• Journal of the Korean Society of Food Science and Nutrition
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• v.46 no.6
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• pp.759-764
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• 2017

Reactive oxygen species (ROS) and advanced glycation end products (AGEs) are valuable therapeutic targets for the regulation of diabetic complications. Activity-guided isolation of the ethylacetate (EtOAc)-soluble portion of 70% ethanolic extract from aerial parts of Ainsliaea acerifolia was performed, followed by AGE formation inhibition assay for the characterization of four dicaffeoylquinic acid derivatives of a previously known structure, methyl 3,5-di-O-caffeoyl-epi-quinate (1), 3,5-di-O-caffeoyl-epi-quinic acid (2), 4,5-di-O-caffeoyl-quinic acid (3), and methyl 4,5-di-O-caffeoyl-quinate (4). The structures of these compounds were confirmed by interpretation of nuclear magnetic resonance (NMR, $^1H-$, $^{13}C-NMR$, two-dimensional NMR) and mass spectroscopic data. Among the isolates, the major secondary metabolites, 3,5-di-O-caffeoyl-epi-quinic acid (2) and 4,5-di-O-caffeoyl-quinic acid (3) showed the most potent inhibitory effects against AGE formation with $IC_{50}$ values of $0.6{\pm}0.1{\mu}M$ and $0.4{\pm}0.1{\mu}M$, respectively. Furthermore, all isolated dicaffeoylquinic acid derivatives were evaluated for their radical scavenging activities using 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical, and compound 3 exhibited the most potent inhibitory effect in a concentration-dependent manner. This result suggests that the caffeoylquinic acid dimers isolated from A. acerifolia might be beneficial for the prevention of diabetic complications and related diseases.

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.3
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• pp.339-344
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• 2012

This study was performed to investigate the effect of germinated Ilpum rough rice extract on blood glucose in C57BL/KsJ-db/db mice. The mice were divided into several groups: normal control (NC), diabetic control (DC), those fed with 0.25% germinated Ilpum rough rice extract (DM-0.25%GIRRE), those fed with 0.5% germinated Ilpum roughrice extract (DM-0.5%GIRRE) and those fed with 1% germinated Ilpum rough rice extract (DM-1%GIRRE). After 8 weeks of treatment, body weight, water intake, and diet intake of the DM-1%GIRRE group were significantly lower than the other DM groups. Blood glucose levels of the DM-1%GIRRE group were significantly lower compared to the DC group. Fasting blood glucose HbA1c level and total glucose tolerance test were significantly lower in the DM-1%GIRRE groups compared to the DC group. There was no significant difference in serum insulin level among each group. Therefore, the results of this study demonstrate that germinated Ilpum rough rice extract alleviates many of the symptoms of diabetes in genetically obese mice and may offer a possibility as a therapeutic supplement for the normalization of blood glucose levels in humans with hyperglycemia. It may also have beneficial effects in patients with non-insulin-dependent diabetes mellitus.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.9
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• pp.1385-1390
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• 2016

Gallic acid is a representative hydroxybenzoic acid and is found in free form in several plants and in various esterified forms as a part of hydolyzable tannins. Convenient enzymatic transformation of trihydroxylated gallic acid with polyphenol oxidase originating from pear was evaluated to investigate whether polyphenol oxidase can be used as a valuable compound to improve the biological activity of gallic acid. Enzymatic oxidation processing of gallic acid using polyphenol oxidase was carried out for five different reaction times. The antioxidant effects of transformed gallic acid for different reaction times were evaluated via radical scavenging assays using 1,1-diphenyl-2-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radicals. In addition, the anti-diabetic property of the transformed gallic acid was measured based on ${\alpha}$-glucosidase. Gallic acid reacted for 5 h showed significantly higher antioxidant and ${\alpha}$-glucosidase inhibitory activities compared to the tested positive control substances. Biotransformation of simple gallic acid induced by polyphenol oxidase might be responsible for enhancing the biological activity of gallic acid.

• Korean Journal of Clinical Pharmacy
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• v.21 no.4
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• pp.364-375
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• 2011

