Journal of Pharmacy And Bioallied Sciences
Journal of Pharmacy And Bioallied Sciences Login  | Users Online: 8137  Print this pageEmail this pageSmall font sizeDefault font sizeIncrease font size 
    Home | About us | Editorial board | Search | Ahead of print | Current Issue | Past Issues | Instructions | Online submission

 Table of Contents  
Year : 2015  |  Volume : 7  |  Issue : 2  |  Page : 121-127  

Effect of naringin on hemodynamic changes and left ventricular function in renal artery occluded renovascular hypertension in rats

Department of Pharmacology, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Pune, Maharashtra, India

Date of Submission08-Apr-2014
Date of Decision27-Jul-2014
Date of Acceptance02-Sep-2014
Date of Web Publication1-Apr-2015

Correspondence Address:
Dr. Subhash L Bodhankar
Department of Pharmacology, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Pune, Maharashtra
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0975-7406.154437

Rights and Permissions

Background: 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. Objective: The objective of this study was to investigate the antihypertensive activity of naringin in RAO induced hypertension in rats.Material and Methods: 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. Conclusion: It is concluded that the antihypertensive activity of naringin may result through inhibition of oxidative stress.

Keywords: Antihypertensive, naringin, oxidative stress, renal artery occlusion

How to cite this article:
Visnagri A, Adil M, Kandhare AD, Bodhankar SL. Effect of naringin on hemodynamic changes and left ventricular function in renal artery occluded renovascular hypertension in rats. J Pharm Bioall Sci 2015;7:121-7

How to cite this URL:
Visnagri A, Adil M, Kandhare AD, Bodhankar SL. Effect of naringin on hemodynamic changes and left ventricular function in renal artery occluded renovascular hypertension in rats. J Pharm Bioall Sci [serial online] 2015 [cited 2022 Dec 6];7:121-7. Available from:

Cardiovascular diseases (CVD) contemplate as the principal cause of bereavement in the world. Hypertension or simply high blood pressure is the one of the most imperative risk factor accountable for atherosclerosis, coronary artery disease, myocardial infarct, heart failure, stroke and renal insufficiency. [1],[2] In the field of nephrology, renal hypertension is postulated as an instigation of acute renal failure. Kidney plays a fundamental role in the continuance of peripheral vascular resistance through the action of angiotensin-II a final product of renin-angiotensin system (RAS) and entail in the volume control of cardiac output by regulating urinary salt and water excretion. Consequently, RAS plays a fundamental role in the progress of renovascular hypertension (RVHT). Renal hypertension is commenced by physiological variations in the kidney through a weird stipulation. Renal ischemia-reperfusion (I/R) injury is a major burden on both surgeons as well as on patient due to frequent cause of acute renal failure which occur during renal artery surgery, renal transplantation as well as in cardiovascular surgery. [3],[4],[5]

Angiotensin spurs intracellular formation of reactive oxygen species (ROS) such as superoxide anion and hydrogen peroxide, which eventually mayhem the physiology of the kidney. [6] During renal ischemia-reperfusion (RIR) injury reactive oxygen and nitrogen species played a promising role in mediating cell damage. [7],[8] Furthermore, RIR is a complex pathophysiological process, which is caused by various confrontations like oxygen free radical formation, mitochondrial dysfunction, tubular cell apoptosis and inflammatory cytokines generation. [9],[10],[11] It has been distinguished that hypertension is the brisk progress of necrosis caused by critical imbalance between the oxygen supply and the demand of the cells. Oxidative stress resulting from augmented production of free radicals allied with reduced levels of antioxidants in the myocardium plays a major role in cardiovascular complications such as ischemic heart disease, atherosclerosis, congestive heart failure, cardiac hypertrophy, and arrhythmias. [12] In addition, generation of toxic ROS such as superoxide radical, hydrogen peroxide, and hydroxyl radical may regard as the principal conjecture for cardiovascular dysfunction. [13] For upholding of customary physiological function free radicals are elementary, however, overabundance or an unconstrained quantity of free radicals instigate as well as promulgate appallingly fatal to the cells. [14],[15]

In recent times copious of studies substantiate that deployment of diets rich in plant provisions are allied with a truncated risk of cardiovascular compactions. [16] For the treatment of CVD researchers have illustrated rehabilitated curiosity in medicinal plants and food products for their certain preventive measures. Flavonoids are extensively disseminated in vegetables fruits tea and wines which are renowned as naturally demonstrating antioxidants that hamper lipid peroxidation in biological membranes. [17],[18],[19],[20] In recent year, flavonoids catch eye of researchers due to strong antioxidant ability of defending human body against oxidative stress and free radical. [21],[22] Moreover, bioflavonoid played decisive biological role, which include function of scavenging ROS. [23],[24] It has been acknowledged that diseases associated to oxidative stress can be treated by consumption of dietary antioxidants. [25],[26],[27],[28],[29] It is well-demonstrated that antioxidant defense system is modulated by scavenging free radicals that are known to exert by isolated bioactive moieties.

