• Food Science and Preservation
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• v.4 no.2
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• pp.181-187
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• 1997

New HPLC method was developed for determination of some flavonoids such as naringin, hesperidin, neohesperidin, rutin, quercitrin, naringenin, hesperetin and apigenin and their contents in citrus juice and citrus peel from citrus varieties Brown in Cheju. Detection was at 280nm and reverse phase ${\mu}$-Bondapak C-18 column was used. Water/methanol/acetic acid as the mobile phase was better than water/acetonitrile/acetic acid. Flavonoids were more stable in 20% n,n-dimethylformamide in methanol(20% DMF) than methanol and pH 12 adjusted by 1N-sodium hydroxide solution. Standard flavonoid solutions were injected three times consecutively and the reproduciability was 0.236 to 3.550%, Correlation coefficient of the calibration curve was 0.9946 to 0.9999. The exiraction efficiency of hesperidin from citrus peel was evaluated with different extraction method such as reflux, ultra-sonicating method, using three solvents (aqueous solutions with pH12 adjusted by 1N-sodium hydroxide, methanol and 20% DMF), respectively. The reflux for 4 hour in 20% DMF was the most efficient of the tested methods and solvents, and recovery percentage were 78.0∼130.0%. Flavonoids were determined in citrus juice. Naringin was 68.2mg/100$m\ell$ in Natsudaidai, Hesperidin were 85.6mg/100$m\ell$ in Sankyool and Neohesperidin was 25.3mg/100$m\ell$ in Dangyooja. Flavonoids were determined in citrus peel. Naringin was 110mg/g in Dangyooja, Hesperidin was 242mg/g in Hungjin and Neohesperidin was 87.9mg/g in Dangyooja.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.2
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• pp.427-436
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• 2012

Targeted therapy has been a very promising strategy of drug development research. Many molecular mechanims of diseases have been known to be regulated by abundance of proteins, such as receptors and hormones. Chemoprevention for treatment and prevention of diseases are continuously developed. Pre-clinical and clinical studies in chemoprevention field yielded many valuable data in preventing the onset of disease and suppressing the progress of their growth, making chemoprevention a challenging and a very rational strategy in future researches. Natural products being rich of flavonoids are those fruits belong to the genus citrus. Ethanolic extract of Citrus reticulata and Citrus aurantiifolia peels showed anticarcinogenic, antiproliferative, co-chemotherapeutic and estrogenic effects. Several examples of citrus flavonoids that are potential as chemotherapeutic agents are tangeretin, nobiletin, hesperetin, hesperidin, naringenin, and naringin. Those flavonoids have been shown to possess inhibition activity on certain cancer cells' growth through various mechanisms. Moreover, citrus flavonoids also perform promising effect in combination with several chemotherapeutic agents against the growth of cancer cells. Some mechanisms involved in those activities are through cell cycle modulation, antiangiogenic effect, and apoptosis induction.Previous studies showed that tangeretin suppressed the growth of T47D breast cancer cells by inhibiting ERK phosphorylation. While in combination with tamoxifen, doxorubicin, and 5-FU, respectively, it was proven to be synergist on several cancer cells. Hesperidin and naringenin increased cytotoxicitity of doxorubicin on MCF-7 cells and HeLa cells. Besides, citrus flavonoids also performed estrogenic effect in vivo. One example is hesperidin having the ability to decrease the concentration of serum and hepatic lipid and reduce osteoporosis of ovariectomized rats. Those studies showed the great potential of citrus fruits as natural product to be developed as not only the source of co-chemotherapeutic agents, but also phyto-estrogens. Therefore, further study needs to be conducted to explore the potential of citrus fruits in overcoming cancer.

• Biomolecules & Therapeutics
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• v.21 no.2
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• pp.138-145
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• 2013

Citrus fruit contain various flavonoids that have multiple biological activities. However, the content of these flavonoids are changed during maturation and immature Citrus is known to contain larger amounts than mature. Chemokines are significant mediators for cell migration, while thymus and activation-regulated chemokine (TARC/CCL17) and macrophage-derived chemokine (MDC/CCL22) are well known as the typical inflammatory chemokines in atopic dermatitis (AD), a pruritic and chronic inflammatory skin disease. We reported recently that the EtOH extract of immature Citrus unshiu inhibits TARC and MDC production. Therefore, we investigated the activity of flavonoids contained in immature Citrus on TARC and MDC levels. As a result, among the various flavonoids, quercetagetin has stronger inhibitory effects on the protein and mRNA expression of TARC and MDC than other flavonoids. Quercetagetin particularly has better activity on TARC and MDC level than quercetin. In HPLC analysis, the standard peak of quercetagetin matches the peaks of extract of immature C. unshiu. This suggests that quercetagetin is an anti-inflammatory component in immature C. unshiu.

