunoreactivity and the number of ${\beta}$-cells in the pancreas. The addition of the HFE to the rats' food supply significantly lowered the serum glucose and the serum triglycerides level and preserved the normal histological appearance of the pancreatic islets. These results indicate that the HEF have a strong antidiabetic potential along with the significant hypoglycemic and hypolipidemic effects, which may be applicable in the pharmaceutical industry.
"Ginseng (Panax ginseng C.A. Meyer) has been a popular herbal remedy used in eastern Asian cultures for thousands of years, and a number of health claims are made for it. Modern therapeutic claims for ginseng refer to vitality, immune function, cancer, cardiovascular diseases, diabetes and sexual function. These claims are mostly based on uncontrolled or non-randomized studies. Among modern therapeutic claims, however, therapeutic effects for diabetes can reasonably be accepted. Following experiment was done recently in our lab: this study was designed to compare the antidiabetic activities between Ginseng Radix Alba (GRA), Ginseng Radix Rubra (GRR) and Panax Quinquefoli Radix (PQR) in multiple low dose (MLD) streptozotocin (STZ) (20mg/kg i.p injection for 5 days) induced diabetic rats. In the glucose tolerance test, 500mg/kg of each ginseng ethanol extract was admoinistered intraperitoneally 30min before glucose challenge. While GRA failed to lower blood glucose level, GRR and PQR both significantly prevented the hyperglycemia when compared with the control group. In the MLD STZ-induced diabetic rats, 300 mg/kg of each ginseng ethanol extract was administered intraperitoneally for 2 weeks. Plasma glucose and insulin levels were markedly improved in all treatment groups. While GRR showed the highest antidiabetic activity, and GRA and PQR revealed somewhat equipotent antidiabetic activities, but less than that in GRR-treated group as for as blood parameters and diabetic symptoms such as polydipsia are concerned. Blood glucose levels were closely associated with plasma insulin levels, and this result may suggest that ginseng ethanol extracts showed the activity to enhance insulin secretion as well as preventing destruction of pancreatic islet cells. To elucidate the relationship between antidiabetic activity and ginsenoside profiles, seven major ginsenoside were quantified by HPLC. We figured out the fact that protopanaxatriol (PPT) : proptopanaxadiol (PPD) ratio might play an important role in its hypoglycemia effects."
Park, Mi-Kyoung;Seo, Su-Yeong;Hong, Sook-Hee;Kim, Hye-Jin;Park, Eun-Jin;Kim, Duk-Kyu;Lee, Hye-Jeong
The Korean Journal of Physiology and Pharmacology
/
제10권1호
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pp.39-44
/
2006
Type I diabetes (T1D) is an organ-specific autoimmune disease caused by the T cell-mediated destruction of the insulin-producing ${\beta}$ cells in the pancreatic islets. The onset of T1D is the consequence of a progressive destruction of islet ${\beta}$ cells mediated by an imbalance between effector $CD4^+$ T helper (Th)1 and regulatory $CD4^+$ Th2 cell function. Since interferon-alpha (IFN-${\alpha}$) has been known to modulate immune function and autoimmunity, we investigated whether administration of adenoviralmediated IFN-${\alpha}$ gene would inhibit the diabetic process in NOD mice. The development of diabetes was significantly inhibited by a single injection of adenoviral-mediated IFN-${\alpha}$ gene before 8 weeks of age. Next, we examined the hypothesis that Th2-type cytokines are associated with host protection against autoimmune diabetes, whereas Th1-type cytokines are associated with pathogenesis of T1D. The expression of IFN-${\alpha}$ induced increase of serum IL-4 and IL-6 (Th2 cytokines) levels and decrease of serum IL-12 and IFN-${\gamma}$ (Th1 cytokines) levels. Therefore, overexpression of IFN-${\alpha}$ by adenoviralmediated delivery provides modulation of pathogenic progression and protection of NOD mice from T1D.
