• 대한화장품학회지
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• 제46권4호
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• pp.391-401
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• 2020

플라보노이드(flavonoid)는 식물 등의 대사체에서 유래한 폴리페놀 계열의 화합물이며, 다양한 인체생리작용을 조절할 수 있는 것으로 알려져 있다. 이중 3,3',3',7-tetrahydroxyflavone (fisetin)은 다양한 과일과 채소에서 발견되며, 최근 노쇠용해(senolytic) 활성을 통해 특정 조직의 기능을 회복시킨다는 것이 알려졌다. 본 연구에서는 인간 표피 각질세포를 대상으로 하여 fisetin의 피부장벽 유전자 발현 조절 및 항노화 효능을 분석하였다. Fisetin은 말단소립 역전사효소(telomerase)의 활성을 증가시켰으며, CDKN1B 유전자의 발현을 감소시켰다. 또한 피부장벽을 구성하는 주요 유전자인 KRT1, FLG, IVL, DSP의 발현을 증가시켰으며, 세라마이드 합성효소의 일종인 CerS3, CerS4 유전자의 발현을 증가시켰다. 이러한 결과는 fisetin의 효능이 노쇠용해에 국한되지 않고 인간 각질세포의 다양한 생리학적 조절에도 관여함을 보여준다. 따라서 fisetin은 화장품 및 의약품 등의 생리활성 조절물질로 활용될 수 있다고 사료된다.

• Bulletin of the Korean Chemical Society
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• 제34권9호
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• pp.2629-2634
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• 2013

Fisetin is a naturally occurring flavonoid with some anti-cancer and anti-inflammation capabilities. In this study, we perform docking studies between human c-Jun N-terminal kinase 1 (JNK 1) and fisetin and proposed a binding model of fisetin and JNK 1, in which the hydroxyl groups of the B ring and oxygen at the 4-position of the C ring play key roles in binding interactions with JNK. Fluorescence quenching and saturation-transfer difference (STD) NMR experiments showed that fisetin exhibits good binding affinity to JNK, $1.32{\times}10^8M^{-1}$. The anti-inflammatory activity of fisetin was also investigated. Fisetin significantly suppressed tumor necrosis factor, the NO production, and macrophage inflammatory cytokine release in LPS-stimulated RAW264.7 mouse macrophages. We found that the anti-inflammatory cascade of fisetin was mediated through the JNK, and cyclooxygenase (COX)-2 pathways. Our findings suggest the potential of fisetin as an anti-inflammatory agent.

• 대한의생명과학회지
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• 제24권2호
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• pp.130-133
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• 2018

The aim of this study was to evaluate the protective function of fisetin, a natural flavonoid in zebrafish heart for the treatment of myocardial infarction in coronary and ischemic heart disease. For this purpose, we induced oxidative stress zebrafish (Danio rerio)-Tg (cmlc2: egfp) by $H_2O_2$ and then administered fisetin, the protective effect of fisetin was determined by measuring the heart rate following fisetin administration. After testing the toxicity of fisetin, we found that the heartt increased in a concentration-dependent manner, however there was no difference between the heart rates of embryos and adults. The improved heart rate demonstrated the cardioprotective effect of fisetin. The result showed that fisetin, at concentration of 3and $5{\mu}M$, significantly increased heart rate compared with the heart with $H_2O_2$ alone. This indicates that fisetin plays an important role in the prevention of heart damage and treatment of cardiovascular diseases caused by oxidative stress due to ischemia / reperfusion.

• Biomolecules & Therapeutics
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• 제23권5호
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• pp.414-420
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• 2015

Flavonoids, such as fisetin (3,7,3',4'-tetrahydroxyflavone), are plant secondary metabolites. It has been reported that fisetin is able to perform numerous pharmacological roles including anti-inflammatory, anti-microbial, and anti-cancer activities; however, the exact anti-inflammatory mechanism of fisetin is not understood. In this study, the pharmacological action modes of fisetin in lipopolysaccharide (LPS)-stimulated macrophage-like cells were elucidated by using immunoblotting analysis, kinase assays, and an overexpression strategy. Fisetin diminished the release of nitric oxide (NO) and reduced the mRNA levels of inducible NO synthase (iNOS), tumor necrosis factor (TNF)-${\alpha}$, and cyclooxygenase (COX)-2 in LPS-stimulated RAW264.7 cells without displaying cytotoxicity. This compound also blocked the nuclear translocation of p65/nuclear factor (NF)-${\kappa}B$. In agreement, the upstream phosphorylation events for NF-${\kappa}B$ activation, composed of Src, Syk, and I${\kappa}B{\alpha}$, were also reduced by fisetin. The phospho-Src level, triggered by overexpression of wild-type Src, was also inhibited by fisetin. Therefore, these results strongly suggest that fisetin can be considered a bioactive immunomodulatory compound with anti-inflammatory properties through suppression of Src and Syk activities.

