Generic placeholder image

Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Review Article

The Potential Role of Naringin and Naringenin as Nutraceuticals Against Metabolic Syndrome

Author(s): Luca Massaro, Anna Raguzzini, Paola Aiello and Débora Villaño Valencia*

Volume 23, Issue 4, 2023

Published on: 31 October, 2022

Page: [428 - 445] Pages: 18

DOI: 10.2174/1871530322666220827141203

Price: $65

Abstract

Metabolic syndrome, an increasing problem in western society, is a cluster of conditions that affect cardiovascular health, lipid and glucose management, increasing the risk of heart diseases, stroke and diabetes. Bioactive flavonoids are a great resource of compounds with proven antiinflammatory activities. Naringin, a natural flavanone found in citrus fruits, and its aglycone have demonstrated to ameliorate obesity, dyslipidemia, and insulin resistance in animal models. The principal mechanisms by which these flavonoids exert their action involve AMPK and PPARα up-regulation and the down-regulation of genes involved in lipid metabolism. Although different studies have been carried out to define the pharmacological effects of these flavonoids, their therapeutic use is still limited.

Keywords: Flavonoids, citrus fruits, anti-inflammatory, naringin, naringenin, metabolic syndrome.

Graphical Abstract
[1]
Chen, L.; Deng, H.; Cui, H.; Fang, J.; Zuo, Z.; Deng, J.; Li, Y.; Wang, X.; Zhao, L. Inflammatory responses and inflammation-associated diseases in organs. Oncotarget, 2017, 9(6), 7204-7218.
[http://dx.doi.org/10.18632/oncotarget.23208] [PMID: 29467962]
[2]
Tripoli, E.; Guardia, M.L.; Giammanco, S.; Majo, D.D.; Giammanco, M. Citrus flavonoids: Molecular structure, biological activity and nutritional properties: A review. Food Chem., 2007, 104, 466-479.
[http://dx.doi.org/10.1016/j.foodchem.2006.11.054]
[3]
Taghipour, Y.D.; Hajialyani, M.; Naseri, R.; Hesari, M.; Mohammadi, P.; Stefanucci, A.; Mollica, A.; Farzaei, M.H.; Abdollahi, M. Nanoformulations of natural products for management of metabolic syndrome. Int. J. Nanomedicine, 2019, 14, 5303-5321.
[http://dx.doi.org/10.2147/IJN.S213831] [PMID: 31406461]
[4]
L’hadj, I.; Azzi, R.; Lahfa, F.; Koceir, E.A.; Omari, N. The nutraceutical potential of Lepidium sativum L. seed flavonoid-rich extract in managing metabolic syndrome components. J. Food Biochem., 2019, 43(3), e12725.
[http://dx.doi.org/10.1111/jfbc.12725] [PMID: 31353542]
[5]
Medzhitov, R. Origin and physiological roles of inflammation. Nature, 2008, 454(7203), 428-435.
[http://dx.doi.org/10.1038/nature07201] [PMID: 18650913]
[6]
Shirani, K.; Yousefsani, B.S.; Shirani, M.; Karimi, G. Protective effects of naringin against drugs and chemical toxins induced hepatotoxicity: A review. Phytother. Res., 2020, 34(8), 1734-1744.
[http://dx.doi.org/10.1002/ptr.6641] [PMID: 32067280]
[7]
El-Desoky, A.H.; Abdel-Rahman, R.F.; Ahmed, O.K.; El-Beltagi, H.S.; Hattori, M. Anti-inflammatory and antioxidant activities of naringin isolated from Carissa carandas L.: In vitro and in vivo evidence. Phytomedicine, 2018, 42, 126-134.
[http://dx.doi.org/10.1016/j.phymed.2018.03.051] [PMID: 29655678]
[8]
Arafah, A.; Rehman, M.U.; Mir, T.M.; Wali, A.F.; Ali, R.; Qamar, W.; Khan, R.; Ahmad, A.; Aga, S.S.; Alqahtani, S.; Almatroudi, N.M. Multi-therapeutic potential of naringenin (4′,5,7-Trihydroxyflavonone): Experimental evidence and mechanisms. Plants, 2020, 9(12), 1784.
