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

• Korean Journal of Pharmacognosy
• /
• v.29 no.2
• /
• pp.136-141
• /
• 1998

To analyze scientifically the polyprescription principle of Daekumeumja(對金飮子), which has been used for alcoholic damage, and Pyungwesan(平胃散), which has been used for indigestion, the transforming rate of hesperidin of these polyprescriptions to hesperetin was investigated. The transforming rate of the former was higher 3 times than that of the latter. The transforming rate of hesperidin of Aurantii nobilis Pericarpium was inhibited by Magnoliae Cortex, but was activated by Glycyrrhizae Radix. The activity of trypsin was inhibited by Glycyrrhizae Radix and Daekumeuja. However, Aurantii nobilis Pericarpium, Atractylodis Rhizoma, Magnoliae Cortex and Pyungwesan did not inhibited it. When human intestinal microflora were cultured with the media containing Daekumeumja, Pyungwesan and herbal medicines consisting of them, Aurantii nobilis Pericarpium and Magnoliae Cortex inhibited the activity of ${\beta}$-glucosidase. These results suggests that the therapeutic effect of Daekumeumja may be better than that of Pyungwesan on alcoholic damage and the therapeutic effect of Pyungwesan may be better than that of Daekumeumja on indigestion, although these prescriptions are consisted of the same herbal medicines.

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

• Nutrition Research and Practice
• /
• v.17 no.5
• /
• pp.899-916
• /
• 2023

BACKGROUND/OBJECTIVES: Oxidative stress is a fundamental neurodegenerative disease trigger that damages and decimates nerve cells. Neurodegenerative diseases are chronic central nervous system disorders that progress and result from neuronal degradation and loss. Recent studies have extensively focused on neurodegenerative disease treatment and prevention using dietary compounds. Heseperetin is an aglycone hesperidin form with various physiological activities, such as anti-inflammation, antioxidant, and antitumor. However, few studies have considered hesperetin's neuroprotective effects and mechanisms; thus, our study investigated this in hydrogen peroxide (H₂O₂)-treated SH-SY5Y cells. MATERIALS/METHODS: SH-SY5Y cells were treated with H₂O₂ (400 µM) in hesperetin absence or presence (10-40 µM) for 24 h. Three-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assays detected cell viability, and 4',6-diamidino-2-phenylindole staining allowed us to observe nuclear morphology changes such as chromatin condensation and apoptotic nuclei. Reactive oxygen species (ROS) detection assays measured intracellular ROS production; Griess reaction assays assessed nitric oxide (NO) production. Western blotting and quantitative polymerase chain reactions quantified corresponding mRNA and proteins. RESULTS: Subsequent experiments utilized various non-toxic hesperetin concentrations, establishing that hesperetin notably decreased intracellular ROS and NO production in H₂O₂-treated SH-SY5Y cells (P < 0.05). Furthermore, hesperetin inhibited H₂O₂-induced inflammation-related gene expression, including interluekin-6, tumor necrosis factor-α, and nuclear factor kappa B (NF-κB) p65 activation. In addition, hesperetin inhibited NF-κB translocation into H₂O₂-treated SH-SY5Y cell nuclei and suppressed mitogen-activated protein kinase protein expression, an essential apoptotic cell death regulator. Various apoptosis hallmarks, including shrinkage and nuclear condensation in H₂O₂-treated cells, were suppressed dose-dependently. Additionally, hesperetin treatment down-regulated Bax/Bcl-2 expression ratios and activated AMP-activated protein kinase-mammalian target of rapamycin autophagy pathways. CONCLUSION: These results substantiate that hesperetin activates autophagy and inhibits apoptosis and inflammation. Hesperetin is a potentially potent dietary agent that reduces neurodegenerative disease onset, progression, and prevention.

• Microbiology and Biotechnology Letters
• /
• v.33 no.4
• /
• pp.288-294
• /
• 2005

Flavonoid compounds show several biological activities and generally exist in the forms of glycones linking sugar moiety to main structure. Flavonoid glycones such as naringin and hesperidin in korean citrus peel are slower absorbed and consequently less active than their aglycone, naringenin and hesperetin, respectively. Therefare to increase the content of flavonoid aglycone in korean citrus peel, we used commercial carbohydrate-hydrolysing enzymes, AMG 300 L, Pectinex 100 L, and Viscozyme for transforming flavonoid glycones to aglycones. Optimal conditions of enzyme reaction were pH 5.0-7.0, $5\%$ enzyme, and 24-48 hrs. The content of naringenin and hesperetin as flavonoid aglycones in untreated citrus peel is $100\~200\;ng/g$ of dried citrus peel. In case of enzyme-treated citrus peel the content of naringenin and hesperetin increased to $1,539\∼6,674\;ng/g\;and\;1,974\∼8,906\;ng/g$ of dried citrus peel, respectively. Finally the content of flavonoid aglycones could be extracted to 10-80 times. Now enzyme-treated citrus peel may be applied to use for functional food because of its higher flavonoid aglycones as more active compounds.