Currently, there is much interest in the usefulness of citrus fruits because of their intake emerges to be linked with reduced risk of certain chronic diseases and increased endurance. [30] In addition, flavonoids have antioxidant capacities that are much stronger than those of Vitamins C and E. [31] Naringin (4', 5, 7-trihydroxyflavanone 7-rhamnoglucoside) is a major and active bioflavonoid occur in grape and citrus fruits with the ability of compelling antioxidative action. [32],[33] Naringin has various potential pharmacological and therapeutic characteristics such as antiinflammatory, antimutagenic, cholesterol lowering, antiulcer, anticancer, free radical scavenging, neuroprotective, colono-protective and antioxidant action. [17],[20],[34],[35],[36] Naringin exhibits a potential cardio-protective effect through modulation of oxidative stress and inflammatory markers in doxorubicin as well as isoproterenol induced cardiotoxicity. [37],[38] It has been reported that naringin revealed protective effect on glycerol-induced acute renal failure in rat kidney. [39] It has been supported that naringin exerts its renoprotective effect in ischemia reperfusion injury in rats conceivably due to overwhelming antioxidant proficiency and free radical scavenging activity. [40] Hence, the present investigation is anticipated to appraise antihypertensive potential of naringin in renal artery occluded (RAO) hypertensive rats through assessment of antioxidant motion on assorted enzymes.

   Materials and Methods Top

Experimental animals and research protocol approval

Adult male Sprague-Dawley rats (180-200 g) were purchased from the National Institute of Biosciences, Pune (India). They were maintained at 24°C ± 1°C, with relative humidity of 45-55% and 12:12 h dark/light cycle. The animals had free access to standard pellet chow (Pranav Agro Industries Ltd., Sangli, India) and water throughout the experimental protocol. All experiments were carried out between 09:00 and 17:00 h. The experimental protocol was approved by the Institutional Animal Ethics Committee of Poona College of Pharmacy, Pune and performed in accordance with the guidelines of Committee for Control and Supervision of Experimentation on Animals.

Drugs and chemicals

Naringin was purchased from Sigma Chemical Co., (St. Louis, MO, USA). 1,1', 3, 3'- Tetraethoxypropane, crystalline beef liver catalase, reduced glutathione (GSH), 5,5'-dithiobis (2-nitrobenzoic acid) were purchased from S. D. Fine Chemicals, Mumbai, India.

Experimental design

Animals were divided randomly into five groups 12 animals each as follows.

Group I: Sham: Rats were exposed to left renal artery but did not receive any occlusion. They were treated with distilled water (10 mg/kg)
Group II: RAO control: Rats were exposed to left renal artery undergoes RAO. They were treated with distilled water (10 mg/kg)
Group III: RAO + N (20): Rats were exposed to left renal artery undergoes RAO. They were received naringin 20 mg/kg, p.o
Group IV: RAO + N (40): Rats were exposed to left renal artery undergoes RAO. They were received naringin 40 mg/kg, p.o
Group V: RAO + N (80): Rats were exposed to left renal artery undergoes RAO.

They were received naringin 80 mg/kg, p.o. Male Wistar rats were divided into five groups containing twelve animals each. Animals in the sham group (Group I) were pretreated with saline for 4 weeks and underwent the exposure of the left renal artery, but did not receive any occlusion. The animals in RAO group (Group II) received 4 h of RAO and pretreatment of saline for 4 weeks. Groups III, IV and V were pretreatment with naringin (20, 40, and 80 mg/kg) for 4 weeks and then received 4 h of RAO. Out of twelve animals in each group six animals were subjected to hemodynamic measurement and remaining were used for the measurement of left ventricular heart function.

Renal artery occluded renovascular hypertension in rats

After 4 weeks of naringin treatment, animals were anaesthetized by intraperitoneal injection of 1.25 g/kg of Urethane. A small cut was made on the left side of peritoneal cavity of the animal to expose left kidney. The left renal artery was occluded for the 4 h using rat bulldog clamp. The jugular vein was cannulated for the administration of test drug. The right carotid artery was cannulated and connected to the blood pressure transducer of powerlab assembly to measure the hemodynamic changes. After stabilization of blood pressure, the rat bulldog clamp was removed. Then, 1/10 th of the administered dose of the naringin, that is, 20, 40 and 80 mg/kg was injected to Group III, IV and V respectively through jugular vein and hemodynamic as well as left ventricular alterations were measured at different time intervals (0, 5, 15, 30, 45, 60 and 90 min). [41]

Invasive measurement of hemodynamic changes

Hemodynamic changes such as heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MABP), left ventricular end diastolic pressure (LVEDP) and Ventricular Contractility Assessment (dp/dt) were measured by means of a polyethylene cannula (PE 50) filled with heparinized saline (100 IU/ml) inserted into the right carotid artery. The cannula was connected to a transducer, and the signal was amplified by means of bioamplifier. Left ventricular systolic pressure was measured by means of a Millar Mikro-Tip transducer catheter (Model SRP-320, Millar Instrument, INC 320-7051, Houston, Texas 77023-5417) inserted into the left ventricle via the right carotid artery and connected to a bioamplifier. The left ventricular functions like dp/dt max , dp/dt min and LVEDP signals were obtained from primary signals (left ventricular systolic pressure and blood pressure) by means of an acquisition data system (AD Instruments Pvt. Ltd., with software (LabChart 7.3; AD Instrument Pvt. Ltd.,). [42]

