• Title, Summary, Keyword: hesperidin

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The Effects of Hesperidin on the Proliferation and Activity of Bone Cells

  • Bae, Moon-Seo;Ko, Seon-Yle;Kim, Se-Won
    • International Journal of Oral Biology
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    • v.31 no.4
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    • pp.119-125
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    • 2006
  • The importance of phytoestrogens to human health is currently being actively investigated. Hesperidin, abundantly found in citrus fruits, is known to possess antioxidant, anticancer, and anti-inflammatory effects. Recently, it has been reported that hesperidin inhibits bone loss and decreases serum and hepatic lipids in ovariectomized mice. In our study, to determine the possible role of hesperidin in the regulation of bone metabolism, we observed the effects of hesperidin on the proliferation and activity of osteoblasts, as well as the effects of hesperidin on osteoclast generation and activity. We observed that, when treated with hesperidin, the number and viability of osteoblastic cells increased, alkaline phosphatase (ALP) activity of osteoblastic cells increased, and osteoprotegerin (OPG) secretion from MG63 cells decreased. Hesperidin treatment had no effect on the osteoclast generation and activity in the bone marrow cell culture, but decreased the number and resorptive activity of osteoclasts generated from RAW/264.7 cells. Taken together, these results indicate that hesperidin increases the proliferation and activity of osteoblasts, while inhibiting generation and activity of osteoclasts. Although the precise role of hesperidin remains to be elucidated, our study suggests that it is one of the important modulators of bone metabolism.

Hesperidin Inhibits Vascular Formation by Blocking the AKT/mTOR Signaling Pathways

  • Kim, Gi Dae
    • Preventive Nutrition and Food Science
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    • v.20 no.4
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    • pp.221-229
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    • 2015
  • Hesperidin has been shown to possess a potential inhibitory effect on vascular formation in endothelial cells. However, the fundamental mechanism for the anti-angiogenic activity of hesperidin is not fully understood. In the present study, we evaluated whether hesperidin has anti-angiogenic effects in mouse embryonic stem cell (mES)-derived endothelial-like cells, and human umbilical vascular endothelial cells (HUVECs), and evaluated their mechanism via the AKT/mammalian target of rapamycin (mTOR) signaling pathway. The endothelial cells were treated with several doses of hesperidin (12.5, 25, 50, and $100{\mu}M$) for 24 h. Cell viability and vascular formation were analyzed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and tube formation assay, respectively. Alteration of the AKT/mTOR signaling in vascular formation was analyzed by western blot. In addition, a mouse aortic ring assay was used to determine the effect of hesperidin on vascular formation. There were no differences between the viability of mES-derived endothelial-like cells and HUVECs after hesperidin treatment. However, hesperidin significantly inhibited cell migration and tube formation of HUVECs (P<0.05) and suppressed sprouting of microvessels in the mouse aortic ring assay. Moreover, hesperidin suppressed the expression of AKT and mTOR in HUVECs. Taken together, these findings suggest that hesperidin inhibits vascular formation by blocking the AKT/mTOR signaling pathways.

Hesperidin Induces Apoptosis in SNU-668, Human Gastric Cancer Cells

  • Park, Hae-Jeong;Ra, Je-Hyun;Han, Mi-Young;Chung, Joo-Ho
    • Molecular & Cellular Toxicology
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    • v.3 no.1
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    • pp.31-35
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    • 2007
  • Hesperidin, known as a flavonoid constituent of citrus, has been known to reduce the proliferation of several cancer cells. We investigated whether hesperidin-induced cell death on SNU-668, human gastric cancer cells. The cytotoxicity of hesperidin on SNU-668 cells was determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay at the concentration of 1, 10, 50, and 100 ${\mu}M$. Cell viability by hesperidin was 53.18$\pm$2.85% of control value at 100 ${\mu}M$. The cell death by hesperidin showed apoptotic features, which were confirmed using a combination of 4, 6-diamidino-2-phenylindole (DAPI) staining and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay. In the apoptosis-regulating genes, treatment of hesperidin decreased mRNA expression of B-cell CLL/lymphoma 2 (BCL2), whereas expression of BCL2-associated X protein (BAX) was increased. The mRNA expression and the activity of caspase3 (CASP3), a major apoptotic factor, was significantly increased by hesperidin treatment. These results suggest that hesperidin could induce apoptosis through CASP3 activation on SNU-668, human gastric cancer cells.

