• Nutrition Research and Practice
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• 제11권5호
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• pp.430-434
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• 2017

BACKGROUND/OBJECTIVE: Chronic hyperglycemia induces oxidative stress via accumulation of reactive oxygen species (ROS) and contributes to diabetic complications. Hyperglycemia induces mitochondrial superoxide anion production through the increased activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. This study aimed to determine whether fisetin and luteolin treatments suppress the oxidative stress by modulating the expression of sirtuins (SIRTs) and forkhead box O3a (FOXO3a) under hyperglycemic conditions in human monocytes. MATERIALS/METHODS: Human monocytic cells (THP-1) were cultured under osmotic control (14.5 mmol/L mannitol), normoglycemic (NG, 5.5 mmol/L glucose), or hyperglycemic (HG, 20 mmol/L glucose) conditions, in the absence or presence of fisetin and luteolin for 48 h. To determine the effect of fisetin and luteolin treatments on high glucose-induced oxidative stress, western blotting and intracellular staining were performed. RESULTS: Hyperglycemic conditions increased the ROS production, as compared to normoglycemic condition. However, fisetin and luteolin treatments inhibited ROS production under hyperglycemia. To obtain further insight into ROS production in hyperglycemic conditions, evaluation of p47phox expression revealed that fisetin and luteolin treatments inhibited p47phox expression under hyperglycemic conditions. Conversely, the expression levels of SIRT1, SIRT3, SIRT6, and FOXO3a were decreased under high glucose conditions compared to normal glucose conditions, but exposure to fisetin and luteolin induced the expression of SIRT1, SIRT3, SIRT6, and FOXO3a. The above findings suggest that fisetin and luteolin inhibited high glucose-induced ROS production in monocytes through the activation of SIRTs and FOXO3a. CONCLUSIONS: The results of our study supports current researches that state fisetin and luteolin as potential agents for the development of novel strategies for diabetes.

• 생약학회지
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• 제27권1호
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• pp.65-74
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• 1996

The studies were conducted to investigate the anti-diabetic activities on the hyperglycemia induced by streptozotocin in rats, Anti-fatigue, Decrease of body weight activities in mouse and anti-gastric ulcer activities in stress-induced rats by Mixed Extracts of Acantopanacis senticosi Radicis Cortex and Eucommiae Cortex in Korea. 1. The blood glucose levels of streptozotocin-induced hyperglycemic rats were dose-dependently decreased by administrations of various doses(100, 200, 400, significantly 200+100mg/kg) of Mixed Extracts from Acantopanacis senticosi Radicis Cortex and Eucommiae Cortex. 2. The serum total cholesterol levels of streptozotocin-induced hyperglycemic rats were dose-dependently decreased by administrations of various doses (100, 200, 400, significantly 200+100mg/kg) of Mixed Extracts from Acantopanacis senticosi Radicis Cortex and Eucommiae Cortex. 3. The serum triglyceride levels of streptozotocin-induced hyperglycemic rats were dose-dependently decreased by administrations of various doses(100, 200, 400, significantly 200+100mg/kg) of Mixed Extracts from Acantopanacis senticosi Radicis Cortex and Eucommiae Cortex. 4. The swimming time levels in mouse were dose-dependently extended by administrations of various doses(100, 200, 400, significantly 200+100mg/kg) of Mixed Extracts from Acantopanacis senticosi Radicis Cortex and Eucommiae Cortex. 5. The body weight levels in mouse were dose-dependently decreased by administrations of various doses(100, 200, 400, significantly 200+100mg/kg) of Mixed Extracts from Acantopanacis senticosi Radicis Cortex and Eucommiae Cortex. 6. Stress-induced gastric ulcer were dose-dependently repaired by administrations of various doses(100, 200, 400, significantly 200+100mg/kg) of Mixed Extracts from Acantopanacis senticosi Radicis Cortex and Eucommiae Cortex.

