• Title/Summary/Keyword: anti-diabetic agent

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Inhibitory activity of Euonymus alatus against alpha-glucosidase in vitro and in vivo

  • Lee, Soo-Kyung;Hwang, Ji-Yeon;Song, Ji-Hyun;Jo, Ja-Rim;Kim, Myung-Jin;Kim, Mi-Eun;Kim, Jung-In
    • Nutrition Research and Practice
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    • v.1 no.3
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    • pp.184-188
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    • 2007
  • The major goal in the treatment of diabetes mellitus is to achieve near-normal glycemic control. To optimize both fasting blood glucose and postprandial glucose levels is important in keeping blood glucose levels as close to normal as possible. ${\alpha}-Glucosidase$ is the enzyme that digests dietary carbohydrate, and inhibition of this enzyme could suppress postprandial hyperglycemia. The purpose of this study was to test the inhibitory activity of methanol extract of Euonymus alatus on ${\alpha}-glucosidase$ in vitro and in vivo to evaluate its possible use as an anti-diabetic agent. Yeast ${\alpha}-glucosidase$ inhibitory activities of methanol extract of E. alatus were measured at concentrations of 0.50, 0.25, 0.10, and 0.05 mg/ml. The ability of E. alatus to lower postprandial glucose was studied in streptozotocin-induced diabetic rats. A starch solution (1 g/kg) with and without E. alatus extract (500 mg/kg) was administered to diabetic rats by gastric intubation after an overnight fast. Plasma glucose levels were measured at 30, 60, 90, 120, 180, and 240 min. Plasma glucose levels were expressed in increments from baseline, and incremental areas under the response curve were calculated. Extract of E. alatus, which had an $IC_{50}$ value of 0.272 mg/ml, inhibited yeast ${\alpha}-glucosidase$ activity in a concentration-dependent manner. A single oral dose of E. alatus extract significantly inhibited increases in blood glucose levels at 60 and 90 min (p<0.05) and significantly decreased incremental response areas under the glycemic response curve (p<0.05). These results suggest that E. alatus has an antihyperglycemic effect by inhibiting ${\alpha}-glucosidase$ activity in this animal model of diabetes mellitus.

Effects of mulberry fruit juice powder on inflammation and microRNA-132/143 regulation in 3T3-L1 adipocytes (뽕나무 열매 착즙 분말이 3T3-L1 지방세포의 염증 및 microRNA-132/143 조절에 미치는 영향)

  • Lee, Mak-Soon;Kim, Yangha
    • Journal of Nutrition and Health
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    • v.54 no.5
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    • pp.448-458
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    • 2021
  • Purpose: Mulberry (Morus alba L.) fruit is widely grown in Asia and consumed as fresh fruit, jam, and juices. The fruit has beneficial health effects, including anti-diabetic, anti-tumor, and anti-obesity properties. However, the mechanisms by which mulberry fruit juice powder (MJ) regulates inflammatory microRNAs (miRs) are not yet known. This study investigated the effect of mulberry fruit juice powder on the regulation of inflammation and miR-132/143 during 3T3-L1 adipocyte differentiation. Methods: The 3T3-L1 cells were induced to differentiate for 2 days and then treated with various concentrations of MJ for 7 days. Cytotoxicity was determined by evaluating cell viability using a water-soluble tetrazolium salt-8 assay kit. Intracellular lipid accumulation was evaluated by oil-red O staining. The levels of the expression of genes involved in adipogenesis and inflammation, and miR-132/143 were measured by quantitative real-time polymerase chain reactions. Results: MJ showed no cytotoxic effect on 3T3-L1 adipocytes at concentrations below 100 ng/mL. Intracellular lipid accumulation was reduced by MJ treatment at concentrations of 100 ng/mL. The messenger RNA (mRNA) levels of proliferator-activated receptor-γ, cytosine-cytosine-adenosine-adenosine-thymidine/enhancer-binding protein-α, and adipocyte protein 2, which are involved in adipogenesis, were suppressed by MJ. A reduction was also seen in mRNA levels of genes related to the inflammatory response, such as tumor necrosis factor-α, interleukin-6, monocyte chemoattractant protein-1, and inducible nitric oxide synthase. The expression of the inflammatory miR-132 and miR-143 was also decreased by MJ. Conclusion: These results suggest that MJ may suppress adipogenesis and inflammation through the regulation of miR-132/143 expression in 3T3-L1 adipocytes. Thus, MJ may be useful as a food agent that prevents obesity-associated inflammation.

