• The Korea Journal of Herbology
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• v.32 no.4
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• pp.53-60
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• 2017

Objectives : Collagen decrease of Skin appears through various path ways. One of causes may be the Advanced glycation endproducts (AGEs) that combine formation of glucose and protein. The aim of this study was to explore the prevent wrinkle formation of Paeoniae radix (PR) and heated Paeoniae radix (HPR) via AGEs path way. Methods : AGEs formation inhibitory activities of PR and HPR measured using bovine serum albumin, glucose, and fructose. To evaluate the protective effects of PR and HPR in diabetic rats induced with streptozotocin (STZ) and methyl glyoxal (MGO), SD rat were distributed into four groups. Normal rats (Nor), AGEs-induced rats (Con), AGEs-induced rats treated with 100 mg/kg PR(PR), AGEs-induced rats treated with 100 mg/kg HPR (HPR). To induce AGEs, streptozotocin (50 mg/kg) was administered intraperitoneally and after 3 days administrated 100mM methyl glyoxal for 3 weeks. Results : The oral administration of HPR inhibited AGEs in skin tissues compared with PR. The increased reactive oxygen species (ROS) levels in the serum were diminished by HPR treatment. The analyses of kidney and skin tissues proteins indicated that HPR treatment effectively reduced AGEs related protein levels as compared to that by PR treatment. Also, HPR decreased anti-oxidant related protein levels in skin tissues such as catalase, glutathione peroxidase. Moreover, it inhibited the reduction of COL1A2 by decreasing MMP-1. Conclusion : Based on these results, it was suggested that PR and HPR could have Improving effects on wrinkle formation. These evidences provide useful information for the development wrinkle formation treated agent.

• The Korean Journal of Physiology
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• v.30 no.2
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• pp.219-229
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• 1996

In order to investigate intra-pancreatic cholinergic roles on insulin action in exocrine secretion, the pancreas was isolated from rats and continuously perfused with modified Krebs-Henseleit solution. Intra-arterial infusion of insulin (100 nM) or cholecystokinin (CCK, 14 pM) alone resulted in stimulation of the volume flow and amylase output. Also insulin potentiated the action of CCK in the exocrine secretion. Tetrodotoxin and atropine completely abolished the potentiating action of insulin and CCK as well as the action of insulin alone, but did not change the action of CCK alone. In order to see an effect of intra-pancreatic neural activation on the insulin action, electrical field stimulation (EFS) with parameters of 20 V, 2 msec and 8 Hz was applied to the isolated pancreas for 10 min under 2.5 or 18 mM glucose background. The EFS voltage-dependently elevated the flow rate and amylase output, and potentiated exocrine secretion in 18 mM glucose infusion compared with 2.5 mM glucose. The potentiating effects of EFS and 18 mM glucose were not observed in the streptozotocin-treated pancreas although it was perfused with 18 mM glucose. However, it was restored when the diabetic pancreas was perfused with porcine insulin(100 nM). Tetrodotoxin and atropine inhibited the pancreatic secretion induced by EFS with the background of 18 mM glucose. The results of present investigation indicate that the intra-pancreatic cholinergic tone exerts a stimulatory influence on the action of insulin in pancreatic exocrine secretion of rats.

• Proceedings of the PSK Conference
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• 2000.04a
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• pp.70-81
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• 2000