Ham, Kyung-Wan;Kim, Eun-Kyung;Song, Mi-Young;Kwon, Kang-Beom;Song, Je-Ho;Seo, Eun-A;Ryu, Do-Gon
Journal of Physiology & Pathology in Korean Medicine
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제22권3호
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pp.580-584
/
2008
In the present study, Radix clematidis extract (RCE) was evaluated to determine if it could protect pancreatic ${\beta}$ cells against multiple low dose streptozotocin (MLDS)-induced diabetes. Injection of mice with MLDS resulted in hyperglycemia and hypoinsulinemia, which was confirmed by immunohistochemical staining. However, the induction of diabetes by MLDS was completely prevented when mice were pre-administrated with RCE. Generation of oxidative stress is implicated in MLDS, a ${\beta}$ cell specific toxin-induced islet cell death. In this context, to elucidate the mechanisms of protective effects in RCE pre-administrated diabetic mice, we investigated the expression of heme oxygenase-1 (HO-1), which is one of the anti-oxidant enzymes. MLDS-induced HO-1 expressions were significantly reduced in MLDS-treated mice. However, the decrease of HO-1 by MLDS were protected by pretreatment of RCE. The molecular mechanism by which RCE inhibits diabetic conditions by MLDS appears to involve inhibition of HO-1 expression. Taken together, these results reveal the possible therapeutic value of RCE for the prevention of type 1 diabetes progression.
The present study was designed to investigate the anti-diabetic effect and mechanism of Korean red ginseng in C57BL/KsJ db/db mice. The db/db mice were divided into three groups: diabetic control group (DC), Korean red ginseng group (KRG, 100 mg/kg) and metformin group (MET, 300 mg/kg), and treated with drugs once per day for 10 weeks. Compared to the DC group, fasting blood glucose levels were decreased by 19.8% in KRG-, 67.7% in MET-treated group. With decreased plasma glucose and insulin levels, the insulin resistance index of the KRG-treated group was reduced by 27.6% compared to the DC group. The HbA1c levels in KRG and MET-treated groups were also decreased by 11.0% and 18.9% compared to that of DC group, respectively. Plasma triglyceride and non-esterified fatty acid levels were decreased by 18.8% and 16.8%, respectively, and plasma adiponectin and leptin levels were increased by 20.6% and 12.1%, respectively, in the KRG-treated group compared to those in DC group. Histological analyses of the liver and fat tissue of mice treated with KRG revealed significantly decreased number of lipid droplets and decreased size of adipocytes compared to the DC group. From the pancreatic islet double-immunofluorescence staining, we observed KRG has increased insulin contents, but decreased glucagon production. To elucidate action mechanism of KRG, effects on AMP-activated protein kinase (AMPK) and its downstream target proteins responsible for fatty acid oxidation and gluconeogenesis were explored in the liver. KRG activated AMPK and acetyl-coA carboxylase (ACC) phosphorylations, resulting in stimulation of fatty acid oxidation. KRG also caused to down regulation of SREBP1a and its target gene expressions such as FAS, SCD1 and GPAT. In summary, our results suggest that KRG exerted the anti-diabetic effect through AMPK activation in the liver of db/db mice.
Reactive oxygen species (ROS) have been suggested to be contributory factors in complications of diabetes mellitus. In the present study, we investigated the generation of superoxide, the lipid peroxide level measured as thiobarbituric acid reactive substances, the vasorelaxation of isolated thoracic aorta and the iNOS expression in kidney of streptozotocin induced diabetic rats. Sprague Dawley rats were divided into four groups: control, ascorbate (400 mg/kg rat weight daily in drinking water), diabetic (single dose of 50 mg of STZ/kg i.p.) and diabetic simultaneously fed with ascorbate for 12 wk. Rats in groups were studied at tri-weekly intervals (0 to 12 wk). Diabetic rats were evaluated periodically with changes of plasma glucose levels and body weight. The ascorbate supplimentation attenuated the development of hyperglycemia and weight loss induced by STZ injection in rats. In the present experimental condition, the ascorbate supplimentation had no significant effect on plasma glucose levels and changes in body weight of normal rate. The superoxide generation, formation of thiobarbituric acid reactive substance and iNOS expression in kidney were significantly increased in STZ-treated rats that were decreased by ascorbate supplimentation. The ascorbate supplimentation had no effect on vasorelaxation of isolated thoracic aorta. These results indicate that ascorbate supplimentation may exert an inhibitory effect on STZ-induced oxidative tissue damage through protection of pancreatic islet cells by scavanging reactive oxygen species. The ascorbate supplimentation may possibly attenuate the renal complication of diabetes mellitus.