Antioxidative effects of hesperidin and hesperetin under cellular system (Hesperidin과 hesperetin의 cellular system에서의 항산화 효과)

  • Cho, Eun-Ju;Li, Li;Yamabe, Noriko;Kim, Hyun-Young
    • Korean Journal of Agricultural Science
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    • v.38 no.4
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    • pp.717-722
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    • 2011
  • In this study, we investigated the antioxidant activity of hesperidin and hesperetin, which are the active compounds from Citrus junos, in the cellular system. Under cellular model of oxidative damage using LLC-$PK_1$ renal epithelial cell, the oxidative damage induced by 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH) led to the loss of cell viability, while treatment of hesperidin and hesperetin increased significantly the cell viability as dose-dependent manner. In addition, NO-induced cellular oxidative damage by sodium nitroprusside were significantly recovered by the treatment of hesperidin and hesperetin, showing the increase of cell viability. But hesperidin and hesperetin showed no significant protective effect on $O_2{^-}$-induced cellular oxidative damage. The present study indicates that hesperidin and hesperetin protect against free radical, especially AAPH-induced peroxyl radical. In particular, hesperetin has stronger protective effect against oxidative stress than hesperidin.

Effects of Citrus Flavonoid, Hesperidin and Naringin on Lipid Metabolism in HepG2 Cells (간배양 HepG2 세포의 지질대사에 미치는 Hesperidin 및 Naringin의 영향)

  • 김범규;차재영;조영수
    • Journal of Life Science
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    • v.9 no.4
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    • pp.382-388
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    • 1999
  • The effects of citrus flavonoids, hesperidin and naringin, on the lipid metabolism were investigated in cultured human hepatocyte HePG2 cells. HepG2 cells were cultured for 6 h and 24 h to the control medium or the media containing hespridin and narigin, which concentrations were 0.5 and 5.0 mg/$m\ell$. There were no significant effects on cell proliferation and cellular protein content, except for increased in these parameters by adding both citrus flavonoids (0.5 mg/$m\ell$). The cellular content of triacylglycerol after 6 h incubation with 0.5 mg/$m\ell$ hesperidin and naringin was markedly increased, and after 24 h incubation that was decreased in both citrus flavonoids supplementation. The supplementation of 5.0 mg/$m\ell$ hesperidin caused a marked decrease in the cellular cholesterol content following 6 h incubation, and that was also reduced markdly, in a dose-dependent manner, during incubation for 24 h. However, there was no significant difference in the cellular cholesterol content in medium supplemented with naringin. The effect of hesperidin and naringin on acyl-CoA: cholesterol acyltransferase (ACAT) activity was studied in vivo and in vitro. The data confirmed that hesperidin inhibit ACAT activity in vivo and in vitro, whereas naringin had no such effect on ACAT activity in vivo but not in vitro. The present study suggests that hesperidin reduces the cellular triacyglycerol and cholesterol contents in human hepatocyte HepG2 cells.

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Hesperidin Induces Apoptosis by Inhibiting Sp1 and Its Regulatory Protein in MSTO-211H Cells

  • Lee, Kyung-Ae;Lee, Sang-Han;Lee, Yong-Jin;Baeg, Seung-Mi;Shim, Jung-Hyun
    • Biomolecules & Therapeutics
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    • v.20 no.3
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    • pp.273-279
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    • 2012
  • Hesperidin, a flavanone present in citrus fruits, has been studied as potential therapeutic agents that have anti-tumor activity and apoptotic effects in several cancers, but there is no report about the apoptotic effect of hesperidin in human malignant pleural mesothelioma through the specificity protein 1 (Sp1) protein. We investigated whether hesperidin inhibited cell growth and regulated Sp1 target proteins by suppressing the levels of Sp1 protein in MSTO-211H cells. The $IC_{50}$ value of hesperidin was determined to be 152.3 ${\mu}M$ in MSTO-211H cells for 48 h. Our results suggested that hesperidin (0-160 ${\mu}M$) decreased cell viability, and induced apoptotic cell death. Hesperidin increased Sub-$G_1$ population in MSTO-211H cells. Hesperidin significantly suppressed mRNA/protein level of Sp1 and modulated the expression level of the Sp1 regulatory protein such as p27, p21, cyclin D1, Mcl-1, and survivin in mesothelioma cells. Also, hesperidin induced apoptotic signaling including: cleavages of Bid, caspase-3, and PARP, upregulation of Bax, and down-regulation of Bcl-$_{xl}$ in mesothelioma cells. These results show that hesperidin suppressed mesothelioma cell growth through inhibition of Sp1. In this study, we demonstrated that Sp1 acts as a novel molecular target of hesperidin in human malignant pleural mesothelioma.