Biochemical estimation

Tissue homogenate preparation

Immediately after assessment of hemodyamic parameters animal were scarified, and kidney tissue homogenates were prepared with 0.1 M tris-HCl buffer (pH 7.4) and supernatant of homogenate was employed to estimate superoxide dismutase (SOD), reduced GSH, lipid peroxidation (malondialdehyde [MDA] content) as described previously. [43]

Histopathological analysis of kidney

Kidney tissue was stored in 10% formalin for 24 h. The specimen was dehydrated and placed in xylene for 1 h (3 times) and later in ethyl alcohol (70, 90 and 100%) for 2 h resp. The infiltration and impregnation were carried out by treating with paraffin wax twice, each time for one h. Tissue specimens were cut into sections of 3-5 μm thickness and were stained with haematoxylin and eosin. The specimen was mounted on the slide by use of distrene pthalate xylene as mounting medium. Sections were examined under a light microscope to obtain a general impression of the histopathology features of specimen and infiltration of cells. The various changes in histological features were graded as Grade 0 (not present or very slight) l; Grade 1 (mild); Grade 2 (moderate); and Grade 3 (severe).

Statistical analysis

Data were expressed as mean ± standard error mean. Data analysis was performed using GraphPad Prism 5.0 software (Graph Pad, San Diego, CA, USA). Data of hemodynamic changes were analyzed using two-way analysis of variance (ANOVA) and Bonferroni's test was applied for post-hoc analysis as well as data of biochemical parameters were analyzed using one-way ANOVA and Dunnett's test was applied for post-hoc analysis. A value of P < 0.05 was considered as statistically significant.

   Results Top

Effect of naringin on heart rate

There was significant (P < 0.001) decreased in HR in RAO control animals from 5, 15, 30, and 45 min as compared to sham animals. Treatment of naringin (40 mg/kg) showed substantial (P < 0.001) improvement in HR at 30 min and 45 min as compared to RAO control rats. Whereas naringin (80 mg/kg) treatment significantly (P < 0.001) increased the HR at 15, 30, 45 and 90 min when compared to RAO control rats [Figure 1]a.
Figure 1: Effect of naringin on hemodynamic parameters (a) heart rate, (b) systolic blood pressure, (c) diastolic blood pressure and (d) mean arterial blood pressure in renal artery occlusion (RAO) induced hypertensive rats. Data are expressed as mean ± standard error mean (n = 6) and analyzed by two-way analysis of variance followed by Bonferroni's multiple range test for each parameter separately. *P < 0.05, **P < 0.01 and ***P < 0.001 as compared to RAO group and #P < 0.05, ##P < 0.01 and ###P < 0.001 as compared to sham group

Click here to view

Effect of naringin on systolic blood pressure, diastolic blood pressure and mean arterial blood pressure

After occlusion of renal artery, there was conspicuous (P < 0.001) elevation in SBP and DBP of RAO control animals throughout the recording of hemodynamic changes as compared to sham rats. Treatment with naringin (40 mg/kg) showed notably (P < 0.01) alleviation in SBP and DBP at 15, 30, 45, 60 and 90 min as compared to sham rats. On the other hand, naringin (80 mg/kg) treatment showed a significant (P < 0.001) an incredible antihypertensive potential by reinstate SBP and DBP at 15, 30, 45, 60, and 90 min when compared to sham animals. After occlusion of renal artery for 4 h of RAO control rats showed substantial (P < 0.001) increase in MABP as compared to sham rats. On the other hand, treatment with naringin (80 mg/kg) appreciably lessened the MABP at 15, 30, 45, 60 and 90 min when compared to RAO control rats [Figure 1]b-d.

Effect of naringin on left ventricular function

Occlusion of renal artery for 4 h resulted in noteworthy (P < 0.001) rise in LEVDP at 30, 45, and 60 min when compared to the sham group. Conversely, treatment with naringin (40 mg/kg) noticeably (P < 0.05 and P < 0.01) ameliorated the LVEDP at 30 min and 45 min as compared to RAO control rats. Administration of naringin (80 mg/kg) illustrated more stupendous antihypertensive effect by significantly lessening (P < 0.001, P < 0.05 and P < 0.001) LVEDP at 30, 45 and 60 min as compared to RAO control rats. There were no imperative changes in maximum first derivative of ventricular pressure (dp/dt max ), and minimum first derivative of ventricular pressure (dp/dt min ) in RAO group after clamp removal and during study period [Table 1].
Table 1: Effect of naringin on left ventricular function in RAO induced hypertensive rats

Click here to view

Effect of naringin on renal superoxide dismutase and glutathione level

Renal SOD and GSH level of RAO control rats were notably decreased (P < 0.001) after occlusion of renal artery for 4 h when compared to sham rats. The renal SOD level in naringin (40 and 80 mg/kg) treated rats was considerably (P < 0.01 and P < 0.001) and dose dependently increased when compared to RAO control rats. Whereas, naringin (40 and 80 mg/kg) treatment showed noteworthy (P < 0.05 and P < 0.001) and dose dependent increased in the GSH level when compared to RAO control animals [Table 2].
Table 2: Effect of naringin on oxidative stress in RAO induced hypertensive rats

Click here to view

Effect of naringin on renal malondialdehyde level

After occlusion of renal artery, lipid peroxidation (MDA) level in kidney was considerably increased (P < 0.001) in RAO control rats when compared to sham rats. The renal MDA level in naringin (40 and 80 mg/kg) treated rats was lessened appreciably (P < 0.01 and P < 0.001) and dose-dependently when compared to RAO control rats [Table 2].

