Naringin Pretreatment Research Articles

Combined effect of naringin and adipose tissue-derived mesenchymal stem cell on cisplatin nephrotoxicity through Sirtuin1/Nrf-2/HO-1 signaling pathway: a promising nephroprotective candidate.

Cisplatin nephrotoxicity is a well-known emergency clinical condition caused by oxidative stress and inflammation. Naringin (NAR) is considered an antioxidant agent with renoprotective effects capable of removing reactive oxygen species. Adipose tissue-derived mesenchymal stem cells (AD-MSCs) are reported to have anti-inflammatory and antioxidant properties. The present research examined the renoprotective effect of the combination of NAR and AD-MSCs as opposed to each one alone on cisplatin-induced nephrotoxicity through SIRT-1/Nrf-2/HO-1 pathway. This study included five groups (n = 8 each) of male Sprague-Dawley rats (200 - 220g): sham, cisplatin: rats receiving cisplatin (6.5 mg/kg, i.p.) on the 4th day; NAR+cisplatin: rats pretreated with NAR (1 week, i.p.) + cisplatin on the 4th day; AD-MSCs: rats receiving AD-MSCs (1 × 106) by injection through the tail vein on the 5th day + cisplatin on the 4th day; and NAR+AD-MSCs+cisplatin. On the 8th day, the animals were anesthetized to obtain tissue and blood samples. Biochemical factors, inflammation, oxidative stress, and gene expression were explored. Cisplatin increased blood urea nitrogen, creatinine, inflammation, and oxidative stress. Moreover, mRNA expression of Sirtuin1, nuclear factor erythroid 2-related factor 2 (Nrf-2), and heme oxygenase-1 (HO-1) remarkably reduced. Furthermore, cisplatin led to a disturbance in kidney structure (glomerular atrophy, cell infiltrations, and tubular dysfunction) as confirmed by histology findings. However, NAR pretreatment, AD-MSC administration, or a combination of both significantly reversed these changes. Overall, when used together, NAR and AD-MSCs had stronger cisplatin-induced effects on kidney dysfunction by inhibiting inflammation, reducing oxidative stress, and increasing the Sirtuin1/Nrf-2/HO-1 pathway.

Short-term pretreatment of naringin isolated from Citrus wilsonii Tanaka attenuates rat myocardial ischemia/reperfusion injury.

Pretreatment or treatment with anti-apoptotic, anti-inflammatory, or anti-oxidative approaches could be critical for attenuated the severity of myocardial ischemia/reperfusion (I/R) injury. Naringin, a natural flavonoid, plays important roles in inflammation-related diseases. Immature dry fruits of Citrus wilsonii Tanaka (Xiang Yuan) are rich in naringin that can be used as traditional Chinese medicine to treat inflammation-related symptoms. However, its roles in cardioprotective role remain unclear. This study aimed to isolate naringin from Citrus wilsonii Tanaka fruit and tested their cardioprotective effect. The dry fruits of Citrus wilsonii Tanaka were extracted with boiling water and then supernatants were freeze-dried to yield aqueous extract (ZQAE). The extract was chemoprofiled using UPLC-MS/MS to stand for major constituents, and then subjected to different chromatographic separation steps, and naringin was isolated in a high yield. The cardioprotective effects of the aqueous extract of ZQAE and naringin were investigated in a myocardial I/R rat model and to elucidate the mechanism underlying its cardioprotective effect. Our results indicated that 5-day ZQAE and naringin pretreatments both promoted histopathological changes and reduced myocardial enzymes (cTnl, CK-MB, CK and LDH) induced by I/R. Moreover, the 50mg/kg and 100mg/kg ZQAE dose pretreatments presented a significantly decreased infarct size as well as myocardial enzyme levels but also inhibited myocardial apoptosis (cleaved-caspase3 protein expression), the inflammatory response (IL-23, IL-6, and TNF-α) and oxidative stress (MDA and SOD). The cardioprotective effect of 5mg/kg dose of naringin pretreatment is comparable with that of 5mg/kg drug ditiazem pretreatment. Additionally, naringin pretreatment exhibited striking decreases in the apoptosis index and downregulation of the protein expression levels of cleaved-Caspase3, Bcl2 and Bax. Meanwhile, naringin downregulated HMGB1 expression and upregulated SIRT1 expression in the myocardium. These findings suggest that short-term pretreatments with ZQAE and naringin both protect against myocardial I/R injury by suppressing myocardial apoptosis, the inflammatory response, and oxidative stress. The cardioprotective effect of naringin involves SIRT1 activation and may interact with HMGB1 and inhibit the release of HMGB1.

