NXP081, DNA Aptamer-Vitamin C Complex Ameliorates DNFB-Induced Atopic Dermatitis in Balb/c Mice.

Atopic dermatitis (AD) is a chronic inflammatory disease characterized by dry and itchy skin. Recently, it has been reported that oxidative stress is involved in skin diseases, possibly including AD. Vitamin C, also referred to as ascorbic acid, is a vital water-soluble compound that functions as an essential nutrient. It plays a significant role as both an antioxidant and an additive in various pharmaceutical and food products. Despite the fact that vitamin C is easily oxidized, we have developed NXP081, a single-stranded DNA aptamer that selectively binds to vitamin C, thereby inhibiting its oxidation. The objective of the current research was to examine the impact of NXP081, an animal model of AD induced by 2,4-dinitrofluorobenzene (DNFB). The experimental drug NXP081, when taken orally, showed promising results in reducing inflammation and improving the skin conditions caused by DNFB. The administration of NXP081 resulted in a significant reduction in ear swelling and a noticeable improvement in the appearance of skin lesions. In addition, the administration of NXP081 resulted in a significant decrease in the migration of mast cells in the skin lesions induced by DNFB. Moreover, NXP081 inhibited the production of interferon-gamma (IFN-γ) in CD4+ T cells that were activated and derived from the lymph nodes. Our findings provide useful information about the anti-inflammatory effect of NXP081 on AD.

Euscaphic acid relieves fatigue by enhancing anti-oxidative and anti-inflammatory effects.

BACKGROUND: Oxidative stress and inflammation are involved in chronic fatigue. Euscaphic acid (EA) is an active compound of Eriobotrya japonica (Loquat) and has anti-oxidative effect. METHODS: The goal of present study is to prove whether EA could relieve fatigue through enhancing anti-oxidant and anti-inflammatory effects in in vitro/in vivo models. RESULTS: EA notably improved activity of superoxide dismutase (SOD) and catalase (CAT), while EA reduced levels of malondiadehyde (MDA) and inflammatory cytokines without cytotoxicity in H2O2-stimulated in myoblast cell line, C2C12 cells. EA significantly reduced levels of fatigue-causing factors such as lactate dehydrogenase (LDH) and creatin kinase (CK), while EA significantly incresed levels of anti-fatigue-related factor, glycogen compared to the H2O2-stimulated C2C12 cells. In treadmill stress test (TST), EA significantly enhanced activities of SOD and CAT as well as exhaustive time and decreased levels of MDA and inflammatory cytokines. After TST, levels of free fatty acid, citrate synthase, and muscle glycogen were notably enhanced by oral administration of EA, but EA decreased levels of lactate, LDH, cortisol, aspartate aminotransferase, alanine transaminase, CK, glucose, and blood urea nitrogen compared to the control group. Furthermore, in forced swimming test, EA significantly increased levels of anti-fatigue-related factors and decreased excessive accumulations of fatigue-causing factors. CONCLUSIONS: Therefore, the results indicate that potent anti-fatigue effect of EA can be achieved via the improvement of anti-oxidative and anti-inflammatory properties, and this study will provide scientific data for EA to be developed as a novel and efficient component in anti-fatigue health functional food.

Autophagy in Crotonaldehyde-Induced Endothelial Toxicity.

Crotonaldehyde is an extremely toxic α,ß-unsaturated aldehyde found in cigarette smoke, and it causes inflammation and vascular dysfunction. Autophagy has been reported to play a key role in the pathogenesis of vascular diseases. However, the precise mechanism underlying the role of acute exposure crotonaldehyde in vascular disease development remains unclear. In the present study, we aimed to investigate the effect of crotonaldehyde-induced autophagy in endothelial cells. Acute exposure to crotonaldehyde decreased cell viability and induced autophagy followed by cell death. In addition, inhibiting the autophagic flux markedly promoted the viability of endothelial cells exposed to high concentrations of crotonaldehyde. Crotonaldehyde activated the AMP-activated protein kinase (AMPK) and p38 mitogen-activated protein kinase (MAPK) pathways, and pretreatment with inhibitors specific to these kinases showed autophagy inhibition and partial improvement in cell viability. These data show that acute exposure to high concentrations of crotonaldehyde induces autophagy-mediated cell death. These results might be helpful to elucidate the mechanisms underlying crotonaldehyde toxicity in the vascular system and contribute to environmental risk assessment.

Parapheromones Suppress Chemotherapy Side Effects.