[http://dx.doi.org/10.3390/plants9121784] [PMID: 33339267]
[9]
Zaidun, N.H.; Thent, Z.C.; Latiff, A.A. Combating oxidative stress disorders with citrus flavonoid. Naringenin. Life Sci., 2018, 208, 111-122.
[http://dx.doi.org/10.1016/j.lfs.2018.07.017] [PMID: 30021118]
[10]
Sharma, M.; Akhtar, N.; Sambhav, K.; Shete, G.; Bansal, A.K.; Sharma, S.S. Emerging potential of citrus flavanones as an antioxidant in diabetes and its complications. Curr. Top. Med. Chem., 2015, 15(2), 187-195.
[http://dx.doi.org/10.2174/1568026615666141209163013] [PMID: 25547100]
[11]
Coelho, R.C.L.A.; Hermsdorff, H.H.M.; Bressan, J. Anti-inflammatory properties of orange juice: Possible favorable molecular and metabolic effects. Plant Foods Hum. Nutr., 2013, 68(1), 1-10.
[http://dx.doi.org/10.1007/s11130-013-0343-3] [PMID: 23417730]
[12]
Rani, N.; Bharti, S.; Krishnamurthy, B.; Bhatia, J.; Sharma, C.; Kamal, M.A.; Ojha, S.; Arya, D.S. Pharmacological properties and therapeutic potential of naringenin: A citrus flavonoid of pharmaceutical promise. Curr. Pharm. Des., 2016, 22(28), 4341-4359.
[http://dx.doi.org/10.2174/1381612822666160530150936] [PMID: 27238365]
[13]
Zeng, W.; Jin, L.; Zhang, F.; Zhang, C.; Liang, W. Naringenin as a potential immunomodulator in therapeutics. Pharmacol. Res., 2018, 135, 122-126.
[http://dx.doi.org/10.1016/j.phrs.2018.08.002] [PMID: 30081177]
[14]
Hernández-Aquino, E.; Muriel, P. Beneficial effects of naringenin in liver diseases: Molecular mechanisms. World J. Gastroenterol., 2018, 24(16), 1679-1707.
[http://dx.doi.org/10.3748/wjg.v24.i16.1679] [PMID: 29713125]
[15]
Mulvihill, E.E.; Assini, J.M.; Sutherland, B.G.; DiMattia, A.S.; Khami, M.; Koppes, J.B.; Sawyez, C.G.; Whitman, S.C.; Huff, M.W. Naringenin decreases progression of atherosclerosis by improving dyslipidemia in high-fat-fed low-density lipoprotein receptor-null mice. Arterioscler. Thromb. Vasc. Biol., 2010, 30(4), 742-748.
[http://dx.doi.org/10.1161/ATVBAHA.109.201095] [PMID: 20110573]
[16]
Orhan, I.E.; Nabavi, S.F.; Daglia, M.; Tenore, G.C.; Mansouri, K.; Nabavi, S.M. Naringenin and atherosclerosis: A review of literature. Curr. Pharm. Biotechnol., 2015, 16(3), 245-251.
[http://dx.doi.org/10.2174/1389201015666141202110216] [PMID: 25483717]
[17]
Mulvihill, E.E.; Burke, A.C.; Huff, M.W. Citrus flavonoids as regulators of lipoprotein metabolism and atherosclerosis. Annu. Rev. Nutr., 2016, 36, 275-299.
[http://dx.doi.org/10.1146/annurev-nutr-071715-050718] [PMID: 27146015]
[18]
Testai, L.; Calderone, V. Nutraceutical value of citrus flavanones and their implications in cardiovascular disease. Nutrients, 2017, 9(5), 502.
[http://dx.doi.org/10.3390/nu9050502] [PMID: 28509871]
[19]
Assini, J.M.; Mulvihill, E.E.; Huff, M.W. Citrus flavonoids and lipid metabolism. Curr. Opin. Lipidol., 2013, 24(1), 34-40.
