Grapefruit contains naringin and hesperidin. Oranges contain only hesperidin. Other foods contain hesperidin also, the bilberry, tangerines, plums. The most remarkable effect is related to glial cell-derived neurotrophic factor (GDNF), which causes growth of the glial cells (including astrocytes and the whole immune system within the brain).
Naringin protects the nigrostriatal dopaminergic projection through induction of GDNF in a neurotoxin model of Parkinson's disease.
Leem E1, Nam JH2, Jeon MT1, Shin WH3, Won SY4, Park SJ5, Choi MS6, Jin BK2, Jung UJ6, Kim SR7. (2014)
This study investigated the effect of naringin, a major flavonoid in grapefruit and citrus fruits, on the degeneration of the nigrostriatal dopaminergic (DA) projection in a neurotoxin model of Parkinson's disease (PD) in vivo and the potential underlying mechanisms focusing on the induction of glia-derived neurotrophic factor (GDNF), well known as an important neurotrophic factor involved in the survival of adult DA neurons. 1-Methyl-4-phenylpyridinium (MPP(+)) was unilaterally injected into the medial forebrain bundle of rat brains for a neurotoxin model of PD in the presence or absence of naringin by daily intraperitoneal injection. To ascertain whether naringin-induced GDNF contributes to neuroprotection, we further investigated the effects of intranigral injection of neutralizing antibodies against GDNF in the MPP(+) rat model of PD. Our observations demonstrate that naringin could increase the level of GDNF in DA neurons, contributing to neuroprotection in the MPP(+) rat model of PD, with activation of mammalian target of rapamycin complex 1. Moreover, naringin could attenuate the level of tumor necrosis factor-α in microglia increased by MPP(+)-induced neurotoxicity in the substantia nigra. These results indicate that naringin could impart to DA neurons the important ability to produce GDNF as a therapeutic agent against PD with anti-inflammatory effects, suggesting that naringin is a beneficial natural product for the prevention of DA degeneration in the adult brain.
Naringin treatment improves functional recovery by increasing BDNF and VEGF expression, inhibiting neuronal apoptosis after spinal cord injury.
Rong W1, Wang J, Liu X, Jiang L, Wei F, Hu X, Han X, Liu Z. (2012)
The aim of this study was to determine the therapeutic efficacy of starting naringin treatment 1 day after spinal cord injury (SCI) in rat and to investigate the underlying mechanism. SCI was induced using the modified weight-drop method in Sprague-Dawley rats. The SCI animals were randomly divided into three groups: vehicle-treated group; 20 mg/kg naringin-treated group; 40 mg/kg naringin-treated group, and additionally with sham group (laminectomy only). Locomotors functional recovery was assessed during the 6 weeks post operation period by performing open-field locomotors tests and inclined-plane tests. At the end of the study, the segments of spinal cord encompassing the injury site were removed for histopathological analysis. Immunohistochemistry was performed to observe the expression of the brain-derived neurotrophic factor (BDNF). The expression of vascular endothelial growth factor (VEGF), B-cell CLL/lymphoma-2 (Bcl-2), BCL-2-associated X protein (Bax) and caspase-3 were detected by Western blot analysis. The apoptotic neural cells were assessed using the TUNEL method. The results showed that the naringin-treated animals had significantly better locomotor function recovery, less myelin loss, and higher expression of BDNF and VEGF. In addition, naringin treatment significantly increased in Bcl-2:Bax ratio, reduced the enzyme activity of caspase-3 and decreased the number of apoptotic cells after SCI. These findings suggest that naringin treatment starting 1 day after SCI can significantly improve locomotor recovery, and this neuroprotective effect may be related to the upregulation of BDNF and VEGF and the inhibition of neural apoptosis. Therefore, naringin may be useful as a promising therapeutic agent for SCI.
Sirt1 is involved in energy metabolism: the role of chronic ethanol feeding and resveratrol.