Naringin Alleviates H2O2-Inhibited Osteogenic Differentiation of Human Adipose-Derived Stromal Cells via Wnt/β-Catenin Signaling.

Osteoporosis is an age-related systemic bone disease that places a heavy burden on patients and society. In this study, we aimed to investigate the effects of naringin (NAR) on the osteogenic differentiation of human adipose-derived stromal cells (ADSCs). The results demonstrated that NAR pretreatment effectively abated H2O2-induced cell death and ROS accumulation in ADSCs undergoing osteogenic differentiation (ADSCs-OD). In addition, we also observed that the impaired extracellular matrix mineralization and ALP activity in H2O2-stimulated ADSCs-OD were notably rescued by NAR pretreatment. Moreover, the effects of H2O2 exposure on Wnt/β-catenin signaling in ADSCs-OD were largely reversed by NAR pretreatment. Collectively, our findings indicated that NAR could protect ADSCs-OD against H2O2-inhibited osteogenic differentiation.

Naringin attenuates acute myocardial ischemia-reperfusion injury via miR- 126/GSK-3β/β-catenin signaling pathway.

ABSTRACTIntroduction:Myocardial ischemia-reperfusion (I/R) injury is one of the mechanisms contributing to the high mortality rate of acute myocardial infarction.Purpose:This study intended to study the role of naringin in cardiac I/R injury.Methods:AC16 cells (human cardiomyocyte cell line) were subjected to oxygen-glucose deprivation/recovery (OGD/R) treatment and/or naringin pretreatment. Then, the apoptosis was examined by flow cytometry and Western blotting. The concentration of IL-6, IL-8 and TNF-α was measured by enzyme-linked immunosorbent assay (ELISA) kits. How naringin influenced microRNA expression was examined by microarrays and quantitative real-time polymerase chain reaction (qRT-PCR). Dual luciferase reporter assay was employed to evaluate the interaction between miR-126 and GSK-3β. The GSK-3β/β-catenin signaling pathway was examined by Western blotting. Finally, rat myocardial I/R model was created to examine the effects of naringin in vivo.Results:Naringin pretreatment significantly decreased the cytokine release and apoptosis of cardiomyocytes exposed to OGD/R. Bioinformatical analysis revealed that naringin upregulated miR-126 expression considerably. Also, it was found that miR-126 can bind GSK-3β and downregulate its expression, suggesting that naringin could decrease GSK-3β activity. Next, we discovered that naringin increased β-catenin activity in cardiomyocytes treated with OGD/R by inhibiting GSK-3β expression. Our animal experiments showed that naringin pre-treatment or miR-126 agomir alleviated myocardial I/R.Conclusions:Naringin preconditioning can reduce myocardial I/R injury via regulating miR-126/GSK-3β/β-catenin signaling pathway, and this chemical can be used to treat acute myocardial infarction.

Study on the role of naringin in attenuating Trimethylamine-N-Oxide-Induced human umbilical vein endothelial cell inflammation, oxidative stress, and endothelial dysfunction.

Trimethylamine-N-oxide (TMAO), a phospholipid metabolite, can modulate cholesterol synthesis and promote vascular inflammation and endothelial dysfunction, thereby increasing the risk of atherosclerosis (AS). Previously, it was found that naringin reduced damage to human umbilical vein endothelial cells (HUVECs) triggered by oxidized low-density lipoprotein. This article continues to explore the role and mechanism of naringin in protecting HUVECs from TMAO-induced damage. After the construction of TMAO-induced AS model in HUVECs, inflammation, oxidative stress, and endothelial function were examined by real-time quantitative polymerase chain reaction, Western blotting, nitric oxide (NO), reactive oxygen species (ROS), superoxide dismutase, and malondialdehyde (MDA) kits. Results showed that naringin pretreatment inhibited endothelial inflammation and oxidative stress, promoted NO release, and inhibited the degradation of Zona occludens-2, occludin, and vascular endothelial-cadherin, thereby restoring the functional and structural integrity of the endothelium. Furthermore, the addition of mitogen-activated protein kinase (MAPK) agonist demonstrated that the therapeutic effect of naringin was achieved through inactivating TMAO-stimulated MAPK signaling in HUVECs.

