Naringin and Naringenin:Potential Multi-Target Agents for Alzheimer’s Disease

Alzheimer’s disease(AD)is one of the most common forms of neurodegenerative dementia.The etiology of AD is multifactorial,and its complex pathophysiology involves tau and amyloid-βdeposition,increased oxidative stress,neuroinflammation,metabolic disorders,and massive neuronal loss.Due to its complex pathology,no effective cure for AD has been found to date.Therefore,there is an unmet clinical need for the development of new drugs against AD.Natural products are known to be good sources of compounds with pharmacological activity and have potential for the development of new therapeutic agents.Naringin,a naturally occurring flavanone glycoside,is predominantly found in citrus fruits and Chinese medicinal herbs.Mounting evidence shows that naringin and its aglycone,naringenin,have direct neuroprotective effects on AD,such as anti-amyloidogenic,antioxidant,anti-acetylcholinesterase,and anti-neuroinflammatory effects,as well as metal chelation.Furthermore,they are known to improve disordered glucose/lipid metabolism,which is a high risk factor for AD.In this review,we summarize the latest data on the impact of naringin and naringenin on the molecular mechanisms involved in AD pathophysiology.Additionally,we provide an overview of the current clinical applications of naringin and naringenin.The novel delivery systems for naringin and naringenin,which can address their widespread pharmacokinetic limitations,are also discussed.The literature indicates that naringin and naringenin could be multilevel,multitargeted,and multifaceted for preventing and treating AD.

Naringin ameliorates H_(2)O_(2)-induced oxidative damage in cells and prolongs the lifespan of female Drosophila melanogaster via the insulin signaling pathway

Naringin exists in a wide range of Chinese herbal medicine and has proven to possess several pharmacological properties.In this study,PC12,HepG2 cells,and female Drosophila melanogaster were used to investigate the antioxidative and anti-aging effects of naringin and explore the underlying mechanisms.The results showed that naringin inhibited H_(2)O_(2)-induced decline in cell viability and decreased,the content of reactive oxygen species in cells.Meanwhile,naringin prolonged the lifespan of flies,enhanced the abilities of climbing and the resistance to stress,improved the activities of antioxidant enzymes,and decreased malondialdehyde content.Naringin also improved intestinal barrier dysfunction and reduced abnormal proliferation of intestinal stem cells.Moreover,naringin down-regulated the mRNA expressions of inr,chico,pi 3k,and akt-1,and up-regulated the mRNA expressions of dilp2,dilp3,dilp5,and foxo,thereby activating autophagy-related genes and increasing the number of lysosomes.Furthermore,the mutant stocks assays and computer molecular simulation results further indicated that naringin delayed aging by inhibiting the insulin signaling(IIS)pathway and activating the autophagy pathway,which was consistent with the result of network pharmacological predictions.

The mechanism of Naringin-enhanced remyelination after spinal cord injury

Our previous study revealed that intragastric administration of naringin improved remyelination in rats with spinal cord injury and promoted the recovery of neurological function of the injured spinal cord.This study sought to reveal the mechanisms by which naringin improves oligodendrocyte precursor cell differentiation and maturation,and promotes remyelination.Spinal cord injury was induced in rats by the weight-drop method.Naringin was intragastrically administered daily（20,40 mg/kg） for 4 weeks after spinal cord injury induction.Behavioral assessment,histopathological staining,immunofluorescence spectroscopy,ultrastructural analysis and biochemical assays were employed.Naringin treatment remarkably mitigated demyelination in the white matter,increased the quality of myelinated nerve fibers and myelin sheath thickness,promoted oligodendrocyte precursor cell differentiation by upregulating the expression of NKx2.2 and 2′3′-cyclic nucleotide 3′-phosphodiesterase,and inhibited β-catenin expression and glycogen synthase kinase-3β（GSK-3β） phosphorylation.These findings indicate that naringin treatment regulates oligodendrocyte precursor cell differentiation and promotes remyelination after spinal cord injury through the β-catenin/GSK-3β signaling pathway.