[http://dx.doi.org/10.1097/MOL.0b013e32835c07fd] [PMID: 23254473]
[20]
Chen, R.; Qi, Q.L.; Wang, M.T.; Li, Q.Y. Therapeutic potential of naringin: An overview. Pharm. Biol., 2016, 54(12), 3203-3210.
[http://dx.doi.org/10.1080/13880209.2016.1216131] [PMID: 27564838]
[21]
Yang, Y.; Trevethan, M.; Wang, S.; Zhao, L. Beneficial effects of citrus flavanones naringin and naringenin and their food sources on lipid metabolism: An update on bioavailability, pharmacokinetics, and mechanisms. J. Nutr. Biochem., 2022, 104, 108967.
[http://dx.doi.org/10.1016/j.jnutbio.2022.108967] [PMID: 35189328]
[22]
Rajadurai, M.; Stanely Mainzen Prince, P. Preventive effect of naringin on lipid peroxides and antioxidants in isoproterenol-induced cardiotoxicity in Wistar rats: Biochemical and histopathological evidences. Toxicology, 2006, 228(2-3), 259-268.
[http://dx.doi.org/10.1016/j.tox.2006.09.005] [PMID: 17084010]
[23]
Salehi, B.; Fokou, P.V.T.; Sharifi-Rad, M.; Zucca, P.; Pezzani, R.; Martins, N.; Sharifi-Rad, J. The therapeutic potential of naringenin: A review of clinical trials. Pharmaceuticals (Basel), 2019, 12(1), 11.
[http://dx.doi.org/10.3390/ph12010011] [PMID: 30634637]
[24]
Ghanbari-Movahed, M.; Jackson, G.; Farzaei, M.H.; Bishayee, A. A systematic review of the preventive and therapeutic effects of naringin against human malignancies. Front. Pharmacol., 2021, 12, 639840.
[http://dx.doi.org/10.3389/fphar.2021.639840] [PMID: 33854437]
[25]
Memariani, Z.; Abbas, S.Q.; Ul Hassan, S.S.; Ahmadi, A.; Chabra, A. Naringin and naringenin as anticancer agents and adjuvants in cancer combination therapy: Efficacy and molecular mechanisms of action, a comprehensive narrative review. Pharmacol. Res., 2021, 171, 105264.
[http://dx.doi.org/10.1016/j.phrs.2020.105264] [PMID: 33166734]
[26]
Ford, E.S. Risks for all-cause mortality, cardiovascular disease, and diabetes associated with the metabolic syndrome: A summary of the evidence. Diabetes Care, 2005, 28(7), 1769-1778.
[http://dx.doi.org/10.2337/diacare.28.7.1769] [PMID: 15983333]
[27]
Phillips, L.K.; Prins, J.B. The link between abdominal obesity and the metabolic syndrome. Curr. Hypertens. Rep., 2008, 10(2), 156-164.
[http://dx.doi.org/10.1007/s11906-008-0029-7] [PMID: 18474184]
[28]
Mamikutty, N.; Thent, Z.C.; Sapri, S.R.; Sahruddin, N.N.; Mohd Yusof, M.R.; Haji Suhaimi, F. The establishment of metabolic syndrome model by induction of fructose drinking water in male Wistar rats. BioMed Res. Int., 2014, 2014, 263897.
[http://dx.doi.org/10.1155/2014/263897] [PMID: 25045660]
[29]
McCracken, E.; Monaghan, M.; Sreenivasan, S. Pathophysiology of the metabolic syndrome. Clin. Dermatol., 2018, 36(1), 14-20.
[http://dx.doi.org/10.1016/j.clindermatol.2017.09.004] [PMID: 29241747]
[30]
Swarup, S.; Goyal, A.; Grigorova, Y.; Zeltser, R. StatPearls Publishing: Treasure Island, FL , 2020.
[31]
Deen, D. Metabolic syndrome: Time for action. Am. Fam. Physician, 2004, 69(12), 2875-2882.
[PMID: 15222652]
[32]
Peluso, I.; Palmery, M. Risks of misinterpretation in the evaluation of the effect of fruit-based drinks in postprandial studies. Gastroenterol. Res. Pract., 2014, 2014, 870547.
