Naringenin is one of the most abundant Citrus bioflavonoids. A high-vegetable diet with various fruits and vegetables daily including on average one glass of orange juice, one-half orange and one-half mandarin provides 130 mg of hesperetin and 30 mg of naringenin.

Naringenin has anti-oxidant and anti-tumor activity. Naringinen may play a role in Cancer, Heart disease, hypertension, circulation, and Alzheimer's disease.

Eyesight Rx with Naringenin
Supports Healthy Vision
Physician Formulas
Developed by Ray Sahelian, M.D.

Unlike some vision products that provide nutrients and herbs for long term healthy vision support, and prevention of visual impairment, but don't seem to have much of an immediate effect on visual acuity, Eyesight Rx was formulated to provide a quick and noticeable vision improvement within hours or days of use.

Reports from Eyesight Rx users indicate enhanced clarity of vision, colors being brighter, better focus, and overall improvement in close and distance vision.

Vitamin C - (Ascorbic acid)
Citrus bioflavonoids
     (eriocitrin, hesperidin, flavonols, flavones, flavonoids, naringenin, and quercetin)
Mixed carotenoids
     (alpha carotene, astaxanthin, beta carotene, cryptoxanthin, Lutein, Lycopene, Zeaxanthin)
Bilberry extract (Vaccinium myrtillus)
Eyebright extract (Euphrasia officianales)
Jujube extract (Zizyphus jujube)
Ginkgo biloba (Ginkgo biloba)
Suma extract (Pfaffia paniculata)
Mucuna pruriens extract (Cowhage)
Cinnamon (Cinnamomum zeylanicum)
Lycium berry extract (Lycium Barbarum) - also known as Goji Berry
Sarsaparila (Sarsaparilla Smilax)
Alpha Lipoic Acid

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Subscribe to a FREE Supplement Research Update newsletter  Twice a month you will be emailed a brief abstract of several new studies on various supplements and natural medicine topics, including naringenin and flavonoids, and their practical interpretation by Ray Sahelian, M.D.

Naringenin Research Update
Naringenin attenuates cisplatin nephrotoxicity in rats.
Life Sci. 2005 Mar 18;76(18):2125-35. Epub 2005 Jan 22.
The effect of naringenin, a naturally occurring citrus flavanone, on the acute nephrotoxicity produced by cisplatin (7 mg/kg, i.v.) was investigated in the rat. Oral administration of NAR (20 mg/kg/day) for 10 days, starting 5 days before cisplatin single i.v. injection, produced significant protection of renal function. Naringenin reduced the extent of cisplatin-induced nephrotoxicity, as evidenced by significant reduction in serum urea and creatinine concentrations, decreased polyuria, reduction in body weight loss, marked reduction in urinary fractional sodium excretion and glutathione S-transferase (GST) activity, and increased creatinine clearance. Cisplatin-induced alterations in renal cortex lipid peroxides and GST activity were markedly improved by Naringenin. Cisplatin-induced alterations in renal cortex antioxidant defense system were greatly prevented by Naringenin. In cisplatin-Naringenin combined treatment group, antioxidant enzymes namely superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) were significantly increased to 54.5, 30.3 and 35.6%, respectively compared to cisplatin treated group. Platinum renal content was not affected by Naringenin treatment. The results provide further insight into the mechanisms of cisplatin-induced nephrotoxicity and confirm the antioxidant potential of Naringenin.

Inhibitory effects of naringenin on tumor growth in human cancer cell lines and sarcoma S-180-implanted mice.
Biol Pharm Bull. 2005 Mar;28(3):527-30.
We have investigated the effect of naringenin on tumor growth in various human cancer cell lines and sarcoma S-180-implanted mice. NGEN showed cytotoxicity in cell lines derived from cancer of the breast (MCF-7, MDA-MB-231), stomach (KATOIII, MKN-7), liver (HepG2, Hep3B, Huh7), cervix (Hela, Hela-TG), pancreas (PK-1), and colon (Caco-2) as well as leukemia (HL-60, NALM-6, Jurkat, U937). Naringenin -induced cytotoxicity was low in Caco-2 and high in leukemia cells compared to other cell lines. Naringenin dose-dependently induced apoptosis, with hypodiploid cells detected in both Caco-2 and HL-60 by flow cytometric analysis. In vivo, Naringenin inhibited tumor growth in sarcoma S-180-implanted mice, following intraperitoneal or peroral injection once a day for 5 d. Naringin (NG) also inhibited tumor growth by peroral injection but not intraperitoneal injection. Naringenin, one of the most abundant flavonoids in citrus fruits, may have a potentially useful inhibitory effect on tumor growth.

