• Journal of Pharmaceutical Investigation
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• v.41 no.1
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• pp.37-43
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• 2011

Urinary steroid levels were investigated in the treatment of CKD-501, a new anti-diabetic drug candidate. CKD-501 was administered orally at the dosage of 1, 2, 4 mg/day for 7 days to normal men (n=18). Urine was collected before, during and after stopping the drug administration and the urinary level of androgen, estrogen, progestin and corticoids were quantified using GC-MS (gas chromatography-mass spectrometry). Only urinary corticosteroid and an androgen, DHEA levels among all the analyzed steroids, have been found to increase progressively, reaching significant levels on the last day of drug treatment and later declined after the drug treatment is withdrawn. Therefore, it was thought that an increase in the urinary corticoid and DHEA levels could be a characteristic of CKD-501, since it prominently acts on the glucose sensitivity and suppresses the triglyceride levels. In conclusion, it was found that CKD-501, an anti-diabetic drug candidate, affects the glucocorticoid and DHEA levels and it plays a crucial role in glucose homeostasis.

• The Korea Journal of Herbology
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• v.23 no.4
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• pp.103-112
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• 2008

Objectives: Indongdeungjikolpi-tang(IJT) is used as a traditional treatment of diabetes in oriental clinincs. This study aimed to evaluate the anti-diabetic effect of Indongdeungjikolpi-tang(IJT) in streptozotocin(STZ)-induced diabetic rats. Methods: Diabetes was induced by intraperitoneal injection of streptozotocin(STZ; 60 mg/kg BW) to Sprague-Dawley male rats. Experimental animals(six per group), were treated by oral administration of IJT(100 and 500 mg/kg BW) and glibendimide(3 mg/kg), a known antidiabetic drug for comparison, during 4 weeks. We measured the levels of glucose, insuline, triglyceride, creatinine and urea in sera of each group. An oral glucose tolerance test(OGTT) was also performed in all groups. Results: IJT(100 and 500 mg/kg) significantly reduced blood glucose levels and increased plasma insulin levels in STZ-induced diabetic rats. IJT also significantly reduced the plasma levels of tryglyceride, creatinine and urea in STZ-induced diabetic rats. The OGTT results showed a significant improvement in glucose tolerance in IJT-administrated rats. Conclusions: These data indicate that IJT may improve glocose homeostasis in STZ-induced diabetes, which could be associated with stimulation of insulin secretion.

• Advances in Traditional Medicine
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• v.8 no.4
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• pp.349-353
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• 2008

Anti-diabetic effect was observed with Thespesia lampas Dalz & Gibs (Family: Malvaceae) when given as a root extract in normal as well as alloxan induced diabetic rats. The effects, however, were more pronounced in diabetic animals in which administration of plant extract for 15 days after alloxan induced diabetes, significantly reduced blood glucose levels. After alloxan induced diabetes it was observed that both standard drug (glibenclamide) and aqueous extract of Thespesia lampas were significantly superior to control in reducing blood sugar on long term treatment (15 days). The aqueous extract of T. lampas (300 and 600 mg/kg) reduced the blood glucose levels from $349.2{\pm}7.2$ to $120.7{\pm}4.6$ and $346.3{\pm}3.4$ to $101.8{\pm}6.3$, respectively. The data suggested that T. lampas could be of beneficial in diabetes mellitus in controlling blood sugar. The present investigation established pharmacological evidence to support the folklore claim as an anti-diabetic.

