| Description: |
Naringin exhibits antioxidant, anti-atherogenic, antiulcer, anti-hypocholesterolemic, anti-lipoperoxidative, and anti-hyperglycemia effects. Naringin reduces Ara-C-induced oxidative stress through both an inhibition of the generation of ROS production and an increase in antioxidant enzyme activities, it blocks apoptosis caused by Ara-C-induced oxidative stress, resulting in the inhibition of the cytotoxicity of Ara-C. Naringin attenuates epidermal growth factor (EGF)-induced MUC5AC secretion in A549 cells by suppressing the cooperative activities of MAPKs-AP-1 and IKKs-IκB-NF-κB signaling pathways. |
| In vitro: |
| J Pharmacol Sci. 2003 Jun;92(2):166-70. | | Effects of naringin on hydrogen peroxide-induced cytotoxicity and apoptosis in P388 cells.[Pubmed: 12832847] | Flavonoids are widely recognized as naturally occurring antioxidants. Naringin (NG) is one of the flavonoid components in citrus fruits such as grapefruit. Hydrogen peroxide (H2O2) causes cytotoxicity through oxidative stress and apoptosis.
METHODS AND RESULTS:
In this paper, we examined the effects of NG on H2O2-induced cytotoxicity and apoptosis in mouse leukemia P388 cells. Cytotoxicity was determined by mitochondrial activity (MTT assay). Apoptosis and DNA damage were analyzed by measuring chromatin condensation and Comet assay (alkaline single cell gel electrophoresis), respectively. H2O2-induced cytotoxicity was significantly attenuated by NG or the reduced form of glutathione (GSH), a typical intracellular antioxidant. NG suppressed chromatin condensation and DNA damage induced by H2O2.
CONCLUSIONS:
These results indicate that NG from natural products is a useful drug having antioxidant and anti-apoptopic properties. | | 2015 Nov 30;10(11):e0143868. | | Naringin Alleviates Diabetic Kidney Disease through Inhibiting Oxidative Stress and Inflammatory Reaction[Pubmed: 26619044] | | Naringin, a flavanone glycoside extracted from Citrus grandis Osbeck, has a wide range of pharmacological effects. In the present study we aimed at demonstrating the protective effect of naringin against diabetic kidney disease (DKD) and elucidating its possible molecular mechanism underlying. The beneficial effect of naringin was assessed in rats with streptozotocin (STZ)-induced diabetes and high glucose-induced HBZY-1 cells. According to our results, first we found that naringin relieved kidney injury, improved renal function and inhibited collagen formation and renal interstitial fibrosis. Second, we confirmed that naringin restrained oxidative stress by activating Nrf2 antioxidant pathway. Moreover, the results suggested that naringin significantly resisted inflammatory reaction by inhibiting NF- κ B signaling pathway. Taken together, our results demonstrate that naringin effectively alleviates DKD, which provide theoretical basis for naringin clinically used to treatment of DKD. | | 2015 Sep;47(3):1061-9. | | Naringin induces autophagy-mediated growth inhibition by downregulating the PI3K/Akt/mTOR cascade via activation of MAPK pathways in AGS cancer cells[Pubmed: 26201693] | | Naringin, one of the major bioflavonoid of Citrus, has been demonstrated as potential anticancer agent. However, the underlying anticancer mechanism still needs to be explored further. This study investigated the inhibitory effect of Naringin on human AGS cancer cells. AGS cell proliferation was inhibited by Naringin in a dose- and time-dependent manner. Naringin did not induce apoptotic cell death, determined by no DNA fragmentation and the reduced Bax/Bcl-xL ratio. Growth inhibitory role of Naringin was observed by western blot analysis demonstrating downregulation of PI3K/Akt/mTOR cascade with an upregulated p21CIPI/WAFI. Formation of cytoplasmic vacuoles and autophagosomes were observed in Naringin-treated AGS cells, further confirmed by the activation of autophagic proteins Beclin 1 and LC3B with a significant phosphorylation of mitogen activated protein kinases (MAPKs). Collectively, our observed results determined that anti-proliferative activity of Naringin in AGS cancer cells is due to suppression of PI3K/Akt/mTOR cascade via induction of autophagy with activated MAPKs. Thus, the present finding suggests that Naringin induced autophagy- mediated growth inhibition shows potential as an alternative therapeutic agent for human gastric carcinoma. |
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| In vivo: |
| J Pharm Bioallied Sci. 2015 Apr-Jun;7(2):121-7. | | Effect of naringin on hemodynamic changes and left ventricular function in renal artery occluded renovascular hypertension in rats.[Pubmed: 25883516] | Renal artery occlusion (RAO) induced hypertension is a major health problem associated with structural and functional variations of the renal and cardiac vasculature. Naringin a flavanone glycoside derived possesses metal-chelating, antioxidant and free radical scavenging properties. The objective of this study was to investigate the antihypertensive activity of Naringin in RAO induced hypertension in rats.