• 생명과학회지
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• 제33권11호
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• pp.851-858
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• 2023

Unique cartilage matrix-associated protein (UCMA)은 γ-카르복실화(Gla) 잔기가 풍부한 간외 비타민 K 의존 단백질이다. UCMA는 조골세포 분화를 촉진하고 뼈 형성을 강화한다고 보고되고 있지만 고혈당 스트레스 하에서 조골세포에 미치는 영향에 대해서는 아직 알려진 바가 없다. 본 연구에서는 고혈당 조건하에서의 MC3T3-E1 조골세포에서 UCMA 효과를 조사하기 위해 MC3T3-E1 조골세포를 높은 포도당에 노출한 후 재조합 UCMA 단백질을 처리하였다. MC3T3-E1 세포에서 활성 산소종(ROS)의 생성은 고혈당 조건하에서 증가했으나 UCMA 단백질 처리 후 감소했음을 CellROX 및 MitoSOX 염색으로 확인하였다. 또한 고혈당 조건에서 UCMA 단백질을 함께 처리한 MC3T3-E1 세포에서 정량적 중합효소 연쇄반응 결과, 항산화 유전자인 nuclear factor erythroid 2-related factor 2 와 superoxide dismutase 1 발현이 증가하였다. 동일 조건하에서 UCMA 단백질 처리에 의해 heme oxygenase-1 발현 감소와 함께 세포질에서 핵으로의 전위가 감소되었고, 미토콘드리아 분열에 관여하는 dynamin-related protein 1 발현이 증가하였으며, AKT 신호 활성은 억제되었다. 종합적으로 UCMA는 고혈당에 노출된 조골세포에서 ROS 생성을 완화하고, 항산화 유전자 발현을 증가시키고, 미토콘드리아 역학에 영향을 미치며, AKT 신호를 조절하는 것으로 보인다. 본 연구는 UCMA의 세포 메커니즘에 대한 이해를 돕고, 대사 장애 관련한 골 합병증에 대한 새로운 치료제로서의 잠재적 사용 가능성을 제시하고 있다.

• Biomolecules & Therapeutics
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• 제17권2호
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• pp.175-180
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• 2009

Taurine is the most abundant free amino acid in the retina and transported into retina via taurine transporter (TauT) at the inner blood-retinal barrier (iBRB). In the present study, we investigated whether the taurine transport at the iBRB is regulated by oxidative stress or disease-like state in a conditionally immortalized rat retinal capillary endothelial cell line (TR-iBRB) used as an in vitro model of iBRB. First, [$^3H$]taurine uptake and efflux by TR-iBRB were regulated in the presence of extracellular $Ca^{2+}$. [$^3H$]Taurine uptake was inhibited and efflux was enhanced under $Ca^{2+}$ free condition in the cells. In addition, oxidative stress inducing agents such as tumor necrosis factor-$\alpha$ (TNF-$\alpha$), lipopolysaccharide (LPS), diethyl maleate (DEM) and glutamate increased [$^3H$]taurine uptake and decreased [$^3H$]taurine efflux in TR-iBRB cells. Whereas, 3-morpholinosydnonimine (SIN-1), which is known to NO donor decreased [$^3H$]taurine uptake. Lastly, TR-iBRB cells exposed to high glucose (25 mM) medium and the [$^3H$]taurine uptake was reduced about 20% at the condition. Also, [$^3H$]taurine uptake was decreased by cytochalasin B, which is known to glucose transport inhibitor. In conclusion, taurine transport in TR-iBRB cells is regulated diversely at extracellular $Ca^{2+}$, oxidative stress and hyperglycemic condition. It suggested that taurine would play a role as a retinal protector in diverse disease states.

• Clinical and Experimental Pediatrics
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• 제51권5호
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• pp.474-480
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• 2008

목 적 : 스트레스성 고혈당은 중환자의 급성 질병기에 흔히 동반되며, 이는 여러 질환의 유병율과 사망률을 증가시킨다. 이 연구는 미숙아에서 생후 48시간 이내에 나타나는 스트레스성 고혈당이 예후에 어떤 영향을 미치는지 알아보고자 하였다. 방 법 : 재태 주령 30주 이하의 신생아 141명을 대상으로, 생후 48시간동안 혈당이 한번이라도 150 mg/dL 이상이었던 고혈당군(n=61)과 모두 150 mg/dL 미만이었던 비고혈당군(n=80)으로 분류하였다. 두 군의 분만력 상의 특징, CRIB score를 이용한 임상적 중증도, 임상 경과, 예후 및 사망률에 대해 비교하였다. 결 과 : 두 군의 재태 주령은 차이가 없었으나, 고혈당군에서 비고혈당군에 비해 출생체중은 더 작았고(P<0.001), CRIB 점수는 더 높았다(P<0.001). 임상적으로 패혈증이 의심된 경우와 파종성 혈관내응고증은 고혈당군에서 더 많았으며(P=0.046, P< 0.001), 사망률은 고혈당군이 41.0%, 비고혈당군이 11.3%로 고혈당군에서 월등히 높았다(P<0.001). 단계적 로지스틱 회귀분석 결과, 고혈당(OR 3.787; 95% CI 1.324 to 10.829)은 CRIB score (OR 1.252; 95% CI 1.047 to 1.496), 출생체중(OR 0.997; 95% CI 0.994 to 1.000)과 함께 사망률에 독립적으로 의미 있는 영향을 미쳤다. 결 론 : 30주 이하의 미숙아에서 생후 48시간 이내에 나타나는 스트레스성 고혈당은 임상 경과의 악화 및 사망률의 증가와 독립적인 연관성을 보였다.