Effect of naringin on histopathology of kidney

Histopathological analysis of kidney from sham control rats showed normal architecture of the kidney. It was devoid of congestion, necrosis and inflammatory infiltration (Grade 0) [Figure 2]a. Basement membrane of the glomerulus was remained intact. Kidney form RAO control rats showed renal damage evident by glomerular structural disruption. It showed the presence of intraluminal cell debris, edema and inflammatory infiltration [Figure 2]b. Histological analysis of kidney from naringin (40 and 80 mg/kg) treated rats showed moderate number of inflammatory cells without any necrosis and edema. Thickens of glomerulus basement membrane was intact [Figure 2]c, d and [Table 3].
Figure 2: Effect of naringin on histopathology alteration produced by renal artery occlusion (RAO) in rat kidney. Photomicrograph of sections of kidney of (a) normal, (b) RAO control rats, (c) naringin (40 mg/kg) treated rats and (d) naringin (80 mg/kg) treated rats. Necrosis (black arrow), inflammatory infiltration (red arrow) and increased thickness of basement membrane (yellow arrow) H and E staining at × 100

Click here to view
Table 3: Effect of naringin on kidney histopathology in RAO induced hypertensive rats

Click here to view

   Discussion Top

Renovascular hypertension is a syndrome that consists of high blood pressure caused by the kidneys hormonal reaction to tapering of the arteries supplying the kidneys. RVHT reflects the fundamental relation between anatomically manifest arterial occlusive ailment and eminent blood pressure. [44] ROA produces ischemia, which instigates the release of renin and a secondary altitude in blood pressure. Rennin endorses conversion of angiotensin-I to angiotensin-II, causing severe vasoconstriction and aldosterone release. RVHT emerges in due to RAO, habitually from atherosclerotic or fibromuscular dysplastic renal disease, since this worsening of renal perfusion pressure causes the kidney to engender surfeit of renin and leads to a persistent commencement of the rennin-angiotensin-aldosterone system.

The present study assessed isolated bioactive moiety naringin to protect against renovscular hypertension in laboratory animals. The literature is scattered with affirmations indicating antioxidants, antiapoptotic, antiinflammatory and ROS scavenging properties of naringin, as the prime components of renovascular damage is generation of ROS leading to vascular damage hence the selection of naringin in this animal model is astute.

The present study of RAO depicts that clamping of renal artery for 45 min. may prompt the RAO induced oxidant damage and treatment of naringin may supersede the defense that was afforded by restitution of hemodynamic alterations in the kidney. Allied with the hypertension of renal artery clipping, the myocardium endures a hypertrophic response as variation to amplified blood pressure. [45] The most liable enlightenment for our findings is that pretreatment with naringin appreciably lessen hemodynamic parameters such as systolic, diastolic, MABP and HR. The utmost boost in systolic, diastolic, MABP and end-diastolic pressure in RAO group was observed at 15 min. after clamp deletion, after which the blood pressures leaned to recuperate up to 60 min. Treatment of naringin illustrated the momentous drop in systolic, diastolic, MABP and end-diastolic pressure at 15 min after clamp removal, and radically improved up to 60 min. Due to clamping on renal artery inconsequential varies were scrutinized in maximum first derivative of ventricular pressure (dp/dt max ), minimum first derivative of ventricular pressure (dp/dt min ).

An assortment of enzymes is conscientious for the cohort of ROS including nitric oxide synthase, NADH/NADPH oxidase, cyclooxygenase, and xanthine oxidase; the mitochondrial electron transport chain is also involved in the generation of ROS. [46],[45],[46],[47],[48],[49] Oxidative stress has a superfluous of components that encompass an assortment of enzymes implicated in the electron transport chain. Moreover, oxidative stress can elicit inflammation, enhance vasoconstrictors accrual, and endorse tubular cell apoptosis and necrosis. [50],[51] This higher level of ROS diminishes the copper-zinc-SOD enzyme motion alongside GSH performance in cardiac cells, which causes consequential hammering of myocardial integrity and necrosis. [52],[53],[54] The prominent cause of lipid peroxidation is an excessive generation of ROS by superoxide anions and their derivatives including hydroxyl radicals in cardiac myocytes. [55] Furthermore, through adaptation of cellular protein and DNA damage lipid peroxidation is measured as foremost cause of oxidative damage. [17],[56] RIR injury is pigeonholed by a surfeit of ROS formation and a diminutive of antioxidants, resulting in mounting oxidative stress and tissue damage. [4],[57] Concrete with this notion, we found that renal IRI drastically lessened SOD, GSH levels and elevated MDA content. This augmented oxidative stress was allied with prejudiced renal function and histological changes as noticed by idiosyncratic renal morphological variations. Conversely, bioflavonoid naringin prohibited severe tiredness of SOD activity in depressed kidney and restrained IRI induced lipid peroxidation and subsequently enhanced kidney function and dent caused by RAO. Research carried out by various workers showed that naringin exerts its protective role via regulating antioxidative capacity by increasing SOD activity and by up-regulating the gene expression of SOD and GSH in renal as well as other diseases. [34],[39],[40],[58] Results of the present investigation are in line with the findings of these researchers. To sum up, naringin exerts antihypertensive potential via its antioxidant activity. However, further study is undertaken to evaluate the exact mechanism of action of naringin in renal artery occluded RVHT.