Effects of naringin, a flavanone glycoside in grapefruits and citrus fruits, on the nigrostriatal dopaminergic projection in the adult brain

Recently, we have demonstrated the ability of naringin, a well-known flavanone glycoside of grapefruits and citrus fruits, to prevent neurodegeneration in a neurotoxin model of Parkinson＇s disease. Intraperitoneal injection of naringin protected the nigrostriatal dopaminergic projection by increasing glial cell line-derived neurotrophic factor expression and decreasing the level of tumor necrosis factor-alpha in dopaminergic neurons and microglia, respectively. These results suggest that naringin can impart to the adult dopaminergic neurons the ability to produce glial cell line-derived neurotrophic factor against Parkinson＇s disease with anti-inflammatory effects. Based on these results, we would like to describe an important perspective on its possibility as a therapeutic agent for Parkinson＇s disease.

Naringin ameliorates acetic acid induced colitis through modulation of endogenous oxido-nitrosative balance and DNA damage in rats

The aim of this study was to evaluate the effect of naringin on experimentally induced inflammatory bowel dis- ease in rats. Naringin （20, 40 and 80 mg/kg） was given orally for 7 days to Wistar rats before induction of colitis by intrarectal instillation of 2 mL of 4% （v/v） acetic acid solution. The degree of colonic mucosal damage was analyzed by examining mucosal damage, ulcer area, ulcer index and stool consistency. Intrarectal administration of 4% acetic acid resulted in significant modulation of serum alkaline phosphatase, lactate dehydrogenase, superoxide dismutase （SOD）, glutathione （GSH）, malondialdehyde （MDA） and myeloperoxidase （MPO） content along with colonic nitric oxide （NO）, xanthine oxidase （XO） level and protein carbonyl content in the colonic tissue as well as in blood. Naringin （40 and 80 mg/kg） exerted a dose dependent （P 〈 0.05） ameliorative effect, as it significantly increased hematological parameter as well as colonic SOD and GSH. There was a significant （P 〈 0.05） and dose dependant inhibition of macroscopical score, ulcer area along with colonic MDA, MPO activity by the 7 days of pretreatment of naringin （40 and 80 mg/kg）. Biochemical studies revealed a significant （P 〈 0.05） dose dependant inhibition in serum alkaline phosphatase （ALP） and lactate dehydrogenase （LDH） levels by pretreatment of naringin. Increased levels of colonic NO, XO, protein carbonyl content and DNA damage were also sig- nificantly decreased by naringin pretreatment. The findings of the present investigation propose that naringin has an anti-inflammatory, anti-oxidant and anti-apoptotic potential effect at colorectal sites as it modulates the production and expression of oxidative mediators such as MDA, MPO, NO and XO, thus reducing DNA damage.

A spectroscopic study of the interaction of the antioxidant naringin with bovine serum albumin

The interaction of naringin with bovine serum albumin has been performed using fluorescence, circular dichroism and fourier transform infrared spectroscopy in 20 mM phosphate buffer of pH 7.0 as well as molecular docking studies. The changes in enthalpy (ΔH°) and entropy (ΔS°) of the interaction were found to be +18.73 kJ/mol and +143.64 J mol-1 K-1 respectively, indicating that the interaction of naringin with bovine serum albumin occurred mainly through hydrophobic interactions. Negative values of free energy change (ΔG°) at different temperatures point toward the spontaneity of the interaction. Circular dichroism studies reveal that the helical content of bovine serum albumin decreased after interaction with naringin. According to the F?rster non-radiative energy transfer theory the distance between Trp 213 residue and naringin was found to be 3.25 nm. Displacement studies suggest that naringin binds to site 1 (subdomain IIA) of bovine serum albumin (BSA) which was also substantiated by molecular docking studies.

Naringin attenuates oxidative stress,inflammation,apoptosis,and oxidative DNA damage in acrylamide-induced nephrotoxicity in rats