[http://dx.doi.org/10.1155/2014/870547] [PMID: 25610461]
[33]
Peluso, I.; Manafikhi, H.; Reggi, R.; Palmery, M. Effects of red wine on postprandial stress: Potential implication in non-alcoholic fatty liver disease development. Eur. J. Nutr., 2015, 54(4), 497-507.
[http://dx.doi.org/10.1007/s00394-015-0877-2] [PMID: 25772634]
[34]
Yarla, N.S.; Polito, A.; Peluso, I. Effects of olive oil on TNF-α and IL-6 in humans: Implication in obesity and frailty. Endocr. Metab. Immune Disord. Drug Targets, 2018, 18(1), 63-74.
[http://dx.doi.org/10.2174/1871530317666171120150329] [PMID: 29165098]
[35]
Kaur, J. A comprehensive review on metabolic syndrome. Cardiol. Res. Pract., 2014, 2014, 943162.
[http://dx.doi.org/10.1155/2014/943162] [PMID: 24711954]
[36]
Cook, N.C.; Samman, S. Flavonoids-chemistry, metabolism, cardioprotective effects, and dietary sources. J. Nutr. Biochem., 1996, 7, 66-76.
[http://dx.doi.org/10.1016/0955-2863(95)00168-9]
[37]
Croft, K.D. The chemistry and biological effects of flavonoids and phenolic acids. Ann. N. Y. Acad. Sci., 1998, 854, 435-442.
[http://dx.doi.org/10.1111/j.1749-6632.1998.tb09922.x] [PMID: 9928450]
[38]
Kumar, S.; Pandey, A.K. Chemistry and biological activities of flavonoids: An overview. ScientificWorldJournal, 2013, 2013, 162750.
[http://dx.doi.org/10.1155/2013/162750] [PMID: 24470791]
[39]
Erlund, I. Review of the flavonoids quercetin, hesperetin, and naringenin. Dietary sources, bioactivities, bioavailability, and epidemiology. Nutr. Res., 2004, 24, 851-874.
[http://dx.doi.org/10.1016/j.nutres.2004.07.005]
[40]
Gattuso, G.; Barreca, D.; Gargiulli, C.; Leuzzi, U.; Caristi, C. Flavonoid composition of Citrus juices. Molecules, 2007, 12(8), 1641-1673.
[http://dx.doi.org/10.3390/12081641] [PMID: 17960080]
[41]
Zhang, J.; Gao, W.; Liu, Z.; Zhang, Z.; Liu, C. Systematic analysis of main constituents in rat biological samples after oral administration of the methanol extract of Fructus aurantii by HPLC-ESI-MS/MS. Iran. J. Pharm. Res., 2014, 13(2), 493-503.
[PMID: 25237344]
[42]
Alam, M.A.; Subhan, N.; Rahman, M.M.; Uddin, S.J.; Reza, H.M.; Sarker, S.D. Effect of citrus flavonoids, naringin and naringenin, on metabolic syndrome and their mechanisms of action. Adv. Nutr., 2014, 5(4), 404-417.
[http://dx.doi.org/10.3945/an.113.005603] [PMID: 25022990]
[43]
Bredsdorff, L.; Nielsen, I.L.; Rasmussen, S.E.; Cornett, C.; Barron, D.; Bouisset, F.; Offord, E.; Williamson, G. Absorption, conjugation and excretion of the flavanones, naringenin and hesperetin from alpha-rhamnosidase-treated orange juice in human subjects. Br. J. Nutr., 2010, 103(11), 1602-1609.
[http://dx.doi.org/10.1017/S0007114509993679] [PMID: 20100371]
[44]
Joshi, R.; Kulkarni, Y.A.; Wairkar, S. Pharmacokinetic, pharmacodynamic and formulations aspects of Naringenin: An update. Life Sci., 2018, 215, 43-56.
[http://dx.doi.org/10.1016/j.lfs.2018.10.066] [PMID: 30391464]
[45]
Kim, D.H.; Jung, E.A.; Sohng, I.S.; Han, J.A.; Kim, T.H.; Han, M.J. Intestinal bacterial metabolism of flavonoids and its relation to some biological activities. Arch. Pharm. Res., 1998, 21(1), 17-23.