   Acknowledgments Top

The authors acknowledge Dr. S. S. Kadam, Vice Chancellor, Bharati Vidyapeeth University and Dr. K. R. Mahadik, Principal, Poona College of Pharmacy for keen interest and providing the necessary facilities to carry out the study.

   References Top

Oparil S. Treating multiple-risk hypertensive populations. Am J Hypertens 1999;12:121S-9.  Back to cited text no. 1
Gosavi T, Kandhare A, Raygude K, Ghosh P, Bodhankar S. A comparative study on the efficacy, safety and cost effectiveness of Viscum album and Rauwolfia serpentina mother tincture in hypertensive patients. Deccan J Nat Prod 2011;2:29-35.  Back to cited text no. 2
Rippe C, Rippe A, Larsson A, Asgeirsson D, Rippe B. Nature of glomerular capillary permeability changes following acute renal ischemia-reperfusion injury in rats. Am J Physiol Renal Physiol 2006;291:F1362-8.  Back to cited text no. 3
Aragno M, Cutrin JC, Mastrocola R, Perrelli MG, Restivo F, Poli G, et al. Oxidative stress and kidney dysfunction due to ischemia/reperfusion in rat: Attenuation by dehydroepiandrosterone. Kidney Int 2003;64:836-43.  Back to cited text no. 4
Pampal A, Ozen IO, Demirogullari B, Gol IH, Guclu MM, Bukan N, et al. Apart from the other members of PDE inhibitors' family, enoximone does not enhance renal ischemic reperfusion injury: The effects of enoximone on renal ischemia reperfusion. Ren Fail 2009;31:971-6.  Back to cited text no. 5
Sachse A, Wolf G. Angiotensin II-induced reactive oxygen species and the kidney. J Am Soc Nephrol 2007;18:2439-46.  Back to cited text no. 6
Nath KA, Norby SM. Reactive oxygen species and acute renal failure. Am J Med 2000;109:665-78.  Back to cited text no. 7
Noiri E, Nakao A, Uchida K, Tsukahara H, Ohno M, Fujita T, et al. Oxidative and nitrosative stress in acute renal ischemia. Am J Physiol Renal Physiol 2001;281:F948-57.  Back to cited text no. 8
Kelly KJ, Williams WW Jr, Colvin RB, Meehan SM, Springer TA, Gutierrez-Ramos JC, et al. Intercellular adhesion molecule-1-deficient mice are protected against ischemic renal injury. J Clin Invest 1996;97:1056-63.  Back to cited text no. 9
Lieberthal W, Koh JS, Levine JS. Necrosis and apoptosis in acute renal failure. Semin Nephrol 1998;18:505-18.  Back to cited text no. 10
López-Martí J, Sola A, Pi F, Alfaro V, Marco A, Hotter G. Nucleotides modulate renal ischaemia-reperfusion injury by different effects on nitric oxide and superoxide. Clin Exp Pharmacol Physiol 2003;30:242-8.  Back to cited text no. 11
Das DK, Maulik N, Moraru II. Gene expression in acute myocardial stress. Induction by hypoxia, ischemia, reperfusion, hyperthermia and oxidative stress. J Mol Cell Cardiol 1995;27:181-93.  Back to cited text no. 12
Vaage J, Valen G. Pathophysiology and mediators of ischemia-reperfusion injury with special reference to cardiac surgery. A review. Scand J Thorac Cardiovasc Surg Suppl 1993;41:1-18.  Back to cited text no. 13
Kaul N, Siveski-Iliskovic N, Hill M, Slezak J, Singal PK. Free radicals and the heart. J Pharmacol Toxicol Methods 1993;30:55-67.  Back to cited text no. 14
Kandhare AD, Bodhankar SL, Singh V, Mohan V, Thakurdesai PA. Anti-asthmatic effects of type-A procyanidine polyphenols from cinnamon bark in ovalbumin-induced airway hyperresponsiveness in laboratory animals. Biomed Aging Pathol 2013;3:23-30.  Back to cited text no. 15
Joffe M, Robertson A. The potential contribution of increased vegetable and fruit consumption to health gain in the European Union. Public Health Nutr 2001;4:893-901.  Back to cited text no. 16
Kandhare AD, Raygude KS, Ghosh P, Ghule AE, Bodhankar SL. Neuroprotective effect of naringin by modulation of endogenous biomarkers in streptozotocin induced painful diabetic neuropathy. Fitoterapia 2012;83:650-9.  Back to cited text no. 17
Kandhare AD, Raygude KS, Ghosh P, Ghule AE, Bodhankar SL. Therapeutic role of curcumin in prevention of biochemical and behavioral aberration induced by alcoholic neuropathy in laboratory animals. Neurosci Lett 2012;511:18-22.  Back to cited text no. 18
Raygude KS, Kandhare AD, Ghosh P, Bodhankar SL. Anticonvulsant effect of fisetin by modulation of endogenous biomarkers. Biomed Prev Nutr 2012;2:215-22.  Back to cited text no. 19