Oliva J1, French BA, Li J, Bardag-Gorce F, Fu P, French SW. (2009)
Sirt1, a deacetylase involved in regulating energy metabolism in response to calorie restriction, is up regulated after chronic ethanol feeding using the intragastric feeding model of alcohol liver disease. PGC1 alpha is also up regulated in response to ethanol. These changes are consistent with activation of the Sirt1/PGC1 alpha pathway of metabolism and aging, involved in alcohol liver disease including steatosis, necrosis and fibrosis of the liver. To test this hypothesis, male rats fed ethanol intragastrically for 1 month were compared with rats fed ethanol plus resveratrol or naringin. Liver histology showed macrovesicular steatosis caused by ethanol and this change was unchanged by resveratrol or naringin treatment. Necrosis occurred with ethanol alone but was accentuated by resveratrol treatment, as was fibrosis. The expression of Sirt1 and PGC1 alpha was increased by ethanol but not when naringin or resveratrol was fed with ethanol. Sirt3 was also up regulated by ethanol but not when resveratrol was fed with ethanol. These results support the concept that ethanol induces the Sirt1/PGC1 alpha pathway of gene regulation and both naringin and resveratrol prevent the activation of this pathway by ethanol. However, resveratrol did not reduce the liver pathology caused by chronic ethanol feeding.
Protective effect of naringin, a citrus flavonoid, against colchicine-induced cognitive dysfunction and oxidative damage in rats.
Kumar A1, Dogra S, Prakash A. (2010)
Alzheimer's disease is a neurodegenerative disorder. Central administration of colchicine is well known to cause cognitive impairment and oxidative damage, which simulates sporadic dementia of the Alzheimer type in humans. The present study has been designed to investigate the protective effects of naringin against the colchicine-induced cognitive impairment and oxidative damage in rats. Colchicine (15 microg/5 microL), administered intracerebroventricularly, resulted in poor memory retention in both the Morris water maze and elevated plus maze task paradigms and caused marked oxidative damage. It also caused a significant decrease in acetylcholinesterase activity. Naringin (40 and 80 mg/kg, p.o.) treatment was given daily for a period of 25 days beginning 4 days prior to colchicine administration. Chronic treatment with naringin caused significant improvement in the cognitive performance and attenuated oxidative damage, as evidenced by lowering of malondialdehyde level and nitrite concentration and restoration of superoxide dismutase, catalase, luciferase, glutathione S-transferase, and reduced glutathione levels, and acetylcholinesterase activity compared to control. The present study highlights the therapeutic potential of naringin against colchicine-induced cognitive impairment and associated oxidative damage.
Naringin treatment induces neuroprotective effects in a mouse model of Parkinson's disease in vivo, but not enough to restore the lesioned dopaminergic system.
Kim HD1, Jeong KH2, Jung UJ3, Kim SR4. (2016)
We recently reported that treatment with naringin, a major flavonoid found in grapefruit and citrus fruits, attenuated neurodegeneration in a rat model of Parkinson's disease (PD) in vivo. In order to investigate whether its effects are universally applied to a different model of PD and whether its treatment induces restorative effects on the lesioned nigrostriatal dopaminergic (DA) projection, we observed the effects of pre-treatment or post-treatment with naringin in a mouse model of PD. For neuroprotective effects, 6-hydroxydopamine (6-OHDA) was unilaterally injected into the striatum of mouse brains for a neurotoxin model of PD in the presence or absence of naringin by daily intraperitoneal injection. Our results showed that naringin protected the nigrostriatal DA projection from 6-OHDA-induced neurotoxicity. Moreover, similar to the effects in rat brains, this treatment induced the activation of mammalian target of rapamycin complex 1 (mTORC1), which is well known as an important survival factor for DA neurons, and inhibited microglial activation in the substantia nigra (SN) of mouse brains treated with 6-OHDA. However, there was no significant change of DA phenotypes in the SN and striatum post-treated with naringin compared with 6-OHDA-lesioned mice, despite the treatment being continued for 12 weeks. These results suggest that post-treatment with naringin alone may not be enough to restore the nigrostriatal DA projection in a mouse model of PD. However, our results apparently suggest that naringin is a beneficial natural product to prevent DA degeneration, which is involved in PD.
