|
 |
| RESEARCH ARTICLE |
|
|
|
| Year : 2012 | Volume
: 44
| Issue : 3 | Page : 382-386 |
| |
Citrus flavonoid naringenin improves aortic reactivity in streptozotocin-diabetic rats
Faramarz Fallahi1, Mehrdad Roghani2, Sanaz Moghadami3
1 Department of Cardiology and Internal Medicine, School of Medicine and Neurophysiology Research Center, Tehran, Iran
2 Department of Physiology, School of Medicine and Neurophysiology Research Center, Tehran, Iran
3 School of Medicine, Shahed University, Tehran, Iran
| Date of Submission | 12-Aug-2011 |
| Date of Decision | 11-Jan-2012 |
| Date of Acceptance | 28-Feb-2012 |
| Date of Web Publication | 17-May-2012 |
Correspondence Address:
Mehrdad Roghani
Department of Physiology, School of Medicine and Neurophysiology Research Center, Tehran
Iran
 Source of Support: Financially supported by Shahed University (Tehran) in 2009, Conflict of Interest: None  | Check |
DOI: 10.4103/0253-7613.96350
Background and Objective: Cardiovascular disorders continue to constitute major causes of morbidity and mortality in diabetic patients. In this study, the effect of chronic administration of naringenin was investigated on aortic reactivity of streptozotocin (STZ)-induced diabetic rats.
Materials and Methods: Male diabetic rats (n=32) were divided into control, naringenin-treated control, diabetic, and naringenin-treated diabetic groups of eight animals each. The latter group received naringenin for 5 weeks at a dose of 10 mg/kg/day after diabetes induction. The contractile responses to potassium chloride (KCl) and phenylephrine (PE) and relaxation response to acetylcholine (ACh) were obtained from aortic rings. Meanwhile, participation of nitric oxide (NO) and endothelial vasodilator factors in response to ACh were evaluated using N (G)-nitro-l-arginine methyl ester (L-NAME) and indomethacin (INDO), respectively.
Results: Maximum contractile response of endothelium-intact rings to KCl and PE was significantly (P<0.05) lower in naringenin-treated diabetic rats as compared to untreated diabetics. Endothelium-dependent relaxation to ACh was significantly (P<0.05-0.01) higher in naringenin-treated diabetic rats as compared to diabetic ones and pretreatment of rings with nitric oxide synthase inhibitor N (G)-nitro-l-arginine methyl ester (L-NAME) significantly (P<0.001) attenuated the observed response.
Conclusion: Chronic treatment of diabetic rats with naringenin could prevent some abnormal changes in vascular reactivity in diabetic rats through nitric oxide and endothelium integrity is necessary for this beneficial effect.
Keywords: Aorta, diabetes mellitus, naringenin, streptozotocin
How to cite this article:
Fallahi F, Roghani M, Moghadami S. Citrus flavonoid naringenin improves aortic reactivity in streptozotocin-diabetic rats. Indian J Pharmacol 2012;44:382-6 |
How to cite this URL:
Fallahi F, Roghani M, Moghadami S. Citrus flavonoid naringenin improves aortic reactivity in streptozotocin-diabetic rats. Indian J Pharmacol [serial online] 2012 [cited 2023 Oct 4];44:382-6. Available from: https://www.ijp-online.com/text.asp?2012/44/3/382/96350 |
| » Introduction | |  |
Cardiovascular disorders continue to constitute major causes of morbidity and mortality in diabetic patients in spite of significant achievements in their diagnosis and treatment. [1] Changes in vascular responsiveness to vasoconstrictors and vasodilators are mainly responsible for development of some vascular complications of diabetics. [2] Most of these complications are due to increased serum glucose and augmented generation of reactive oxygen species that lead to endothelium dysfunction. [3]
Epidemiological findings show that there exists a relationship between health maintenance and the consumption of foods rich in phenolic flavonoids. [4] Naringenin is one such naturally occurring flavanone that is mainly present in citrus fruits. [5] Naringenin treatment could prevent inflammation, [6] thrombosis, [4] tumorigenesis, [7] atherosclerosis and hypercholesterolemia. [8] Recent studies have also shown that naringenin elicits antidiabetic effect by suppressing carbohydrate absorption from the intestine, thereby reducing the postprandial increase in blood glucose levels. [9] Further, naringenin prevents hepatic steatosis and improves insulin sensitivity in animals fed a high fat diet. [8] Naringenin also induces concentration-dependent relaxation in aortic tissue from normal rats. [10] The vasorelaxant, antioxidant and cyclic nucleotide phosphodiesterase (PDE) inhibitory effects of naringenin have also been reported in aortic tissue. [11] Until now, vasorelaxant property of naringenin in an in vivo system and its mechanisms for live protective effect on the vascular system in diabetes have not been reported. Therefore, this study was designed to assess the beneficial effect of chronic naringenin treatment on improvement of aortic reactivity dysfunction of STZ-diabetic rats and to investigate some underlying mechanisms.