• The Korea Journal of Herbology
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• v.28 no.5
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• pp.53-60
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• 2013

Objectives : To prove the channel-tropism theory in herbology, we investigated the anti-diabetic effect of six herbal plants used for lower wasting-thirst in streptozotocin-induced diabetic rats. Methods : Diabetes was induced in male Sprague-Dawley rats by consecutive injection of streptozotocin (30 mg/kg i.p.) for 5 days. The rats were divided into normal control, diabetic control, and diabetic treatment with Lycii Radicis Cortex (LRC, 300 mg/kg); Corni Fructus (CF, 300 mg/kg); Bombyx Batryticatus (BB, 50 mg/kg); Lycii Fructus (LF, 300 mg/kg); Phellodendri Cortex (PC, 300 mg/kg); Epimedii Herba (EH, 300 mg/kg); and glibenclimide (10 mg/kg) as a reference drug. Herbal extracts or reference drug were administered orally for 28 days. The changes of body weight, food intake and water intake, and serological markers such as blood glucose, serum total cholesterol, triglyceride (TG), blood urea nitrogen (BUN), and creatinine (Cr) were measured. Results : The decrease of body weight and the increase of food and water intake in STZ-induced diabetic rats was improved by the administration of CF and LF. Also, the enhancement of blood glucose and serum total cholesterol, TG, BUN and Cr in STZ-induced diabetic rats was significantly inhibited by the administration of CF, BB, LF and glibenclimide. On the other hand, EH strongly inhibited the increase of BUN and Cr in the sera of STZ-induced diabetic rats. Conclusions : These results suggest that among six herbal medicines used lower emaciation of emaciation-thirst disease, CF, BB, LF and EH show a characteristics including the channel-tropism theory.

• The Korean Journal of Food And Nutrition
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• v.30 no.6
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• pp.1332-1340
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• 2017

In this study, we assessed antioxidant, anti-diabetic, and anti-Alzheimer activities of Opuntia ficus-indica var. saboten (OFI) at harvest time. OFIs were cultivated December 2015~November 2016 in Jeju island. The 70% ethanol extracts of OFI were used to investigate total polyphenol and flavonoid contents, antioxidant(DPPH and ABTS radical scavenging assay), anti-diabetic(yeast ${\alpha}$-glucosidase and rat ${\alpha}$-glucosidase inhibition assay), and anti-Alzheimer(Acetylcholinesterase and butyrylcholinesterase inhibition assay) activities. Total polyphenol and flavonoid contents of OFIs were $17.40{\sim}23.11{\mu}g$ garlic acid/mg Ex and 2.17~6.22 ug (+)-catechine/mg Ex, respectively. DPPH and ABTS radical scavenging activity of OFIs were 131.98~184.90 mg ascorbic acid(AA) eq/100 g and 63.60~101.83 mg AA eq/100 g, respectively. In the anti-diabetic and anti-Alzheimer activities, 70% ethanol extracts of OFI exhibited moderate inhibition activity, compared to control (acarbose and beberine). Total polyphenol and flavonoid contents, antioxidant, anti-diabetic, and anti-Alzheimer activities were no significant differences by season, respectively. Therefore, information on comparative biological evaluations of OFI may be a beneficial in exploring functional food and drug development.

• Proceedings of the PSK Conference
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• 2005.04a
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• pp.61-62
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• 2005

• Biomolecules & Therapeutics
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• v.22 no.5
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• pp.400-405
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• 2014

G-protein coupled receptor 119 (GPR119) has emerged as a novel target for the treatment of type 2 diabetes mellitus. GPR119 is involved in glucose-stimulated insulin secretion (GSIS) from the pancreatic b-cells and intestinal cells. In this study, we identified a novel small-molecule GPR119 agonist, HD047703, which raises intracellular cAMP concentrations in pancreatic ${\beta}$-cells and can be expected to potentiate glucose-stimulated insulin secretion from human GPR119 receptor stably expressing cells (CHO cells). We evaluated the acute efficacy of HD047703 by the oral glucose tolerance test (OGTT) in normal C57BL/6J mice. Then, chronic administrations of HD047703 were performed to determine its efficacy in various diabetic rodent models. Single administration of HD047703 caused improved glycemic control during OGTT in a dose-dependent manner in normal mice, and the plasma GLP-1 level was also increased. With respect to chronic efficacy, we observed a decline in blood glucose levels in db/db, ob/ob and DIO mice. These results suggest that HD047703 may be a potentially promising anti-diabetic agent.