Membrane Free Stem Cell Extract from Adipose Tissue Enhances Glucose Uptake in 3T3-L1 Cells (무막줄기세포추출물의 3T3-L1 세포에서 포도당 흡수 촉진 효과)

  • Kim, Ji Hyun;Kim, Min Jeong;Park, Hye Sook;Kim, Young Sil;Cho, Eun Ju
    • Journal of Korean Medicine for Obesity Research
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    • v.19 no.2
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    • pp.89-96
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    • 2019
  • Objectives: We investigated whether membrane free stem cell extract from adipose tissue (MFSCE) has anti-diabetic effect. Methods: To determine glucose uptake effect of MFSCE, we carried out glucose uptake assay in 3T3-L1 adipocytes. The regulatory mechanisms of MFSCE on glucose uptake were examined by Western blot analysis. Results: When MFSCE was treated to adipocytes at the concentration of 0.5, 1, 2.5, and 5 ㎍/mL, 2-deoxyglucose-6-phosphate uptake was elevated approximately 1.8-fold compared to cells not treated with MFSCE. It indicated that MFSCE enhances glucose uptake in 3T3-L1 adipocytes. In addition, MFSCE reduced phosphorylation of insulin receptor substrate-1 at serine 307 and induced Akt and glucose transporter 4 protein expressions that were related to insulin signaling. Furthermore, MFSCE regulated adenosine monophosphate-activated protein kinase (AMPK) pathway by increases of increase phosphorylation of AMPK and acetyl-CoA carboxylase that were related to AMPK pathway. Conclusions: These results indicated that MFSCE promotes glucose uptake via modulation of insulin signaling and AMPK pathway. Therefore, MFSCE could be a promising agent for treatment of diabetes mellitus.

Bio-assay Guided Isolation and Identification of α-Glucosidase Inhibitors from the Leaves of Diospyros lotus (고욤나무 잎으로부터 활성유도 분획법에 의한 α-Glucosidase 저해물질 분리 및 확인)

  • Kim, Sang Jun;Kim, Ji-Ae;Kim, Da Hye;Kwak, Seol Hwa;Yu, Kang-Yeol;Jang, Seon Il;Kim, Seon-Yeong;Jeong, Seung-Il
    • Korean Journal of Pharmacognosy
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    • v.46 no.2
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    • pp.105-108
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    • 2015
  • To establish the anti-diabetic(α-glucosidase inhibitory) activity of D. lotus leaf extract, isolate and identify the constituents responsible for the activity. The methanolic extract of leaves was partitioned between water, n-butanol and ethyl acetate. Bio-assay guided fractionation, based on inhibition of ;${\alpha}$-glucosidase, allowed isolation and identification of the active components. Liquid chromatography/mass spectrometry(LC/MS), 1 H-NMR and 13 C-NMR spectra analyses demonstrated that the active compound was myricetin-3-O-;${\alpha}$-L-rhamnoside(1). Compound 1 demonstrated a strong inhibition on the α-glucosidase, in vitro and ;${\alpha}$-glucosidase inhibitory value was calculated as 98.08%, when that of a reference drug, acarbose was estimated as 83.03%. The present study indicates compound 1 could be considered as an ;${\alpha}$-glucosidase inhibitor and developed as an important antidiabetes agent for type II diabetes therapy.

Ozonated Sunflower Oil (OSO) Alleviates Inflammatory Responses in Oxazolone-Induced Atopic Dermatitis (AD)-Like Mice and LPS- Treated RAW 264.7 Cells

  • Su-Young Kim;Jung Ok Lee;Sue Lee;Jihye Heo;Kyung-Hyun Cho;Ashutosh Bahuguna;Kwang-Ho Yoo;Beom Joon Kim
    • Journal of Microbiology and Biotechnology
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    • v.34 no.4
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    • pp.765-773
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    • 2024
  • Ozone, a highly reactive oxidant molecule, is widely used as a complementary therapy for various skin diseases, including wound healing, pressure ulcers, diabetic foot, and infections. However, there is limited research on the effectiveness of ozone for atopic dermatitis (AD). Ozonated sunflower oil (OSO) is an active ingredient obtained from partially ozonated sunflower oil (SO). OSO markedly reduced the LPS-induced increase in IL-1β and nitric oxide (NO) levels in RAW 264.7 mouse macrophage cells. Oxazolone (OXZ) was applied to hairless mice to induce AD-like skin symptoms and immune response. OSO significantly alleviated the OXZ-induced increases in the number of infiltrating mast cells, epidermal thickness, AD symptoms, thymic stromal lymphopoietin (TSLP), and filaggrin, as well as the serum levels of NO, IgE, IL-1β, and TNF-α. Furthermore, OSO inhibited the IL-4/STAT3/MAPK pathway and the expression of NF-κB. Our results suggest that OSO treatment could relieve AD-mediated skin damage through its anti-inflammatory and antioxidant activities. Therefore, it can be used as a therapeutic agent against AD-related skin diseases.