Given that single blockade with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) can achieve only partial and undurable suppression of the Renin Angiotensin System (RAS), it has been hypothesized that dual blockage would be more beneficial in the management of blood pressure (BP) reduction and prevention of progressive chronic kidney disease (CKD) than either agent alone. Thus, it has been suggested that the combination of an ACEI and an ARB might provide renal benefits to hypertensive patients over and above BP reduction. However, this might also expose patients to additive or synergistic side effects. We attempted to conduct a systematic review to evaluate the benefits and harms of combination therapy in hypertensive patients with or without kidney diseases. MEDLINE and KoreaMed were searched for relevant randomized clinical trials in adult hypertensive patients with or without diabetes (restricted to 1997, limited to trials published in English). Results were summarized using the random-effects model, and between-studies heterogeneity was estimated with $I^2$. A final analysis of ten trials (23,928 patients) revealed that the combination of an ACEI and an ARB reduced blood pressure (SBP/DBP) by 3.95/2.02 mmHg (95% confidence interval [CI], -4.38 to -3.53/-2.33 to -1.71) compared with ACEI monotherapy, and 2.83/2.64 mmHg (95% CI, -3.25 to -2.41/-4.95 to -0.33) compared with ARB monotherapy. Eight trials (391 patients) demonstrated a significant reduction in 24h-proteinuria (weighted mean difference, 0.16 g/day, 95% CI, -0.26-0.05), but they did not translate into an improvement in GFR. Tests for heterogeneity showed no difference in effect among the studies. The combination therapy reduced proteinuria by 30% (95% CI, 23% to 37%) and 39% (95% CI, 31% to 48%) compared with ACEI monotherapy and ARB monotherapy, respectively. However, in patients who had proteinuria more than 0.5 g/day, the combination therapy failed to show significant reduction in urinary protein excretion. The current cumulative evidence suggests that diabetic patients with proteinuria on dual RAS blockade have an increase risk of adverse events such as hyperkalemia, hypotension, and so on, compared with ACEI or ARB alone. It is, therefore, proposed that the combination therapy should not be routinely used for the treatment of hypertension with or without compelling indications.

• Journal of Physiology & Pathology in Korean Medicine
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• v.30 no.3
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• pp.164-176
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• 2016

This study was perfomed to investigate the effects of Chunghyul-plus(CHP) on oxidative damage and hyperlipidemia in db/db mouse. After treatment with CHP, safety in cytotoxicity, heavy metal toxicity, production of reactive oxygen species(ROS), nitric oxide (N0) and proinflammatory cytokine IL-Ib, TNF-a, IL-6 in RAW 264.7 cells. Serum total cholesterol, LDL cholesterol, HDL cholesterol, triglyceride, insulin, GLP-1, glucose, food intake, body weight, organ weight, AST, ALT, ALP, BUN, creatine and histologic change of liver and aorta were measured in db/db mouse after oral administration of CHP. CHP showed safety in cytotoxicity and toxicity of liver and kidney for logn time administration. CHP increased the DPPH and ABTS radical scavenging activity. CHP showed significant inhibitory effect on reactive oxygen species (ROS), and showed inhibitory effect on nitiric oxide(NO) compared to control group. CHP decreased cytokine IL-6 production significantly, and decreased IL-1β and TNF-α compared to control group. CHP decreased body and organ weitht, intake food, and glucose levels compared to control group. CHP decreased total cholesterol and triglyceride significantly, and decreased LDL-cholesterol levels and increased HDL-cholesterol levels compared to control group. CHP decreased atherogenic index and cardiac risk factor significantly. CHP increased serum insulin and GLP-1 compared to control group. In histologic examination, lipophagy in the liver and aorta decreased in CHP treated mice and the cell was regular and boundary of vessel wall was clear compared to control group. These results suggest that CHP is effective in antioxidation activity and treatment and prevention of hyperlipidemia, atherosclerosis, diabetes, ischemic heart disease, stroke and other cardiocerebrovascular disease.

• 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.

• Journal of Korean Medicine for Obesity Research
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• v.22 no.2
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• pp.93-101
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• 2022

Objectives: This study aimed to observe the anti-diabetic effect and underlying mechanisms of Galgunhwanggumhwangryun-tang (GHH; Gegen-Qinlian-decoction) in the C2C12 myotubes. Methods: GHH (1.0 mg/ml) or metformin (0.75 mM) or insulin (100 nM) were treated in C2C12 myotubes after 4 days differentiation. The glucose uptake was assessed by 2-[N-(7-160 nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose uptake by C2C12 cells. The expression of adenosine monophosphate-activated protein kinase (AMPK) and phosphorylation AMPK (pAMPK) were measured by western blot. We also evaluated gene expression of glucose transporter type 4 (Slc2a4, formerly known as GLUT4), glucokinase (Gk), carnitine palmitoyltransferase IA (Cpt1a), nuclear respiratory factors 1 (Nrf1), mitochondrial transcription factor A (Tfam), and peroxisome proliferator-activated receptor γ coactivator 1α (Ppargc1a) by quantitative real-time polymerase chain reaction. Results: GHH promoted glucose uptake in C2C12 myotubes. The expression of AMPK protein, which plays an essential role in glucose metabolism, was increased by treatment with GHH. GHH treatment tended to increase gene expression of Slc2a4, Gk, and Nrf1 but was not statistically significant. However, GHH significantly improved Tfam and Ppargc1a gene expression in C2C12 myotubes. Conclusions: In summary, GHH treatment promoted glucose uptake in C2C12 myotubes. We suggest that these effects are associated with increased gene expression involved in mitochondrial biosynthesis and oxidative phosphorylation, such as Tfam and Ppargc1a, and increased expression of AMPK protein.