Structure-activity relationship (SAR) between some natural flavonoids and ocular blood flow in the rabbit.
J Ocul Pharmacol Ther. 2004 Feb;20(1):35-42.
PURPOSE: Flavonoids with two to five hydroxy groups, with or without sugar, and/or methoxy groups were studied on their effects to affect ocular blood flow. METHODS: Colored microsphere technique was used to determine the ocular blood flow in rabbit eyes. RESULTS: Flavonoids with three free hydroxy (OH) groups seemed to produce the optimal effects in increasing ocular blood flow (naringenin and hesperitin, Pfalts and Bauer, Waterbury, CT). Whether the OH groups are below three (naringenin, hesperitin, Pfalts and Bauer, Waterbury, CT) or above four (Quercetin, Pfalts and Bauer, Waterbury, CT), they produced no effects on the ocular blood flow. When OH groups are four (rutin, Aldrich, Milwaukee, WI), it produced mixed effects on ocular blood flow. The attachment of rutinose and/or methoxy group in the structure did not affect the ocular blood flow one way or the other. CONCLUSION: The ocular blood flow is increased significantly by the number of OH group in the molecule, with three the best to increase the ocular blood flow.

Naringenin from Citrus junos has an inhibitory effect on acetylcholinesterase and a mitigating effect on amnesia.
Dement Geriatr Cogn Disord. 2004;17(3):151-7.
This study was performed to identify safe and more effective acetylcholinesterase (AChE) inhibitors in the treatment of Alzheimer's disease. The total methanol extract of Citrus junos had a significant inhibitory effect on AChE in vitro. By sequential fractionation of C.junos, the active component was finally identified as naringenin. Naringenin inhibited AChE activity in a dose-dependent manner. In this study, we also evaluated the anti-amnesic activity of naringenin, a major flavanone constituent isolated from C. junos, in vivo using ICR mice with amnesia induced by scopolamine (1 mg/kg body weight). Naringenin, when administered to mice at 4.5 mg/kg body weight, significantly ameliorated scopolamine-induced amnesia as measured in both the passive avoidance and the Y-maze test. These results suggest that naringenin may be a useful chemopreventive agent against Alzheimer's disease.

The citrus-derived flavonoid naringenin exerts uterotrophic effects in female mice at human relevant doses.
Basic Clin Pharmacol Toxicol. 2004 Jan;94(1):30-6.
Gavage administration of the citrus flavonoid naringenin, 3',4,5,7-tetrahydroxyflavanon for 4 consecutive days, to immature female mice (postnatal day 17-20) at 4 or 100 mg/kg b.wt. significantly increased uterine weights 3 and 4 times, respectively. Analysis of uterine oestrogen receptor alpha revealed that naringenin significantly increased the cytosolic concentration of oestrogen receptor alpha, whereas in nuclei the oestrogen receptor alpha concentration was significantly decreased as compared to the solvent control. This was in contrast to the positive control 17 beta-oestradiolacetate which acted as a true oestrogen by increasing the concentration of both total and nuclear oestrogen receptor alpha. Both naringenin and 17 beta-oestradiolacetate, however, significantly, induced nuclear oestrogen receptor alpha in the liver, suggesting a tissue specific effect of naringenin on oestrogen receptor alpha distribution. In order to investigate the tissue levels at which the uterotrophic effect was observed, the distribution of an oral dose of tritiated naringenin (4 mg/kg) was investigated in 3-week-old female mice. The radioactivity content (ng naringenin equivalents/g tissue) was found to be highest in the gastrointestinal-tract, followed by the kidneys and liver. Uterus and ovaries were also found to contain relatively high and approximately equal amounts of naringenin. The concentration of naringenin in uterus and ovaries was found to be ten times higher as compared to the mammary tissue. The urinary excretion of more than 25% of the administered dose, within 8 hr after dosing indicated that naringenin is absorbed extensively in mice. The plasma concentration of 0.5 microM found in the present study is similar to the peak plasma concentration of naringenin (0.6 microM) observed in man following ingestion of 400-760 ml of orange juice (Erlund et al. 2001). This could be taken to suggests that ingestion of orange juice and other citrus fruits and juices may give rise to sufficiently high tissue levels of naringenin in man to exert a biological effect.

The variable effect on proliferation of a colon cancer cell line by the citrus fruit flavonoid Naringenin.
Colorectal Dis. 2003 Mar;5(2):149-52.
OBJECTIVE: Naringenin, a naturally occurring flavonoid found in citrus fruits, is known to have anticarcinogenic properties. We have examined the effect of Naringenin on cell proliferation of an HT-29 colon cancer cell line. METHODS: HT-29 colon cancer cells were cultured in 96-well tissue culture plates. Naringenin concentrations ranging from 0.02 to 2.85 mmol were added to the wells of the Test group. The Control group contained all the elements present in the Test group with the exception of Naringenin. Cell proliferation was measured by colourimetric assay using the 2% WST-1 cell proliferation kit. RESULTS: Significant inhibition of cell proliferation was observed in HT29 colon cancer cells exposed to Naringenin at doses greater than 0.71 mmol. CONCLUSIONS: These results suggest a potential role for citrus fruits as a source of chemoprotective agents for colon cancer.

