Dietary Naringenin Research Articles

Protective efficacy of naringenin against cadmium-induced redox imbalance in Labeo rohita: an integrated biomarker approach.

The protective efficacy of dietary naringenin (NG) has been investigated against the toxicity caused by cadmium chloride (CdCl2) using biomarkers of oxidative stress in the liver, gills and kidney of Labeo rohita. The fish were exposed to environmentally relevant concentrations of CdCl2 (0.37 and 0.62mg/L) and simultaneously orally administered with NG (50mg/kg bw/day) for 60days. Tissue (gills, liver and kidney) samples were collected on days 15, 30 and 60 of the experiment and analysed for endogenous antioxidants and oxidative stress biomarkers. CdCl2 exposure for 15 and 30days induced the development of adaptive mechanism as demonstrated by the enhanced activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase in all three tissues. However, on the 60th day, CdCl2-induced oxidative damage was stipulated by a decline in the enzyme activities and reduced glutathione (GSH) content significantly (p < 0.05) below control levels along with enhanced levels of lipid peroxidation. Oral administration of NG in toxicant exposed fish significantly restored the altered levels of antioxidants, oxidative enzymes and lipid peroxidation. Besides, integrated biomarker response (IBR) analysis was applied by combining all the biomarkers to indicate the overall stress response index. IBR analysis confirmed the altered levels of biomarkers, the oxidative stress induced by CdCl2 exposure and the ameliorative potential of NG. The present study suggested that NG might have protective role against Cd-induced oxidative insult which might be ascribed to the ability of NG to chelate metals and scavenge free radicals.

Back Cover: Dietary Naringenin Preserves Insulin Sensitivity and Grip Strength and Attenuates Inflammation but Accelerates Weight Loss in a Mouse Model of Cancer Cachexia

Mol. Nutr. Food Res. 2021, 65, 202100268 DOI: 10.1002/mnfr.202100268 In article number 2100268, Martha A. Belury and co-workers found that dietary supplementation of naringenin improves multiple aspects of metabolic disturbance during cancer cachexia progression in the C-26 mouse model. The cover image by graphic designer Pamela Galante is a pattern depicting food sources of naringenin, the metabolic interplay between tumor, adipose, and muscle tissues, inflammation, and the insulin receptor.

Dietary Naringenin Preserves Insulin Sensitivity and Grip Strength and Attenuates Inflammation but Accelerates Weight Loss in a Mouse Model of Cancer Cachexia.

Cancer cachexia is characterized by the loss of skeletal muscle resulting in functional impairment, reduced quality of life and mortality. Naringenin, a flavonoid found in citrus fruits, improves insulin sensitivity and reduces inflammation and tumor growth in preclinical models. Therefore, the study hypothesizes that dietary supplementation of naringenin will improve insulin sensitivity, decrease inflammation, slow body weight loss, and delay tumor growth in a mouse model of cancer cachexia. Mice are fed 2 wt% dietary naringenin before and during initiation of cancer cachexia using inoculated adenocarcinoma-26 cells (C-26). Food intake, body weight, body composition, muscle function, insulin tolerance, and inflammatory status are assessed. Although naringenin-fed tumor-bearing mice exhibit reductions in body weight and food intake earlier than control diet-fed tumor-bearing mice, dietary naringenin is protective against loss of muscle strength, and attenuates the onset of insulin resistance and markers of inflammation. Dietary supplementation of naringenin improves multiple aspects of metabolic disturbance and inflammation during cancer cachexia progression in [C-26 tumor-bearing] mice. However, the acceleration of anorexia and weight loss is also observed. These findings emphasize the link between inflammation and insulin resistance as a basis for understanding their roles in the pathogenesis of cancer cachexia.