| » Materials and Methods | | |
Animals
Male albino Wistar rats (Pasteur's institute, Tehran, Iran) weighing 210-280 g were housed in an air-conditioned room at 21 ± 2°C, supplied with standard pellet diet and tap water ad libitum. Procedures involving animals and their care were conducted in conformity with NIH guidelines. The experiment protocol was approved by Ethics Committee of Shahed University (Tehran, Iran).
Experimental Protocol
Male diabetic rats (n=32) were divided into control, naringenin-treated control, diabetic, and naringenin-treated diabetic groups. The rats were rendered diabetic by a single intraperitoneal dose of 60 mg kg -1 streptozotocin (STZ) freshly dissolved in ice-cold 0.1 M citrate buffer (pH 4.5). Age-matched normal rats received an equivalent volume of buffer comprised a non-diabetic control group. One week after STZ injection, overnight fasting blood samples were collected and serum glucose concentrations were measured using glucose oxidation method (Zistchimie, Tehran). Only those animals with a serum glucose level higher than 250 mg/dl were selected as diabetic. During the next week, diabetes was reconfirmed by the presence of polyphagia, polydipsia, polyuria, and weight loss. Normal and diabetic rats were divided into four groups of (eight in each): Normal vehicle-treated control, naringenin-treated control, diabetic, and naringenin-treated diabetic. Naringenin was daily administered i.p. at a dose of 10 mg/kg b.w. dissolved in cremophor for five weeks. Dose of naringenin was chosen according to our pilot study and earlier reports. [12] Body weight were regularly recorded before STZ injection and at 3 rd and 6 th weeks after the study.
After 6 weeks, the rats were anesthetized with diethyl ether, decapitated. The abdomen was opened, descending thoracic aorta was carefully excised and placed in a Petri dish More Details filled with cold Krebs solution. The aorta was cleaned of excess connective tissue and fat, and cut into rings of approximately 4 mm in length. Aortic rings were suspended between the bases of two triangular-shaped wires. One wire was attached to a fixed tissue support in a 50 ml isolated tissue bath containing Krebs solution (pH 7.4) maintained at 37°C and continuously aerated with a mixture of 5% CO 2 and 95% O 2 . The other end of each wire attached by a cotton thread to a F60 isometric force transducer (Narco Biosystems, USA) connected to a computer. Care was taken to avoid damaging the luminal surface of endothelium. Aortic rings were allowed to equilibrate at a resting tension of 1.5 g for at least 45 min. In some experiments, the endothelium was mechanically removed by gently rubbing the internal surface with a filter paper. Isometric contractions were induced by the addition of phenylephrine (PE, 1 μM) and once the contraction was stabilized, acetylcholine (ACh) was added to the bath to attain a concentration of 1 μM in order to assess the endothelial integrity of the preparations. Endothelium was considered to be intact when ACh elicited a vasorelaxation ≥50% of the maximal contraction obtained in vascular rings precontracted with phenylephrine (PE). The absence of acetylcholine relaxant action in the vessels indicated the total removal of endothelial cells. After assessing the integrity of the endothelium, vascular tissues were allowed to recuperate for at least 30 min.
At the end of the equilibration period, dose-response curves with KCl (10-50 mM) and PE (10 -9 -10 -5 M) in the presence and absence of endothelium were obtained in aortic rings in a cumulative manner. To evaluate ACh (10 -9 -10 -4 M)-induced vasodilatation in rings with endothelium, they were preconstricted with a submaximal concentration of PE (10 -6 M) which produced 70-80% of maximal response. The sensitivity to the agonists was evaluated as pD2, which is the negative logarithm of the concentration of the drug required to produce 50% of the maximum response.