Naringin prevents cyclophosphamide-induced erythrocytotoxicity in rats by abrogating oxidative stress.

Earlier reports have shown that Cyclophosphamide (CYCP), an anti-malignant drug, elicited cytotoxicity; and that naringin has several beneficial potentials against oxidative stress and dyslipidaemias. We investigated the influence of naringin on free radical scavenging, cellular integrity, cellular ATP, antioxidants, oxidative stress, and lipid profiles in the CYCP-induced erythrocytotoxicity rat model. Rats were pretreated orally by gavage for fourteen consecutive days with three doses (50, 100, and 200 mg/kg) naringin before single CYCP (200 mg/kg, i.p.) administration. Afterwards, the rats were sacrificed. Naringin concentrations required for 50 % scavenging hydrogen peroxide and nitric oxide radical were 0.27 mg/mL and 0.28 mg/mL, respectively. Naringin pretreatment significantly (p < 0.05) protected erythrocytes plasma membrane architecture and integrity by abolishing CYCP-induced decrease in the activity of erythrocyte LDH (a marker of ATP). Pretreatment with naringin remarkably (p < 0.05) reversed CYCP-induced decreases in the erythrocytes glutathione levels, activities of glutathione-S-transferase, catalase, glutathione peroxidase, and glutathione reductase; attenuated CYCP-mediated increases in erythrocytes levels of malondialdehyde, nitric oxide, and major lipids (cholesterol, triacylglycerol, phospholipids, and non-esterified fatty acids). Taken together, different acute pretreatment doses of naringin might avert CYCP-mediated erythrocytes dysfunctions via its antioxidant, free-radical scavenging, and anti-dyslipidaemia properties.

Naringin protects endothelial cells from apoptosis and inflammation by regulating the Hippo-YAP Pathway.

Atherosclerosis is the primary cause of several cardiovascular diseases. Oxidized low-density lipoprotein (ox-LDL)-induced apoptosis, endothelial–mesenchymal transition (EndMT), and inflammation are crucial for the progression of cardiovascular diseases, including atherosclerosis. Naringin, a major compound from tomatoes, grapefruits, and related citrus, reportedly exhibits potential protective effects during atherosclerosis development; however, its effect on ox-LDL-induced human umbilical vein endothelial cell (HUVEC) damage remains unknown. In the present study, we investigated the anti-apoptotic and anti-inflammatory activities of naringin against ox-LDL-induced endothelial cells, and the underlying mechanism. Naringin pretreatment significantly and concentration-dependently inhibited ox-LDL-induced cell injury and apoptosis. Additionally, naringin restored endothelial barrier integrity by preventing VE-cadherin disassembly and F-actin remodeling, and down-regulated pro-inflammatory factors like IL-1β, IL-6, and IL-18, in the HUVECs. We also demonstrated that naringin treatment restored ox-LDL-induced YAP (yes-associated protein) down-regulation, given the YAP-shRNA attenuated cytoprotective effect of naringin on ox-LDL-induced endothelial cell injury and apoptosis. Collectively, our data indicate that naringin reversed ox-LDL-triggered HUVEC apoptosis, EndMT, and inflammation by inhibiting the YAP pathway. Therefore, naringin may have a therapeutic effect on endothelial injury-related disorders.

Protective Effects of Naringin in Cerebral Infarction and Its Molecular Mechanism.