Naringenin attenuates experimental autoimmune encephalomyelitis by protecting the intact of blood-brain barrier and controlling inflammatory cell migration

Targeting pathogenic immune cell trafficking poses an attractive opportunity to attenuate autoimmune disorders such as multiple sclerosis (MS). MS and its animal model, experimental autoimmune encephalomyelitis (EAE), are characterized by the immune cells-mediated demyelination and neurodegeneration of the central nervous system (CNS). Our previous study has proven that dietary naringenin ameliorates EAE clinical symptoms via reducing the CNS cell infiltration. The present study examined the beneficial effects of naringenin on maintaining the blood-brain barrier in EAE mice via dietary naringenin intervention. The results showed that naringenin-treated EAE mice had an intact blood-CNS barrier by increasing tight junction-associated factors and decreasing Evans Blue dye in the CNS. Naringenin decreased the accumulation and maturation of conventional dendritic cells (cDCs), CCL19, and CCR7 in the CNS. Also, naringenin blocked the chemotaxis and antigen-presenting function of cDCs that resulted in reducing T-cell secreting cytokines (IFN-γ, IL-17, and IL-6) in the spleen. Importantly, naringenin blocked pathogenic T cells infiltrated into the CNS and attenuates passive EAE. Therefore, by blocking chemokine-mediated migration of DCs and pathogenic T cells into the CNS, naringenin attenuates EAE pathogenesis and might be a potential candidate for the treatment of autoimmune diseases, such as MS and other chronic T-cell mediated autoimmune diseases.

Beneficial Effects of Naringenin in Cigarette Smoke-Induced Damage to the Lung Based on Bioinformatic Prediction and In Vitro Analysis.

Naringenin is found mainly in citrus fruits, and is thought to be beneficial in the prevention and control of lung diseases. This study aims to investigate the mechanisms of naringenin against the damage in the lung caused by cigarette smoke. A system bioinformatic approach was proposed to predict the mechanisms of naringenin for protecting lung health. Then, we validated this prediction in BEAS-2B cells treated with cigarette smoke extract (CSE). System bioinformatic analysis indicated that naringenin exhibits protective effects on lung through the inhibition of inflammation and suppression of oxidative stress based on a multi-pathways network, mainly including oxidative stress pathway, Nrf2 pathway, Lung fibrosis pathway, IL-3 signaling pathway, and Aryl hydrocarbon receptor pathway. The in vitro results showed that naringenin significantly attenuated CSE-induced up-regulation of IL-8 and TNF-α. CSE stimulation increased the mRNA expressions of Nrf2, HO-1, and NQO1; the levels of total protein and nuclear protein of Nrf2; and the activity of SOD on days 2 and 4; but decreased these indexes on day 6. Naringenin can balance the antioxidant system by regulating Nrf2 and its downstream genes, preliminarily validating that Nrf2 pathway is involved in the protection offered by naringenin against cigarette smoke-induced damage to the lung. It suggests that dietary naringenin shows possible potential use in the management of lung health.

Antimicrobial and Wound Healing Potential of Dietary Flavonoid Naringenin

Background: Naringenin belongs to the class flavanones, and chemically it is known as 5,7-dihydroxy-2-(4-hydroxyphenyl) chroman-4-one. It is one of the dietary poly-phenolic constituents of the citrus fruits and vegetables. Naringenin possesses excellent antioxidant, antiinflammatory, and antimicrobial activities. These activities promote wound healing activity. Naringenin has been incorporated in the gel base to be applied on the wounded skin. The wound healing property of naringenin gel has not been studied extensively in the literature to date. &lt;/P&gt;&lt;P&gt; Objective: The present study aims to unveil the wound healing property of naringenin gel formulation on excision and incision model. &lt;/P&gt;&lt;P&gt; Materials and Methods: 0.5% and 1% naringenin was incorporated in a carbopol gel base formulation and evaluated for physicochemical parameters. Incision and excision wound models were used to study wound contraction, tensile strength, healing index, the period of epithelization and histopathological parameters. Antimicrobial activity was performed using agar plate method. Results: Naringenin (0.5% and 1%) treatment shows a significant increase in the percentage of wound contraction, good healing index and shorter epithelization period. Histopathology of naringenin gel treated wound tissue showed more fibroblasts, less macrophage infiltration, and wellformed collagen fibers as compared to control. In incision wound model, the animals were treated with 0.5% and 1% naringenin gel for nine days and showed a significant increase in the tensile strength. Naringenin exerts antimicrobial activity against fungus and E. coli. Conclusion: The present study explored potent wound healing activity of naringenin gels.