Choi, Mi Ran;Kwak, Su Min;Bang, Sol Hee;Jeong, Jo-Eun;Kim, Dai-Jin
Journal of Ginseng Research
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제41권4호
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pp.503-512
/
2017
Background: Chronic heavy alcohol consumption may raise the risk of developing type 2 diabetes mellitus. Saponins inhibit apoptosis of pancreatic islet cells and reduce lipid parameters. The present study was designed to investigate the effect of saponin on chronic ethanol-treated diabetic rats. Methods: Long-Evans Tokushima Fatty (LETO) and Otsuka Long-Evans Tokushima Fatty (OLETF) rats were pair-fed a Lieber-DeCarli diet with and without 5% ethanol for 12 wks. Two weeks after starting the pair-feeding with the Lieber-DeCarli diet, intraperitoneal injection of saponin was performed for 10 wks. To perform the experiments, rats were divided as follows: LETO-Control (LC), LETO-Ethanol (LE), LETO-Ethanol-Saponin (LES), OLETF-Control (OC), OLETF-Ethanol (OE), and OLETF-Ethanol-Saponin (OES). Results: The weights of epididymal and mesenteric fat tissue in LES and OES rats were the lightest from among the LETO and OLETF groups, respectively. The secretion of alanine aminotransferase and cholesterol in OES rats decreased significantly compared to their secretion in OC and OE rats, respectively. The islets of the pancreas in LE and OE rats showed clean, unclear, and smaller morphology compared to those of LC, LES, OC, and OES rats. In addition, the expression of insulin in the islets of the pancreas in LC, LES, OC, and OES rats was higher than in LE and OE rats. Conclusion: Saponin may not only be helpful in alleviating the rapid progress of diabetes due to chronic alcohol consumption in diabetic patients, but may also show potential as an antidiabetic drug candidate for diabetic patients who chronically consume alcohol.
It is well known that diabetes mellitus is associated with metabolic derangements, such as hyper-glycemia, ketosis, glycosuria, and also widespread alterations in the blood vessels, kidneys, eyes, peripheral nerves and heart. It is also recognized that healing of skin wound is delayed in diabetics. In bone, according to Aegerter, osteopenia develops in diabetes mellitus and it is chiefly ascribed to overutilization of protein. Shim claims that total blood flow to the entire skeletal system is approximately 4 to 8 percent of resting cardiac output and blood supply to the skeletal system would be decreased on account of secondary arteriosclerotic changes in the diabetics. An adequate blood supply is an essential factor in the healing process of fracture, and disturbed blood flow, either local or systemic, will invariably delay union of the fragments or the fragments from being fused. As the author has encountered several cases of diabetics in whom healing of fracture was delayed or incomplete, this experimental study was undertaken to elucidate the effects of hyperglycemia and diabetes mellitus on the healing process of fracture. In this experiment adult albino rabbits, weighing about 2 kg. were used and divided into 6 groups. The femur of each animal was fractured surgically, and then the healing process of fracture was periodically checked by radiography at an interval of one week for a period of 6 weeks. Thereafter, all the rabbits were killed to obtain tissue preparation of the femur. The experimental groups were as follows; 1) Control group: Six rabbits sustained a surgical fracture to the femur, without being given any other treatment or drug. 2) Alloxan-treated group: For inducing diabetes, alloxan was given intravenously to 17 rabbits in various dose as follows; to 7 of them 40 mg/kg, to 6 rabbits 80 mg/kg and to 4 rabbits 120 mg/kg of body weight, respectively. 3) Insulin-treated group: Protamine-zinc insulin was injected subcutaneously to each of 6 rabbits in a daily dose of 1 unit per kilogram of body weight. 4) Group treated with insulin after alloxan: Four rabbits were given 80 mg of alloxan once and than 1 unit of insulin per kilogram of body weight daily. Another 5 rabbits were injected 1 unit of insulin per kg of body weight daily following administration of alloxan in a dose of 120 mg/kg. 5) Homotransplantation group: Following intravenous injection of alloxan in a dose of 120 mg/kg, 10 rabbits underwent homotransplantation of a short bone segment to the femur. Five of them were subsequently given 1 unit/kg of insulin daily. 6) Sugar-treated group: six rabbits were fed $15{\sim}20$ gm of sugar daily throughout the period of experiment. The results obtained are summarized as follows; 1. Blood sugar level and damage to the pancreatic islet increased proportionately when alloxan was given to the rabbits in various doses. No appreciable change could be observed in the islets when the blood sugar level was altered by either oral administration of sugar or subcutaneous injection of insulin. 