To determine the participation of nitric oxide (NO), rings were incubated 30 min before the experiment with N (G)-nitro-l-arginine methyl ester (L-NAME) (100 μM, a non-selective NOS inhibitor). To determine the participation of endothelial vasodilator factors in response to ACh, segments were incubated with indomethacin (INDO) (10 μM, an inhibitor of cyclooxygenase-derived prostanoid synthesis) 30min before the experiment with ACh.
After each vasoreactivity experiment, aortic rings were blotted, weighed, and the cross-sectional area (csa) was calculated using the following formula: Cross-sectional area (mm 2 ) = weight (mg) × [length (mm) × density (mg mm 3 -1)] -1 . The density of the preparation was regarded as 1.05 mg/mm 2 .
Drugs
Phenylephrine, naringenin, cremophor, STZ, ACh, INDO, and L-NAME were purchased from Sigma Chemical (St. Louis, MO, USA). All other chemicals were purchased from Merck (Germany) and Darupakhsh Co (Iran). Indomethacin solution was prepared in ethanol concentration less than 0.001% (v/v).
Data and Statistical Analysis
All values were given as means ± SEM. Contractile response to PE was expressed as grams of tension per cross-sectional area of tissue. Relaxation response for ACh was expressed as a percentage decrease of the maximum contractile response induced by PE. Statistical analysis was carried out using repeated measure ANOVA and one-way ANOVA followed by Tukey post hoc test. P<0.05 was considered statistically significant.
| » Results | | |
Body Weight
Body weight of the diabetic group was significantly lower versus control group at sixth week after the study (P<0.05) and naringenin-treated diabetic group had a significantly higher body weight as compared to diabetic group (P<0.05) [Figure 1]. | Figure 1: Comparison of body weight and serum glucose level in diabetic rats treated with naringenin (means ± S.E.M) (n=8). *P<0.05, **P<0.01, ***P<0.005, ****P<0.0005 (as compared to week 0 in the same group) $ P<0.05, $$ P<0.01, P<0.005 (vs. Diabetic in the same week).
Click here to view |
Serum Glucose Level
Diabetic group had a significantly higher serum glucose level relative to control group at 3 rd and 6 th weeks after the study (P<0.0005) and treatment of diabetic group with naringenin significantly lowered serum glucose level relative to diabetic group at the same weeks (P<0.01) and 6 (P<0.005), respectively. In addition, naringenin treatment of control rats did not lead to any significant change in this respect [Figure 1].
Vascular Reactivity
Cumulative addition of KCl (10-50 mM) and PE (10 -9 -10 -5 M) resulted in concentration dependent contractions in aortas of all groups [Figure 2]. The maximum contractile responses to KCl and PE in the aorta from vehicle-treated diabetic rats in the presence of endothelium were found to be significantly (P<0.01) greater than vehicle-treated control rats and concentration-response curve of endothelium-intact aortas from naringenin-treated diabetic rats to KCl and PE was significantly attenuated compared to vehicle-treated diabetics (P<0.05). In addition, aortic rings with endothelium from naringenin-treated control group showed a non-significant reduction in contractile response to KCl and a significant reduction in contractile response to PE (P<0.05) as compared to vehicle-treated controls. There were also no significant differences among the groups in terms of the pD2 (data not shown), indicating that there has not been any significant change in the sensitivity of aortic rings from different groups. | Figure 2: Cumulative concentration-response curves for KCl (a) and phenylephrine (PE) (b) in aortic preparations 6 weeks after experiment (means ± S.E.M). *P<0.05, **P<0.01 (As compared to control), # P<0.05 (as compared to diabetic), $ P<0.05 (as compared to control).
Click here to view |
Addition of ACh resulted in concentration-dependent relaxations in all aortic rings precontracted with PE [Figure 3]. Endothelium-dependent relaxation responses induced by ACh was significantly lower in vehicle-treated diabetic rats in relation to vehicle-treated controls (P<0.05-0.005). The existing difference between naringenin-treated and vehicle-treated diabetic rats was only significant (P<0.05-0.01) at concentrations higher than 10 -6 M. Relaxation response of naringenin-treated control rats was significantly greater than control group at concentrations higher than 10 -5 M (P<0.05). | Figure 3: Cumulative concentration-response curves for ACh in aortic rings precontracted with PE. *P<0.05, **P<0.01 (as compared to diabetic), $ P<0.05 (as compared to control).