BackgroundCerebral infarction is a cardiovascular disease with high morbidity and mortality. At present, many studies have reported the treatment of cerebral infarction by traditional Chinese medicine. Naringin, a flavonoid, is a major traditional Chinese medicine. However, the effect and mechanism of naringin on cerebral infarction is unclear.Material/MethodsIn our study, we established a rat model of cerebral infarction through middle cerebral artery occlusion (MCAO) to study the influence of naringin on cerebral infarction in vivo. After treatment with naringin, brain water content was detected to assess brain edema. Cerebral infarction volume and neurological deficits were also measured. Production of the inflammatory factors tumor necrosis factor (TNF)-α and interleukin (IL)-6) was measured using enzyme-linked immunosorbent assay (ELISA). Besides, the effect of naringin on cerebral infarction was investigated in vitro by establishing an oxygen-glucose deprivation (OGD) model in neuronal cells. Cell apoptosis and cell viability was determined using flow cytometry and MTT assay.ResultsWe found that naringin pretreatment significantly decreased the brain water content, cerebral infarction volume, and neurological deficit scores of MCAO subjected rats. And naringin treatment reduced apoptosis of nerve cells in rat hippocampus and the secretion of inflammatory factor such as TNF-α and IL-6. Besides, we found that naringin increased cell viability and inhibited apoptosis in OGD induced neuronal cells. Finally, we found that naringin promoted the expression of p-AKT protein in a concentration-dependent manner and activated the PI3K/AKT pathway in OGD induced neurons.ConclusionsNaringin played a protective role in cerebral infarction via suppressing neuronal apoptosis and inflammation.

Naringin, a Natural Flavonoid, Modulates UVB Radiation-Induced DNA Damage and Photoaging by Modulating NER Repair and MMPS Expression in Mouse Embryonic Fibroblast Cells.

We have proven that naringin, a phytonutrient, diminishes oxidative damage and inflammatory responses by modulating PPAR-γ expressions in ultraviolet-B radiation (UVB)-induced NIH-3T3 cells. However, the role of naringin against DNA damage, photoaging, and apoptosis in NIH-3T3 cells has yet to be studied, necessitating investigation. We show that Naringin pretreatment significantly reduces UVB-induced alkaline DNA damage and potentially modulates NER gene (XPC, TFIIH, XPE, ERCC1, and GAPDH) expression, thereby augmenting DNA repair. We determined experimentally that naringin pretreatment prevents UVB-induced nuclear fragmentation in NIH-3T3 cells, as well as altering UVB-induced apoptotic marker (Bax, BCl-2, Caspase-9, and Caspase-3) expression in them. In addition, naringin pretreatment inhibits UVB-stimulated matrix metalloproteinase (MMP-2, MMP-9 and MMP-13) expression in these 3T3 cells. Therefore, we report that naringin can effectively avert UVB-mediated DNA damage, photoaging, and apoptosis in NIH-3T3 cells.

Naringin Protects Against Interleukin 1β (IL-1β)-Induced Human Nucleus Pulposus Cells Degeneration via Downregulation Nuclear Factor kappa B (NF-κB) Pathway and p53 Expression.

BackgroundLow back pain (LBP) is regarded as a frequent disease that causes disability. We aimed to explore the effect of naringin on intervertebral disc degeneration (IDD) in IL-1β-induced human nucleus pulposus (NP) cells and its corresponding molecular mechanisms.Material/MethodsHuman NP cells were identified by toluidine blue and Safranin O staining. Cell viability was determined by MTT assay. The expression levels of matrix metalloproteinases (MMP-3, MMP-13, ADAMTS-4, ADAMTS-5, collagen II, aggrecan), inflammatory genes (tumor necrosis factor [TNF]-α, interleukin [IL]-6), kappa B kinase α (IκBα), p65 and p53 were determined by quantitative real-time polymerase chain reaction (qPCR) and western blotting. Immunofluorescence study was performed to detect the position and expression of p65 protein in IL-1β-induced human NP cells.ResultsHuman NP cells were successfully separated from intervertebral disc tissue. We found that naringin could significantly reduce the expressions of matrix metalloproteinases (MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5) and inflammatory genes in IL-1β-stimulated human NP cells, while collagen II and aggrecan were increased at mRNA and protein level. Immunofluorescence showed that naringin pretreatment decreased the p65 protein expression in the nucleus and suppressed the phosphorylation of IκBα and p65.ConclusionsThese results demonstrated that naringin could attenuate matrix metalloproteinase catabolism and inflammation in IL-1β-treated human nucleus pulposus cells via downregulating NF-κB pathway and p53 expression, suggesting that naringin has the potential to prevent and treat IDD.