Anti-Obestic Effects of Artemisiae Capillaris Herba, Artemisia Capillaris Stem Aqueous Extracts on the High Fat Diet Supplied Mice (고지방 사료 급여 마우스에서 인진쑥 추출물의 항비만 효과)

  • Kim, Hong-Tae;Kim, Dae-Dong;Ku, Sae-Kwang;Kim, Ju-Wan;Jang, Kwang-Ho;Oh, Tae-Ho;Lee, Keun-Woo
    • Journal of Veterinary Clinics
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    • v.27 no.4
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    • pp.348-365
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    • 2010
  • Artemisia capillaries THUNB is a perennial herb that belongs to the family compositae spp. and the most common plant among the various herbal folk remedies used in treatment of abdominal pain, hepatitis, chronic liver disease, jaundice and coughing in Korea. The object of this study is to observe the dosage-dependent anti-obestic effects of an aqueous extracts of dried aqueous extracts of stems of Artemisia capillaris Thunberg. [Artemisiae capillaris Herba, In-Jin in Korean, INJ] on 45%/Kcal high fat diet (HFD) supplied mice. 45%/Kcal rodent HFD are supplied to ICR mice from 1 week before initiation of INJ administration throughout the 12 weeks, and after the end of 12 weeks of 62.5, 125 and 250 mg/kg/day of INJ administration, the efficacy was divided into five categories 1) hypoglycemic, 2) hepato-protective, 3) nephroprotective, 4) hypolipemic, and 5) anti- obesity effects. The effects were compared to those of simvastatin (for hypolipemic activity), silymarin (for hepatoprotective and free radical scavenger effects) and metformin (for hypoglycemic and related anti-obesity effects). 7 animals per group (8 groups; total 56adapted mice on HFD were selected base on the body weight at 6 days after initiation of HFD supply) were used in this experiment. INJ and all three different reference drugs were directly suspended or dissolved in distilled water, and administered at a volume of 10 mL/kg, once a day for 84 days from 1 week after HFD supply. As results of 91 days of continuous HFD supply, mice showed marked obese states, hyperglycemia, hyperlipemia, liver damages and kidney damages. These mean the obesity, diabetes, diabetic hepatopathies, nephropathies and hyperlipemia were induced by HFD supply. After end of 84 days of continuous treatment of three different dosages of INJ, all diabetes related complications were inhibited; relatively favorable anti-obesity, hypolipemic, hepatoprotective, hypoglycemic and nephroprotective effects. These favorable effects showed relatively good dose-relations between all three different dosages of INJ treated, and INJ 250 mg/kg showed enough favorable effects on diabetes and related four complications tested as compared with one of each three different references. Otherwise, the efficacy of 62.5 and 125 mg/kg of INJ was somewhat slighter than those of all three reference drugs. Therefore, the suitable effective dosage of INJ is considered as 250 mg/kg/day in the present study. The overall anti-obesity effects of INJ 250 mg/kg-treated group was similar or more favorable than those of metformin 250 mg/kg-treated group, and INJ 250 mg/kg showed slighter hypoglycemic effects with silymarin 100 mg/kg and metformin 250 mg/kg, similar hypolipemic effects with simvastatin 10 mg/kg, and similar hepatoprotective effects with silymarin 100 mg/kg, and similar nephroprotective effects with that of silymarin 100 mg/kg and metformin 250 mg/kg, respectively. Obese, hyperglycemia, hyperlipemia, steatohepatitis and related nephropathies induced by HFD supply were dramatically inhibited by 84 days of continuous treatment of all three different dosages of INJ. It is, therefore expected that INJ extracts will be a favorable alternative agent for diet-related diabetes and complications.

Protective effect of lycopene against cytokine-induced β-cell apoptosis in INS-1 cells (라이코펜이 사이토카인에 의해 유도된 베타세포 사멸에 미치는 효과 및 기전 연구)