Click here to view |
Regarding relaxation response to ACh, pre-incubation of aortic rings with L-NAME almost completely abolished the vasodilator response to ACh in segments from naringenin-treated control and diabetic rats, indicating the important role of endothelium-derived nitric oxide (NO) in the vascular effect of naringenin [Figure 4]. Preincubation of aortic segments from naringenin-treated diabetic rats with INDO non-significantly diminished the endothelial vasodilator response to ACh [Figure 5]. | Figure 4: Maximum relaxation response for ACh in aortic rings precontracted with phenylephrine in the presence and absence of L-NAME. *P<0.05, **P<0.01, ***P<0.005 (vs. control), # P<0.05, ## P<0.01 (vs. diabetic), $ P<0.05 (vs. diabetic + L-NAME).
Click here to view |
 | Figure 5: Maximum relaxation response for ACh in aortic rings precontracted with phenylephrine in the presence and absence of indomethacin. *P<0.05 (vs. control), # P<0.05 (vs. diabetic).
Click here to view |
| » Discussion | | |
In this study, chronic administration of naringenin had a moderate and significant hypoglycemic effect, it reduced the enhanced contractility of aortic rings to KCl and PE and increased ACh-induced relaxation which was partly due to involvement of NO pathway since the relaxation was blocked in the presence of L-NAME. In the presence of INDO, relaxation response to ACh was non-significantly attenuated.
Vascular dysfunction is one of the complicating features of diabetes in humans and its experimental model and hyperglycemia is the primary cause of micro and macrovascular complications in diabetic condition. [13] Compared to the aortic rings from control animals, contraction of aortas to KCl and PE from diabetic rats significantly increased in our study that was consistent with some previous studies. [14] Impaired endothelial function, [15] enhanced sensitivity of calcium channels, [16] an increase in vasoconstrictor prostanoids due to increased superoxide anions and increased sensitivity to adrenergic agonists [17] might all be responsible for increased contractile responses in diabetic rats, which could have been improved following naringenin treatment. In endothelial cells of most vascular beds, ACh could stimulate production and release of endothelial-derived relaxing factors including NO, prostacyclin and endothelium-derived hyperpolarizing factor and in this way leads to relaxation of vascular smooth muscle in an endothelium-dependent manner. [18],[19],[20] The ACh-induced relaxation response is endothelium-dependent and NO-mediated. [14]
The present work reveals that the endothelium-dependent relaxant response reduced in aorta from STZ-induced diabetic rats. Although some researchers asserted that the sensitivity to ACH decreases in diabetes, [17] the results of this research, in accordance with those of many previous ones [21] reveals that diabetes in long-term only decrease the maximum responses to ACh but not the sensitivity (pD2). Impaired endothelium-dependent relaxation in STZ-induced diabetic rat might be due to increased blood glucose level and decreased blood insulin level. It has been shown that hyperglycemia causes tissue damage with several mechanisms, including advanced glycation end product (AGE) formation, increased polyol pathway flux, apoptosis and reactive oxygen species formation. [22]
Our results showed that naringenin treatment could exert a clear and significant hypoglycemic effect in STZ-induced diabetic rats. Therefore, its beneficial effect on aortic tissue of diabetic rats may be in part due to its hypoglycemic effect. In addition, the effect on vascular tissue of diabetic animals is believed to be due to enhanced oxidative stress, as shown by enhanced malondialdehyde (MDA) and decreased activity of defensive enzymes like superoxide dismutase. [23] This could lead to diabetes-induced functional changes in vascular endothelial cells and the development of altered endothelium-dependent vasoreactivity. In the present study, chronic treatment of naringenin may have decreased MDA content and enhanced SOD activity in aortic tissue from diabetic rats, indicating that the improvement in vascular responsiveness from naringenin may be partly due to ameliorating lipid peroxidation and oxidative injury. The latter mechanism warrants further investigation in future studies. In this study, part of vascular beneficial effect of naringenin has been through NO-mediated pathway, because L-NAME pretreatment blocked its effect. In this respect, naringenin could have upregulated the expression of eNOS, indicating the ability of this flavonoid to induce NO synthesis. In support of these ideas, it has been reported that naringenin could reduce oxidative damage and increase NO bioavailability in some metabolic disorders. [24]
In conclusion, in vivo chronic treatment of diabetic rats with naringenin could prevent the functional changes in vascular reactivity in diabetic rats through nitric oxide- and not prostaglandin-dependent pathway. Our data may be helpful in the development of new natural drugs to improve endothelial function and prevent cardiovascular diseases.
| » Acknowledgment | | |
The results of this study was obtained from MD thesis project, approved and financially supported by Shahed University (Tehran) in 2009. Authors would also like to appreciate Miss Fariba Ansari for her great technical assistance.
| » References | | |
| 1. | Coccheri S. Approaches to prevention of cardiovascular complications and events in diabetes mellitus. Drugs 2007;67:997-1026. 