Naringin inhibits lipopolysaccharide-induced activation of microglia cells

The purpose of this study was to investigate the effect of naringin on lipopolysaccharide (LPS)-induced activation of BV2 microglia and inflammatory factor release, and the mechanism involved. Different concentrations of naringin were used to pretreat BV2 cells for 30 min, after which they were stimulated with 100 ng/mL LPS for different durations. The levels of NO, IL-1β and TNF-α in the cell culture medium was determined with ELISA and Griess method. The mRNA expressions of IL-1β and TNF-α was determined with RT-PCR. Changes in ERK and p65/NF-κB signaling pathway proteins were assayed with Western blotting. After 12 h stimulation of BV2 cells with LPS, the levels of IL-1β and TNF-α in the cell culture medium were significantly increased, but naringin had no significant effect on these inflammatory factors. In the cells pretreated with naringin, LPS stimulated the activation of microglia to produce IL-1β and TNF-α in a dose-dependent manner. Naringin inhibited LPS-induced release of IL-1β, to a certain extent. The TNF-α gene was overexpressed. In addition, LPS stimulated a dose-dependent decrease in NO production by BV2 after pretreatment with different concentrations of naringin. Naringin pretreatment of cells significantly inhibited the activation of p65/NF-κB in a concentration-dependent manner. In BV2 microglia, naringin inhibits LPO-induced production of NO and inflammatory factors, through a mechanism involving inhibition of activation of the p65/NF-κB signaling pathway.

The renoprotective effects of naringin and trimetazidine on renal ischemia/reperfusion injury in rats through inhibition of apoptosis and downregulation of micoRNA-10a.

Renal Ischemia-Reperfusion (IR) injury occurs due to circulatory shock and renal transplantation, leading to mortality and morbidity worldwide. The primary purpose of the current study was to evaluate the renoprotective effects of the naringin (NAR) and trimetazidine (TMZ) on IR injury, renal hemodynamics, antioxidant capacity, microRNA-10a, and expression of apoptosis factors. Forty rats were divided into five groups randomly: Sham, IR injury, (TMZ, 5 mg/kg), (NAR pretreatment, 100 mg/kg), and TMZ plus NAR. The sham group underwent the identical surgical procedure as the other groups, except for the application of clamps. After anesthesia, IR injury was induced by 45 min of ischemia, followed by reperfusion for 4 h. Tissue and blood samples were collected for evaluation of renal function, antioxidant activity and, biochemical and molecular parameters. Administration of the NAR, TMZ, and their combination decreased the plasma level of microRNA-10a, caspase-3, and Bcl-2 associated x protein (Bax) mRNA expression, but increased the B- cell lymphoma 2 (Bcl-2) mRNA expression in the kidney tissue. In addition, antioxidant activity, renal blood flow, creatinine clearance (CCr), and fractional excretion of sodium (FENa) were improved. The NAR, TMZ, and their combination can prevent renal I/R injury through promotion of the level of antioxidant enzymes, as well as decrease of microRNA-10a and anti-apoptosis properties. Our data also suggest that NAR, TMZ, or their combination might be beneficial as potent therapeutic factors against renal IR injury.

Ameliorative effect of naringin in acetaminophen-induced hepatic and renal toxicity in laboratory rats: role of FXR and KIM-1

Context: Acetaminophen (APAP) is an analgesic and antipyretic agent commonly known agent to cause hepatic and renal toxicity at a higher dose. Naringin, a bioflavonoid possesses multiple pharmacological properties such as antioxidant, anti-inflammatory, analgesic and anti-hyperlipidemic activity. Objective: To evaluate the effect of naringin against the APAP-induced hepatic and renal toxicity. Materials and methods: Male Wistar albino rats (180–220 g) were divided into various groups, and toxicity was induced by APAP (700 mg/kg, p.o., 14 days). Naringin (20, 40 and 80 mg/kg, p.o.) or Silymarin (25 mg/kg) was administered to rats 2 h before APAP oral administration. Various biochemical, molecular and histopathological parameter were accessed in hepatic and renal tissue. Results: Naringin pretreatment significantly decreased (p < 0.05) serum creatinine, blood urea nitrogen, bilirubin, aspartate transaminase, alanine transaminase, lactate dehydrogenase, low-density lipoprotein, very low-density lipoprotein, cholesterol and triglycerides as compared with APAP control rats. Decreased level of serum albumin, uric acid, and high-density lipoprotein were also significantly restored (p < 0.05) by naringin pretreatment. It also significantly restores (p < 0.05) the altered level of superoxide dismutase, reduced glutathione, malondialdehyde and nitric oxide in hepatic and renal tissue. Moreover, altered mRNA expression of hepatic farnesoid X receptor and renal injury molecule-1 (KIM-1) were significantly restored (p < 0.05) by naringin treatment. Naringin treatment also reduced histological alteration induced by APAP in the liver and kidney. Conclusion: Naringin exerts its hepato- and nephroprotective effect via modulation of oxido-nitrosative stress, FXR and KIM-1 mRNA expression.