[http://dx.doi.org/10.1007/BF03216747] [PMID: 9875509]
[46]
Nyane, N.A.; Tlaila, T.B.; Malefane, T.G.; Ndwandwe, D.E.; Owira, P.M.O. Metformin-like antidiabetic, cardio-protective and non-glycemic effects of naringenin: Molecular and pharmacological insights. Eur. J. Pharmacol., 2017, 803, 103-111.
[http://dx.doi.org/10.1016/j.ejphar.2017.03.042] [PMID: 28322845]
[47]
Cao, H.; Chen, L.; Xiao, J. Binding Citrus flavanones to human serum albumin: Effect of structure on affinity. Mol. Biol. Rep., 2011, 38(4), 2257-2262.
[http://dx.doi.org/10.1007/s11033-010-0356-z] [PMID: 20878474]
[48]
Zhang, Y.; Li, Y.; Dong, L.; Li, J.; He, W.; Chen, X.; Hu, Z. Investigation of the interaction between naringin and human serum albumin. J. Mol. Struct., 2008, 875, 1-8.
[http://dx.doi.org/10.1016/j.molstruc.2007.03.063]
[49]
Xie, M.X.; Xu, X.Y.; Wang, Y.D. Interaction between hesperetin and human serum albumin revealed by spectroscopic methods. Biochim. Biophys. Acta, 2005, 1724(1-2), 215-224.
[http://dx.doi.org/10.1016/j.bbagen.2005.04.009] [PMID: 15923087]
[50]
Singha Roy, A.; Tripathy, D.R.; Chatterjee, A.; Dasgupta, S. A spectroscopic study of the interaction of the antioxidant naringin with bovine serum albumin. J. Biophys. Chem., 2010, 1, 141-152.
[http://dx.doi.org/10.4236/jbpc.2010.13017]
[51]
Zbarsky, V.; Datla, K.P.; Parkar, S.; Rai, D.K.; Aruoma, O.I.; Dexter, D.T. Neuroprotective properties of the natural phenolic antioxidants curcumin and naringenin but not quercetin and fisetin in a 6-OHDA model of Parkinson’s disease. Free Radic. Res., 2005, 39(10), 1119-1125.
[http://dx.doi.org/10.1080/10715760500233113] [PMID: 16298737]
[52]
Guimarães, R.; Barros, L.; Barreira, J.C.M.; Sousa, M.J.; Carvalho, A.M.; Ferreira, I.C.F.R. Targeting excessive free radicals with peels and juices of citrus fruits: Grapefruit, lemon, lime and orange. Food Chem. Toxicol., 2010, 48(1), 99-106.
[http://dx.doi.org/10.1016/j.fct.2009.09.022] [PMID: 19770018]
[53]
Cavia-Saiz, M.; Busto, M.D.; Pilar-Izquierdo, M.C.; Ortega, N.; Perez-Mateos, M.; Muñiz, 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(7), 1238-1244.
[http://dx.doi.org/10.1002/jsfa.3959] [PMID: 20394007]
[54]
Berhow, M.A.; Vandercook, C.E. Sites of naringin biosynthesis in grapefruit seedlings. J. Plant Physiol., 1991, 138(2), 176-179.
[http://dx.doi.org/10.1016/S0176-1617(11)80266-X]
[55]
Zhang, X.; Li, L.; Xu, Z.; Liang, Z.; Su, J.; Huang, J.; Li, B. Investigation of the interaction of naringin palmitate with bovine serum albumin: Spectroscopic analysis and molecular docking. PLoS One, 2013, 8(3), e59106.
[http://dx.doi.org/10.1371/journal.pone.0059106] [PMID: 23527100]
[56]
Khan, M.K.; Rakotomanomana, N.; Dufour, C.; Dangles, O. Binding of citrus flavanones and their glucuronides and chalcones to human serum albumin. Food Funct., 2011, 2(10), 617-626.
[http://dx.doi.org/10.1039/c1fo10077g] [PMID: 21952533]
[57]
Tu, B.; Wang, Y.; Mi, R.; Ouyang, Y.; Hu, Y.J. Evaluation of the interaction between naringenin and human serum albumin: Insights from fluorescence spectroscopy, electrochemical measurement and molecular docking. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2015, 149, 536-543.