The net U.S. consumption of oranges (including store-bought juice) is about 80 oranges per person per year, or 24 billion oranges per year. Yet if my recommendation for hesperidin is to be met, this must be increased to over 200 billion, roughly 730 oranges per person per year (two per day). It's the same story with grapefruits... the average U.S. consumption is nowhere near the recommended 365 grapefruits per person per year. It's a measly 30. Some people are doing their work, stuffing their faces with good stuff. But most aren't.
Consumption of grapefruit is associated with higher nutrient intakes and diet quality among adults, and more favorable anthropometrics in women, NHANES 2003–2008
Mary M. Murphy, Leila M. Barraj, and Gail C. Rampersaud (2014)
Background
Dietary guidance recommends consumption of a nutrient-dense diet containing a variety of fruits. The purpose of this study was to estimate usual nutrient intakes and adequacy of nutrient intakes among adult grapefruit consumers and non-consumers, and to examine associations between grapefruit consumption and select health parameters.
Methods
The analysis was conducted with data collected in the National Health and Nutrition Examination Survey (NHANES) 2003–2008. Respondents reporting consumption of any amount of grapefruit or 100% grapefruit juice at least once during the 2 days of dietary recall were classified as grapefruit consumers.
Results
Among adults aged 19+ years with 2 days of dietary recall (n=12,789), 2.5% of males and 2.7% of females reported consumption of 100% grapefruit juice or fresh, canned, or frozen grapefruit during the recalls. Grapefruit consumers were less likely to have usual intakes of vitamin C (males: 0% vs. 47%; females: 0% vs. 43%; P<0.001) and magnesium (P<0.05) below the estimated average requirement (EAR) compared to non-consumers, and they were more likely to meet adequate intake levels for dietary fiber (P<0.05). Potassium and β-carotene intakes were significantly higher among grapefruit consumers (P<0.001). Diet quality as assessed by the Healthy Eating Index-2005 (HEI-2005) was higher in grapefruit consumers (males: 66.2 [95% CI: 61.0–71.5] vs. 55.4 [95% CI: 54.4–56.4]; females: 71.4 [95% CI: 65.1–77.6] vs. 61.2 [95% CI: 59.8–62.6]). Among women, grapefruit consumption was associated with lower body weight, waist circumference, body mass index (BMI), triglycerides, C-reactive protein (CRP), and higher high-density lipoprotein (HDL) cholesterol (P<0.05), However, risk of being overweight/obese was not associated with grapefruit consumption.
Conclusion
Consumption of grapefruit was associated with higher intakes of vitamin C, magnesium, potassium, dietary fiber, and improved diet quality. Grapefruit may provide a healthful option for adults striving to meet fruit recommendations.
Quercetin itself has interesting antiviral properties[!] It also modulates allergies and "mast" cells, and is suspected to lower cholesterol and promote longevity. A prevalent compound in grapefruit, quercetin is often mistakenly assumed to underlie its interaction with medications and liver enzymes, but quercetin is only active in vitro[!], so other compounds are responsible. Due to its wide array of healthful compounds, grapefruit plays a protective role in everything from encephalitis and dementia to Parkinson's (see first quote block)! Even its scent has been reported to improve reaction time and to make one more discerning[!]
But the hesperidin is not to be underestimated. It has a potent effect on ghrelin signalling[1], which is orexigenic and blocks the 5-HT2C receptor[2]. Blocking 5-HT2C is known to stimulate a global dopamine release, a favorable cascade achieved during coitus. Hesperidin itself interacts with the 5-HT1A receptor, and this is responsible for most of its antidepressive qualities.
Evidence for the involvement of the serotonergic 5-HT(1A) receptors in the antidepressant-like effect caused by hesperidin in mice.