Preconditioning L6 Muscle Cells with Naringin Ameliorates Oxidative Stress and Increases Glucose Uptake.

Enhanced oxidative stress contributes to pathological changes in diabetes and its complications. Thus, strategies to reduce oxidative stress may alleviate these pathogenic processes. Herein, we have investigated Naringin mediated regulation of glutathione (GSH) & intracellular free radical levels and modulation of glucose uptake under oxidative stress in L6 cell lines. The results from the study demonstrated a marked decrease in glutathione with a subsequent increase in free radical levels, which was reversed by the pretreatment of Naringin. We also observed that the increased malondialdehyde level, the marker of lipid peroxidation on induction of oxidative stress was retrieved on Naringin pretreatment. Addition of Naringin (100 μM) showed approximately 40% reduction in protein glycation in vitro. Furthermore, we observed a twofold increase in uptake of fluorescent labeled glucose namely 2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)Amino)-2-Deoxyglucose (2 - NBDG) on Naringin treatment in differentiated L6 myoblast. The increased uptake of 2-NBDG by L6 myotubes may be attributed due to the enhanced translocation of GLUT4. Our results demonstrate that Naringin activate GSH synthesis through a novel antioxidant defense mechanism against excessive Reactive Oxygen Species (ROS) production, contributing to the prevention of oxidative damage in addition to its effect on glycemic control.

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 disease 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 significantly 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.

Inhibition of TNF-α/IFN-γ induced RANTES expression in HaCaT cell by naringin

Context: Naringin is a bioflavonoid derivative and is predominantly found in Citrus paradisi Macf., Citrus sinensis (Linn.) Osbeck, Citrus unshiu Marc., Citrus reticulata Blanco cv. Nobilis, Citrus tachibana (Makino) Tanaka, Citrus junos Sieb. ex Tanaka (Rutaceae), and related citrus species. It has anti-inflammatory effects that have been well-documented, but the mechanism is poorly characterized.Objective: The effect of naringin on production of RANTES (regulated upon activation normal T-cell expressed and secreted) in human HaCaT cells was investigated here for the first time.Materials and methods: The HaCaT cells were cultured in Dulbecco’s modified Eagle’s medium (DMEM) and the proliferation of cell was determined by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT). The cells were divided into three groups including control group, tumor necrosis factor alpha (TNF-α)/interferon gamma (IFN-γ)-stimulated group, and naringin pretreatment group (first incubated in the presence of naringin and then exposed to TNF-α/IFN-γ). The concentration of RANTES in the supernatants was determined by enzyme-linked immunosorbent assay (ELISA). The expression of RANTES mRNA was analyzed by reverse transcription-polymerase chain reaction (RT-PCR). The expression of nuclear factor kappa B (NF-κB) P65 protein was detected with immunocytochemical method and western blot method.Results: Naringin hardly inhibits HaCaT cells growth at concentrations rising from 0.25 to 1 mmol/L. However, RANTES expression detected in supernatant stimulated with TNF-α/IFN-γ reduced 15 and 16%, respectively, when cultured with 0.25, 0.5 mmol/L naringin. Furthermore, 1 mmol/L naringin significantly decreased RANTES mRNA level. Finally, naringin decreased the expression of NF-κB P65 protein in nuclei.Discussion and conclusion: Naringin can inhibit the increased production of RANTES, which is partially via NF-κB-dependent signal pathway.