The cytotoxic drugs used in chemotherapy are often accompanied by nausea and vomiting. Despite the use of antiemetic drugs, chemotherapy-induced nausea and vomiting (CINV) remain significant side effects for cancer patients and are associated with serotonin type 3 receptor (5-HT3R) activation in the brainstem. Farnesol and nerolidol are sesquiterpene alcohols found in essential oils of plants such as roses, citronella, and lemon grass and are used as antiemetic parapheromones. Medicinal plants often are effective in treating gastrointestinal disorders, including CINV, although the mechanism of action remains unclear. In the current work, the antiemetic efficacy of the naturally occurring racemic mixture of farnesol (m-farnesol) and nerolidol (m-nerolidol) against cisplatin CINV was tested using the pica behavior (consumption of nonnutritive substances) of rats. Animals treated with m-farnesol or m-nerolidol consumed a smaller amount of kaolin than of saline-treated control animals. This result is consistent with the antiemetic efficacy of farnesol and nerolidol. Compared with controls, m-farnesol- but not m-nerolidol-treated animals consumed more food and lost less body weight. Thus, farnesol effectively reduced appetite suppression and weight loss induced by cisplatin. In separate experiments, isomers of farnesol and nerolidol were tested on 5-HT-induced responses of acutely isolated nodose neurons using patch-clamp methods. All the tested constituents inhibited 5-HT3R-mediated current in a noncompetitive manner. Thus, both farnesol and nerolidol may exert antiemetic efficacy by inhibiting 5-HT signaling in cranial visceral afferents, resulting in interruption of emetogenic signaling; however, nerolidol failed to suppress cisplatin-induced anorexia and weight loss, suggesting that additional mechanisms may contribute.

Effect of Chaenomeles sinensis Extract on Choline Acetyltransferase Activity and Trimethyltin-Induced Learning and Memory Impairment in Mice.

The aim of this study was to search for a novel choline acetyltransferase (ChAT) activator from plants traditionally grown in Korea. An ethanol extract from Chaenomeles sinensis Koehne showed the highest ChAT-activating effect in vitro in an assay that used human neuroblastoma cells and [(14)C]acetyl-CoA. The active compound was speculated to be stearic acid methyl ester (SAME). In an in vivo experiment, C. sinensis extract and SAME improved trimethyltin (TMT)-induced deficits in learning and memory in mice as assessed by a Y-maze behavioral test and a passive avoidance test. The C. sinensis extract might attenuate the TMT-induced brain disorder. This study suggests that SAME from C. sinensis might be useful in the treatment of Alzheimer's disease.

Characterization of Nutritional Composition, Antioxidative Capacity, and Sensory Attributes of Seomae Mugwort, a Native Korean Variety of Artemisia argyi H. Lév. & Vaniot.

Few studies have investigated Seomae mugwort (a Korean native mugwort variety of Artemisia argyi H. Lév. & Vaniot), exclusively cultivated in the southern Korean peninsula, and the possibility of its use as a food resource. In the present study, we compared the nutritional and chemical properties as well as sensory attributes of Seomae mugwort and the commonly consumed species Artemisia princeps Pamp. In comparison with A. princeps, Seomae mugwort had higher contents of polyunsaturated fatty acids, total phenolic compounds, vitamin C, and essential amino acids. In addition, Seomae mugwort had better radical scavenging activity and more diverse volatile compounds than A. princeps as well as favorable sensory attributes when consumed as tea. Given that scant information is available regarding the Seomae mugwort and its biological, chemical, and sensory characteristics, the results herein may provide important characterization data for further industrial and research applications of this mugwort variety.

Eriodictyol Protects Endothelial Cells against Oxidative Stress-Induced Cell Death through Modulating ERK/Nrf2/ARE-Dependent Heme Oxygenase-1 Expression.