[http://dx.doi.org/10.1016/j.saa.2015.04.087] [PMID: 25978022]
[58]
Hu, Y.J.; Wang, Y.; Ou-Yang, Y.; Zhou, J.; Liu, Y. Characterize the interaction between naringenin and bovine serum albumin using spectroscopic approach. J. Lumin., 2010, 130(8), 1394-1399.
[http://dx.doi.org/10.1016/j.jlumin.2010.02.053]
[59]
Skrt, M.; Benedik, E.; Podlipnik, C.; Ulrih, N.P. Interactions of different polyphenols with bovine serum albumin using fluorescence quenching and molecular docking. Food Chem., 2012, 135(4), 2418-2424.
[http://dx.doi.org/10.1016/j.foodchem.2012.06.114] [PMID: 22980822]
[60]
Zargar, S.; Alamery, S.; Bakheit, A.H.; Wani, T.A. Poziotinib and bovine serum albumin binding characterization and influence of quercetin, rutin, naringenin and sinapic acid on their binding interaction. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2020, 235, 118335.
[http://dx.doi.org/10.1016/j.saa.2020.118335] [PMID: 32278151]
[61]
Das, S.; Ghosh, P.; Koley, S.; Singha Roy, A. Binding of naringin and naringenin with hen egg white lysozyme: A spectroscopic investigation and molecular docking study. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2018, 192, 211-221.
[http://dx.doi.org/10.1016/j.saa.2017.11.015] [PMID: 29145059]
[62]
Liu, X.; Luo, F.; Li, P.; She, Y.; Gao, W. Investigation of the interaction for three Citrus flavonoids and α-amylase by surface plasmon resonance. Food Res. Int., 2017, 97, 1-6.
[http://dx.doi.org/10.1016/j.foodres.2017.03.023] [PMID: 28578029]
[63]
Maity, S.; Chakraborty, S.; Chakraborti, A.S. Critical insight into the interaction of naringenin with human haemoglobin: A combined spectroscopic and computational modeling approaches. J. Mol. Struct., 2017, 1129, 256-262.
[http://dx.doi.org/10.1016/j.molstruc.2016.09.085]
[64]
Nunes, N.M.; de Paula, H.M.C.; Coelho, Y.L.; da Silva, L.H.M.; Pires, A.C.S. Surface plasmon resonance study of interaction between lactoferrin and naringin. Food Chem., 2019, 297, 125022.
[http://dx.doi.org/10.1016/j.foodchem.2019.125022] [PMID: 31253281]
[65]
Zhang, X.F.; Han, R.M.; Sun, X.R.; Li, G.Y.; Yang, Q.F.; Li, Q.; Gai, W.; Zhang, M.; Chen, L.; Yang, G.; Tang, Y.L. The effect of the skeleton structure of flavanone and flavonoid on interaction with transferrin. Bioorg. Med. Chem. Lett., 2013, 23(24), 6677-6681.
[http://dx.doi.org/10.1016/j.bmcl.2013.10.042] [PMID: 24239187]
[66]
Yang, L.; Nan, G.; Meng, X.; Zhang, L.; Song, N.; Liu, Y.; Liu, Z.; Wang, Y.; Yang, G. Study on the interaction between lovastatin and three digestive enzymes and the effect of naringin and vitamin C on it by spectroscopy and docking methods. Int. J. Biol. Macromol., 2020, 155, 1440-1449.
[http://dx.doi.org/10.1016/j.ijbiomac.2019.11.120] [PMID: 31739011]
[67]
Li, X.; Peng, Y.; Liu, H.; Xu, Y.; Wang, X.; Zhang, C.; Ma, X. Comparative studies on the interaction of nine flavonoids with trypsin. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2020, 238, 118440.
[http://dx.doi.org/10.1016/j.saa.2020.118440] [PMID: 32438292]
[68]
Bharti, S.; Rani, N.; Krishnamurthy, B.; Arya, D.S. Preclinical evidence for the pharmacological actions of naringin: A review. Planta Med., 2014, 80(6), 437-451.