Kumar VS, Rajmane AR, Adil M, Kandhare AD, Ghosh P, Bodhankar SL. Naringin ameliorates acetic acid induced colitis through modulation of endogenous oxido-nitrosative balance and DNA damage in rats. J Biomed Res 2014;28:132-45.  Back to cited text no. 20
Bors W, Heller W, Michel C, Stettmaier K. Flavonoids and polyphenols: Chemistry and biology, in: Handbook of Antioxidants, E. Cadenas, L. Packer (eds). New York, Marcel Dekker, 1996, p. 409-466.  Back to cited text no. 21
Visnagri A, Kandhare AD, Chakravarty S, Ghosh P, Bodhankar SL. Hesperidin, a flavanoglycone attenuates experimental diabetic neuropathy via modulation of cellular and biochemical marker to improve nerve functions. Pharm Biol 2014;52:814-28.  Back to cited text no. 22
Pietta P, Simonetti P. Dietary flavonoids and interaction with endogenous antioxidants. IUBMB Life 1998;44:1069-74.  Back to cited text no. 23
Kandhare A, Raygude K, Ghosh P, Bodhankar S. The ameliorative effect of fisetin, a bioflavonoid, on ethanol-induced and pylorus ligation-induced gastric ulcer in rats. Int J Green Pharm 2011;5:236-43.  Back to cited text no. 24
  Medknow Journal  
Kandhare AD, Ghosh P, Ghule AE, Bodhankar SL. Elucidation of molecular mechanism involved in neuroprotective effect of Coenzyme Q10 in alcohol-induced neuropathic pain. Fundam Clin Pharmacol 2013;27:603-22.  Back to cited text no. 25
Kandhare AD, Raygude KS, Ghosh P, Ghule AE, Gosavi TP, Badole SL, et al. Effect of hydroalcoholic extract of Hibiscus rosa sinensis Linn. leaves in experimental colitis in rats. Asian Pac J Trop Biomed 2012;2:337-44.  Back to cited text no. 26
Patil MV, Kandhare AD, Bhise SD. Effect of aqueous extract of Cucumis sativus Linn. fruit in ulcerative colitis in laboratory animals. Asian Pac J Trop Biomed 2012;2:S962-9.  Back to cited text no. 27
Patil MV, Kandhare AD, Bhise SD. Pharmacological evaluation of ethanolic extract of Daucus carota Linn root formulated cream on wound healing using excision and incision wound model. Asian Pac J Trop Biomed 2012;2:S646-55.  Back to cited text no. 28
Patil MV, Kandhare AD, Ghosh P, Bhise SD. Determination of role of GABA and nitric oxide in anticonvulsant activity of Fragaria vesca L. ethanolic extract in chemically induced epilepsy in laboratory animals. Orient Pharm Exp Med 2012;12:255-64.  Back to cited text no. 29
Chen H, Ward MH, Graubard BI, Heineman EF, Markin RM, Potischman NA, et al. Dietary patterns and adenocarcinoma of the esophagus and distal stomach. Am J Clin Nutr 2002;75:137-44.  Back to cited text no. 30
Prior RL, Cao G. Antioxidant phytochemicals in fruits and vegetables: Diet and health implications. HortScience 2000;35:588-92.  Back to cited text no. 31
Haenen GR, Paquay JB, Korthouwer RE, Bast A. Peroxynitrite scavenging by flavonoids. Biochem Biophys Res Commun 1997;236:591-3.  Back to cited text no. 32
Ng TB, Liu F, Wang ZT. Antioxidative activity of natural products from plants. Life Sci 2000;66:709-23.  Back to cited text no. 33
Jeon SM, Park YB, Choi MS. Antihypercholesterolemic property of naringin alters plasma and tissue lipids, cholesterol-regulating enzymes, fecal sterol and tissue morphology in rabbits. Clin Nutr 2004;23:1025-34.  Back to cited text no. 34
Parmar NS. The gastric anti-ulcer activity of naringenin, a specific histidine decarboxylase inhibitor. Int J Tissue React 1983;5:415-20.  Back to cited text no. 35
Motilva V, Alarcón de la Lastra C, Martín MJ. Ulcer-protecting effects of naringenin on gastric lesions induced by ethanol in rat: Role of endogenous prostaglandins. J Pharm Pharmacol 1994;46:91-4.  Back to cited text no. 36
Reddy T, Nagaraju I, Kumar K, Lokanatha V, Reddy C, Jagetia G. Cardioprotective effect of naringin in mice treated with doxorubicin. Planta Med 2008;74:337-8.  Back to cited text no. 37
Rajadurai M, Stanely Mainzen Prince P. Preventive effect of naringin on cardiac markers, electrocardiographic patterns and lysosomal hydrolases in normal and isoproterenol-induced myocardial infarction in Wistar rats. Toxicology 2007;230:178-88.  Back to cited text no. 38
Singh D, Chander V, Chopra K. Protective effect of naringin, a bioflavonoid on glycerol-induced acute renal failure in rat kidney. Toxicology 2004;201:143-51.  Back to cited text no. 39