METHODS AND RESULTS:
Male Wistar rats (180-200 g) were divided into five groups Sham, RAO, Naringin (20, 40 and 80 mg/kg). Animals were pretreated with Naringin (20, 40 and 80 mg/kg p.o) for 4 weeks. On the last day of the experiment, left renal artery was occluded with renal bulldog clamp for 4 h. After assessment of hemodynamic and left ventricular function various biochemical (superoxide dismutase [SOD], glutathione [GSH] and malondialdehyde [MDA]) and histological parameters were determined in the kidney. RESULTS: RAO group significantly (P < 0.001) increased hemodynamic parameters at 15, 30 and 45 min of clamp removal. Naringin (40 and 80 mg/kg) treated groups showed a significant decrease in hemodynamic parameters at 15 min. after clamp removal that remained sustained for 60 min. Naringin (40 and 80 mg/kg) treated groups showed significant improvement in left ventricular function at 15, 30 and 45 min after clamp removal. Alteration in level of SOD, GSH and MDA was significantly restored by Naringin (40 and 80 mg/kg) treatment. It also reduced histological aberration induced in kidney by RAO.
CONCLUSIONS:
It is concluded that the antihypertensive activity of naringin may result through inhibition of oxidative stress. | | Life Sci. 2010 Jun 19;86(25-26):928-35. | | Nitric oxide mechanism in the protective effect of naringin against post-stroke depression (PSD) in mice.[Pubmed: 20433854 ] | The present study has been designed to explore the nitric oxide mechanism in the protective effect of naringin against I/R induced neurobehavioral alterations, oxidative damage and mitochondrial dysfunction in mice.
METHODS AND RESULTS:
Laca mice (25-30 g) were subjected twice to BCCAO occlusion (5 min) at the interval of 10 min, followed by 96 h reperfusion. Naringin (50 and 100 mg/kg) was administered for 10 days, starting 7 days before the animals were subjected to I/R injury. On day 10, various neurobehavioral parameters followed by biochemical parameters and mitochondrial enzyme complex activities were assessed.
Ischemia reperfusion injury caused significant (increased immobility period, neurological score and decreased locomotor activity) oxidative damage (increased lipid peroxidation and nitrite concentration and depleted reduced glutathione, glutathione-S-transferase, superoxide dismutase and catalase) and altered mitochondrial enzyme complex activities (complex I to IV) as compared to sham treatment. Naringin (50 and 100 mg/kg) treatment significantly attenuated neurobehavioral alterations, oxidative damage and restored mitochondrial enzyme complex activities as compared to control (ischemia reperfusion) group. Further, protective effect of naringin (50 mg/kg) was attenuated by l-arginine (100 mg/kg) or sildenafil (5 mg/kg) pretreatment. Further, L-NAME (10 mg/kg) or 7-NI (10 mg/kg) pretreatment with naringin (50 mg/kg) significantly potentiated their protective effect as compared to their treatment alone.
CONCLUSIONS:
The present study suggests the involvement of nitric oxide mechanism in the protective effect of naringin against post-stroke depression induced neurobehavioral, biochemical and cellular alterations in mice. | | Toxicology. 2007 Feb 12;230(2-3):178-88. | | Preventive effect of naringin on cardiac markers, electrocardiographic patterns and lysosomal hydrolases in normal and isoproterenol-induced myocardial infarction in Wistar rats.[Pubmed: 17188415 ] | Diets rich in natural antioxidants are associated with reduced risk of heart diseases.