Dietary naringenin supplementation attenuates experimental autoimmune encephalomyelitis by modulating autoimmune inflammatory responses in mice

Autoimmune disease is highly prevalent in humans. Since conventional therapies have limited efficacy and often come with significant side effects, nutrition may provide an alternative and complementary approach to improving autoimmune disorders. Naringenin, a flavonoid found in citrus fruits, has been shown to have anti-inflammatory and antioxidant properties. Using the experimental autoimmune encephalomyelitis (EAE), a rodent model of human multiple sclerosis, we determined the effect of dietary naringenin (0.5%) on autoimmune disease. We found that naringenin reduced the incidence, delayed the onset, and attenuated the symptoms of EAE, which were accompanied by reduced immune cell infiltration and demyelination in the spinal cord. Additionally, the pro-inflammatory CD4+ T cell subsets Th1, Th9, and Th17 cells together with their respective transcription factors T-bet, PU.1, and RORγt were reduced in both the central nervous system (CNS) and lymph nodes of EAE mice fed naringenin while no difference was found in Th2 and regulatory T cell (Treg) populations in either CNS or lymph nodes between the two groups. We further showed that pathologic T cell proliferation induced by ex vivo re-stimulation with MOG35–55 and proinflammatory cytokines IL-6 and TNF-α were lower in naringenin-fed mice than in the control mice. Additionally, we found that naringenin treatment inhibited mRNA expression of CXCL10 (Th1 recruiting chemokine), vascular cell adhesion molecule-1 (VCAM-1), and VLA-4 (VCAM-1 ligand) in the CNS of EAE mice. Altogether, these results indicate that naringenin may have a potential to ameliorate autoimmune disease by favorably modulating autoimmune response.

Naringenin interferes with the anti-diabetic actions of pioglitazone via pharmacodynamic interactions.

Pioglitazone is a peroxisome proliferator-activated receptor gamma (PPARγ) full agonist and useful for the treatment of type 2 diabetes mellitus. Naringenin is a citrus flavonoid with anti-inflammatory actions, which has been shown to prevent obesity-related diseases and to activate PPARγ. The aim of this study was to investigate whether dietary naringenin affects the actions of pioglitazone. We administered naringenin (100mg/kg) and pioglitazone (10mg/kg) to Tsumura Suzuki Obese Diabetes (TSOD) mice for 4weeks and then conducted an oral glucose tolerance test. We found that oral administration of naringenin attenuated the hypoglycemic action of pioglitazone in TSOD mice. However, pioglitazone and naringenin did not affect fasting blood glucose levels, epididymal fat pad weight and body weight changes in this administration period. Pioglitazone suppressed expression of obesity-related adipokines such as tissue inhibitor of metalloproteinases-1 in adipose tissue of TSOD mice, but this effect was attenuated by naringenin. However, naringenin did not affect the pharmacokinetics of pioglitazone after single or repeated administration. Naringenin exhibited weak partial agonist activity in time-resolved fluorescence resonance energy transfer assay, but naringenin interfered with pioglitazone agonism, consistent with partial agonism. Our results suggest that it is advisable to avoid administering a combination of naringenin and pioglitazone.

Citrus flavonoid, naringenin, increases locomotor activity and reduces diacylglycerol accumulation in skeletal muscle of obese ovariectomized mice.

Estrogen deficiency has been associated with central obesity, muscle loss and metabolic syndrome in postmenopausal women. This study assessed naringenin accumulation in tissues and investigated the hypothesis that naringenin reverses diet-induced metabolic disturbances in obese ovariectomized mice. In study 1, we measured naringenin concentrations in plasma, liver, perigonadal and subcutaneous adipose tissues, and muscle of ovariectomized C57BL/6J female mice after 11 weeks of naringenin supplementation. Naringenin accumulated 5-12 times more in mice fed a 3% naringenin diet than in mice fed a 1% naringenin diet. In study 2, ovariectomized mice were fed a high-fat diet (60 kcal% fat) for 11 weeks and half of the mice were then supplemented with 3% naringenin for another 11 weeks. Dietary naringenin suppressed weight gain, lowered hyperglycemia and decreased intra-abdominal adiposity evaluated by magnetic resonance imaging. Naringenin-fed mice exhibited elevated locomotor activity monitored by infrared beam breaks, maintained muscle mass and reduced muscle diacylglycerol content. Real-time PCR analysis in muscle revealed decreased mRNA level for genes involved in de novo lipogenesis, lipolysis and triglyceride synthesis/storage. Long-term 3% naringenin supplementation resulted in significant naringenin accumulation in plasma and tissues, associated with attenuated metabolic dysregulation and muscle loss in obese ovariectomized mice.