The pathophysiology of cardiovascular diseases is complex and may involve oxidative stress-related pathways. Eriodictyol is a flavonoid present in citrus fruits that demonstrates anti-inflammatory, anti-cancer, neurotrophic, and antioxidant effects in a range of pathophysiological conditions including vascular diseases. Because oxidative stress plays a key role in the pathogenesis of cardiovascular disease, the present study was designed to verify whether eriodictyol has therapeutic potential. Upregulation of heme oxygenase-1 (HO-1), a phase II detoxifying enzyme, in endothelial cells is considered to be helpful in cardiovascular disease. In this study, human umbilical vein endothelial cells (HUVECs) treated with eriodictyol showed the upregulation of HO-1 through extracellular-regulated kinase (ERK)/nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathways. Further, eriodictyol treatment provided protection against hydrogen peroxide-provoked cell death. This protective effect was eliminated by treatment with a specific inhibitor of HO-1 and RNA interference-mediated knockdown of HO-1 expression. These data demonstrate that eriodictyol induces ERK/Nrf2/ARE-mediated HO-1 upregulation in human endothelial cells, which is directly associated with its vascular protection against oxidative stress-related endothelial injury, and propose that targeting the upregulation of HO-1 is a promising approach for therapeutic intervention in cardiovascular disease.

Aspartame Attenuates 2, 4-Dinitrofluorobenzene-Induced Atopic Dermatitis-Like Clinical Symptoms in NC/Nga Mice.

Atopic dermatitis (AD) is a common multifactorial chronic skin disease that has a multiple and complex pathogenesis. AD is gradually increasing in prevalence globally. In NC/Nga mice, repetitive applications of 2, 4-dinitrofluorobenzene (DNFB) evoke AD-like clinical symptoms similar to human AD. Aspartame (N-L-α-aspartyl-L-phenylalanine 1-methyl ester) is a methyl ester of a dipeptide, which is used as an artificial non-nutritive sweetener. Aspartame has analgesic and anti-inflammatory functions that are similar to the function of nonsteroidal anti-inflammatory drugs such as aspirin. We investigated whether aspartame can relieve AD-like clinical symptoms induced by DNFB treatment in NC/Nga mice. Sucrose did not relieve AD-like symptoms, whereas aspartame at doses of 0.5 µg kg(-1) and 0.5 mg kg(-1) inhibited ear swelling and relieved AD-like clinical symptoms. Aspartame inhibited infiltration of inflammatory cells including eosinophils, mast cells, and CD4(+) T cells, and suppressed the expression of cytokines including IL-4 and IFN-γ, and total serum IgE levels. Aspartame may have therapeutic value in the treatment of AD.

Effects of Eicosapentaenoic Acid on the Cytoprotection Through Nrf2-Mediated Heme Oxygenase-1 in Human Endothelial Cells.

Consumption of omega-3 polyunsaturated fatty acid, particularly eicosapentaenoic acid (EPA), is associated with a significant reduction in the risk of developing cardiovascular disease. The aim of this study was to investigate whether heme oxygenase-1 (HO-1) induction contributes to the cytoprotective effects of EPA in endothelial cells threatened with oxidative damage. In this study, we investigated the effect of EPA on the induction of HO-1 by NF-E2-related factor 2 (Nrf2) in human umbilical vein endothelial cells. In cells treated with low concentrations of EPA (10-25 µM), HO-1 expression increased in a time- and concentration-dependent manner. Additionally, EPA treatment increased Nrf2 nuclear translocation and antioxidant response element activity, leading to the upregulation of HO-1 expression. Furthermore, treatment with EPA reduced hydrogen peroxide (H(2)O(2))-induced cell death. The reduction in cell death was reversed by treatment with zinc protoporphyrin, an inhibitor of HO-1, indicating that HO-1 contributed to the protective effect of EPA. These data suggest that EPA protects against H(2)O(2)-induced oxidative stress in endothelial cells by activating Nrf2 and inducting HO-1 expression.

Production and applications of rosmarinic acid and structurally related compounds.

Rosmarinic acid (α-o-caffeoyl-3,4-dihydroxyphenyllactic acid; RA) is a naturally occurring hydroxylated compound commonly found in species of the subfamily Nepetoideae of the Lamiaceae and Boraginaceae, such as Rosmarinus officinalis, Salvia officinalis, and Perilla frutescens. RA is biosynthesized from the amino acids L-phenylalanine and L-tyrosine by eight enzymes that include phenylalanine ammonia lyase and cinnamic acid 4-hydroxylase. RA can also be chemically produced by the esterification of caffeic acid and 3,4-dihydroxyphenyllactic acid. RA and its numerous derivatives containing one or two RA with other aromatic moieties are well known and include lithospermic acid, yunnaneic acid, salvianolic acid, and melitric acid. Recently, RA and its derivatives have attracted interest for their biological activities, which include anti-inflammatory, anti-oxidant, anti-angiogenic, anti-tumor, and anti-microbial functions. Clinically, RA attenuates T cell receptor-mediated signaling, attenuates allergic diseases like allergic rhinitis and asthma, and 2,4-dinitrofluorobenzene-induced atopic dermatitis-like symptoms, protects from neurotoxicity, and slows the development of Alzheimer's disease. These attributes have increased the demand for the biotechnological production and application of RA and its derivatives. The present review discusses the function and application of RA and its derivatives including the molecular mechanisms underlying clinical efficacy.