DA-5018 is a synthetic capsaicin derivative under development as a non-narcotic a analgesic ag$\varepsilon$nt. DA-50 18 showed a potent analgesic activity against acute and chronic pain m model(Tablel, 2.), but it had a narrow margin of safety. DA-5018 did not bind to opioid(${\kappa}, {\delta}, {\mu}$), NKl, CGRP receptors in vitro and its analgesic effect was not antagonized by naloxone, a and it did not develop analgesic tolerance. In addition DA-5018 had no inhibitory effects against c cyclooxygenase and 5-lipooxygenase activities. DA-5018 significantly increased the relcase of substance P from the slices of the rat spinal cord. These results suggest that DA-50 18 is not a narcotic nor aspirin-like analgesic and the release of substance P is one of analgesic mechanism of action of DA-5018. We found that DA-5018 was almost ten times more potent and was at l least IOO-times less irritable compared to capsaicin. Accordingly development of topical formula was adopted. Topical formula was desiged and screened by flux test of DA-5018 using hairless mouse skin and several formulas were selected. With these topical formulas we a assessed the analgesic efficacy and carried out the toxicity, skin irritation and pharmacokinetic studies. In streptozotocin-induced hyperalgesic rat and 50 % galactose-fed hyperalgesic rat as diabetic pain models, DA-5018 cream increased the pain thresh이ds up to 77.0% and 24.4% respectively, while Zostrix-HP(capsaicin cream) incr$\varepsilon$as cd by 65.9% and 21.0%. DA-5018 c cream showed a good analgesic effect as welI in FCA-induced arthritic rat. DA-5018 cream did not show any toxicological signs in acute and chronic toxicity test and had little skin irritation in car swclIing and scratching t$\varepsilon$st. Pharmacokinetics of DA-50 18 were studied after topical application of ${14}^C$-Iabelled or unlabelIed DA-5018 cream. Plasma and skin concentrations c except applied skin wcre below the dctection limit and after 7-day cummulative application, plasma concentrations were also below detection limit DA-50 18 may have an advantag$\varepsilon$ ov$\varepsilon$r c capsaicin and is now being developed as a topical agent for the treatment of pains. DA-50 18 cream was approved for Korean IND and is now under a Phase II clinical study for arthritic pain a after finising Phase I study. DA-50 18 was also liscensed out to Stiefel Company in America in

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.6
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• pp.427-438
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• 2022

Pyroptosis, a form of cell death associated with inflammation, is known to be involved in diabetic nephropathy (DN), and discoid domain receptor 1 (DDR1), an inflammatory regulatory protein, is reported to be associated with diabetes. However, the mechanism underlying DDR1 regulation and pyroptosis in DN remains unknown. We aimed to investigate the effect of DDR1 on renal tubular epithelial cell pyroptosis and the mechanism underlying DN. In this study, we used high glucose (HG)-treated HK-2 cells and rats with a single intraperitoneal injection of streptozotocin as DN models. Subsequently, the expression of pyroptosis-related proteins (cleaved caspase-1, GSDMD-N, Interleukin-1β [IL-1β], and interleukin-18 [IL-18]), DDR1, phosphorylated NF-κB (p-NF-κB), and NLR family pyrin domain-containing 3 (NLRP3) inflammasomes were determined through Western blotting. IL-1β and IL-18 levels were determined using ELISA. The rate of pyroptosis was assessed by propidium iodide (PI) staining. The results revealed upregulated expression of pyroptosisrelated proteins and increased concentration of IL-1β and IL-18, accompanied by DDR1, p-NF-κB, and NLRP3 upregulation in DN rat kidney tissues and HG-treated HK-2 cells. Moreover, DDR1 knockdown in the background of HG treatment resulted in inhibited expression of pyroptosis-related proteins and attenuation of IL-1β and IL-18 production and PI-positive cell frequency via the NF-κB/NLRP3 pathway in HK-2 cells. However, NLRP3 overexpression reversed the effect of DDR1 knockdown on pyroptosis. In conclusion, we demonstrated that DDR1 may be associated with pyroptosis, and DDR1 knockdown inhibited HG-induced renal tubular epithelial cell pyroptosis. The NF-κB/NLRP3 pathway is probably involved in the underlying mechanism of these findings.

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.12
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• pp.1727-1733
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• 2012

This study was conducted to investigate the effects of Vaccinium uliginosum L. (bilberry) on chemically induced diabetes and hypercholesterolemia. Sprague Dawley (SD) rats were divided into six groups, control (CON), bilberry added group (CBB), streptozotocin (STZ)-induced diabetic group (STZ), STZ and bilberry added group (SBB), high fat fed group (HFF) and high fat and bilberry added group (HFB). Diabetes was chemically induced by intravenous injection of 45 mg/kg body weight STZ in citrate buffer (pH 4.5). Serum triglycerides decreased significantly (p<0.05) in the STZ group that was fed bilberry. Additionally, the athrogenic index (AI) decreased significantly (p<0.05) when compared to the STZ group, while the liver triglycerides tended to decrease in the STZ group. HDL-cholesterol also increased significantly in response to bilberry. When compared to the STZ group, steady attenuation of the blood glucose level was observed upon fasting, 15 min, 30 min, 60 min and 120 min after oral glucose administration. The blood glucose level in the bilberry fed group decreased by 24% when compared to STZ group, while the superoxide dismutase (SOD) became significantly higher (p<0.05) in the STZ group when compared to the CON group. Overall, the results of this study suggest that bilberry stimulates lipid metabolism in both the serum and liver and has a positive effect on glucose metabolism in chemically induced diabetic rats.