Abstract 903: Comparison of the citrus flavonoid naringenin and metformin for effects on breast cancer in obese ovariectomized mice

Abstract Metformin has been shown to decrease breast cancer incidence in diabetic women, suggesting that improvement of metabolic status may be a useful approach to decrease breast cancer risk. As the putative cellular target of metformin, AMP-activated protein kinase (AMPK) not only regulates energy metabolism in liver, muscle, and adipose tissue but also inhibits protein synthesis and induces cell cycle arrest and apoptosis. Naringenin is a flavonoid abundant in citrus fruits that may have beneficial effects on metabolic health and tumorigenesis. Our in vitro data showed that naringenin inhibited proliferation of E0771 murine breast cancer cells, increased AMPK activity, and reduced expression of cell cycle regulatory proteins Cyclin D1 and anti-apoptotic Bcl-2 protein. In this study, we evaluated whether dietary naringenin acts like metformin to suppress mammary tumor growth in a mouse model of postmenopausal obesity. Ovariectomized female C57BL/6J mice were fed a high-fat diet (60% energy as fat) for 3 weeks to induce obesity. Then mice were randomized to experimental diets of HF (continued the high-fat diet), LN (high fat + 1% wt/wt naringenin in diet), HN (high fat + 3% wt/wt naringenin in diet), and Met (high fat + 180 mg/kg metformin in water) for 5 weeks. After 2 weeks of treatment, 5 × 10(5) E0771 cells were injected into one thoracic mammary fat pad. Mice were maintained on study diets for another 3 weeks. For all mice tumor weight correlated with weight gain in the first 5 weeks prior to cell inoculation (r = 0.51, p &amp;lt; 0.01). There was no difference in fasting glucose levels among the groups on week 8. No difference was observed between the HF and LN groups regarding final body weight, food intake, tissue weights, and tumor mass. HN significantly decreased final body weight, food intake, and adipose depot mass. mRNA expression of two inflammatory cytokines, interleukin 6 and monocyte chemoattractant protein-1 were decreased in perigonadal fat of the HN group. Although tumor growth (cm2) decreased over time in HN mice, there was no significant difference in tumor mass between HF and HN groups at necropsy (p = 0.4). HN did not affect AMPK activity in tumor tissue, but decreased Bcl-2 protein expression. Additionally, dietary naringenin resulted in a dose ­dependent accumulation in plasma, tumor, and mammary fat. In comparison to naringenin enriched diets, metformin significantly reduced tumor growth and final tumor weight, without affecting body weight, food intake, and tissue weights. Metformin decreased protein expression of Cyclin D1 in mammary tumors. However, we did not observe AMPK activation and changes in Bcl-2 protein levels in tumors. Taken together, these data suggest that metformin may inhibit mammary tumor growth without affecting metabolic status as assessed by body weight, adiposity, and fasting glucose. There may be different mechanisms of action for naringenin and metformin to alter mammary tumorigenesis. Citation Format: Jia-Yu Ke, Yung-Hsuan Hsiao, Shana R. Straka, Lisa D. Yee, Martha A. Belury. Comparison of the citrus flavonoid naringenin and metformin for effects on breast cancer in obese ovariectomized mice. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 903. doi:10.1158/1538-7445.AM2015-903

Abstract 2151: Evaluation of a citrus flavonoid as a chemopreventive agent against breast cancer