[PUBMED] [FULLTEXT] |
| 2. | Nasri S, Roghani M, Baluchnejadmojarad T, Rabani T, Balvardi M. Vascular mechanisms of cyanidin-3-glucoside response in streptozotocin-diabetic rats. Pathophysiology 2011;18:273-8.
[PUBMED] [FULLTEXT] |
| 3. | Naito M, Fujikura J, Ebihara K, Miyanaga F, Yokoi H, Kusakabe T, et al. Therapeutic impact of leptin on diabetes, diabetic complications, and longevity in insulin-deficient diabetic mice. Diabetes 2011;60:2265-73.
[PUBMED] [FULLTEXT] |
| 4. | Stoclet JC, Schini-Kerth V. Dietary flavonoids and human health. Ann Pharm Fr 2011;69:78-90.
[PUBMED] [FULLTEXT] |
| 5. | Cavia-Saiz M, Busto MD, Pilar-Izquierdo MC, Ortega N, Perez-Mateos M, Muniz P. Antioxidant properties, radical scavenging activity and biomolecule protection capacity of flavonoid naringenin and its glycoside naringin: A comparative study. J Sci Food Agric 2010;90:1238-44.
|
| 6. | Shi Y, Dai J, Liu H, Li RR, Sun PL, Du Q, et al. Naringenin inhibits allergen-induced airway inflammation and airway responsiveness and inhibits NF-kappaB activity in a murine model of asthma. Can J Physiol Pharmacol 2009;87:729-35.
[PUBMED] [FULLTEXT] |
| 7. | Qin L, Jin L, Lu L, Lu X, Zhang C, Zhang F, et al. Naringenin reduces lung metastasis in a breast cancer resection model. Protein Cell 2011;2:507-16.
[PUBMED] [FULLTEXT] |
| 8. | Mulvihill EE, Assini JM, Sutherland BG, DiMattia AS, Khami M, Koppes JB, et al. Naringenin decreases progression of atherosclerosis by improving dyslipidemia in high-fat-fed low-density lipoprotein receptor-null mice. Arterioscler Thromb Vasc Biol 2010;30:742-8.
[PUBMED] [FULLTEXT] |
| 9. | Ortiz-Andrade RR, Sanchez-Salgado JC, Navarrete-Vazquez G, Webster SP, Binnie M, Garcia-Jimenez S, et al. Antidiabetic and toxicological evaluations of naringenin in normoglycaemic and NIDDM rat models and its implications on extra-pancreatic glucose regulation. Diabetes Obes Metab 2008;10:1097-104.
|
| 10. | Saponara S, Testai L, Iozzi D, Martinotti E, Martelli A, Chericoni S, et al. (+/-)-Naringenin as large conductance Ca (2+)-activated K+ (BKCa) channel opener in vascular smooth muscle cells. Br J Pharmacol 2006;149:1013-21.
[PUBMED] |
| 11. | Orallo F, Camina M, Alvarez E, Basaran H, Lugnier C. Implication of cyclic nucleotide phosphodiesterase inhibition in the vasorelaxant activity of the citrus-fruits flavonoid (+/-)-naringenin. Planta Med 2005;71:99-107.
|
| 12. | Badary OA, Abdel-Maksoud S, Ahmed WA, Owieda GH. Naringenin attenuates cisplatin nephrotoxicity in rats. Life Sci 2005;76:2125-35.
[PUBMED] [FULLTEXT] |
| 13. | Madonna R, De Caterina R. Cellular and molecular mechanisms of vascular injury in diabetes-part I: Pathways of vascular disease in diabetes. Vascul Pharmacol 2011;54:68-74.
[PUBMED] [FULLTEXT] |
| 14. | Roghani M, Baluchnejadmojarad T. Chronic epigallocatechin-gallate improves aortic reactivity of diabetic rats: Underlying mechanisms. Vascul Pharmacol 2009;51:84-9.