[http://dx.doi.org/10.1055/s-0034-1368351] [PMID: 24710903]
[69]
O’Neill, S.; O’Driscoll, L. Metabolic syndrome: A closer look at the growing epidemic and its associated pathologies. Obes. Rev., 2015, 16(1), 1-12.
[http://dx.doi.org/10.1111/obr.12229] [PMID: 25407540]
[70]
Saklayen, M.G. The global epidemic of the metabolic syndrome. Curr. Hypertens. Rep., 2018, 20(2), 12.
[http://dx.doi.org/10.1007/s11906-018-0812-z] [PMID: 29480368]
[71]
Ormazabal, V.; Nair, S.; Elfeky, O.; Aguayo, C.; Salomon, C.; Zuñiga, F.A. Association between insulin resistance and the development of cardiovascular disease. Cardiovasc. Diabetol., 2018, 17(1), 122.
[http://dx.doi.org/10.1186/s12933-018-0762-4] [PMID: 30170598]
[72]
Malik, V.S.; Popkin, B.M.; Bray, G.A.; Després, J.P.; Willett, W.C.; Hu, F.B. Sugar-sweetened beverages and risk of metabolic syndrome and type 2 diabetes: A meta-analysis. Diabetes Care, 2010, 33(11), 2477-2483.
[http://dx.doi.org/10.2337/dc10-1079] [PMID: 20693348]
[73]
Edwardson, C.L.; Gorely, T.; Davies, M.J.; Gray, L.J.; Khunti, K.; Wilmot, E.G.; Yates, T.; Biddle, S.J. Association of sedentary behaviour with metabolic syndrome: A meta-analysis. PLoS One, 2012, 7(4), e34916.
[http://dx.doi.org/10.1371/journal.pone.0034916] [PMID: 22514690]
[74]
Xi, B.; He, D.; Zhang, M.; Xue, J.; Zhou, D. Short sleep duration predicts risk of metabolic syndrome: A systematic review and meta-analysis. Sleep Med. Rev., 2014, 18(4), 293-297.
[http://dx.doi.org/10.1016/j.smrv.2013.06.001] [PMID: 23890470]
[75]
Castro, A.V.; Kolka, C.M.; Kim, S.P.; Bergman, R.N. Obesity, insulin resistance and comorbidities? Mechanisms of association. Arq. Bras. Endocrinol. Metabol, 2014, 58(6), 600-609.
[http://dx.doi.org/10.1590/0004-2730000003223] [PMID: 25211442]
[76]
Viswanatha, G.L.; Shylaja, H.; Keni, R.; Nandakumar, K.; Rajesh, S. A systematic review and meta-analysis on the cardio-protective activity of naringin based on pre-clinical evidences. Phytother. Res., 2022, 36(3), 1064-1092.
[http://dx.doi.org/10.1002/ptr.7368] [PMID: 35084066]
[77]
Alam, M.A.; Kauter, K.; Brown, L. Naringin improves diet-induced cardiovascular dysfunction and obesity in high carbohydrate, high fat diet-fed rats. Nutrients, 2013, 5(3), 637-650.
[http://dx.doi.org/10.3390/nu5030637] [PMID: 23446977]
[78]
Rodríguez, V.; Plavnik, L.; Tolosa de Talamoni, N. Naringin attenuates liver damage in streptozotocin-induced diabetic rats. Biomed. Pharmacother., 2018, 105, 95-102.
[http://dx.doi.org/10.1016/j.biopha.2018.05.120] [PMID: 29852394]
[79]
Sui, G.G.; Xiao, H.B.; Lu, X.Y.; Sun, Z.L. Naringin activates AMPK resulting in altered expression of SREBPs, PCSK9, and LDLR to reduce body weight in obese C57BL/6J mice. J. Agric. Food Chem., 2018, 66(34), 8983-8990.
[http://dx.doi.org/10.1021/acs.jafc.8b02696] [PMID: 30092639]
[80]
Pu, P.; Gao, D.M.; Mohamed, S.; Chen, J.; Zhang, J.; Zhou, X.Y.; Zhou, N.J.; Xie, J.; Jiang, H. Naringin ameliorates metabolic syndrome by activating AMP-activated protein kinase in mice fed a high-fat diet. Arch. Biochem. Biophys., 2012, 518(1), 61-70.