Interaction between flavonoids and the blood-brain barrier: in vitro studies.
J Neurochem. 2003 Apr;85(1):180-92.
There is considerable current interest in the neuroprotective effects of flavonoids. This study focuses on the potential for dietary flavonoids, and their known physiologically relevant metabolites, to enter the brain endothelium and cross the blood-brain barrier (BBB) using well-established in vitro models (brain endothelial cell lines and ECV304 monolayers co-cultured with C6 glioma cells). We report that the citrus flavonoids, hesperetin, naringenin and their relevant in vivo metabolites, as well as the dietary anthocyanins and in vivo forms, cyanidin-3-rutinoside and pelargonidin-3-glucoside, are taken up by two brain endothelial cell lines from mouse (b.END5) and rat (RBE4). In both cell types, uptake of hesperetin and naringenin was greatest, increasing significantly with time and as a function of concentration. In support of these observations we report for the first time high apparent permeability (Papp) of the citrus flavonoids, hesperetin and naringenin, across the in vitro BBB model (apical to basolateral) relative to their more polar glucuronidated conjugates, as well as those of epicatechin and its in vivo metabolites, the dietary anthocyanins and to specific phenolic acids derived from colonic biotransformation of flavonoids. The results demonstrate that flavonoids and some metabolites are able to traverse the BBB, and that the potential for permeation is consistent with compound lipophilicity.

Comparison of antioxidant effects of naringin and probucol in cholesterol-fed rabbits.
Clin Chim Acta. 2002 Mar;317(1-2):181-90.
BACKGROUND: Due to the strong evidence on the involvement of active oxygen species in a variety of disorders, the role of antioxidants against oxidative stress has recently received increased attention. METHODS: Twenty male rabbits were served a high-cholesterol (HC, 5 g/kg diet) diet or high-cholesterol diet supplemented with naringin (0.5 g/kg diet) or probucol (0.5 g/kg diet) for 8 weeks to compare the antioxidative effects of the citrus bioflavonoid (naringin) and antioxidative cholesterol-lowering drug (probucol). RESULTS: The plasma thiobarbituric acid-reactive substances (TBARS) concentration was not significantly different between the groups, whereas the hepatic TBARS concentration was significantly lower in the probucol group than in both normal and HC control or naringin group. Probucol and naringin supplementation led to an increase in the hepatic superoxide dismutase (SOD) and catalase (CAT) activities, and a decrease in the hepatic mitochondrial hydrogen peroxide (H(2)O(2)) content compared to the HC-control group. However, there was no difference in the cytosolic H(2)O(2) content or cytosolic glutathion peroxidase (GSH-Px) activity in the liver between the groups. Both naringin and probucol supplements significantly increased the plasma vitamin E concentration compared to the HC-control group. As regards the antioxidant enzyme gene expressions, naringin significantly increased the expression of three antioxidant enzyme mRNAs compared to the HC-control group, whereas probucol significantly increased the only SOD mRNA expression. CONCLUSIONS: The probucol supplement was very potent in the antioxidative defense system, whereas naringin exhibited a comparable antioxidant capacity based on increasing the gene expressions in the antioxidant enzymes, while also increasing the hepatic SOD and CAT activities, sparing plasma vitamin E, and decreasing the hepatic mitochondrial H(2)O(2) content.

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Flavanone absorption after naringin, hesperidin, and citrus administration.
Clin Pharmacol Ther. 1996 Jul;60(1):34-40.
Disposition of citrus flavonoids was evaluated after single oral doses of pure compounds (500 mg naringin and 500 mg hesperidin) and after multiple doses of combined grapefruit juice and orange juice and of once-daily grapefruit. Cumulative urinary recovery indicated low bioavailability ( < 25%) of naringin and hesperidin. The aglycones naringenin and hesperitin were detected in urine and plasma by positive chemical ionization-collisionally activated dissociation tandem mass spectrometry (PCI-CAD MS/MS). After juice administration, PCI-CAD MS/MS detected naringenin, hesperitin, and four related flavanones, tentatively identified as monomethoxy and dimethoxy derivatives. These methoxyflavanones appear to be absorbed from juice. Absorbed citrus flavanones may undergo glucuronidation before urinary excretion.