METHODS AND RESULTS:
This study was aimed to evaluate the preventive role of naringin on cardiac troponin T (cTnT), lactate dehydrogenase (LDH)-isoenzyme, cardiac marker enzymes, electrocardiographic (ECG)-patterns and lysosomal enzymes in isoproterenol (ISO)-induced myocardial infarction (MI) in male Wistar rats. Rats subcutaneously injected with ISO (85mg/kg) at an interval of 24h for 2 days showed a significant increase in the levels of cTnT, intensity of the bands of LDH-isoenzyme (LDH1 and LDH2) and the activities of cardiac marker enzymes such as creatine kinase-MB (CK-MB), creatine kinase (CK), LDH, aspartate transaminase (AST) and alanine transaminase (ALT) in serum with subsequent decrease in the activities of CK, LDH, AST and ALT in the heart and alterations in ECG-patterns. The activities of lysosomal enzymes (beta-glucuronidase, beta-N-acetyl glucosaminidase, beta-galactosidase, cathepsin-B and cathepsin-D) were increased significantly in serum and the heart of ISO-induced rats, but the activities of beta-glucuronidase and cathepsin-D were decreased significantly in the lysosomal fraction of the heart. Pretreatment with naringin (10, 20 or 40mg/kg) daily for a period of 56 days positively altered the levels of cTnT, intensity of the bands of the LDH1 and LDH2-isoenzyme and the activities of cardiac marker enzymes, ECG-patterns and lysosomal hydrolases in ISO-induced rats.
CONCLUSIONS:
Thus, naringin possess cardioprotective effect in ISO-induced MI in rats. | | Pharmacology. 1994 Sep;49(3):144-50. | | Antiulcer effect of naringin on gastric lesions induced by ethanol in rats.[Pubmed: 7972328] | This study was designed to determine the gastroprotective properties of naringin on and the involvement of endogenous prostaglandins in mucosal injury produced by absolute ethanol.
METHODS AND RESULTS:
Oral pretreatment with the highest dose of naringin (400 mg/kg), 60 min before absolute ethanol was the most effective antiulcer treatment. Subcutaneous administration of indomethacin (10 mg/kg) to the animals treated with naringin (400 mg/kg) partially inhibited gastric protection, but the prostaglandin E2 determination did not show any increase in prostanoid levels. The contents of gastric mucus and total proteins were not significantly modified. Naringin-treated rats showed a marked increase in hexosamine levels, but this increase was less in animals pretreated with indomethacin.
CONCLUSIONS:
These results show that naringin has a 'cytoprotective' effect against ethanol injury in the rat, but this property appears to be mediated by non-prostaglandin-dependent mechanisms. | | 2015 Nov;409(1-2):199-211. | | Neuroprotective efficacy of naringin on 3-nitropropionic acid-induced mitochondrial dysfunction through the modulation of Nrf2 signaling pathway in PC12 cells[Pubmed: 26280522] | | Oxidative stress and mitochondrial dysfunction are implicated in neuronal apoptosis associated with Huntington's disease. Naringin is the flavanone present in grapefruit and related citrus species possess diverse pharmacological and therapeutic properties including antioxidant, anti-apoptotic, and neuroprotective properties. The aim of this study was to investigate the protective effect of naringin on 3-nitropropionic acid (3-NP)-induced neurotoxicity in pheochromocytoma cells (PC12) cells and to explore its mechanism of action. Naringin protects PC12 cells from 3-NP neurotoxicity, as evaluated the by cell viability assays. The lactate dehydrogenase release was decreased upon naringin treatment in 3-NP-induced PC12 cells. Naringin treatment enhances the antioxidant defense by increasing the activities of enzymatic antioxidants and the level of reduced glutathione. The increase in levels of reactive oxygen species and lipid peroxidation induced by 3-NP were significantly decreased by naringin. PC12 cells induced with 3-NP showed decrease in the mitochondrial membrane potential and mitochondrial respiratory complex enzymes, succinate dehydrogenase and cytochrome c oxidase activities, and it was significantly altered to near normal upon naringin treatment. Naringin reduced the 3-NP-induced apoptosis through the modulation in expressions of B-cell lymphoma 2 and Bcl-2-associated X protein. Further, naringin enhances the nuclear translocation of Nrf2 and induces the
Nad(p)h: quinone oxidoreductase-1 and Heme oxygenase-1 expressions through the phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway. Taken together, the above findings suggest that naringin augments cellular antioxidant defense capacity and reduces the 3-NP-induced neurotoxicity in PC12 cells through the PI-3K/Akt-dependent Nrf2 activation in PC12 cells.
Keywords: 3-Nitropropionic acid; Apoptosis; Mitochondrial dysfunction; Naringin; Nrf2; Oxidative stress; PI-3K/Akt. |
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