Protective Effects of Rutin and Naringin on Gentamycin Induced Testicular Oxidative Stress

Aim: The aim of this study was to investigate the protective effects of bioflavonoid compounds i.e. rutin and naringin on gentamycin induced testicular oxidative stress in rats. Method: A total of 42 male wistar albino rats were divided in to 7 groups, each contains 6 rats. Gentamycin, 5 mg/kg, I.P was administered to the rats from day 1 to day 10. Rutin and naringin were given in different doses (5mg/kg, 10/kg) for a period of 35 days from day 1 to day 35 to the gentamycin treated animals. A sham control group animals with water, control group animals with gentamycin and vehicle control group animals with 0.1% sod CMC were also maintained until completion of 35 days. On 36th day bilateral orchiectomies were performed for all the animals. The testicular tissue was evaluated for various sperm parameters, biochemical estimations and histological changes. Result: Animals treated with 5mg/kg and 10mg/kg of rutin and naringin (Groups 4, 5, 6, 7) have shown significant and dose dependent reduction in MDA levels and increase in levels of antioxidant enzymes, SOD and Catalase when compared to control group animals (Group 2). Sperm count, motility, viability were also protected and normalized with rutin and naringin. Specimens from group 2 had a histological injury with disordered germinal cells. Drug treated groups shown improved testicular architecture. Rutin was more effective in all the parameters when compared to Naringin. Both the bioflavonoids were effective in reducing the gentamycin induced testicular oxidative stress. Conclusion: Rutin and Naringin pretreatment have shown protective and beneficial effect on gentamycin induced oxidative stress in rats.

Effect of naringin pretreatment on bioavailability of verapamil in rabbits

The aim of present study is to investigate the effect of naringin on the pharmacokinetics of verapamil and its major metabolite, norverapamil in rabbits. The pharmacokinetic parameters of verapamil and norverapamil were determined after administering verapamil (9 mg/kg) orally to rabbits in the pretreated with naringin (1.5, 7.5, and 15 mg/kg). Naringin pretreatment significantly altered the pharmacokinetic parameters of verapamil. Compared with the control group (given verapamil alone), the Ka, Cmax and AUC of verapamil were significantly (p<0.05 or p<0.01) increased in the pretreatment of naringin, However there were no significant change in Tmax and t1/2 of verapamil. Consequently, pretreatment of naringin significantly (p<0.05, p<0.01) increased the AB% of verapamil significantly in a dose dependent manner (p<0.05 or p<0.01), and elevated the RB% of verapamil by 1.26- to 1.69-fold. the MR of verapamil were significantly (p<0.05) increased in the pretreatment of naringin, implying that pretreatment of naringin may effectively inhibit the CYP3A4-mediated metabolism of verapamil. In conclusion, pretreatment of naringin enhanced the oral bioavailability of verapamil. Based on these results, the verapamil dosage should be adjusted when given with naringin or a naringin-containing dietary supplement.

Influence of naringin on ferric iron induced oxidative damage in vitro

Background: Iron is essential for oxygen transport and a variety of cellular processes like respiration and DNA synthesis. It may become toxic when not handled carefully by cellular proteins and shielded from surrounding media. Naringin treatment may help to overcome the iron-induced toxic effects in vitro. Methods: HepG 2 cells were treated with 0.5, 1, 2.5, and 5 mmol/l naringin 1 h before exposure to 0.1, 0.25, 0.5, and 1 mmol/l ferric iron. The effect of iron or naringin or their combination treatment was studied on cell survival, DNA double-strand break induction, DNA oxidation, lipid peroxidation, and various antioxidants. Results: The exposure of cells to iron caused a dose-dependent decline in their clonogenic potential, while naringin pretreatment resulted in a significant elevation in the cell survival. Exposure of cells to iron resulted in a time-dependent elevation in DNA strand breaks and a peak level of DNA strand breaks was observed at 24 h, while naringin pretreatment inhibited the DNA double-strand breaks accompanied by an early repair. Similarly, treatment of HepG 2 cells with iron caused increased DNA oxidation that showed reduction when cells were pretreated with naringin. The iron overload caused a significant elevation in the lipid peroxidation accompanied by depletion in glutathione (GSH) concentration, while naringin inhibited lipid peroxidation and arrested the iron-induced depletion in the GSH concentration. Iron treatment also reduced various antioxidant enzymes like glutathione peroxidase (GSHPx), catalase, and superoxide dismutase (SOD). Pretreatment of HepG 2 cells with naringin resulted in an elevation in all the antioxidant enzymes. Conclusions: E-nhanced antioxidant status by naringin could compensate the oxidative stress and may facilitate an early recovery from iron-induced genomic insult in vitro.