Abstract Naringenin is a flavonone found in citrus fruits and tomatoes that may have anti-tumor properties. Previously, our lab discovered that naringenin induced the activity of AMP-activated protein kinase (AMPK) and reduced phosphorylation of eukaryotic translation initiation factor 4E-binding protein 1 (4EBP) in MCF-7 human breast cancer cells. These properties have been linked with anti-tumor actions of drugs such as metformin and mTOR inhibitors. Based on these findings, we tested the ability of naringenin (0 uM - 200 uM) to modulate growth of MCF-7 human breast cancer cells and E0771 murine mammary tumor cells. In both models for cancer cell growth, naringenin dose-dependently decreased live cell number in a time-dependent manner. Furthermore, results of flow cytometry and propidium iodide staining assays showed accumulation of apoptotic cells after naringenin treatment. Naringenin also decreased expression of cyclin D1 and elevated expression of pro-apoptotic protein Bax suggesting that naringenin may inhibit the proliferation of mammary tumor cells by inducing cell cycle arrest and promoting apoptosis. To test for dose-dependent accumulation of naringenin in mammary gland tissue, female mice were fed varying doses of naringenin (control, 0%; low dose,1.0 wt%; or high dose, 3.0 wt% naringenin) in a high saturated fat diet for 11 weeks. Body weights and cumulative food intake were not different between diet groups. Dietary naringenin resulted in dose-responsive accumulation in mammary gland. Relative accumulation of naringenin in tissues was greatest in liver (low dose, 7.61 ± 1.14 umol/kg tissue and high dose, 37.04 ± 8.33 umol/kg tissue) followed by mammary gland and muscle which had a similar magnitude of naringenin accumulation (low dose ∼ 0.4 umol/kg tissue and high dose naringenin, 2.5 umol/kg tissue) of accumulation. Naringenin and monoglucuronide naringenin were two of the main forms of accumulated flavonoid in mammary gland raising the possibility that naringenin and/or metabolites are the active form of flavonoid responsible for anti-tumor activity against mammary cancer. Evaluating the species of naringenin metabolites in mammary gland that exert pro-apoptotic actions will be important to evaluate in order to understand the potential of naringenin-rich foods to contribute to prevention of breast cancer in women. Citation Format: Jia-Yu Ke, Min Tian, Kara L. Kliewer, Steve J. Schwartz, Ken M. Reidl, Shin-yu Tsai, Lisa D. Yee, Martha A. Belury. Evaluation of a citrus flavonoid as a chemopreventive agent against breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2151. doi:10.1158/1538-7445.AM2014-2151

Accumulation of dietary naringenin and metabolites in mice

Naringenin is a grapefruit flavonoid that may ameliorate metabolic disturbances and exert anti‐carcinogenic actions in mice. The bioavailability of naringenin and its metabolites in tissues is still unknown. In a pilot study, we used LC‐MS/MS to analyze naringenin metabolites in plasma, inguinal adipose tissue, and liver. Male mice fed a diet with 3wt% naringenin did not show differences in food intake or tissue weights after 12 days of feeding. Plasma contained the highest concentration of naringenin (13.38 ± 4.00 μM). Naringenin monoglucuronides were the major derivatives identified in inguinal adipose tissue, while free naringenin was the dominant form of accumulated naringenin in liver. Currently, we are analyzing tissue samples from ovariectomized female mice fed with high fat diets containing 1% or 3% naringenin to compare the concentration of metabolites in tissues. Evaluation of naringenin metabolites and their concentration in metabolically relevant tissues will improve our understanding of the cellular and molecular mechanism by which diets/foods enriched in naringenin may exert beneficial effects on metabolic disturbances and carcinogenesis.Grant Funding Source: 1R03CA162551–01A1

Effect of Anthocyanidin on MUC5AC and MUC5B Expression in Airway Epithelial Cells