• Natural Product Sciences
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• 제15권3호
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• pp.167-172
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• 2009

The protective effects of Phaleria macrocarpa (PM) against oxidative stress in diabetic rats were investigated. Diabetes was induced in male Sprague Dawley rats using alloxan (150 mg/kg i.p). After the administration of PM fractions for two weeks the diabetic symptoms, nephropathy and renal antioxidant enzymes were evaluated. The results showed that the oral PM treatments reduced blood glucose levels in diabetic rats. The PM fractions decreased kidney hypertrophy and diminished blood urea nitrogen (BUN) in diabetic rats. Malondialdehyde (MDA), a lipid peroxidation marker, was increased in diabetic animals, but was suppressed by the PM treatments. In addition, the superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities, and glutathione (GSH) level in the alloxan-induced diabetic rats were significantly decreased compared with those in the normal rats, but were restored by PM treatments. The PM fractions also suppressed the level of MDA in the kidney. In conclusion, the anti hyperglycemic and anti-nephropathy of P. macrocarpa may be correlated to the increased renal antioxidant enzyme activity in the kidney.

• Nutrition Research and Practice
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• 제8권1호
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• pp.20-26
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• 2014

Obesity is an epidemic disease characterized by an increased inflammatory state and chronic oxidative stress with high levels of pro-inflammatory cytokines and lipid peroxidation. Moreover, obesity alters cholesterol metabolism with increases in low-density lipoprotein (LDL) cholesterols and triglycerides and decreases in high-density lipoprotein (HDL) cholesterols. It has been shown that mulberry leaf and fruit ameliorated hyperglycemic and hyperlipidemic conditions in obese and diabetic subjects. We hypothesized that supplementation with mulberry leaf combined with mulberry fruit (MLFE) ameliorate cholesterol transfer proteins accompanied by reduction of oxidative stress in the high fat diet induced obesity. Mice were fed control diet (CON) or high fat diet (HF) for 9 weeks. After obesity was induced, the mice were administered either the HF or the HF with combination of equal amount of mulberry leaf and fruit extract (MLFE) at 500mg/kg/day by gavage for 12 weeks. MLFE treatment ameliorated HF induced oxidative stress demonstrated by 4-hydroxynonenal (4-HNE) and modulated the expression of 2 key proteins involved in cholesterol transfer such as scavenger receptor class B type 1 (SR-B1) and ATP-binding cassette transporter A1 (ABCA1) in the HF treated animals. This effect was mainly noted in liver tissue rather than in cutaneous tissue. Collectively, this study demonstrated that MLFE treatment has beneficial effects on the modulation of high fat diet-induced oxidative stress and on the regulation of cholesterol transporters. These results suggest that MLFE might be a beneficial substance for conventional therapies to treat obesity and its complications.

• Natural Product Sciences
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• 제15권1호
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• pp.37-43
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• 2009