[PUBMED] [FULLTEXT] |
| 15. | Olukman M, Sezer ED, Ulker S, Sozmen EY, Cinar GM. Fenofibrate treatment enhances antioxidant status and attenuates endothelial dysfunction in streptozotocin-induced diabetic rats. Exp Diabetes Res 2010;2010:828531.
|
| 16. | Chang KC, Chung SY, Chong WS, Suh JS, Kim SH, Noh HK, et al. Possible superoxide radical-induced alteration of vascular reactivity in aortas from streptozotocin-treated rats. J Pharmacol Exp Ther 1993;266:992-1000.
[PUBMED] |
| 17. | Abebe W. Effects of taurine on the reactivity of aortas from diabetic rats. Life Sci 2008;82:279-89.
[PUBMED] [FULLTEXT] |
| 18. | Zhang LN, Vincelette J, Chen D, Gless RD, Anandan SK, Rubanyi GM, et al. Inhibition of soluble epoxide hydrolase attenuates endothelial dysfunction in animal models of diabetes, obesity and hypertension. Eur J Pharmacol 2011;654:68-74.
[PUBMED] [FULLTEXT] |
| 19. | Flammer AJ, Luscher TF. Human endothelial dysfunction: EDRFs. Pflugers Arch 2010;459:1005-13.
|
| 20. | Takaki A, Morikawa K, Murayama Y, Yamagishi H, Hosoya M, Ohashi J, et al. Roles of endothelial oxidases in endothelium-derived hyperpolarizing factor responses in mice. J Cardiovasc Pharmacol 2008;52:510-7.
[PUBMED] [FULLTEXT] |
| 21. | Silan C. The effects of chronic resveratrol treatment on vascular responsiveness of streptozotocin-induced diabetic rats. Biol Pharm Bull 2008;31:897-902.
[PUBMED] [FULLTEXT] |
| 22. | Hartge MM, Unger T, Kintscher U. The endothelium and vascular inflammation in diabetes. Diab Vasc Dis Res 2007;4:84-8.
[PUBMED] [FULLTEXT] |
| 23. | Baluchnejadmojarad T, Roghani M. Chronic administration of genistein improves aortic reactivity of streptozotocin-diabetic rats: Mode of action. Vascul Pharmacol 2008;49:1-5.
[PUBMED] [FULLTEXT] |
| 24. | Kannappan S, Palanisamy N, Anuradha CV. Suppression of hepatic oxidative events and regulation of eNOS expression in the liver by naringenin in fructose-administered rats. Eur J Pharmacol 2010;645:177-84.
[PUBMED] [FULLTEXT] |
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
| This article has been cited by | | 1 |
Naringin and naringenin counteract taxol-induced liver injury in Wistar rats via suppression of oxidative stress, apoptosis and inflammation |
|
| Shimaa S. Khaled, Hanan A. Soliman, Mohammed Abdel-Gabbar, Noha A. Ahmed, El-Shaymaa El-Nahass, Osama M. Ahmed | | Environmental Science and Pollution Research. 2023; | | [Pubmed] | [DOI] | | | 2 |
Effect of Citrus Flavanones on Diabetes: A Systematic Review |
|
| Sameen Azhar, Ribka Sabahat, Rameen Sajjad, Fatima Nadeem, Aruba Amjad, Nawal Hafeez, Taram Nayab, Saba Wahid, Afifa Tanweer | | Current Diabetes Reviews. 2023; 19(5) | | [Pubmed] | [DOI] | | | 3 |
The Potential Role of Naringin and Naringenin as Nutraceuticals Against
Metabolic Syndrome |
|
| Luca Massaro, Anna Raguzzini, Paola Aiello, Débora Villaño Valencia | | Endocrine, Metabolic & Immune Disorders - Drug Targets. 2023; 23(4): 428 | | [Pubmed] | [DOI] | | | 4 |
Effects of Gold Nanoparticles Functionalized with Cornus mas L. Fruit Extract on the Aorta Wall in Rats with a High-Fat Diet and Experimental-Induced Diabetes Mellitus—An Imaging Study |
|
| Remus Moldovan, Daniela-Rodica Mitrea, Adrian Florea, Luminita David, Laura Elena Muresan, Irina Camelia Chis, Soimi?a Mihaela Suciu, Bianca Elena Moldovan, Manuela Lenghel, Liviu Bogdan Chiriac, Irina Ielciu, Daniela Hanganu, Timea Bab, Simona Clichici | | Nanomaterials. 2023; 13(6): 1101 | | [Pubmed] | [DOI] | | | 5 |