Souza LC1, de Gomes MG, Goes AT, Del Fabbro L, Filho CB, Boeira SP, Jesse CR. (2013)
The present study investigated a possible antidepressant-like activity of hesperidin using two predictive tests for antidepressant effect in mice: the forced swimming test (FST) and the tail suspension test (TST). Results demonstrated that hesperidin (0.1, 0.3 and 1 mg/kg, intraperitoneal, i.p.) decreased the immobility time in the FST and TST without affecting the locomotor activity in the open field test. The antidepressant-like effect of hesperidin (0.3 mg/kg) on the TST was prevented by the pretreatment of mice with p-chlorophenylalanine methyl ester (pCPA; 100 mg/kg, i.p., an inhibitor of serotonin synthesis) and WAY100635 (0.1 mg/kg, subcutaneous, s.c., a selective 5-HT(1A) receptor antagonist). Pretreatment of mice with prazosin (1 mg/kg, i.p., an α(1)-adrenoceptor antagonist), yohimbine (1 mg/kg, i.p., an α(2)-adrenoceptor antagonist), propranolol (2 mg/kg, i.p., a β-adrenoceptor antagonist), AMPT (100 mg/kg, i.p., an inhibitor of tyrosine hydroxylase), SCH23390 (0.05 mg/kg, s.c., a dopamine D(1) receptor antagonist), sulpiride (50 mg/kg, i.p., a dopamine D(2) receptor antagonist), ketanserin (1mg/kg, i.p., a 5-HT(2A/2C) receptor antagonist) or MDL72222 (1 mg/kg, i.p., a 5-HT(3) receptor antagonist) did not block the antidepressant-like effect of hesperidin (0.3 mg/kg, i.p.) in the TST. Administration of hesperidin (0.01 mg/kg, i.p.) and fluoxetine (1 mg/kg), at subeffective doses, produced an antidepressant-like effect in the TST. The antidepressant-like effect caused by hesperidin in mice in the TST was dependent on an interaction with the serotonergic 5-HT(1A) receptors. Taken together, these results suggest that hesperidin possesses antidepressant-like property and may be of interest source for therapeutic agent for the treatment of depressive disorders.
Protective effect of hesperidin and naringin against 3-nitropropionic acid induced Huntington's like symptoms in rats: possible role of nitric oxide.
Kumar P1, Kumar A. (2010)
3-Nitropropionic acid (3-NP) is a well known experimental model to study Huntington's disease (HD) and associated neuropsychiatric problems. Present study has been designed to explore the protective effects of hesperidin, naringin, and their nitric oxide mechanism (if any) against 3-nitropropionic acid induced neurotoxicity in rats. Systemic 3-nitropropionic acid (10 mg/kg) treatment for 14 days in rats significantly induced HD like symptoms in rats as indicated by reduced locomotor activity, body weight, grip strength, oxidative defense and mitochondrial complex enzymes (complex-I, -II, and -IV) activities in striatum. Naringin and hesperidin pretreatment significantly attenuated behavioral alterations, oxidative stress and mitochondrial enzymes complex dysfunction in 3-NP treated group. L-Arginine (50 mg/kg) pretreatment with lower dose of hesperidin (50 mg/kg) and naringin (50 mg/kg) significantly attenuated the protective effect of hesperidin and naringin respectively. Whereas L-NAME (10 mg/kg), a non-selective NOS inhibitor pretreatment with hesperidin (50 mg/kg) and naringin (50 mg/kg) significantly potentiated their protective effect which was significant as compared to their effect per se. Study highlights the therapeutic potential of hesperidin and naringin against Huntington's like conditions and further indicates that these drugs might act through nitric oxide mechanism.
Both flavonoids also have potential in the heart, the second most important organ, vitally supportive of brain health. Whether supporting the capillaries and smooth muscle at the molecular level, the inflammation of the heart, or the recovery or prevention of stroke victims... grapefruit is a serious underdog!
Hesperidin contributes to the vascular protective effects of orange juice: a randomized crossover study in healthy volunteers
Christine Morand, Claude Dubray, Dragan Milenkovic, Delphine Lioger, Jean François Martin, Augustin Scalbert, and Andrzej Mazur (2010)
Background: Although numerous human studies have shown consistent effects of some polyphenol-rich foods on several intermediate markers for cardiovascular diseases, it is still unknown whether their action could be specifically related to polyphenols.
