• Journal of Nutrition and Health
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• 제53권1호
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• pp.1-12
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• 2020

본 연구에서는 고혈당으로 인해 유발되는 당뇨병성 신장병증의 대표적인 증상인 사구체 경화증을 완화시키는 nobiletin의 효능에 대해 알아보고자 하였다. 신장 세포인 HRMC를 이용하여 고혈당에서의 세포외 기질 축적 단백질의 발현과 경화에 관여하는 신호 전달 억제 효능을 확인한 결과 nobiletin은 고혈당의 자극에 의해 증가하는 섬유화 단백질인 collagen IV, fibronectin 그리고 CTGF의 발현을 억제하였으며, 여기에 관여하는 TGF-β1-Src-caveolin-1 신호 전달 경로를 통해 사구체 경화증을 억제하는 것을 확인하였다. 따라서 nobiletin은 고혈당으로 유도된 당뇨병성 신장병증에 있어 사구체 경화증을 예방하는 기능성 성분으로서의 활용 가능성을 확인하였다.

• The Korean Journal of Physiology and Pharmacology
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• 제22권3호
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• pp.311-319
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• 2018

Mitochondrial calcium overload is a crucial event in determining the fate of neuronal cell survival and death, implicated in pathogenesis of neurodegenerative diseases. One of the driving forces of calcium influx into mitochondria is mitochondria membrane potential (${\Delta}{\psi}_m$). Therefore, pharmacological manipulation of ${\Delta}{\psi}_m$ can be a promising strategy to prevent neuronal cell death against brain insults. Based on these issues, we investigated here whether nobiletin, a Citrus polymethoxylated flavone, prevents neurotoxic neuronal calcium overload and cell death via regulating basal ${\Delta}{\psi}_m$ against neuronal insult in primary cortical neurons and pure brain mitochondria isolated from rat cortices. Results demonstrated that nobiletin treatment significantly increased cell viability against glutamate toxicity ($100{\mu}M$, 20 min) in primary cortical neurons. Real-time imaging-based fluorometry data reveal that nobiletin evokes partial mitochondrial depolarization in these neurons. Nobiletin markedly attenuated mitochondrial calcium overload and reactive oxygen species (ROS) generation in glutamate ($100{\mu}M$)-stimulated cortical neurons and isolated pure mitochondria exposed to high concentration of $Ca^{2+}$ ($5{\mu}M$). Nobiletin-induced partial mitochondrial depolarization in intact neurons was confirmed in isolated brain mitochondria using a fluorescence microplate reader. Nobiletin effects on basal ${\Delta}{\psi}_m$ were completely abolished in $K^+-free$ medium on pure isolated mitochondria. Taken together, results demonstrate that $K^+$ influx into mitochondria is critically involved in partial mitochondrial depolarization-related neuroprotective effect of nobiletin. Nobiletin-induced mitochondrial $K^+$ influx is probably mediated, at least in part, by activation of mitochondrial $K^+$ channels. However, further detailed studies should be conducted to determine exact molecular targets of nobiletin in mitochondria.

• 대한화학회지
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• 제46권3호
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• pp.205-212
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• 2002

청피의 생리활성 물질인 methoxy flavonoids를 컬럼크로마토그래피와 preparative-HPLC 방법으로분리하였으며 흰쥐의 기관지 평활근에 미치는 이완효과를 조사하였다. Acetylcholine($ED_{50}:3{\times}10^{-6}M$)으로 흰쥐의 기관지 평활근을 수축시킨 후, 크로마토그래피의 분획별로 처리하였다. 수축된 기관지 평활근을 에칠아세테이트의 2차분리 분획무로 처리한 결과 methoxy기가 6개인 flavonoid(nobiletin)의 분획물이 가장 좋은 결과를 나타내었다. 이로써 nobiletin과 그의 유사물질이 기관지 천식이나 해소의 유망한 치료제로 작용할 수 있음을 알았다.