• 약학회지
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• 제56권5호
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• pp.326-332
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• 2012

Mast cells play pivotal pathologic roles in allergic disease involving T helper 2 (Th2) cytokine such as interleukin (IL)-4 and IL-13. Fisetin has been known as an anti-allergic agent having inhibitory effects on the IL-4 and IL-13 gene expressions in inflammatory immune cells. However, its molecular mechanisms for suppressive effects of fisetin on IL-4 and IL-13 in activated mast cells have been incompletely elucidated. In this study we found that fisetin significantly inhibited the phorbol 12-myristate 13-acetate (PMA) and ionomycin (PI)-induced production of IL-4 and IL-13 in mast cells. The levels of mRNA were dramatically decreased by fisetin, indicating the suppression might be regulated at the transcriptional levels. Western blot analysis of the nuclear expression of various transcription factors involved in the promoter activation indicated that suppression of c-Fos was prominent together with significant down-regulation of nuclear factor of activated T-cell (NF-AT) and NF-${\kappa}B$, but not c-Jun. Furthermore, the nuclear expression of GATA binding protein 2 (GATA-2) transcription factor was significantly down-regulated by fisetin. Taken together, our study indicated fisetin has suppressive effects on IL-4 and IL-13 gene expression through the regulation of selective transcription factors.

• 생명과학회지
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• 제17권1호
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• pp.64-69
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• 2007

본 연구에서는 UVB에 조사된 NIH3T3 세포에서 세포고사와 DNA 단사절단에 미치는 fisetin후처리의 효과에 대해서 연구하였다. 세포에 UVB $(200J/m^2)$를 조사하고 정상배지에서 48시간 배양한 세포의 세포고사에 수반되는 핵분절은 50% 정도의 세포에서 관찰되었다. 흥미롭게도 배양배지에 fisetin이 첨가될 경우 핵분절을 보이는 세포의 빈도는 상당한 감소를 보였다. 알칼리 아가로스 겔에 의한 DNA 단사절단 분석에서 자외선 조사 후 fisetin처리는 정상배지 배양시보다 단사절단의 빈도를 감소시켜 DNA크기의 증가를 유도하였는데 이는 fisetin이 UVB에 의한 DNA 상해의 회복에 긍정적 효과를 나타냄을 시사한다 Western blot 분석에 의해 fisetin은 자외선 조사에 의해 활성화되는 p53의 수준을 유의한 수준으로 감소시키며 자외선 상해의 결과 세포주기의 정지에 수반되는 PCNA의 감소 경향을 다소 완화시켰다. 이러한 결과들은 fisetin이 DNA 회복의 활성을 통해 세포고사의 감소에 기여하며 이 과정에서 p53 및 PCNA의 수준변화와 관련하여 행동함을 시사한다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권22호
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• pp.9835-9839
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• 2014

Fisetin is an effective compound extracted from lacquer which has been used in the treatment of various diseases. Preliminary data indicate that it also exerts specific anti-cancer effects. However, the manner in which fisetin regulates cancer growth remains unknown. In this study, we elucidated interference of fisetin with targets of the nuclear factor ${\kappa}B$ signal transduction pathway activated by Epstein-Barr virus encoding latent membrane protein 1 (LMP1)in nasopharyngeal carcinoma (NPC) cells, Results showed that fisetin inhibited the survival rate of CNE-LMP1 cells and NF-${\kappa}B$ activation caused by LMP1. Fisetin also suppressed nuclear translocation of NF-${\kappa}B$ (p65) and $I{\kappa}B{\alpha}$ phosphorylation, while inhibiting CyclinD1, all key targets of the NF-${\kappa}B$ signal transduction pathway. It was suggested that interference effects of fisetin with signal transduction activated by LMP1 encoded by the Epstein-Barr virus may play an important role in its anticancer potential.

• 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.

• Biomolecules & Therapeutics
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• 제24권1호
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• pp.57-61
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• 2016

Fisetin, a natural flavonoid found in a variety of vegetables and fruits, has been shown to possess many biological functions. The present study was undertaken to investigate the influence of fisetin on vascular smooth muscle contractility and to determine the mechanism involved. Denuded aortic rings from male rats were used and isometric contractions were recorded and combined with molecular experiments. Fisetin significantly relaxed fluoride-, thromboxane $A_2$- or phorbol ester-induced vascular contraction suggesting as a possible anti-hypertensive on the agonist-induced vascular contraction regardless of endothelial nitric oxide synthesis. Furthermore, fisetin significantly inhibited fluoride-induced increases in pMYPT1 levels and phorbol ester-induced increases in pERK1/2 levels suggesting the mechanism involving the inhibition of Rho-kinase activity and the subsequent phosphorylation of MYPT1 and MEK activity and the subsequent phosphorylation of ERK1/2. This study provides evidence regarding the mechanism underlying the relaxation effect of fisetin on agonist-induced vascular contraction regardless of endothelial function.

• 대한화학회지
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• 제65권1호
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• pp.67-69
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• 2021