Singh D, Chopra K. The effect of naringin, a bioflavonoid on ischemia-reperfusion induced renal injury in rats. Pharmacol Res 2004;50:187-93.  Back to cited text no. 40
Sakat S, Wankhede S, Juvekar A, Mali V, Bodhankar S. Antihypertensive effect of aqueous extract of Elaeocarpus ganitrus Roxb. seeds in renal artery occluded hypertensive rats. Int J PharmTech Res 2009;1:779-82.  Back to cited text no. 41
Visnagri A, Kandhare AD, Ghosh P, Bodhankar SL. Endothelin receptor blocker bosentan inhibits hypertensive cardiac fibrosis in pressure overload-induced cardiac hypertrophy in rats. Cardiovasc Endocrinol 2013;2:85-97.  Back to cited text no. 42
Visnagri A, Kandhare AD, Shiva Kumar V, Rajmane AR, Mohammad A, Ghosh P, et al. Elucidation of ameliorative effect of Co-enzyme Q10 in streptozotocin-induced diabetic neuropathic perturbation by modulation of electrophysiological, biochemical and behavioral markers. Biomed Aging Pathol 2012;2:157-72.  Back to cited text no. 43
Mehta AN, Fenves A. Current opinions in renovascular hypertension. Proc (Bayl Univ Med Cent) 2010;23:246-9.  Back to cited text no. 44
Mejía-Vilet JM, Ramírez V, Cruz C, Uribe N, Gamba G, Bobadilla NA. Renal ischemia-reperfusion injury is prevented by the mineralocorticoid receptor blocker spironolactone. Am J Physiol Renal Physiol 2007;293:F78-86.  Back to cited text no. 45
Nakamura K, Kusano K, Nakamura Y, Kakishita M, Ohta K, Nagase S, et al. Carvedilol decreases elevated oxidative stress in human failing myocardium. Circulation 2002;105:2867-71.  Back to cited text no. 46
Farquharson CA, Butler R, Hill A, Belch JJ, Struthers AD. Allopurinol improves endothelial dysfunction in chronic heart failure. Circulation 2002;106:221-6.  Back to cited text no. 47
Kandhare AD, Ghosh P, Ghule AE, Zambare GN, Bodhankar SL. Protective effect ofPhyllanthus amarusby modulation of endogenous biomarkers and DNA damage in acetic acid induced ulcerative colitis: Role of phyllanthin and hypophyllanthin. Apollo Med 2013;10:87-97.  Back to cited text no. 48
Kandhare AD, Kumar VS, Adil M, Rajmane AR, Ghosh P, Bodhankar SL. Investigation of gastro protective activity of Xanthium strumarium L. by modulation of cellular and biochemical marker. Orient Pharm Exp Med 2012;12:287-99.  Back to cited text no. 49
Ajis A, Bagnall NM, Collis MG, Johns EJ. Effect of endothelin antagonists on the renal haemodynamic and tubular responses to ischaemia-reperfusion injury in anaesthetised rats. Exp Physiol 2003;88:483-90.  Back to cited text no. 50
Bonventre JV, Weinberg JM. Recent advances in the pathophysiology of ischemic acute renal failure. J Am Soc Nephrol 2003;14:2199-210.  Back to cited text no. 51
Rathore N, John S, Kale M, Bhatnagar D. Lipid peroxidation and antioxidant enzymes in isoproterenol induced oxidative stress in rat tissues. Pharmacol Res 1998;38:297-303.  Back to cited text no. 52
Srivastava S, Chandrasekar B, Gu Y, Luo J, Hamid T, Hill BG, et al. Downregulation of CuZn-superoxide dismutase contributes to beta-adrenergic receptor-mediated oxidative stress in the heart. Cardiovasc Res 2007;74:445-55.  Back to cited text no. 53
Raygude KS, Kandhare AD, Ghosh P, Ghule AE, Bodhankar SL. Evaluation of ameliorative effect of quercetin in experimental model of alcoholic neuropathy in rats. Inflammopharmacology 2012;20:331-41.  Back to cited text no. 54
Hemnani T, Parihar MS. Reactive oxygen species and oxidative DNA damage. Indian J Physiol Pharmacol 1998;42:440-52.  Back to cited text no. 55
Kandhare AD, Raygude KS, Shiva Kumar V, Rajmane AR, Visnagri A, Ghule AE, et al. Ameliorative effects quercetin against impaired motor nerve function, inflammatory mediators and apoptosis in neonatal streptozotocin-induced diabetic neuropathy in rats. Biomed Aging Pathol 2012;2:173-86.  Back to cited text no. 56
Mizuno S, Nakamura T. Prevention of neutrophil extravasation by hepatocyte growth factor leads to attenuations of tubular apoptosis and renal dysfunction in mouse ischemic kidneys. Am J Pathol 2005;166:1895-905.  Back to cited text no. 57
Jeon SM, Bok SH, Jang MK, Lee MK, Nam KT, Park YB, et al. Antioxidative activity of naringin and lovastatin in high cholesterol-fed rabbits. Life Sci 2001;69:2855-66.  Back to cited text no. 58