• Preventive Nutrition and Food Science
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• 제14권4호
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• pp.362-366
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• 2009

To determine the effect of electron-beam irradiation on the contents of polymethoxylated flavones (PMFs) extracts from citrus pomaces (CP), CP was irradiated at 0, 1, 2, or 5 kGy. Methanol extract of the irradiated CP were prepared and the PMF (nobiletin, sinensetin, and tangeretin) content of the extract was determined. Nobiletin and sinensetin of CP extract significantly increased with irradiation dose-dependent. However, electron-beam irradiation decreased the amount of tangeretin in the CP extract. These data suggest that irradiation can liberate phenolic compounds such as nobiletin or sinensetin, but tangeretin might have different pathway of conversion by irradiation. Therefore, irradiation can be a tool to change the composition of PMFs in CP.

• Natural Product Sciences
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• 제2권2호
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• pp.106-114
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• 1996

Four polymethoxyfavones were isolated from the leaves of Citrus deliciosa, three of which (nobiletin, 5-O-demethylnobiletin, and tangeritin) are bioactive. The fourth (7,4'-dihydroxy-5,6,8,3'-tetramethoxyflavone) is reported for the first time in the genus Citrus and is a potential chemotaxonomic marker. The structures of these flavones were confirmed by analysing their spectral data and comparison with similar compounds. The previously reported $^{13}C$ NMR assignment of 5-O-demethylnobiletin has been revised on the basis of 2D NMR experiments (HETCOR, COSY, and COLOC). The chemotaxonomic value of the present finding is verified.

• Journal of Medicine and Life Science
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• 제15권1호
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• pp.6-11
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• 2018

Previous studies have suggested that Citrus fruits might suppress the proliferation of various cancer cells. However, little is known about any specific ingredients in the extract of Citrus fruits to exert its anti-proliferative activity in cancer cells. The present study aimed to identify the active ingredients in Citrus fruits to suppress the proliferation of rat hepatocellular carcinoma cells. Among tested compounds, two polymethoxylated flavones (nobiletin and tangeritin) showed significant anti-proliferative activity whereas other compounds (synephrine, rutin, hesperidin) did not. Interestingly, nobiletin as well as tangeritin also decreased the protein amount of gluconeogenic enzymes, PEPCK and G6Pase. The possible involvement of gluconeogenic activity in the proliferation of hepatocellulacarcinoma cells are further to be investigated.

• Nutrition Research and Practice
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• 제15권4호
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• pp.431-443
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• 2021

BACKGROUND/OBJECTIVES: Nobiletin (NOB), a citrus flavonoid, is reported to have beneficial effects on cardiovascular and metabolic health. However, there is limited research investigating the effect of long-term supplementation with low-dose NOB on high-cholesterol diet (HCD)-induced hypercholesterolemia and non-obese nonalcoholic fatty liver disease (NAFLD). Therefore, we investigated the influence of NOB on hypercholesterolemia and NAFLD in HCD-fed mice. SUBJECTS/METHODS: C57BL/6J mice were fed a normal diet (ND) or HCD (35 kcal% fat, 1.25% cholesterol, 0.5% cholic acid) with or without NOB (0.02%) for 20 weeks. RESULTS: HCD feeding markedly reduced the final body weight compared to ND feeding, with no apparent energy intake differences. NOB supplementation suppressed HCD-induced weight loss without altering energy intake. Moreover, NOB significantly decreased the total cholesterol (TC) levels and the low-density lipoprotein (LDL)/very-LDL-cholesterol to TC ratio, and increased the high-density lipoprotein-cholesterol/TC ratio in plasma, compared to those for HCD feeding alone. The plasma levels of inflammatory and atherosclerosis markers (C-reactive protein, oxidized LDL, interleukin [IL]-1β, IL-6, and plasminogen activator inhibitor-1) were significantly lower, whereas those of anti-atherogenic adiponectin and paraoxonase were higher in the NOB-supplemented group than in the HCD control group. Furthermore, NOB significantly decreased liver weight, hepatic cholesterol and triglyceride contents, and lipid droplet accumulation by inhibiting messenger RNA expression of hepatic genes and activity levels of cholesterol synthesis-, esterification-, and fatty acid synthesis-associated enzymes, concomitantly enhancing fatty acid oxidation-related gene expression and enzyme activities. Dietary NOB supplementation may protect against hypercholesterolemia and NAFLD via regulation of hepatic lipid metabolism in HCD-fed mice; these effects are associated with the amelioration of inflammation and reductions in the levels of atherosclerosis-associated cardiovascular markers. CONCLUSIONS: The present study suggests that NOB may serve as a potential therapeutic agent for the treatment of HCD-induced hypercholesterolemia and NAFLD.