Objective:To explore the possible effects of naringin on acrylamide-induced nephrotoxicity in rats.Methods:Sprague-Dawley rats weighing 200-250 g were randomly divided into five groups.The control group was given intragastric(i.g.)saline(1 mL)for 10 d.The acrylamide group was given i.g.acrylamide in saline(38.27 mg/kg titrated to 1 mL)for 10 d.The treatment groups were administered with naringin in saline(50 and 100 mg/kg,respectively)for 10 d and given i.g.acrylamide(38.27 mg/kg)1 h after naringin injection.The naringin group was given i.g.naringin(100 mg/kg)alone for 10 d.On day 11,intracardiac blood samples were obtained from the rats when they were under anesthesia,after which they were euthanized.Urea and creatinine concentrations of blood serum samples were analyzed with an autoanalyzer.Enzyme-linked immunosorbent assay was used to quantify malondialdehyde,superoxide dismutase,glutathione,glutathione peroxidase,catalase,tumor necrosis factor-α,nuclear factor-κB,interleukin(IL)-33,IL-6,IL-1β,cyclooxygenase-2,kidney injury molecule-1,mitogen-activated protein kinase-1,and caspase-3 in kidney tissues.Renal tissues were also evaluated by histopathological and immunohistochemical examinations for 8-OHdG and Bcl-2.Results:Naringin attenuated acrylamide-induced nephrotoxicity by significantly decreasing serum urea and creatinine levels.Naringin increased superoxide dismutase,glutathione,glutathione peroxidase,and catalase activities and decreased malondialdehyde levels in kidney tissues.In addition,naringin reduced the levels of inflammatory and apoptotic parameters in kidney tissues.The histopathological assay showed that acrylamide caused histopathological changes and DNA damage,which were ameliorated by naringin.Conclusions:Naringin attenuated inflammation,apoptosis,oxidative stress,and oxidative DNA damage in acrylamide-induced nephrotoxicity in rats.

Naringin as a beneficial natural product against degeneration of the nigrostriatal dopaminergic projection in the adult brain

The progressive degeneration of nigral dopaminergic（DA）neurons and the biochemical reduction of striatal dopamine levels are associated with major clinical symptoms,including tremor at rest,rigidity of the limbs,slowness and paucity of voluntary movement（bradykinesia）.

Determination of Naringin Content in Peel of Guangxi Citrus maxima (Burm.) Merr by HPLC

[Objectives]To establish a method for determining the naringin content in the peel of Guangxi Citrus maxima(Burm.)Merr.[Methods]The high performance liquid chromatography(HPLC)method was applied.The chromatographic column was Agilent HC-C18(4.6 mm×250 mm,5μm);the mobile phase was acetonitrile-0.1%phosphoric acid(18∶82);the flow rate was 1.0 mL/min;the column temperature was 25℃;the detection wavelength was 283 nm.[Results]Naringin showed a good linear relationship in the range of 0.164-3.27μg,r=0.9999.The average recovery rate was 98.66%,and RSD=1.80%(n=6).[Conclusions]This method is simple,feasible,reproducible,and accurate,so it can be used for the determination of naringin content in the peel of Guangxi C.maxima.

Self-assembled Cyclodextrin Metal-Organic Frameworks on Graphene Oxide as Filter Membrane for Tracelevel Naringin Pre-enrichment before Analysis

A green,renewable composite was designed and fabricated based on self-assembly of cyclodextrin metal-organic framework(CD-MOF)on graphene oxide(GO).Then,the GO@CD-MOF was embedded in 0.45μm PTFE membrane to produce a dual-functional membrane which could carry out sample enrichment by capturing naringin molecules.The membrane filter was further improved by investigating the effects of the experimental parameters including amount of GO@CD-MOF,enrichment time and elution solvent on enrichment efficiency of naringin.Further,the present method had been successfully applied to citrus sample and obtained satisfied recovery value(79.7%-100.3%).Moreover,the extraction of naringin can be achieved for 2 min,and GO@CD-MOF loaded membrane can be reused at least for 5 times.The results demonstrate that the fabrication of the novel filter membrane based on GO@CD-MOF is a fast,simple and reliable,and possesses great potential in the determination of naringin from real samples by dual-function of separation and enrichment.

Effect of naringin on despair behavior and neuroprotective mechanisms in mouse model of menopausal depression