Received March 11, 2013 Revised April 18, 2013 Accepted April 21, 2013 Address for correspondence Yong-Dae Kim, MD, PhD Department of OtorhinolaryngologyHead and Neck Surgery, College of Medicine, Yeungnam University, 170 Hyeonchung-ro, Nam-gu, Daegu 705-703, Korea Tel +82-53-620-3781 Fax +82-53-628-7884 E-mail ydkim@med.yu.ac.kr Background and ObjectivesZZNaringenin and delphinidin are types of anthocyanidin, which are flavonoids and thus have anti-inflammatory property. Moderate consumption of natural dietary naringenin and delphinidin is believed to do anti-inflammatory action, but the action mechanism is unclear. Therefore, this study aimed to investigate the effects of naringenin and delphinidin on interleukin-1β (IL-1β)and lipopolysaccharide (LPS)-induced MUC5AC and MUC5B expressions in airway epithelial cells. Materials and MethodZZIn NCI-H292 cells and cultured nasal polyp epithelial cells, the effects of naringenin and delphinidin on IL-1βand LPS-induced MUC5AC and MUC5B expressions were analyzed by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. ResultsZZDelphinidin attenuated IL-1βand LPS-induced MUC5AC and MUC5B mRNA and glycoprotein expression in a dose-dependent pattern in NCI-H292 cells and in cultured nasal polyp epithelial cells. Naringenin partially attenuated IL-1βand LPS-induced MUC5AC and MUC5B mRNA and glycoprotein expression at a high dose. ConclusionZZThese results suggest that delphinidin attenuates MUC5AC and MUC5B expressions in the airway epithelial cells. Between anthocyanidin and delphinidin, delphinidin exhibits greater potential as an ideal therapeutic agent for the control of mucus-hypersecretion in the treatment of airway inflammatory diseases. Korean J Otorhinolaryngol-Head Neck Surg 2013;56:291-6

The effect of naringenin on the phosphorylation of AMPK in diet‐induced obese mice

Previously, we reported that naringenin, the predominant flavanone in grapefruit, acted like metformin to decrease glucose output from hepatocytes. The objective of this study is to investigate whether dietary naringenin modulates energy balance and metabolism through p‐AMPK, a central regulator of glucose and lipid metabolism in several tissues. Male FVB mice were fed a high fat diet for 19 days, and then switched to AIN‐93G diet with (N= 10) or without (N=8) naringenin for 13 days. Body weight and food intake of mice fed naringenin were not significantly different than values in mice fed diet without naringenin. Mice were fasted for 12 hr then necropsy performed. There was a trend of enhanced p‐AMPK:AMPK in quadriceps muscle in mice fed diet with naringenin but p‐AMPK:AMPK was not significantly different in liver or inguinal fat pad. The induction of p‐AMPK in skeletal muscle suggests that naringenin exerts effects on energy pathways regulated by AMPK. Currently, we are conducting a new study to investigate the effects of various doses of naringenin on p‐AMPK activity and energy balance and metabolism in a mouse model for diet‐induced obesity.

Dietary naringenin increases hepatic peroxisome proliferators–activated receptor α protein expression and decreases plasma triglyceride and adiposity in rats

Naringenin, a flavonoid present in grapefruit, has recently been shown to exert hypolipidemic and hypocholesterolemic effects, which has a particular importance for protecting against chronic diseases. However, the lipid-lowering potential of naringenin at the concentrations in the dietary range and its underlying mechanisms have yet to be fully elucidated. The aim of the present study was (1) to investigate the effects of dietary naringenin on plasma and hepatic triglyceride and cholesterol levels and on adipose deposition in rat and (2) to determine the contribution of hepatic peroxisome proliferators-activated receptor α (PPARα) expression to fatty acid oxidation. Male Long-Evans hooded rats were fed a diet supplemented with naringenin (0.003, 0.006, and 0.012%) for 6weeks. We analyzed plasma and hepatic lipid contents and determined the protein expression of PPARα, carnitine-palmitoyl transferase 1L (CPT-1), and uncoupling protein 2 (UCP2), all of which are critical genes for fatty acid oxidation. Naringenin supplementation caused a significant reduction in the amount of total triglyceride and cholesterol in plasma and liver. In addition, naringenin supplementation lowered adiposity and triglyceride contents in parametrial adipose tissue. Naringenin-fed animals showed a significant increase in PPARα protein expression in the liver. Furthermore, expression of CPT-1 and UCP2, both of which are known to be regulated by PPARα, was markedly enhanced by naringenin treatment. Our results indicate that the activation of PPARα transcription factor and upregulation of its fatty acid oxidation target genes by dietary naringenin may contribute to the hypolipidemic and anti-adiposity effects in vivo.