• YAKHAK HOEJI
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• v.59 no.2
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• pp.59-65
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• 2015

KR-67500, trans-4-(2-(4-methyl-1,1-dioxido-6-(2,4,6-trichlorophenyl)-1,2,6-thiadiazinan-2-yl)acetamido)adamantane-1-carboxamide, is a novel $11{\beta}$-HSD1 inhibitor with its therapeutic effects of its anti-diabetic, anti-adipogenic and anti-osteoporotic activity. This study was performed to evaluate in vitro and in vivo pharmacokinetic properties of KR-67500 as a new drug candidate. KR-67500 was stable and highly bound to proteins in rat plasma. The microsomal stabilities of KR-67500 in human and rat liver were high. The inhibitory effect of KR-67500 for five cytochrome P450 enzymes was low. Preclinical pharmacokinetic studies have been carried out with intravenous or oral administrations of KR-67500 (10 mg/kg) to male rats and monkey. KR-67500 showed low clearance (0.68 l/h/kg) and high oral bioavailability (102%) in male rats. These results suggest that KR-67500 has good drug-like pharmacokinetic properties with a low first-pass effect and high bioavailability for an oral therapeutic agent of diabetes and osteoporosis.

• Microbiology and Biotechnology Letters
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• v.36 no.1
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• pp.43-48
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• 2008

The present study investigated the effect of physiologically active polysaccharide (SP1) isolated from Salicornia herbacea on streptozotocin-induced diabetic rats. Male Spraque-Dawley rats were divided into four groups which were normal control group (NC), diabetic control group (DC), diabetic CSP group (DCSP), and diabetic SP1 group (DSP1). Animals were administrated with 2% experimental drinks for 6 weeks. The levels of glucose, triglyceride, total cholesterol, and high density lipoprotein (HDL)-cholesterol in the serum were measured before and after intake of test compounds. The levels of glucose and triglyceride in the DSP1 were significantly lower than those in the DC by 25% and 20%, respectively. The levels of total cholesterol and high density lipoprotein (HDL)-cholesterol in the DSP1 were similar to those in the DC. These results suggest that SP1 substantially exhibit anti-hyperglycemic and anti-hypertriglyceridemic activity in diabetic rats. Therefore SP1 is believed to show remarkable anti-diabetic effect on streptozotocin-induced diabetic rats.

• Natural Product Sciences
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• v.9 no.4
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• pp.291-298
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• 2003

Anti-diabetic effect of various fractions of Cordyceps militaris (CM), CCCA (crude cordycepin containing adenosine), CMESS (ethanol soluble supernatant), and cordycepin were evaluated in streptozotocin (STZ) induced diabetic mice, CMESS showed potent inhibitory activity of 34.7% in starch-loaded mice (2 g/kg) while acarbose as a positive standard exhibited 37.8% of inhibition rate. After 3 days administration (50 mg/kg), cordycepin (0.2 mg/kg), and acarbose (10 mg/kg) dramatically reduced blood glucose level (inhibition ratio: 46.9%, 48.4% and 37.5% respectively). CCCA that has high contents of cordycepin (0.656 mg/4 mg) did not influence on reducing blood glucose level. The proliferation of splenocytes and peritoneal macrophages derived from STZ-induced diabetic mice administered samples were evaluated out by addition of mitogens to see the stability of the usage of these herbal medicines. Proliferation of T-lymphocyte was significantly decreased; while NO production was increased more than two fold to STZ control in the cordycepin-administered group. Changes of serum enzyme levels of glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) were also evaluated. Cordycepin administered group was appeared to acarbose. We conclude that CMESS and cordycepin may be useful tools in the control of blood glucose level in diabetes and promising new drug as an anti-hyperglycemic agent without defects of immune responses and other side effects.