  • Kim, Kyong;Jang, Se-Eun;Bae, Gong Deuk;Jun, Hee-Sook;Oh, Yoon Sin
    • Journal of Nutrition and Health
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    • v.51 no.6
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    • pp.498-506
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    • 2018
  • Purpose: Lycopene, a carotenoid with anti-oxidant properties, occurs naturally in tomatoes and pink grapefruit. Although the beneficial effects of lycopene on various disorders have been established, little attention has been paid to the possible anti-diabetic effects of lycopene focusing on ${\beta}$-cells. Therefore, this study investigated the potential of lycopene to protect ${\beta}$-cells against apoptosis induced by a cytokine mixture. Methods: For toxicity experiments, the cells were treated with 0.1 ~ 10 nM of lycopene, and the cell viability in INS-1 cells (a rat ${\beta}$-cell line) was measured using a MTT assay. To induce cytokine toxicity, the cells were treated with a cytokine mixture (20 ng/mL of $TNF{\alpha}$ + 20 ng/mL of IL-$1{\beta}$) for 24 h, and the effects of lycopene (0.1 nM) on the cytokine toxicity were measured using the MTT assay. The expression levels of the apoptotic proteins were analyzed by Western blotting, and the level of intracellular reactive oxidative stress (ROS) was monitored using a DCFDA fluorescent probe. The intracellular ATP levels were determined using a luminescence kit, and mRNA expression of the genes coding for anti-oxidative stress response and mitochondrial function were analyzed by quantitative reverse-transcriptase PCR. Results: Exposure of INS-1 cells to 0.1 nM of lycopene increased the cell viability significantly, and protected the cells from cytokine-induced death. Lycopene upregulated the mRNA and protein expression of B-cell lymphoma-2 (Bcl-2) and reduced the expression of the Bcl-2 associated X (Bax) protein. Lycopene inhibited apoptotic signaling via a reduction of the ROS, and this effect correlated with the upregulation of anti-oxidative stress response genes, such as GCLC, NQO1, and HO-1. Lycopene increased the mRNA expression of mitochondrial function-related genes and increased the cellular ATP level. Conclusion: These results suggest that lycopene reduces the level of oxidative stress and improves the mitochondrial function, contributing to the prevention of cytokine-induced ${\beta}$-cell apoptosis. Therefore, lycopene could potentially serve as a preventive and therapeutic agent for the treatment of type 2 diabetes.

Systematic Review : Comparative Safety and Efficacy of Mono- and Combination Therapy of Anti-hypertensive Agents Acting on the Renin-Angiotensin System (레닌-안지오텐신계에 작용하는 항고혈압 약제의 단독요법과 병용요법의 안전성 및 유효성에 대한 체계적 문헌고찰)

  • Choi, Kyung-Eob;Kim, Hyun-Kyung
    • 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.

Skin Wrinkle Improvement Effect of Paeoniae radix and processed Paeoniae radix Through inhibition of Advanced glycation end products (AGEs) (작약 및 포제작약의 최종당화산물 억제를 통한 피부 주름 개선 효과)

  • Kim, SuJi;Lee, AhReum;Kim, SooHyun;Kim, KyeongJo;Kwon, OJun;Choi, JoonYoung;Koo, JinSuk;Roh, Seong-Soo
    • 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.

Residual characteristic of tebuconazole and fludioxonil in Allium victorialis (Allium ochotense Prokh.) (소면적 재배작물 산마늘(Allium ochotense Prokh.) 중 살균제 Tebuconazole 및 Fludioxonil의 잔류특성)

  • Woo, Min-Ji;Hur, Kyung-Jin;Kim, Ji-Yoon;Saravanan, Manoharan;Kim, Se-Weon;Hur, Jang-Hyeon
    • The Korean Journal of Pesticide Science
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    • v.19 no.4
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    • pp.354-360
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    • 2015
  • In recent years, Allium victorialis has been extensively used as a pharmacological agent for various diseases in the form of anti-arteriosclerotic, anti-diabetic and anti-cancer. Allium victorialis is severely affected by various fungal diseases since it naturally grow in the shady and humid environments in Korea. In this case, different types of fungicides are applied to control the fungal diseases in Allium victorialis. The present study was aimed to determine the residual characteristics of two fungicides namely tebuconazole and fludioxonil on Allium victorialis. For this study, the fungicides were drenched soil on Allium victorialis in the cultivation area Pyeongchang by the standard (two thousand fold) and double (thousand fold) dilutions. At the end of $15^{th}$, $30^{th}$ and $40^{th}$ days samples were collected for residue analysis. Residues of tebuconazole and fludioxonil were analyzed using GC/NPD (Gas Chromatography/Nitrogen Phosphorus Detector) and their recovery were found to be 108.8~119.5% and 91.3~104.8%, respectively. The method of limits of quantification for both fungicides was $0.01mg\;kg^{-1}$. Further, the results of this study shows that the residue levels of both fungicides on Allium victorialis were <$0.01{\sim}0.12mg\;kg^{-1}$ and $0.01{\sim}0.09mg\;kg^{-1}$ and their % ADI (% Acceptable Daily Intake) were 17.44% and 25.75%, respectively. Based on the results obtained in this study, we suggest that the residue levels of both of the fungicides on Allium victorialis are safe and these fungicides can also be used to control fungal diseases in Allium victorialis.