The Effects of Selected Dietary Bioflavonoid Supplementation on Dental Caries in Young Rats Fed a High-Sucrose Diet

Recent evidence suggests that certain bioflavonoids reduce dental caries and cariogenic bacteria incidence. The present study evaluates two separate, but related, dietary trials -- trial 1, 0.09%, 0.18%, 0.36%, and 0.72% dietary naringenin (NAR) supplementation; and trial 2, 0.57% dietary rutin (R), quercetin (Q), and naringin (N) supplementation-on dental caries formation in 40 different male albino rats, at the expense of dextrose, for periods of 42 days. All rats were fed 40% sucrose. In dietary trial 1, rats were evaluated for dental caries, dental plaque accumulation, and saliva flow rates using oneway analysis of variance, post hoc Tukey's test, Kruskal-Wallis test, and Spearman's correlations. In dietary trial 2, rats were evaluated for occlusal dental caries only using a Kruskal-Wallis H test and analysis of variance. A 5% level of statistical significance was adopted throughout. In dietary trial 1, NAR showed a statistically significant effect on dental caries, plaque, and saliva flow rate reduction compared with the control group (P < .05-.01). An inverse dose-dependent relationship was established among the NAR experimental groups and control group. Dietary NAR supplementation significantly reduced dental caries formation, possibly because of reduced dental plaque accumulation. In dietary trial 2, statistically significant reductions in occlusal caries were observed for R, Q, and N in the maxillary molars and for Q and N in the mandibular molars compared with the control group (P < .05). Significant associations were observed among the experimental groups and maxillary (P < .05) and mandibular (P < .01) occlusal dental caries. Hence, selected bioflavonoids may show promise as an alternative means of reducing dental caries.

Effect of the Citrus Flavanone Naringenin on Oxidative Stress in Rats

Flavonoids are non-nutrient plant phenolic compounds proposed to provide health benefits in humans. The antioxidant and prooxidant effects of the citrus flavanone naringenin have been tested only in vitro. The dose-response effect of naringenin consumption was tested in weanling rats (n=6-8/group) with a 2x4 factorial design using high or low oxidative stress (Hox or Lox, respectively) diets, created by adequate or deficient amounts of vitamin E and selenium, with three increasing naringenin concentrations (30, 60, or 120 mg/kg of diet). Hox compared to Lox rats exhibited reduced growth and liver hypertrophy, which was not prevented by naringenin consumption. Also, Hox rats exhibited severalfold higher liver NAD(P)H:quinone oxidoreductase-1 activity, which was further elevated in proportion to naringenin intake, but this was not sufficient to protect against oxidative stress indicated by higher liver total aldehydes. In addition, dietary naringenin did not affect antioxidant nutrient status or physiological markers of growth under Lox conditions. Thus, dietary naringenin did not exhibit antioxidant or prooxidant effects in vivo in this rat model.

The Effects of Dietary Naringenin Supplementation on Physiological Changes in Molar Crestal Alveolar Bone–Cemento-Enamel Junction Distance in Young Rats

The objective of this study was to evaluate the influence of dietary naringenin (NAR) supplementation on physiological molar crestal alveolar bone (CAB)-cemento-enamel junction (CEJ) distances in young male albino rats. The effects of diets supplemented with 0.09%, 0.18%, 0.36%, and 0.72% NAR, at the expense of dextrose, were tested on 40 young rats, divided equally into five groups, for a period of 42 days. Rat skulls were defleshed, and CAB-CEJ distance was scored according to the modified method of Keyes and Gold. Data were analyzed using one-way analysis of variance, post hoc Tukey's test, and Spearman's (R(2)) correlation. P < .05 was used to reject the null hypothesis. NAR showed a statistically significant inverse dose-dependent relationship on CAB-lingual alveolar bone distance (P < .05). In all cases lingual CAB-CEJ distance was larger than buccal CAB-CEJ distance. Thus dietary NAR supplementation was shown to significantly reduce molar CAB-CEJ distance (P < .001-.05) during alveolar development in young male rats.