  [Figure 1], [Figure 2]

  [Table 1], [Table 2], [Table 3]

This article has been cited by
1 A systematic review and meta-analysis on the cardio-protective activity of naringin based on pre-clinical evidences
Gollapalle Lakshminarayanashastry Viswanatha, Hanumanthappa Shylaja, Raghuvir Keni, Krishnadas Nandakumar, Subbanna Rajesh
Phytotherapy Research. 2022;
[Pubmed] | [DOI]
2 Ameliorative mechanisms of turmeric-extracted curcumin on arsenic (As)-induced biochemical alterations, oxidative damage, and impaired organ functions in rats
Anam Ishaq, Huma Gulzar, Ali Hassan, Muhammad Kamran, Muhammad Riaz, Aasma Parveen, Muhammad Sohaib Chattha, Noman Walayat, Sana Fatima, Sobia Afzal, Shah Fahad
Environmental Science and Pollution Research. 2021;
[Pubmed] | [DOI]
3 Emerging Renoprotective Role of Citrus Flavonoid Naringin: Current Pharmaceutical Status and Future Perspectives
Nirmala Sehrawat, Sushil Kumar Upadhyay, Anil Kumar Sharma, Sunil Kumar, Mukesh Yadav
Current Pharmacology Reports. 2021; 7(3): 96
[Pubmed] | [DOI]
4 Nephroprotective effect of naringin in methotrexate induced renal toxicity in male rats
Hany Elsawy, Abdullah M. Alzahrani, Manal Alfwuaires, Ashraf M. Abdel-Moneim, Mahmoud Khalil
Biomedicine & Pharmacotherapy. 2021; 143: 112180
[Pubmed] | [DOI]
5 The antihypertensive potential of flavonoids from Chinese Herbal Medicine: A review
Yi Cao, Long Xie, Kai Liu, Youdan Liang, Xiaolin Dai, Xian Wang, Jing Lu, Xumin Zhang, Xiaofang Li
Pharmacological Research. 2021; 174: 105919
[Pubmed] | [DOI]
6 Vitexin, a fenugreek glycoside, ameliorated obesity-induced diabetic nephropathy via modulation of NF-?B/IkBa and AMPK/ACC pathways in mice
Guangju Zhou, Jiale Cui, Suhua Xie, Haiyan Wan, Yan Luo, Gang Guo
Bioscience, Biotechnology, and Biochemistry. 2021; 85(5): 1183
[Pubmed] | [DOI]
7 The renoprotective effects of naringin and trimetazidine on renal ischemia/reperfusion injury in rats through inhibition of apoptosis and downregulation of micoRNA-10a
Negin Amini, Alireza Sarkaki, Mahin Dianat, Seyyed Ali Mard, Akram Ahangarpour, Mohammad Badavi
Biomedicine & Pharmacotherapy. 2019; 112: 108568
[Pubmed] | [DOI]
8 Elucidation of protective efficacy of Pentahydroxy flavone isolated from Madhuca indica against arsenite-induced cardiomyopathy: Role of Nrf-2, PPAR-?, c-fos and c-jun
Anwesha A. Mukherjee,Amit D. Kandhare,Subhash L. Bodhankar
Environmental Toxicology and Pharmacology. 2017; 56: 172
[Pubmed] | [DOI]
9 Anti-inflammatory and antioxidant potential of Guaianolide isolated from Cyathocline purpurea : Role of COX-2 inhibition
Urmila U. Tambewagh,Amit D. Kandhare,Varsha S. Honmore,Parag P. Kadam,Vijay M. Khedkar,Subhash L. Bodhankar,Supada R. Rojatkar
International Immunopharmacology. 2017; 52: 110
[Pubmed] | [DOI]
10 Naringin prevents the inhibition of intestinal Ca 2+ absorption induced by a fructose rich diet
V. Rodríguez,M. Rivoira,S. Guizzardi,N. Tolosa de Talamoni
Archives of Biochemistry and Biophysics. 2017; 636: 1
[Pubmed] | [DOI]


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

  In this article
    Materials and Me...
    Article Figures
    Article Tables

 Article Access Statistics
    PDF Downloaded122    
    Comments [Add]    
    Cited by others 10    

Recommend this journal