• Korean Journal of Pharmacognosy
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• v.40 no.3
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• pp.196-204
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• 2009

This study was carried out to investigate the in vivo and in vitro inhibitory effect of a traditional herbal complex (HC) extract prepared from a mixture of four oriental herbs (Dioscorea Rhizoma, Glycine soja Sieb. et Zucc, Bombycis corpus, Fermented Glycine soja) that have been widely used for the treatment and prevention of diabetes mellitus on hyperglycemia. The water extract of HC showed potent inhibitory effect on $\alpha$-glucosidase with $IC_{50}$ value of 1.24 mg/mL. Additionally, the ethanol extract of HC was also found to exhibit significant inhibitory effect against protein tyrosine phosphatase $1{\beta}$ ($PTP1{\beta}$), which is known as a major regulator of both insulin and leptin signaling. In the $PTP1{\beta}$ inhibitory assay, the most active n-hexane fraction obtained from the ethanol extract of HC, was identified as a mixture of fatty acid derivatives by gas chromatography-mass spectrometry (GC-MS). In high-fat diet-low dose streptozotocin (STZ)-induced diabetic rat, the water extract of HC improved the oral glucose intolerance as compared with rosiglitazone. HC also caused a marked decrease of body weight and fasting blood glucose and a significant improvement on glucose tolerance in metabolic syndrome mice model. These findings support that this traditional HC may be useful in the control of blood glucose in diabetes mellitus and metabolic syndrome.

• Journal of Ginseng Research
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• v.28 no.2
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• pp.111-119
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• 2004

The renoprotective effects of Korean Red Ginseng were examined in STZ-induced diabetic spontaneously hypertensive rats (SHR). After 3 day administration of streptozotocin (STZ), animals were divided into four groups : Group 1, hypertensive rats (H); Group 2, hypertensive rats with diabetes (HD); Group 3, hypertensive rats with diabetes administered with 100 mg/kg of ginseng total saponin(GTS); Group 4, hypertensive rats with diabetes administered with 600 mg/kg of ginseng non-saponin (GNS). After 2 weeks oral administraions of GTS and GNS, body weight, kidney weight, plasma glucose, urinary albumin excretion, serum creatinine, urea nitrogen and blood pressure were examined. After 3,7 and 21 day of STZ administration, expressions of TGF-${\beta}$1 and fibronectin in kidney were analyzed by immunoblotting and/or immunohistochemistry. GTS and GNS treatments slightly decreased blood pressure when compared to H and HD groups. Also, GTS and GNS treatments ameliorated kidney hypertrophy without affecting plasma glucose levels. Meanwhile, GNS treatment increased Cu/Zn-SOD activity in kidney and generally showed more efficient renoprotective effects than GTS. We suggest that the renoprotective effects of ginseng partially result from downregulations of TGF-${\beta}$1, fibronectin expressions and anti-oxidative activity of ginseng non-saponin.

• Journal of the Korean Applied Science and Technology
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• v.37 no.5
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• pp.1078-1087
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• 2020