Heat Shock Protein 70 Mediates the Protective Effect of Naringenin on High-Glucose-Induced Alterations of Endothelial Function |
|
| Zhihan Zhang, Hui Liu, Xiang Hu, Yikang He, Lu Li, Xinyu Yang, Changhua Wang, Mingbai Hu, Shengxiang Tao, Vikas Kumar Roy | | International Journal of Endocrinology. 2022; 2022: 1 | | [Pubmed] | [DOI] | | | 6 |
The Preventive Effects of Naringin and Naringenin against Paclitaxel-Induced Nephrotoxicity and Cardiotoxicity in Male Wistar Rats |
|
| Shimaa S. Khaled, Hanan A. Soliman, Mohammed Abdel-Gabbar, Noha A. Ahmed, Kandil Abdel Hai Ali Attia, Hesham A. Mahran, El-Shaymaa El-Nahass, Osama M. Ahmed, Mohammed El-Magd | | Evidence-Based Complementary and Alternative Medicine. 2022; 2022: 1 | | [Pubmed] | [DOI] | | | 7 |
New Perspectives in the Pharmacological Potential of Naringin in Medicine |
|
| María Angélica Rivoira, Valeria Rodriguez, Germán Talamoni, Nori Tolosa de Talamoni | | Current Medicinal Chemistry. 2021; 28(10): 1987 | | [Pubmed] | [DOI] | | | 8 |
An Up-to-Date Review on Citrus Flavonoids: Chemistry and Benefits in Health and Diseases |
|
| Osama M. Ahmed, Sameh F. AbouZid, Noha A. Ahmed, Mohamed Y. Zaky, Han Liu | | Current Pharmaceutical Design. 2021; 27(4): 513 | | [Pubmed] | [DOI] | | | 9 |
A review of the lipolytic effects and the reduction of abdominal fat from bioactive compounds and moro orange extracts |
|
| Lucas Pinheiro de Lima, Antony de Paula Barbosa | | Heliyon. 2021; 7(8): e07695 | | [Pubmed] | [DOI] | | | 10 |
Melatonin reverses cognitive deficits in streptozotocin-induced type 1 diabetes in the rat through attenuation of oxidative stress and inflammation |
|
| Ala Albazal, Alireza-Azizzadeh Delshad, Mehrdad Roghani | | Journal of Chemical Neuroanatomy. 2021; 112: 101902 | | [Pubmed] | [DOI] | | | 11 |
Relaxation effect of narirutin on rat mesenteric arteries via nitric oxide release and activation of voltage-gated potassium channels |
|
| Emily Sze-Wan Wong, Rachel Wai-Sum Li, Jingjing Li, Renkai Li, Sai-Wang Seto, Simon Ming-Yuen Lee, George Pak-Heng Leung | | European Journal of Pharmacology. 2021; 905: 174190 | | [Pubmed] | [DOI] | | | 12 |
Medicinal plants and bioactive natural products as inhibitors of
NLRP3
inflammasome
|
|
| Mohammad Bagherniya, Hamed Khedmatgozar, Omid Fakheran, Suowen Xu, Thomas P. Johnston, Amirhossein Sahebkar | | Phytotherapy Research. 2021; 35(9): 4804 | | [Pubmed] | [DOI] | | | 13 |
Structure – Activity Relationship and Therapeutic Benefits of Flavonoids in the Management of Diabetes and Associated Disorders |
|
| Santram Lodhi, Mohan Lal Kori | | Pharmaceutical Chemistry Journal. 2021; 54(11): 1106 | | [Pubmed] | [DOI] | | | 14 |
Fetal Hypothyroidism Impairs Aortic Vasorelaxation Responses in Adulthood: Involvement of Hydrogen Sulfide and Nitric Oxide Cross talk |
|
| Davood Nourabadi, Tourandokht Baluchnejadmojarad, Seyed M. M. Zarch, Samira Ramazi, Morteza N. Serenjeh, Mehrdad Roghani | | Journal of Cardiovascular Pharmacology. 2021; 77(2): 238 | | [Pubmed] | [DOI] | | | 15 |
Citrus Flavonoids as Promising Phytochemicals Targeting Diabetes and Related Complications: A Systematic Review of In Vitro and In Vivo Studies |
|