• Korean Journal of Pharmacognosy
• /
• v.30 no.1
• /
• pp.34-39
• /
• 1999

To search for less toxic antiherpetic agents, the inhibitory effects of twelve kinds of flavonoids including chrysin, quercetin, quercitrin, rutin, fisetin, gossypin, kaempferol, morin, naringenin, naringin, hesperetin and hesperidin on the plaque formation of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in Vero cells were examined by plaque reduction assay in vitro. Some flavonoids tested in this study showed potent antiherpetic activity, reducing intracellular replication of herpes simplex viruses when Vero cell monolayers were infected and subsequently cultured in medium containing flavonoids. Naringenin showed the most potent antiviral activity against HSV-1 with selectivity index (SI) of 19.1 and hesperetin showed the most potent antiviral activity against HSV-2 with SI of 9.8. These results suggest that some flavonoids may be a potential therapeutic agent for the treatment and prevention of herpes simplex virus infections.

• Journal of Veterinary Clinics
• /
• v.30 no.1
• /
• pp.27-31
• /
• 2013

We investigated the effects of Ponciri Fructus (PF) and Aurantii Fructus Immaturus (AI) on the cicular and longitudinal smooth muscle of rat gastric fundus. Methanol extracts of PF (PFM) and AI (AIM), water-fractions (PFW, AIW) and chloroform-fractions (PFC, AIC) of the extracts induced relaxation in the rat fundic circular muscle pre-contracted by U46619. All extracts showed relaxation without significant differences among the extracts. In the longitudinal smooth muscle, PFM and its water fraction, PFW, showed multiphasic effects, fast relaxation and rebound contraction followed by lasting relaxation. AIM and AIW showed diphasic effects, transient contraction followed by lasting relaxation. However, PFC and AIC induced only relaxation in the rat fundic longitudinal muscle contracted by U46619. PFM showed significantly more effective relaxation compared with PFW, AIM and AIW. Hesperidin, flavonoids known as common constituent of PF and AI and it's an aglycon, hesperetin, induced relaxation in both fundic circular and longitudinal smooth muscle pre-contracted by U46619. Poncirin, known as flavonoid content of PF showed also induced relaxation in the both circular and longitudinal smooth muscle pre-contracted by U46619. These results suggest that both PF and AI has relaxing effects on the gastric fundus smooth muscle and its effects might be caused by their flavonoids constituents.

• Preventive Nutrition and Food Science
• /
• v.7 no.1
• /
• pp.1-4
• /
• 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.

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

• Food Science and Preservation
• /
• v.15 no.1
• /
• pp.94-98
• /
• 2008

To search functional biomaterials of citrus pressed cake, the chemical constituents were analyzed Moisture content of citrus pressed cake varied slightly with sampling time. Moisture, non-nitrogen compounds, crude protein, crude fat, and ash of citrus pressed cake were 82.23% 16.94% 1.27% 2.5%, 0.58% (all w/w) on average, respectively. The chemical composition of citrus pressed cake was more similar to the peel than to the flesh of Citrus unshiu var: miyakawa. The pH, acid content, and pectin content were 3.57, 0.43% (w/w) and 1.49% (w/w), respectively. The vitamin C content of peel of Citrus unshiu var. miyakawa was 87.1mg/100g, and was higher than the 46.4mg/100g of citrus pressed cake. Total carotenoids of citrus pressed cake, and the peel and flesh of Citrus unshiu var. miyakawa, were 512.2mg/kg, 2,649.5mg/kg, and 199.4mg/kg, respectively. Therefore, citrus pressed cake may be utilized as a natural source of pectin, flavonoids and carotenoids. The major inorganic elements of citrus pressed cake were 201.3mg/100g of K, 47.9mg/100g of Ca, 19.4/100g of P, and 17.8/100g of Mg. The major free sugar contents of citrus pressed cake were 3.05% (w/w) fructose, 2.91% (w/w) glucose, and 4.94%(w/w) sucrose. Total free sugar was 9.91% (w/w), corresponding to 58.5% of 1be non-nitrogen compounds. The main flavonoids of Citrus unshiuwere narirutin, hesperidin, and rutin. Neohesperidin and hesperetin were also detected in trace amounts. Themajor flavonoids of citrus pressed cake were hesperidin and narirutin, and the content of hesperidin was 194.6mg/100g.