ß2 integrins (CD11/18) are essential for the chemosensory adhesion and migration of polymorphonuclear leukocytes on bacterial cellulose.

Bacterial cellulose (BC) has been studied widely for applications in biomedical materials such as prosthetic artificial blood vessels owing to its unique characteristics, which include nontoxicity and nonimmunogenicity as compared with synthetic biopolymers such as expanded polytetrafluorethylene (ePTFE). However, to date, studies on the relative effect of leukocytes on BC as a prosthetic vascular graft are insufficient. Polymorphonuclear leukocytes (PMN) play a pivotal role in early-phase immune response to bacterial or periprosthetic infection. PMN recruitment at sites of infection or inflammation mediated by various integrins such as ß2 integrin family (CD11/CD18 family). Therefore, we discuss our investigations into the mechanisms by which ß2 integrins-mediated chemosensory adhesion and migration of PMN on the vascular graft surface, BC. Our results show that CD11b/CD18 components mainly mediate PMN adherence on BC. CD11b/CD18 displays weak coordination with the other two α subunits (CD11a and CD11c). Furthermore, it was found that the ß subunit (CD18) plays a critical role in both the adhesion and migration of N-formylmethionyl-leucyl-phenylalanine (fMLP)-stimulated PMN on BC. The activity of CD18 contrasts with that of the individual α subunits. Among these, only CD11b displayed inhibition of PMN migration on BC surfaces.

Prostaglandin potentiates 5-HT responses in stomach and ileum innervating visceral afferent sensory neurons.

Gastrointestinal disorder is a common symptom induced by diverse pathophysiological conditions that include food tolerance, chemotherapy, and irradiation for therapy. Prostaglandin E2 (PGE2) level increase was often reported during gastrointestinal disorder and prostaglandin synthetase inhibitors has been used for ameliorate the symptoms. Exogenous administration of PGE2 induces gastrointestinal disorder, however, the mechanism of action is not known. Therefore, we tested PGE2 effect on visceral afferent sensory neurons of the rat. Interestingly, PGE2 itself did not evoked any response but enhanced serotonin (5-HT)-evoked currents up to 167% of the control level. The augmented 5-HT responses were completely inhibited by a 5-HT type 3 receptor antagonist, ondansetron. The PGE2-induced potentiation were blocked by a selective E-prostanoid type 4 (EP4) receptors antagonist, L-161,982, but type 1 and 2 receptor antagonist AH6809 has no effect. A membrane permeable protein kinase A (PKA) inhibitor, KT5720 also inhibited PGE2 effects. PGE2 induced 5-HT current augmentation was observed on 15% and 21% of the stomach and ileum projecting neurons, respectively. Current results suggest a synergistic signaling in visceral afferent neurons underlying gastrointestinal disorder involving PGE2 potentiation of 5-HT currents. Our findings may open a possibility for screen a new type drugs with lower side effects than currently using steroidal prostaglandin synthetase inhibitors by selectively targeting EP4 receptor/PKA pathway without interrupt prostaglandin synthesis.

Ligularia fischeri extract protects against oxidative-stress-induced neurotoxicity in mice and PC12 cells.

Alzheimer's disease (AD) is pathologically characterized by the presence of amyloid plaques in brain and the overproduction of amyloid beta (Aß), leading to learning and memory impairment and intense oxidative stress. In this study, the protective effect of Ligularia fischeri extract was investigated using PC12 cells. L. fischeri extract attenuated hydrogen-peroxide-induced DNA fragmentation in cells. In vivo behavioral tests were performed to examine the effects of the extract on amyloid-ß peptide1-42-induced impairment of learning and memory in mice. A diet containing the extract increased alternation behaviors in the Y-maze test and step-through latency of passive avoidance task. Moreover, we found that consumption of the extract decreased lipid peroxidation in a biochemical study of brain tissue in mice. High-performance liquid chromatography was used to identify the active compounds in the extract. These results suggest that L. fischeri extract could be protective against Aß-induced neurotoxicity, possibly due to the antioxidative capacity of its constituent, 3-O-caffeoylquinic acid.