Objective: We investigated the effect of orange juice and its major flavonoid, hesperidin, on microvascular reactivity, blood pressure, and cardiovascular risk biomarkers through both postprandial and chronic intervention studies.
Design: Twenty-four healthy overweight men (age 50–65 y) were included in a randomized, controlled, crossover study. Throughout the three 4-wk periods, volunteers consumed daily 500 mL orange juice, 500 mL control drink plus hesperidin (CDH), or 500 mL control drink plus placebo (CDP). All measurements and blood collections were performed in overnight-fasted subjects before and after the 4-wk treatment periods. The postprandial study was conducted at the beginning of each experimental period.
Results: Diastolic blood pressure (DBP) was significantly lower after 4 wk consumption of orange juice or CDH than after consumption of CDP (P = 0.02), whereas microvascular endothelium-related reactivity was not significantly affected when measured after an overnight fast. However, both orange juice and CDH ingestion significantly improved postprandial microvascular endothelial reactivity compared with CDP (P < 0.05) when measured at the peak of plasma hesperetin concentration.
Conclusions: In healthy, middle-aged, moderately overweight men, orange juice decreases DBP when regularly consumed and postprandially increases endothelium-dependent microvascular reactivity. Our study suggests that hesperidin could be causally linked to the beneficial effect of orange juice. This trial is registered at clinicaltrials.gov as NCT00983086.
Effects of Hesperidin on cardiac electrophysiology of diabetic rats
W. Wang, J.-M. Cao, Z.-F. Yang, C.-Z. Li (2010)
Objective: To investigate the effects of Hesperidin on cardiac electrophysiology of diabetic rats.Methods: Thirty SD rats were randomly divided into three groups. Diabetic model group (n = 12): diabetic model was induced by intraperitoneal injection of large amount of streptozotocin (STZ); Hesperidin intervention group (n = 12): diabetic model was established, and were intragastrically administrated with 10 mg/kg Hesperidin daily; control group (n = 6): without model establishment and intervention. After treatment for 4 weeks, in vivo and in vitro ECG and characteristics of action potentials of ventricular muscles were recorded and compared. Papillary muscles of ventricle of diabetic model group were perfused with 1 × 10 -6 mol/L or 5 × 10 -6 mol/L Hesperidin, and changes of action potentials were continuously recorded.
Results: In vivo ECG analysis revealed that the heart rates of diabetic model group and Hesperidin intervention group were much faster than that of control group (P < 0.01, P < 0.05), QT interval of diabetic model group significantly prolonged (P < 0.05), while there was no significant difference in QT interval between control group and Hesperidin intervention group (P > 0.05). In vitro ECG analysis indicated that the prevalence of tachyarrhythmia in diabetic model group was 75.0%, significantly higher than that of Hesperidin intervention group (16.7%) (P < 0.05). Analysis of action potentials of ventricular muscles revealed that the resting membrane potential, amplitude of action potential and maximum upstroke velocity of phase 0 of diabetic model group were significantly lower than those of control group, while the action potential duration was longer than that of control group. Compared with diabetic model group, the parameters of action potentials in Hesperidin intervention group were more approximate with those of control group. Perfusion tests with two concentrations of Hesperidin demonstrated that 5 × 10 -6 mol/L Hesperidin perfusion performed better than 1 × 10 -6 mol/L Hesperidin perfusion in recovery of action potentials of papillary muscles of ventricle of diabetic rats.
Conclusion: Hesperidin may dose-dependently decrease the prevalence of arrhythmia by reversing the abnormal electrophysiological activities in diabetic rats.