• 한국자원식물학회지
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• 제28권1호
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• pp.16-25
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• 2015

온주밀감 60품종에 대하여 착색 개시기에 과즙의 플라보노이드 조성 및 함량을 분석하고 품종들과의 연관관계를 조사하였다. 온주밀감 과즙에서는 flavanones에 속하는 narirutin, hesperidin과, flavones인 rutin, polymethoxylated flavones인 sinensetin, tangeretin, nobiletin 등 6종을 함유하고 있는 것으로 나타났다. 온주밀감 과즙 중에는 narirutin, hesperidin 함량이 가장 높아 대표적인 기능성 성분으로 나타났으며, 기능성이 우수한 polymethoxylated flavones인 sinensetin, tangeretin, nobiletin도 함유하고 있었다. Hesperidin 함량 범위는 41~196 mg/L로, narirutin 함량은 25~230 mg/L로 나타났다. Rutin 함량은 평균 2.2 mg/L로 미량이 검출되었고 일부 품종에서는 전혀 검출이 이루어지지 않았다. 감귤에 특이적으로 나타나는 polymethoxylated flavones류인 sinensetin, nobiletin, tangeretin은 미량이지만 모든 품종에서 검출되었다. 온주밀감 과즙 중에 함유된 플라보노이드 조성 및 함량과 품종의 수확기와의 연관성을 분석하고자 R 프로그램으로 계층적 군집분석을 실시한 결과, 플라보노이드 성분별 함량에 따라 A, B1, B2 집단으로 구분할 수 있었으나 세집단 모두에서 극조생온주밀감, 조생온주밀감, 보통온주밀감이 산재하여 있어 착색개시기 과즙 중 플라보노이드 분포와 과실의 성숙기와는 관련성이 적은 것으로 나타났다.

• 분석과학
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• 제14권4호
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• pp.331-339
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• 2001

감귤류와 한국산 청피에 함유된 methoxylated flavonoids (sinenstin, nobiletin, tangeretin)를 HPLC, mass 그리고 NMR로 분리하고 분석하였다. Methoxylated flavonoids는 Chung-pi(I)과 Chung-pi(II)에 가장 풍부하게 함유되었다. 한국산 밀감에서 얻어진 Chung-pi(I), (II)의 methoxylated flavonoids 함유량은 밀감성숙도에 따라 증가하였으며, 10월 중순이후에는 서서히 감소하였다.

• Preventive Nutrition and Food Science
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• 제7권1호
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• pp.1-4
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• 2002

Eleven flavonoids, including rutin, naringin, hesperidin, neohesperidin, quercetin, naringenin, kaempferol, hesperetin, nobiletin, 3,5,6,7,8,3',4'-methoxylated flavone and tangeretin in the peel of late maturing citrus fruit species of Mucott (smith tangerine), Singamha (C. natsudidai), Sambogam (C. sulcata), Hongpalsak (C. hassaku), Seminol (Dancy tangerine) and Jawdung (C. aurantium) harvested during from August to December were analyzed with HPLC. The mobile phase consisted of water and acetonitrile with 0.5% acetic acid. Wavelength in UV detector was determined at 254 nm. Naringin and neohesperidin content in the peel of Jawdung harvested at the early stage of maturation were 34.02 mg/g and 13.68 mg/g, respectively, and it was highest among the tested citrus fruits. Hesperidin content in the peel of Mucott harvested at the earthy stage of maturation was 12.48 mg/g. Rutin content of Sambogam harvested at the early stage of maturation was 5.13 mg/g. Quercetin, naringein, kaempferol, nobiletin, 3,5,6,7,8,3',4'-methoxylated flavone flavonoids were in trace. Flavonoid contents of Singamha, Sambogam and Jawdung were high in the peel of fruits at the early stage of maturation, after which time they decreased rapidly.