Ginger and its pungent constituents non-competitively inhibit serotonin currents on visceral afferent neurons.

Nausea and emesis are a major side effect and obstacle for chemotherapy in cancer patients. Employ of antiemetic drugs help to suppress chemotherapy-induced emesis in some patients but not all patients. Ginger, an herbal medicine, has been traditionally used to treat various kinds of diseases including gastrointestinal symptoms. Ginger is effective in alleviating nausea and emesis, particularly, for cytotoxic chemotherapy drug-induced emesis. Ginger-mediated antiemetic effect has been attributed to its pungent constituents-mediated inhibition of serotonin (5-HT) receptor activity but its cellular mechanism of action is still unclear. Emetogenic chemotherapy drugs increase 5-HT concentration and activate visceral vagal afferent nerve activity. Thus, 5-HT mediated vagal afferent activation is essential to provoke emesis during chemotherapy. In this experiment, water extract of ginger and its three major pungent constituent's effect on 5-HT-evoked responses were tested on acutely dispersed visceral afferent neurons with patch-clamp methods. The ginger extract has similar effects to antiemetic drug ondansetron by blocking 5-HT-evoked responses. Pungent constituents of the ginger, [6]-shogaol, [6]-gingerol, and zingerone inhibited 5-HT responses in a dose dependent manner. The order of inhibitory potency for these compounds were [6]-shogaol>[6]-gingerol>zingerone. Unlike well-known competitive 5-HT3 receptor antagonist ondansetron, all tested ginger constituents acted as non-competitive antagonist. Our results imply that ginger and its pungent constituents exert antiemetic effects by blocking 5-HT-induced emetic signal transmission in vagal afferent neurons.

Immunosuppressive effects of fisetin against dinitrofluorobenzene-induced atopic dermatitis-like symptoms in NC/Nga mice.

Atopic dermatitis (AD) is a multifactorial chronic skin disorder that is increasing in prevalence globally. In NC/Nga mice, repetitive epicutaneous applications of 2-4-dinitrofluorobenzene (DNFB) induces AD-like clinical symptoms. Bioflanonol fisetin (3,7,3',4'-tetrahydroxyflavone) is a dietary component found in plants, fruits and vegetables. Fisetin has various physiological effects that include anti-oxidation, anti-angiogenesis, anti-carcinogenesis and anti-inflammation. In this study, we investigated whether fisetin relieves AD-like clinical symptoms induced by repeated DNFB treatment in NC/Nga mice. Fisetin significantly inhibited infiltration of inflammatory cells including eosinophils, mast cells and CD4(+) T and CD8(+) T cells, and suppressed the expressions of cytokines and chemokines associated with dermal infiltrates in AD-like skin lesions. Total serum immunoglobulin E (IgE) levels and the ratio of phospho-NF-κB p65 to total NF-κB p65 were markedly reduced by fisetin. Fisetin also reduced the production of interferon-gamma and interleukin-4 by activated CD4(+) T cells in a dose-dependent manner, whereas the anti-inflammatory cytokine, interleukin-10 was increased. These results implicate fisetin as a potential therapeutic for AD.

Effects of brussels sprouts and their phytochemical components on oxidative stress-induced neuronal damages in PC12 cells and ICR mice.

In this study, the protective effects of Brussels sprouts extract and its major constituents against oxidative stress-induced damages were investigated in rat pheochromocytoma cells and Institute of Cancer Research mice. The major constituents of Brussels sprouts (3,4',5,7-tetrahydroxyflavone (kaempferol), indole-3-carbinol, and phenethyl isothiocyanate) were selectively tested. Of these, the flavonoid compound, kaempferol exhibited the highest potency in radical scavenging activity (1,1-diphenyl-2-picryl hydrazyl assay and oxygen radical absorbance capacity assay) and was most protective against oxidative stress in neuronal cell assays (measurement of intracellular oxidative stress levels and cell viability). In mice, after 4 weeks of kaempferol administration, significant protection against amyloid beta (Aß) peptide-induced neurotoxicity was also observed, as assessed through the passive avoidance test. Taken together, the results suggest that Brussels sprouts could be protective against Aß-induced neurotoxicity, possibly due to the antioxidative capacity of its major constituent, kaempferol.

2,4-Di-tert-butylphenol from sweet potato protects against oxidative stress in PC12 cells and in mice.