Analysis and Quantitative Distribution of Glycosided Flavonoids in Citruses and Korean Chung-pi (감귤류와 한국산 청피에 함유된 Glycosided Flavonoids의 분석과 정량적 분포)

  • Baik, S.O.;Bock, J.Y.;Chun, H.J.;Jeong, S.I.;Baek, S.H.;Oh, H.B.;Kim, I.K.
    • Analytical Science and Technology
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    • v.14 no.4
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    • pp.340-348
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    • 2001
  • Glycosided flabonoids (naringenin, naringin, narirutin, hesperidin, and hesperetin) in Citrus and Korea Chung-pi were isolated and analyzed with HPLC, GC-mass, UV and high resolution NMR. Contents of glycosided flavonoids were compared according to kinds of Citrus and fruit ripening periods. Major compound of Korean Chung-pi was hesperidin and minors were narirutin and hesperetin. Major compounds of Gisil were naringin, narirutin, naringenin and were narirutin, hesperidin in Gigak. Major compounds of milgam and orange were narirutin, hesperidin, and the contents of glycoside flavonoids decreased according to the age of maturity.

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Isolation, Purification and Hypotensive Effect of Bioflavonoids in Citrus sinensis (감귤의 Bioflavonoids 분리, 정제 및 혈압강하효과)

  • 손흥수;김현숙;권태봉;주진순
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.21 no.2
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    • pp.136-142
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    • 1992
  • The crude bioflavonoids were obtained by methanol and butanol extraction from Iyophilized orange (Citrus sinensis) peel. And then, its yield was about 0.26% in dry base. Two bioflavonoids were purified by gel filtration and HPLC, and could be identified narirutin and hesperidin through TLC, HPLC, UV spertrum and NMR analysis. The yields of narirutin and hesperidin from a gram of crude bioflavonoids were 42mg and 530mg respectively, and the main fraction of bioflavonoid from orange peel was supposed to be hesperidin. Each component was intravenously injected into Sprague-Dawley rats (1mg/100g body weight) and hesperidin was found to lower their blood pressure significantly (p < 0.001).

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Effects of Hesperidin and Naringin on Antioxidative Capacity in the Rat (Hesperidin 과 Naringin 이 흰쥐의 항산화능에 미치는 영향)

  • 손정숙
    • Journal of Nutrition and Health
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    • v.31 no.4
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    • pp.687-696
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    • 1998
  • This study was performed to investigate effects of hesperidin and naringin on linpid peroxide formation and antioxidative enzyme activities in rats. Thiobarbituric acid reactive substance (TBARS) concentrations were measured in plasma and liver. Catalase, superoxide dismutase, and glutathione peroxidase activities were measured in erythrocyte and liver. Forty-nine male Sprague-Dauley rats weighing 275.3$\pm$3.3g were blocked into seven groups according to body weight and were raised fro four weeks on diets containing 0.25, 0.50 or 1.00%(w/w) hesperidin or naringin . Food intake, weight gain , food efficiency ratio, and weights of liver, kidney, spleen ,and epididymal fat pad were not significantly different among groups. In 0.50 and 1.00% naringin groups , plasma TBARS concentrations were significantly decreased with a dose response patter. In 0.25, 0.50 and 1.00% hesperidin groups, liver TBARS concentrations were significantly decreased without a dose dependent patter. Antiosidative enzyme activities in erythrocyte and liver were not significantly affected by type and amountof dietary bioflavonoid, but in the 1.00% hesperidin group, catalase, superoxide dismutase, and glutahione perosidase activities in linver showed a tendency to increase. In conclusion, naringin inhibited lipid peroxide formation with a dose response pattern in plasma without changing the activities of antioxidative enzymes. Hesperidin adminstration, regardless of the level in the diet, inhibited lipid peroxide formation in liver.

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Anti-inflammatory Effects and its Mechanisms of Hesperidin in an Asthmatic Mouse Model Induced by Ovalbumin

  • Chang, Jeong-Hyun
    • Biomedical Science Letters
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    • v.16 no.2
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    • pp.83-90
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    • 2010
  • Hesperidin, a member of the flavanone group of flavonoids, can be isolated in large amounts from the rinds of some citrus species [e.g., Citrus aurantium L. (bitter orange), Citrus sinensis L. (sweet orange) and Citrus unshiu Marcov. (satsuma mandarin)], and has been reported to have anticarcinogenic, antihypotensive and antimicrobial properties. Despite the efficacy of these polyphenolic compounds as immune modulators, the effects of the flavonoids are poorly understood about allergic effect. In this study, we investigated whether hesperidin could influence on Th1 and Th2 balance. Allergic reactions included an increase in the number of eosinophils in bronchoalveolar lavage (BAL) fluid, an increase in inflammatory cell infiltration into the lung tissue around blood vessels and airways, airway luminal narrowing, the development of airway hyper-responsiveness (AHR). The administration of hesperidin before the last airway OVA challenge resulted in a significant inhibition of all asthmatic reactions. Accordingly, this study may provide evidence that hesperidin plays a critical role in the amelioration of the pathogenetic process of asthma in mice. These findings provide new insight into the immunopharmacological role of hesperidin in terms of its effects in a murine model of asthma, and also broaden current perspectives in our understanding of the immunopharmacological functions of hesperidin.