Oxidative stress is caused by an imbalance between the production of reactive oxygen and an ability of a biological system, to readily detoxify the reactive intermediates or easily repair the resulting damage. It has been suggested that developmental alloxan-induced liver damage is mediated through increases in oxidative stress. The anti-diabetic effect and antioxidant activity of Phaleria macrocarpa (PM) fractions were investigated in alloxan-induced diabetic rats. After two weeks administration of PM, the liver antioxidant enzyme and hyperglycemic state were evaluated. The results showed that oral administration of PM treatments reduced blood glucose levels in diabetic rats by oral administration (P < 0.05). Serum glutamic-oxaloacetic transaminase (sGOT) and serum glutamic-pyruvate-transaminase (sGPT) were also diminished by PM supplementation. The superoxide dismutase (SOD), catalase (CAT) and glutathione-peroxidase (GPx) activities, and glutathione (GSH) level in the alloxan-induced diabetic rats were significantly decreased (P < 0.05) compared to those in the normal rats but were restored by PM treatments. PM fractions also repressed the level of malondialdehyde (MDA) in the liver. Glutathione reductase (GR), glutathione-S-transferase (GST) and $\gamma$-glutamylcysteine synthase (GCS) were also reduced in alloxan-induced diabetic rats. PM fractions could restore the GR and GST activities, but the GCS activity was not affected in rat livers. From the results of the present study, the diabetic effect of the butanol fraction of PM against alloxan-induced diabetic rats was concluded to be mediated either by preventing the decline of hepatic antioxidant status or due to its indirect radical scavenging capacity.

• 한국식품과학회지
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• 제49권6호
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• pp.668-675
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• 2017

본 연구에서는 눈개승마(Aruncus dioicus var. kamtschaticus)의 in vitro 산화방지활성 및 고당(intensive glucose)과 과산화수소($H_2O_2$)로 야기된 산화적 스트레스로부터의 뇌신경세포 손상에 대한 보호효과와 더불어 알파글루코사이드가수분해효소 및 아세틸콜린에스터가수분해효소 억제효과를 확인하였으며 또한 HPLC를 이용하여 주요 물질을 분석하였다. 눈개승마 아세트산에틸 분획물(ethylacetate fraction from Aruncus dioicus var. kamtschaticus: EFAD)은 매우 우수한 총 페놀화합물 함량(430.08 mg GAE/g)과 총 플라보노이드 함량(511.72 mg RE/g)을 나타냈으며, 높은 ABTS 라디칼 소거 활성과 과산화지방질생성물의 억제력을 확인하였다. 또한 고당(intensive glucose)과 과산화수소($H_2O_2$)로 야기된 뇌신경세포에서의 산화적 스트레스 및 이로 인한 뇌신경세포 사멸을 측정한 결과, 눈개승마 아세트산에틸 분획물(EFAD)의 유의적인 뇌신경세포 보호효과를 확인할 수 있었다. 추가적으로 다당류 분해 효소인 알파글루코사이드가수분해효소 억제효과 및 아세틸콜린 분해 효소인 아세틸콜린에스터가수분해효소 억제효과를 살펴봄으로써 혈당 상승 억제효과와 뇌신경전달물질의 세포 내 유지 효과를 확인하였다. 마지막으로 눈개승마 아세트산에틸 분획물(EFAD)의 주요 페놀성 물질을 확인하기 위해 HPLC분석을 한 결과 카페산으로 추정되었다. 본 연구 결과들을 고려할 때, 눈개승마는 고혈당 지연 또는 개선을 통한 고혈당 예방 소재로서의 가능성뿐만 아니라 이로 인해 야기되는 산화적 스트레스로부터 뇌신경 세포를 보호함으로써 고혈당에 의한 대사성 뇌신경질환 예방 소재로도 활용 가능성이 있을 것이라 판단된다.

• 대한한방내과학회지
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• 제31권1호
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• pp.25-39
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• 2010

Background : At high glucose levels in $\beta$-cells, cell viability and insulin secretion are decreased by glucotoxicity. Sopyung-tang(SPT) had an effect on blood glucose level decrease and antioxidant enzyme activities in streptozotocin-induced diabetic rats. Objectives : This study performed a series of experiment to verify the effects of SPT extract on the cell viability, antioxidant enzyme activities, insulin secretion and insulin mRNA expression at hyperglycemic states of RIN-m5F. Methods : After treatment at various concentrations of SPT added to the RIN-m5F cells, cell viability by MTT assay, free radical-scavenging activity, SOD activity and insulin secretion were measured. Additionally, insulin-related gene expression was measured using real-time RT-PCR. Results : Compared to the control group, SPT extract showed considerable effects on RIN-m5F cell viability, DPPH radical-scavenging activity, superoxide dismutase (SOD) activity, insulin secretion and insulin-related gene expression. Conclusions : This study showed that SPT extract has an effect on $\beta$-cell cell viability, insulin secretion and insulin-related gene expression. Thus, SPT extract may be used for treatment of diabetes and its complications. Further mechanism studies of SPT seem to be necessary on the glucotoxicity and oxidative stress.