In this study, the protective effect of sweet potato extract against hydrogen peroxide-induced oxidative stress and cytotoxicity on the pheochromocytoma cell line (PC12) was investigated. The active component of the sweet potato extract was purified and determined to be 2,4-di-tert-butylphenol. The antioxidant capacity of 2,4-di-tert-butylphenol was measured by using 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid (ABTS) radical. To examine the effects of 2,4-di-tert-butylphenol on amyloid-beta peptide (Aß11₋42)-induced learning and memory impairment in mice, in vivo behavioral tests were performed. Administration of 2,4-di-tert-butylphenol increased alternation behavior in mice injected with Aß1₋42. These results suggest that sweet potato extract could be protective against Aß-induced neurotoxicity, possibly due to the antioxidative capacity of its constituent, 2,4-di-tert-butylphenol.

Rubus coreanus Miquel inhibits acetylcholinesterase activity and prevents cognitive impairment in a mouse model of dementia.

To find acetylcholinesterase (AChE) inhibitors for the prevention of neurological disorders, such as Alzheimer's disease, ethanol extracts of promising traditional edible Korean plants were tested. Among them, Rubus coreanus Miquel extract exhibited the most significant AChE inhibitory activity. The effect of R. coreanus extract on trimethyltin-induced memory impairment in mice was investigated using Y-maze and passive avoidance tests. Our results showed that administration of R. coreanus extract significantly improved alternation behavior and step-through latency. In addition, R. coreanus extract was sequentially fractionated, and the purified constituent was determined to be 3,4,5-trihydroxybenzoic acid.

Crotonaldehyde induces heat shock protein 72 expression that mediates anti-apoptotic effects in human endothelial cells.

Crotonaldehyde is a highly reactive aldehyde and a common environmental pollutant. It occurs in cigarette smoke and automobile exhaust, and is also endogenously generated by lipid peroxidation. Reactive aldehydes, such as crotonaldehyde, are considered to be important mediators of cell damage. Since endothelial apoptosis is considered to be the first step in the pathogenesis of cardiovascular disease, there have been many efforts to protect endothelial cell from oxidative stress. Heat shock protein 72 (HSP72) is a representative stress-inducible HSP70 family protein, and its synthesis is increased in response to multiple stressors. In the present study, we investigated the effect of crotonaldehyde on the up-regulation of HSP72 in human umbilical vein endothelial cells (HUVECs). Crotonaldehyde treatment caused nuclear accumulation of the heat shock transcription factor 1 (HSF1), leading to the induction of HSP72. Inhibition of the c-Jun N-terminal kinases (JNK) signaling pathways, reduction of intracellular calcium level and blocking of reactive oxygen species (ROS) generation resulted in significant blockage of crotonaldehyde-mediated HSP72 induction. In addition, HSP72 silencing by siRNA or calcium chelating by BAPTA/AM resulted in an obvious increase in the rate of apoptosis in crotonaldehyde-stimulated HUVECs. In summary, our data demonstrated that crotonaldehyde-induced HSP72 expression in HUVECs is mediated by the JNK-HSF1 pathway, and involves calcium ions and ROS, which is an adaptive response to oxidative stress caused by crotonaldehyde.

The inhibitory effect of naringenin on atopic dermatitis induced by DNFB in NC/Nga mice.

AIMS: Atopic dermatitis (AD) is a chronic and relapsing inflammatory dermatitis characterized by pruritic and eczematous skin lesions. Here, we investigated the therapeutic effect of the fruit flavonoid naringenin on DNFB induced atopic dermatitis mice model. MAIN METHODS: AD-like skin lesion was induced by repetitive skin contact with DNFB in NC/Nga mice and the effects of the fruit flavonoid naringenin were evaluated on the basis of histopathological findings of skin, ear swelling and cytokine production of CD4(+)T cells. KEY FINDINGS: Intraperitoneal injection of naringenin for one week after DNFB challenge significantly lowered ear swelling and improved back skin lesions. In addition, naringenin significantly suppressed production of interferon-gamma (IFN-γ) by activated CD4(+) T cells and serum IgE level. Furthermore, naringenin reduced DNFB-induced infiltration of eosinophils, mast cells, CD4(+) T cells, and CD8(+) T cells in skin lesions. SIGNIFICANCE: Naringenin may suppress the development of AD-like skin lesions in DNFB-treated NC/Nga mice by reducing IFN-γ production of activated CD4(+) T cells, serum IgE levels and infiltration of immune cells to skin lesion.