• Journal of Applied Biological Chemistry
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• v.44 no.3
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• pp.143-146
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• 2001

Eight flavonoids, including rutin, naringin, hesperidin, quercetin, hesperetin, nobiletin, 3,5,6,7,8,3',4'-methoxylated flavone, and tangeretin, in the peels of satsuma mandarin (Citrus unshiu) species of Halla, Gungcheon, Hungjin, Namgam-20, Illnam-1, and Chungdo harvested between August and December were analyzed through HPLC. Hesperidin content of Halla harvested during early maturation was 28.70 mg/g, and was the highest among the tested citrus fruits. Rutin content of Hungjin harvested during early maturation was 2.66 mg/g. Naringin in all citrus species and hesperetin in Halla, Gungchun, Namgam-20, and Chungdo were only detected in the peel of fruits harvested during early maturation. Hesperidin and rutin were detected mainly in all citrus species, and other flavonoids in trace. Flavonoid content in the peel of fruits was high during early maturation. Flavonoid contents in the peels of all fruit samples were generally high in the early stage of maturation, which then decreased rapidly.

• International Journal of Oral Biology
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• v.45 no.2
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• pp.33-41
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• 2020

Neuroinflammation is known as the main mechanism implicated in the advancement of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. The main feature of neuroinflammation is associated with the activation of microglia. The activated microglia increase proinflammatory cytokine production and induce progressive neuronal cell death. Citrus flavonoids show neuroprotective effects that are associated with the anti-inflammatory action of flavonoids in neurodegenerative diseases. Among these citrus flavonoids, kaempferol, naringin, and nobiletin show inhibitory effects on nuclear factor-κB and mitogen-activated protein kinase signaling pathways that can modulate inflammatory conditions in microglial cells. In the present review, we present the anti-inflammatory activities of citrus flavonoids and therapeutic potential of flavonoids as neuroprotective agents.

• Applied Biological Chemistry
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• v.44 no.2
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• pp.122-128
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• 2001

This review showed a discussion on the biofunctional activities of citrus flavonoids. The major flavonoids of citrus species, hesperidin, hesperetin, naringin, and naringenin, were selected to evaluate their biological effects on the lipid metabolism in rats and hamsters, the proliferation of human hepatocyte HepG2 cells, and the antioxidative effect in lipid peroxidation models. These flavonoids showed hypotriglyceridemic effect in hamsters and hypochloesterolemic effect in rats. They also significantly inhibited the activities of phosphatidate phophohydrolase and acyl-CoA: cholesterol acyltransferase, which are key enzymes for biosynthesis of triglyceride and cholesterol, repectively, in vivo and in vitro experiments. These biofunctional activities by citrus flavonoids were shown more potent in the aglycone flavonoids, hespreretin and naringenin, than their corresponding glycoside flavonoids, hesperidin and naringin. These aglycone flavonoids also have inhibitory effects on proliferation of human hepatocyte cancer HepG2 cells. Hesperidin showed lowering activities of cellular triglyceride and cholesterol concentrations in HepG2 cells. Citrus flavonoids have significant importance in functional food industry as biofunctional active ingredients.

• Journal of Korean Clinical Health Science
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• v.2 no.1
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• pp.73-78
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• 2014

Purpose. Citrus aurantium L.(familyRutaceae), alsoknownasbitter orange, have been used as traditional herbal medicine in many Asian countries since ancient times. Hence, the purpose of the study was to briefly discuss the new findings about anti-inflammatory and anti-cancer activities of Citrus aurantium L in-vitro. Methods. The articles for this study were collected from pubmed and scopus electronic resources. Results. Citrus aurantium L contains an abundant Flavonoids, including hesperidin, naringin and nobiletin. These Flavonoids has reported to have various medicinal benefits that include antioxidant, antimicrobial, anti-inflammatory, anticancer, anti-diabetic activities, and also used to treat cardiovascular diseases. Conclusion. Based on the above evidence, we propose that Flavonoids from Korea Citrus aurantium L would be a therapeutic potential for cancer treatment and pharmacological benefit for inhibiting the inflammatory effect.

• Horticultural Science & Technology
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• v.30 no.2
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• pp.214-219
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• 2012

This study aimed to develop a new type of functional citrus beverage (Citurs-F) containing flavonoids extracted from the young fruits of satsuma mandarin ($Citrus$ $unshiu$) and matured fruits of Jeju native dangyooja ($C.$ $grandis$). We made beverages that contained 30% of satsuma mandarin extract with different percentages of concentrated dangyooja-derived flavonoid extracts. In sensory evalution, the highest response indices of color, taste and aroma were from the beverages based on the 30% young fruit extracts plus 15% (Citrus-F-15) and 20% (Citrus-F-20) flavonoids extract from the dangyooja using the KILO prep. In the changes of body weight after oral administration of the Citrus-F, the rat group with HF diet plus the Citrus-F decreased the body weight compared to the rat group fed only HF diet. This effect was to be continued for 9 weeks until the end of experiment. In the lipid content in blood, the rat group with oral administration of citrus extractions merely tended to resolve it in serum test. However, all the 0.1% Citrus-F-15 and Citrus-F-20 treated rat groups from the beginning or after 5 weeks appeared the lowest lipid contents in the blood. In the cholesterol contents, the rat group feeding the KILO-prep's extraction from the beginning weren't significantly recognized them in the group but the rat group feeding 0.1% Citrus-F-15 acted to reduce in the cholesterol contents from 5 weeks. The results indicated that the Citrus-F-15 with rich flavonoids might be main source alleviating the vascular diseases and obesity in human diet.

• 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.

• Preventive Nutrition and Food Science
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• v.7 no.1
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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.