Objective:To explore the effect of naringin on hippocampus estrogen receptor and neuronal cell apoptosis in a mouse model of menopausal depression.Methods:The menopausal depression model was replicated by bilateral ovariectomy(OVX)combined with chronic unpredictable mild stimulation(CUMS),54 female Kunming mice were randomly divided into Blank group,Model group(OVX+CUMS group),Sham operation group(SHAM group),Estradiol group(E2 group 20.090 mg∙Kg-1∙d-1),Naringin group(100 mg∙Kg-1∙d-1),Naringin+ICI182780 group(100 mg∙Kg-1∙d-1+0.075 mg∙Kg-1∙d-1),each group of 9 mice were administered for 21 consecutive days.The depression-like behaviour changes of each group of mice were observed by tail suspension and forced swimming experiments;The morphological changes of hippocampal neurons were observed by HE staining;Immunohistochemical method was used to detect the expression of ERαand ERβpositive cells in the hippocampus of mice;The expression of ERβ,GluR2,CAMK栻,NMDAR1,Bad,Bcl-2 and Caspase3 proteins in the hippocampus of the mice was detected by western blot.Results:Compared with the Blank group,the immobility time of the mice in the OVX+CUMS group was significantly increased(P<0.01),mice hippocampal neurons with a sparsely organized cell arrangement,nuclear fixation,the expressions of ERβ,GluR2,and Bcl-2 were decreased(P<0.01,P<0.001),and the expressions of NMDAR1,CAMK栻,Bad,and Caspase3 were increased(P<0.05,P<0.01);Compared with the OVX+CUMS group,the immobility time of the mice in the SHAM group,E2 group and Naringin group was significantly reduced(P<0.01),mice hippocampal neuronal cells are relatively intact and tightly packed,the expressions of ERβ,GluR2 and Bcl-2 were increased(P<0.01,P<0.05),and the expressions of NMDAR1,CAMK栻,Bad and Caspase3 were decreased(P<0.05,P<0.01);Compared with the Naringin group,the quiescent time of the mice in the Naringin+ICI182780 group was increased(P<0.05),the smaller cell body of mouse hippocampal neurons,the expressions of ERβ,GluR2,and Bcl-2 were decreased(P<0.01,P>0.05,P<0.05),and the expressions of NMDAR1,CAMK栻,Bad,and Caspase3 were increased(P<0.01,P<0.05).Conclusions:Naringin may reduce neuronal cell excitotoxicity caused by glutamate receptor activation,reduce neuronal cell apoptosis and improve depression-like behavior by activating ERβreceptors in the hippocampus in a mouse model of menopause depression.

Determination of Naringin Content in Rhizoma Drynariae by High Performance Liquid Chromatography

[Objectives]To accurately determine the naringin content in Rhizoma Drynariae.[Methods]The high performance liquid chromatography(HPLC)method was applied in the determination of the naringin content in Rhizoma Drynariae.The sample was sonicated at room temperature.The mobile phase was 0.1%phosphoric acid-acetonitrile(75∶25),detected by diode array detector at the wavelength of 284 nm,and quantified by external standard method.[Results]The linearity of naringin was good in the concentration range of 5-500μg/mL with a correlation coefficient of 0.9999.[Conclusions]This method has good linearity,easy operation,correctness and reproducibility as required,and is expected to provide a method for the determination of naringin content in Rhizoma Drynariae.

New Method for Isolation of Naringin Compound from <i>Citrus maxima</i>

This research aims to know the proper isolation method to isolate naringin compound from Citrus maxima for natural product chemistry laboratory. This natural product chemistry laboratory provides students with the essential skills and knowledge required to perform the extraction, isolation, and structural identification. The isolation began with sample preparation, extraction with methanol, partition with n-hexane, purification by crystallization using isopropanol, by analyzing the purity with Thin Layer Chromatography (TLC) tested, and the presence of functional groups with Fourier Transform Infrared (FT-IR) spectrophotometer test. The result of FT-IR spectrophotometer analysis contains hydroxy group (-OH), aromatic cyclic groups (C=C), CH2, CH3, and ether groups.

p38 Signaling Mediates Naringin-Induced Osteogenic Differentiation of Porcine Metanephric Mesenchymal Cells

Objective:To explore the potential of metanephric mesenchymal cells(MMCs)for osteogenesis and naringin’s ability to enhance this process and its molecular mechanism.Methods:Porcine MMCs at 70 days of gestation were used as tool cells,cultured in osteogenic induction medium,identified by immunocytochemistry staining.Osteogenic potential of porcine MMCs and naringin’s ability to enhance this process was tested by detecting changes in cell viability,alkaline phosphatase(ALP)activity,the expression of runt-related transcription factor 2(Runx2),osteopontin(OPN)and osteocalcin(OCN),and the formation of mineralized nodules,and the application of the p38 signaling pathway inhibitor SB203580 vitiated the osteogenesis-promoting effect of naringin.Results:Immunocytochemical staining showed that the cells were Vimentin and Six2(+),E-cadherin and CK-18(−).Naringin can activate the p38 signaling pathway to enhance the osteogenesis of porcine MMCs by increasing cell viability,ALP activity,the expressions of Runx2,OPN and OCN,and the formation of mineralized nodules(P<0.05).The application of p38 signaling pathway inhibitor SB203580 vitiated the osteogenesis-promoting effect of naringin,manifested by decreased ALP activity,the expressions of Runx2,OPN and OCN,and the formation of mineralized nodules(P<0.05).Conclusion:Naringin,the active ingredient of Chinese herbal medicine Rhizoma Drynariae for nourishing Shen(Kidney)and strengthening bone,enhances the osteogenic differentiation of renal MMCs through the p38 signaling pathway.