The current study was carried out to investigate the effect of oral administration for 30 days of the Jijang kimchi extracts on prevention of diabetes, alcoholic liver injury and reduction of blood lipids in laboratory rats with alcoholic liver injury and diabetes induced by streptozotocin. In a diabetic model animals, the blood lipid profile, ALT, and AST levels were lower in kimchi extract groups compared to DC (diabetes control) group, and blood glucose level of DCJK (DC+oral administration with Jijang kimchi extracts) group was lower than that of DCCK (DC+oral administration with commercial kimchi extracts) group. Insulin levels were increased in order of NC (normal control), DCJK > DCCK > DC groups. In alcoholic liver injury model animals, ALT, AST and bilirubin were lowed in order of AC (alcohol group received 1 bottle of soju) > ACCK (1 bottle of soju plus oral administration with commercial kimchi extracts) ACJK (AC plus oral administration with Jijang kimchi extracts) > NC groups. In the clinical pathologic findings of liver tissue, AC group was severely injured, and tended to be improved in groups eating a 1 bottle of soju plus oral administration with kimchi extracts, especially Jijang kimchi extract group. The results suggest that eating Jijang kimchi can improve insulin secretion ability while lowering blood lipid profile, blood sugar and ALT, AST, and bilirubin levles in diabetic and alcoholic liver injury model animals.

• Journal of the Korean Society of Food Science and Nutrition
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• v.38 no.4
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• pp.415-422
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• 2009

We previously demonstrated that zinc plus arachidonic acid (ZA) treatment lowered blood glucose levels in streptozotocin-induced diabetic rats, genetically diabetic obese (ob/ob) mice, and genetically diabetic, non-obese Goto-Kakizaki rats. However, plasma insulin levels did not increase with ZA treatment, suggesting that ZA lowers blood glucose levels not by stimulating pancreatic insulin secretion. However, it is unclear whether these agents lower blood glucose levels by decreasing hepatic glucose output (HGO) or by increasing glucose utilization in peripheral tissues, or both. In order to determine ZA target organ of insulin action, we divided 18 Sprague-Dawley rats weighing ${\sim}130g$ into 3 groups (6 rats per group) and treated them for four weeks with: (1) Control diet (regular rat chow), (2) High fructose (60.0%) diet only, and (3) the same fructose diet plus zinc (10 mg/L) and arachidonic acid (50 mg/L) containing drinking water. After 4 weeks, insulin action was assessed using the hyperinsulinemic euglycemic clamp technique. Food intake and body weights were comparable in all three groups of rats throughout the study period. Plasma glucose and insulin concentrations, glucose uptake, and HGO in the basal state were all the same in these three rat groups. During the clamp study, fructose-treated and fructose+ZA treated rat groups did not exhibit any detectable change on insulin-mediated glucose uptake compared to controls. High fructose feeding impaired insulin mediated suppression of HGO, compared to controls during clamp (4.39 vs. 2.35 mg/kg/min; p<0.05). However, ZA treatment in high fructose-fed rats showed a remarkable increase in hepatic insulin sensitivity compared to high fructose-fed rats, reflected by a complete recovery in suppression of HGO during the clamp (4.39 vs. 2.18 mg/kg/min; p<0.05). This data suggests that ZA increases insulin sensitivity in liver but not glucose utilization of peripheral tissues in high fructose-fed rats.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.5
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• pp.682-688
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• 2011

The purpose of this study was to measure the blood glucose level and glycemic index (GI) in response to persimmon (Diospyros kaki Thunb) syrup extracted from persimmon and extract of persimmon by-products. Major component analyses of persimmon syrup I (PSI, 95:5 mixture of purified persimmon syrup and non-purified persimmon syrup) and persimmon syrup II (PSII, 50:50 mixture ratio of purified persimmon syrup and non-purified persimmon syrup) were $0.3{\pm}0.1$ and $0.6{\pm}0.2$ mg/g for total polyphenolic compounds and $70.6{\pm}0.6$ and $66.6{\pm}1.6%$ for total carbohydrates, respectively. Blood glucose responses of PSI and PSII were determined using both normal ICR mice and streptozotocin (STZ)-induced diabetic male Sprague-Dawley (SD) rats. Further, oral glucose tolerance test (OGTT) was performed on diabetic rats to assess the effects of the experimental diets. Blood glucose response and OGTT showed that blood glucose levels were significantly lower in mice and diabetic rats fed PSI and PSII compared to those fed diets of sugar, maple syrup, or honey. The GIs of healthy volunteers in response to PSI and PSII were calculated to be 51.9 and 35.7, respectively. On the contrary, the GIs of healthy volunteers fed diets including sugar, maple syrup, or honey were 52.6, 20.0, and 93.0, respectively. These results suggest that persimmon syrup can be used for both the treatment of diabetics and healthy people due to its beneficial effects on blood glucose level.