2. Comparing with the control group, healing of fracture was delayed in the alloxan-treated group, while callus formation and periosteal reaction were shown to be more prominent in this group and subsequently, the ultimate osseous tissue formed at the fracture site was significantly smaller in amount and less compact. These findings were more marked as the amount of alloxan increased. 3. Administration of insulin prevented the delay in healing process of fracture in the rabbits with alloxan-induced hyperglycemia. In this case, the course and progression of fracture healing were almost similar to those of control group. 4. Union between the host bone and the fragment transplanted from other rabbit of the same species was more delayed in the group treated with alloxan alone than in the group to which insulin was administered after development of alloxan-induced diabetes. In both groups periosteal new bone developed from the ends of the host bone, above and below the transplanted fragment, and directly fused with failure of periosteal callus to bridge the adjacent ends of the host bone and the transplanted fragment. 5. The healing process of fracture was not inhibited by alteration in blood sugar level when the blood sugar was abnormally increased by excessive sugar intake or lowered by administration of insulin alone. The healing of fracture in these groups progressed similarly as in the control group. In brief summary, it appears that the healing process of fracture would be definitely disturbed in diabetic state brought about by damage to the pancreatic islet. As such an inhibition could be overcome with insulin, it seems that insulin plays an important role in healing of fracture, but alteration in blood sugar level alone does not modify healing process of fracture to significant degree.
Korean ginseng (Panax ginseng) is associated with a variety of therapeutic effects, including antioxidative, anti-inflammatory, vasorelaxative, antiallergic, antidiabetic, and anticancer effects. Accordingly, the use of ginseng has reached an all-time high among members of the general public. However, the safety and efficacy of ginseng in transplant recipients receiving immunosuppressant drugs have still not been elucidated. Transplantation is the most challenging and complex of surgical procedures and may require causation for the use of ginseng. In this regard, we have previously examined the safety, immunological benefits, and protective mechanisms of ginseng with respect to calcineurin inhibitor-based immunosuppression, which is the most widely used regimen in organ transplantation. Using an experimental model of calcineurin inhibitor-induced organ injury, we found that ginseng does not affect drug levels in the peripheral blood and tissue, favorably regulates immune response, and protects against calcineurin inhibitor-induced nephrotoxicity and pancreatic islet injury. On the basis of our experimental studies and a review of the related literature, we propose that ginseng may provide benefits in organ transplant recipients administered calcineurin inhibitors. Through the present review, we aimed to briefly discuss our current understanding of the therapeutic benefits of ginseng related to transplant patient survival.
We evaluated the anti-diabetic effects of Triticum aestivum sprout water extract (TA) in diabetes mellitus type 2. For the experiments, the diabetic animal model db/db mice were divided to 3 groups: diabetic control (db/db) and two experimental groups orally treated with 25 and 100 mg/kg single dose of TA (TA-25 and TA-100, respectively). The lean mice were used as the non-diabetic normal control. All mice have free access to water and AIN-93 diet. TA was administrated to diabetic mice for 5 weeks and the diabetic clinical markers, including blood glucose level, body weight, food intake and insulin level, were measured at a time. After administration for 5 weeks, the blood glucose level was decreased 1.10 and 1.98 folds in TA-25 and TA-100 groups, respectively, compared with db/db group. The body weight and diet consumption were significantly reduced by TA treatment in dose-dependent manner. The treatments of TA-100 also significantly decreased remarkedly liver weight and slightly serum insulin levels when compared with them of the diabetic control group. However the immunohistochemical staining for insulin clearly showed high expression of insulin in the pancreatic islet cells derived from all db/db mice, even if TA was administrated. Moreover, TA-100 treatment significantly improved impaired glucose tolerance in diabetic db/db mice. The results suggest that TA has anti-hyperglycemic effect attenuating blood glucose in the animal model of type 2 diabetes and might be useful as a functional diet for human diabetic diseases.
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