Protective effects of naringin on fipronil-induced cardiovascular and renal dysfunctions in rats

Background:Naringin as a bioflavanone glycoside is abundant in citrus fruits,which since ancient times have been utilized as natural herbal treatments in traditional medicine.Naringin has potent antioxidant effect that may mitigate oxidative stress mediated cardiovascular and renal dysfunctions in mammalian systems.Objective:To explore probable modulatory actions of naringin on fipronil-induced cardio-renal dysfunctions.Methods:Twenty-four Wistar rats weighing 140±3.0 g were divided into four groups including normal control(saline),10 mg/kg Fipronil(FIP),FIP+100 mg/kg naringin,and 100 mg/kg naringin.Administration of naringin and fipronil was by oral gavage for 28 consecutive days.Urinalysis,blood pressure monitoring,biochemical assays,histology,and immunohistochemical evaluations were performed.Results:Naringin significantly(P<0.001)lessened blood pressure parameters,oxidative stress markers but significantly(P<0.001)heightened the systemic antioxidants.Likewise,naringin prevented fipronil-induced histopathological lesions such as congestion and cellular infiltration in cardiac and renal tissues.Moreover,naringin attenuated the immunohistochemical expression of troponin 1 and matrix metalloperoxidase-2 in cardiac tissues,but heightened angiotensin converting enzyme 2 expression in contrast to that of fipronil group.Conclusion:The observation in this study shows potent attenuation of fipronil-induced toxicity by naringin,through inhibiting processes related to oxidation and inflammation.

Biotransformation of naringin by human intestinal flora

Naringin （1）, the highest-content flavanone glycoside in sour oranges, was incubated with human intestinal flora, and four biotransforrnation products （2-5） were obtained from the incubated mixture by chromatographic methods. The chemical structures of the four products were elucidated as naringin-6＂acetate （2）, naringenin （3）, phloretic acid （4）, and phloroglucinol （5） on the basis of their spectroscopic data. Naringin-6＂-acetate was specifically formed by acetylation at C6-OH of glucosyl group of 1. The result obtained in the present research could account for the lower bioavailability of 1 after oral administration, suggesting that some biological properties of 1 in vivo may be mediated by its intestinal flora converted product 3. The biotransforrnation of 1 by intestinal flora leading to their systemic absorption deserves further attention and may provide valuable insights into pre-systemic drug metabolism, delivery or toxicity.

Comparative pharmacokinetics of naringin and neohesperidin after oral administration of flavonoid glycosides from Aurantii Fructus Immaturus in normal and gastrointestinal motility disorders mice

Objective: To compare the pharmacokinetics of naringin and neohesperidin after oral administration of Zhishi total flavonoid glycosides(ZSTFG) extracted from Aurantii Fructus Immaturus in normal and gastrointestinal motility disorders(GMD) mice.Methods: ZSTFG was orally given to normal and GMD mice induced by atropine or dopamine. The plasma samples were incubated with β-glucuronidase/sulfatase, the total(free + conjugated) naringenin and hesperitin were extracted with acetonitrile. The validated HPLC-MS/MS method was successfully applied to the pharmacokinetic study.Results: The results showed that, compared with the normal group, AUC0–∞, AUC0–tand Cmaxfor total naringenin and hesperitin were significantly higher(P < 0.01 or P < 0.05), while CLZ/F for total naringenin and hesperitin was significantly lower(P < 0.01) in the GMD group. Tmax, t1/2 z, MRT0-t, and MRT0-∞for naringenin were longer(P < 0.01) in the GMD group than those in the normal group.Conclusion: The results showed that there were significant differences in pharmacokinetic parameters of naringenin and hesperitin between normal and GMD groups. It was suggested that the absorption of naringenin and hesperitin was increased, and the elimination processes of naringenin and hesperitin were slower in the GMD group than the normal group. The data are of value for further pharmacological studies of ZSTFG and would be useful to provide a reference for improving the therapeutic regimen of ZSTFG in clinical trials.