• Journal of Practical Agriculture & Fisheries Research
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• v.10 no.1
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• pp.67-75
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• 2008

Tartary buckwheat is one of specialized plants in Pyeongchang county, Korea and contains rutin much more than common buckwheat. Rutin is a kind of flavonoid (polyphenol compound) that has effects on blood vascular disease, strengthen capillary, and anti-inflammatory effect. This study was conducted to determine the possibility of development of beverage extracted from sugar-treated plants and sprouts of tartary buckwheat. By using two types of undiluted solution extracted from plant and sprouts of tartary buckwheat, we analyzed their nutrition components and did experiment on mice to find out pharmaceutical effects. In an experiment on mice, we administered various concentration of buckwheat to induced diabetic mellitus mice for 1 weeks. As a result, the buckwheat effected finely on lowering blood sugar and decreased LDL-cholesterol and total lipid level but increased HDL-cholesterol level.

• Journal of the Korean Society of Food Science and Nutrition
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• v.42 no.3
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• pp.325-334
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• 2013

The objective of this study was to compare the content and metabolic activities between fresh pine needle juice (PNJ) and fermented pine needle juice (FPNJ). A variety of factors were measured, including total phenolic content (TPC), antioxidant activity [DPPH radical scavenging activity (RSA), total radical-trapping antioxidant potential (TRAP), oxygen radical absorbance capacity (ORAC), cellular antioxidant capacity (CAC)], anti-genotoxic activity, ${\alpha}$-glucosidase inhibitory activity, and angiotensin converting enzyme (ACE) inhibitory activity. The TPC was $17.3{\pm}0.2$ and $4.6{\pm}0.0$ mg GAE/g in PNJ and FPNJ, respectively. The DPPH RSA, TRAP, and ORAC values increased in a dose-dependent manner for both PNJ and FPNJ, with significantly higher activities in PNJ than FPNJ. The CAC against AAPH-induced oxidative stress in HepG2 cells was protected by both PNJ and FPNJ. Pretreatment with PNJ and FPNJ in human leukocytes produced significant reductions in $H_2O_2$-induced DNA damage at a concentration of $50{\mu}g/mL$. ${\alpha}$-Glucosidase inhibitory activity was significantly higher in FPNJ than PNJ. The ACE inhibitory activity was about 87.1% and 60.0% in 1:1 diluted PNJ and FPNJ, respectively. This study suggests that the fermentation of PNJ could enhance the regulation of blood glucose metabolism and both PNJ and FPNJ might be a new potential source of natural antioxidant, anti-diabetic, and anti-hypertensive agents applicable to food.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.2
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• pp.153-160
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• 2016

The objective was to investigate the hypoglycemic action of catalpol in spontaneous diabetes db/db mice. 40 db/db mice were randomly divided into five groups: model control gourp; db/db plus catalpol 40, 80, 120 mg/kg body wt. groups and db/db plus metformin 250 mg/kg group. Age-matched db/m mice were selected as normal control group. The mice were administered with corresponding drugs or solvent by gavage for 4 weeks. The oral glucose tolerance test was carried out at the end of $3^{rd}$ week. After 4 weeks of treatment, the concentrations of fasting blood glucose (FBG), glycated serum protein (GSP), insulin (INS), triglyceride (TG), total cholesterol (TC) and adiponection (APN) in serum were detected. The protein expressions of phosphorylation-$AMPK{\alpha}$1/2 in liver, phosphorylation-$AMPK{\alpha}$1/2 and glucose transporter-4 (GLUT-4) in skeletal muscle and adipose tissues were detected by western blot. Real time RT-PCR was used to detect the mRNA expressions of acetyl-CoA carboxylase (ACC) and Hydroxymethyl glutaric acid acyl CoA reductase (HMGCR) in liver. Our results showed that catalpol could significantly improve the insulin resistance, decrease the serum concentrations of INS, GSP, TG, and TC. The concentrations of APN in serum, the protein expression of phosphorylation-$AMPK{\alpha}$1/2 in liver, phosphorylation-$AMPK{\alpha}$1/2 and GLUT-4 in peripheral tissue were increased. Catalpol could also down regulate the mRNA expressions of ACC and HMGCR in liver. In conclusion, catalpol ameliorates diabetes in db/db mice. It has benefit effects against lipid/glucose metabolism disorder and insulin resistance. The mechanism may be related to up-regulating the expression of phosphorylation-$AMPK{\alpha}$1/2.