| Gopalsamy Rajiv Gandhi, Alan Bruno Silva Vasconcelos, Ding-Tao Wu, Hua-Bin Li, Poovathumkal James Antony, Hang Li, Fang Geng, Ricardo Queiroz Gurgel, Narendra Narain, Ren-You Gan | | Nutrients. 2020; 12(10): 2907 | | [Pubmed] | [DOI] | | | 16 |
Molecules Isolated from Mexican Hypoglycemic Plants: A Review |
|
| Sonia Marlen Escandón-Rivera, Rachel Mata, Adolfo Andrade-Cetto | | Molecules. 2020; 25(18): 4145 | | [Pubmed] | [DOI] | | | 17 |
Virulence Genes Analysis of Vibrio parahaemolyticus and Anti-vibrio Activity of the Citrus Extracts |
|
| Chatchawan Singhapol, Sirikhwan Tinrat | | Current Microbiology. 2020; 77(8): 1390 | | [Pubmed] | [DOI] | | | 18 |
Improving Rooster Sperm Quality by Adding Different Levels of Naringenin after Freezing-Thawing Process |
|
| Mahdiyeh Mehdipour, Hossein Daghigh Kia | | Research on Animal Production. 2019; 10(25): 61 | | [Pubmed] | [DOI] | | | 19 |
The citrus flavanone naringenin reduces gout-induced joint pain and inflammation in mice by inhibiting the activation of NF?B and macrophage release of IL-1ß |
|
| Kenji W. Ruiz-Miyazawa, Sergio M. Borghi, Felipe A. Pinho-Ribeiro, Larissa Staurengo-Ferrari, Victor Fattori, Glaura S.A. Fernandes, Antonio M. Casella, Jose C. Alves-Filho, Thiago M. Cunha, Fernando Q. Cunha, Rubia Casagrande, Waldiceu A. Verri | | Journal of Functional Foods. 2018; 48: 106 | | [Pubmed] | [DOI] | | | 20 |
Hesperetin, a citrus flavonoid, attenuates testicular damage in diabetic rats via inhibition of oxidative stress, inflammation, and apoptosis |
|
| Alireza Samie, Reza Sedaghat, Tourandokht Baluchnejadmojarad, Mehrdad Roghani | | Life Sciences. 2018; 210: 132 | | [Pubmed] | [DOI] | | | 21 |
Diosgenin ameliorates development of neuropathic pain in diabetic rats: Involvement of oxidative stress and inflammation |
|
| Zahra Kiasalari, Tayebeh Rahmani, Narges Mahmoudi, Tourandokht Baluchnejadmojarad, Mehrdad Roghani | | Biomedicine & Pharmacotherapy. 2017; 86: 654 | | [Pubmed] | [DOI] | | | 22 |
Naringenin adds to the protective effect of l-arginine in monocrotaline-induced pulmonary hypertension in rats: Favorable modulation of oxidative stress, inflammation and nitric oxide |
|
| Lamiaa A. Ahmed,Al Arqam Z. Obaid,Hala F. Zaki,Azza M. Agha | | European Journal of Pharmaceutical Sciences. 2014; 62: 161 | | [Pubmed] | [DOI] | | | 23 |
Molecular mechanisms of citrus flavanones on hepatic gluconeogenesis |
|
| Rodrigo Polimeni Constantin,Renato Polimeni Constantin,Adelar Bracht,Nair Seiko Yamamoto,Emy Luiza Ishii-Iwamoto,Jorgete Constantin | | Fitoterapia. 2014; 92: 148 | | [Pubmed] | [DOI] | | | 24 |
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, Satyajit D. Sarker | | Advances in Nutrition. 2014; 5(4): 404 | | [Pubmed] | [DOI] | | | 25 |
Naringenin attenuates testicular damage, germ cell death and oxidative stress in streptozotocin induced diabetic rats: naringenin prevents diabetic rat testicular damage |
|
| Souvik Roy,Noorjaman Rahaman,Faiqa Ahmed,Satyajit Metya,Santanu Sannigrahi | | Journal of Applied Biomedicine. 2013; 11(3): 195 | | [Pubmed] | [DOI] | | | 26 |
Pharmacokinetics of Hesperetin and Naringenin in the Zhi Zhu Wan, a Traditional Chinese Medicinal Formulae, and its Pharmacodynamics Study |
|
| Hui Sun,Tianwei Dong,Aihua Zhang,Jinfeng Yang,Guangli Yan,Tetsuro Sakurai,Xiuhong Wu,Ying Han,Xijun Wang | | Phytotherapy Research. 2013; 27(9): 1345 | | [Pubmed] | [DOI] | |
|
|
|
|
|
|
|
|