Population Pharmacokinetics of Naringin in Total Flavonoids of Drynaria Fortunei(Kunze) J.Sm.in Chinese Women with Primary Osteoporosis

Objective： To evaluate the effect of covariates on the pharmacokinetic profiles of naringin in the total flavonoids of Drynaria fortunei （Kunze） J. Sin. in the Qianggu Capsule （强骨胶囊） by evaluating Chinese women with primary osteoporosis. Methods： A total of 98 female patients from the communities of Jingshan, Beixinqiao, Jiaodaokou, Chaoyangmen, and Donghuamen in Beijing, China, aged 40 to 80 years, were included in this study. Blood samples were collected before and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 h after a single oral dose of Qianggu Capsule. The concentration in blood samples from 32 patients before and 0.5, 1, 2, 3, and 4 h after drug administration were determined by liquid chromatography-tandem mass spectrometry （LC-MS/MS） method, and full set of pharmacokinetic data was analyzed with nonlinear mixed-effect modeling （NONMEM） software. The mean of population parameters clearance （C1）, central distribution volume （V）, absorption rate constant （Kal）, inter-compartmental clearance （C2）, peripheral distribution volume （V2） were set as parameters and estimated through base model, covariate model, and final model. Age, height, weight, blood urea nitrogen （BUN）, serum creatinine （Scr）, alanine transaminase （ALT）, aspartate transaminase （AST）, hyperlipidemia, Liver （Gan） Kidney （Shen） yin insufficiency （GSYI）, Kidney （Shen） yang insufficiency （SYI） were set as covariates. Results： The relationships between these parameters and covariates were analyzed. The results showed that C1 was the main parameter influenced by the selected covariates among the population parameters, and the relationships between the covariates and C1 were analyzed, among the selected covariates hyperlipidemia was identified as significant covariate of C1. Conclusion： The pharmacokinetic behaviors of naringin are altered with hyperlipidemia in Chinese women with primary osteoporosis.

从柚子落果中提取柚皮苷的杂质谱研究

柚皮苷是一种具有广泛用途的二氢黄酮类化合物,为建立基于碱提酸沉柚皮苷提取工艺的质量标准提供物质基础。通过反复重结晶,正向柱层析,制备液相及半制备液相等方法分离纯化,经NMR,圆二色谱等手段鉴定结构。从微量杂质中分离鉴定12个杂质,分别为佛手酚(1)、7-Hydroxy-1-benzopiran-2-one(2)、Marmin(3)、Protocatechuic acid(4)、8-(6,7-dihydroxy-3,7-dimethyloct-1-en-3-yl)-5-hydroxy-6,7-furocoumarin(5)、Obacunone(6)、柚皮素(7)、7,4′-Dihydroxyflavone(8)、Rhoifolin(9)、Vicenin(10)、Neoeriocitrin(11)和2 S-Neoeriocitrin(12)。化合物5为首次从柚的果实中分离得到,为建立碱提酸沉工艺提取柚皮苷的质量标准建立提供物质基础。

Aerobic glycolysis in colon cancer is repressed by naringin via the HIF1Α pathway

Metabolic reprogramming is a common phenomenon in cancer,with aerobic glycolysis being one of its important characteristics.Hypoxia-inducible factor-1α(HIF1Α)is thought to play an important role in aerobic glycolysis.Meanwhile,naringin is a natural flavanone glycoside derived from grapefruits and many other citrus fruits.In this work,we identified glycolytic genes related to HIF1Αby analyzing the colon cancer database.The analysis of extracellular acidification rate and cell function verified the regulatory effects of HIF1Αoverexpression on glycolysis,and the proliferation and migration of colon cancer cells.Moreover,naringin was used as an inhibitor of colon cancer cells to illustrate its effect on HIF1Αfunction.The results showed that the HIF1Αand enolase 2(ENO2)levels in colon cancer tissues were highly correlated,and their high expression indicated a poor prognosis for colon cancer patients.Mechanistically,HIF1Αdirectly binds to the DNA promoter region and upregulates the transcription of ENO2;ectopic expression of ENO2 increased aerobic glycolysis in colon cancer cells.Most importantly,we found that the appropriate concentration of naringin inhibited the transcriptional activity of HIF1Α,which in turn decreased aerobic glycolysis in colon cancer cells.Generally,naringin reduces glycolysis in colon cancer cells by reducing the transcriptional activity of HIF1Αand the proliferation and invasion of colon cancer cells.This study helps to elucidate the relationship between colon cancer progression and glucose metabolism,and demonstrates the efficacy of naringin in the treatment of colon cancer.