The effect of hesperidin on cardiac pumping function and heart rate variability of diabetic rat
WANG Wei;YANG Zhi-fang;WANG Hong-wei;ZHANG Ying;LI Ci-zhen;LIU Yuan-mou;CAO Jiu-mei;ZHAO Yong-ju (2010)
Objective To study the effects and mechanism of hesperidin on the pumping function of streptozotocin induced diabetic rat heart.Methods Thirty rats were randomly divided into three groups: control(n=6),diabetic(n=12) and hesperidin-treated(n=12)groups.Diabetes was induced by streptozotocin.Langendorff perfusion system on isolated heart and heart rate variability(HRV) analysis were used to study the effect of hesperidin on cardiac contractility,coronary artery blood flow,QRS wave of electrocardiography and HRV.
Results Hesperidin 10��10-6 mol/L could increase the coronary blood flow and contractility of the diabetic rat heart by 106.0% and 87.3%,respectively;meanwhile it shortened the QRS wave by 33.3%.In diabetic rats,the heart rate increased,standard deviation of sinus RR intervals(SDNN)decreased and ratio of sympathetic and vagal tone(LF/HF)increased.All these three parameters recovered somewhat after treated with hesperidin.
Conclusions Hesperidin could improve the coronary blood flow and heart pumping function of streptozotocin induced diabetic rat heart and could reverse the changes of HRV produced by diabetes as well.
Effect of Citrus Flavonoids, Naringin and Naringenin, on Metabolic Syndrome and Their Mechanisms of Action
M. Ashraful Alam, Nusrat Subhan, M. Mahbubur Rahman, Shaikh J. Uddin, Hasan M. Reza, and Satyajit D. Sarker (2014)
Flavonoids are important natural compounds with diverse biologic activities. Citrus flavonoids constitute an important series of flavonoids. Naringin and its aglycone naringenin belong to this series of flavonoids and were found to display strong anti-inflammatory and antioxidant activities. Several lines of investigation suggest that naringin supplementation is beneficial for the treatment of obesity, diabetes, hypertension, and metabolic syndrome. A number of molecular mechanisms underlying its beneficial activities have been elucidated. However, their effect on obesity and metabolic disorder remains to be fully established. Moreover, the therapeutic uses of these flavonoids are significantly limited by the lack of adequate clinical evidence. This review aims to explore the biologic activities of these compounds, particularly on lipid metabolism in obesity, oxidative stress, and inflammation in context of metabolic syndrome.
Preventive Effects of Hesperidin, Glucosyl Hesperidin and Naringin on Hypertension and Cerebral Thrombosis in Stroke-prone Spontaneously Hypertensive Rats
Dr Yasuto Sasaki and Kobe Gakuin (2012)
The effects of hesperidin, glucosyl hesperidin (G-hesperidin), a water-soluble derivative of hesperidin, and naringin on blood pressure and cerebral thrombosis were investigated using stroke-prone spontaneously hypertensive rats (SHRSP). Hesperidin, G-hesperidin and naringin were mixed with diet and fed to the animals for 4 weeks. No effect was evident on body weight, but the supplements significantly suppressed the age related increase in blood pressure. Thrombotic tendency, as assessed using a He-Ne laser technique in the cerebral blood vessels, was significantly decreased in the treated animals compared with the control animals. Measurements of 8-hydroxy-2′-deoxyguanosine (8-OHdG) demonstrated that the supplements had strong antioxidant activity. Furthermore, these supplements significantly increased the production of nitric oxide (NO) metabolites in urine measured with Griess reagent. Vasodilation induced by acetylcholine-mediated NO production in the endothelium was assessed using thoracic aortic ring preparations and indicated that endothelial function was significantly improved by the administration of these supplements.
These findings suggest that the strong antioxidant properties of hesperidin, G-hesperidin and naringin could modulate the inactivation of NO and protect endothelial function from reactive oxygen species (ROS). In this manner, the flavonoids could contribute beneficial effects on the mechanisms of hypertension and thrombosis by increasing the bioavailability of NO.
Nitric oxide mechanism in the protective effect of naringin against post-stroke depression (PSD) in mice.
Aggarwal A1, Gaur V, Kumar A. (2010)
AIM:
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.
MAIN METHODS:
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.
KEY FINDINGS:
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.
SIGNIFICANCE:
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.
Edited by gamesguru, 19 September 2016 - 04:59 PM.