[http://dx.doi.org/10.1016/j.abb.2011.11.026] [PMID: 22198281]
[81]
Xulu, S.; Oroma Owira, P.M. Naringin ameliorates atherogenic dyslipidemia but not hyperglycemia in rats with type 1 diabetes. J. Cardiovasc. Pharmacol., 2012, 59(2), 133-141.
[http://dx.doi.org/10.1097/FJC.0b013e31823827a4] [PMID: 21964158]
[82]
Sharma, A.K.; Bharti, S.; Ojha, S.; Bhatia, J.; Kumar, N.; Ray, R.; Kumari, S.; Arya, D.S. Up-regulation of PPARγ, heat shock protein-27 and -72 by naringin attenuates insulin resistance, β-cell dysfunction, hepatic steatosis and kidney damage in a rat model of type 2 diabetes. Br. J. Nutr., 2011, 106(11), 1713-1723.
[http://dx.doi.org/10.1017/S000711451100225X] [PMID: 21736771]
[83]
Chanet, A.; Milenkovic, D.; Deval, C.; Potier, M.; Constans, J.; Mazur, A.; Bennetau-Pelissero, C.; Morand, C.; Bérard, A.M. Naringin, the major grapefruit flavonoid, specifically affects atherosclerosis development in diet-induced hypercholesterolemia in mice. J. Nutr. Biochem., 2012, 23(5), 469-477.
[http://dx.doi.org/10.1016/j.jnutbio.2011.02.001] [PMID: 21684135]
[84]
Cho, K.W.; Kim, Y.O.; Andrade, J.E.; Burgess, J.R.; Kim, Y.C. Dietary naringenin increases hepatic peroxisome proliferators-activated receptor α protein expression and decreases plasma triglyceride and adiposity in rats. Eur. J. Nutr., 2011, 50(2), 81-88.
[http://dx.doi.org/10.1007/s00394-010-0117-8] [PMID: 20567977]
[85]
Murunga, A.N.; Miruka, D.O.; Driver, C.; Nkomo, F.S.; Cobongela, S.Z.; Owira, P.M. Grapefruit derived flavonoid naringin improves ketoacidosis and lipid peroxidation in type 1 diabetes rat model. PLoS One, 2016, 11(4), e0153241.
[http://dx.doi.org/10.1371/journal.pone.0153241] [PMID: 27073901]
[86]
Priscilla, D.H.; Jayakumar, M.; Thirumurugan, K. Flavanone naringenin: An effective antihyperglycemic and antihyperlipidemic nutraceutical agent on high fat diet fed streptozotocin induced type 2 diabetic rats. J. Funct. Foods, 2015, 14, 363-373.
[http://dx.doi.org/10.1016/j.jff.2015.02.005]
[87]
Assini, J.M.; Mulvihill, E.E.; Sutherland, B.G.; Telford, D.E.; Sawyez, C.G.; Felder, S.L.; Chhoker, S.; Edwards, J.Y.; Gros, R.; Huff, M.W. Naringenin prevents cholesterol-induced systemic inflammation, metabolic dysregulation, and atherosclerosis in Ldlr/ mice. J. Lipid Res., 2013, 54(3), 711-724.
[http://dx.doi.org/10.1194/jlr.M032631] [PMID: 23269394]
[88]
Jung, U.J.; Kim, H.J.; Lee, J.S.; Lee, M.K.; Kim, H.O.; Park, E.J.; Kim, H.K.; Jeong, T.S.; Choi, M.S. Naringin supplementation lowers plasma lipids and enhances erythrocyte antioxidant enzyme activities in hypercholesterolemic subjects. Clin. Nutr., 2003, 22(6), 561-568.
[http://dx.doi.org/10.1016/S0261-5614(03)00059-1] [PMID: 14613759]
[89]
Ikemura, M.; Sasaki, Y.; Giddings, J.C.; Yamamoto, J. Preventive effects of hesperidin, glucosyl hesperidin and naringin on hypertension and cerebral thrombosis in stroke-prone spontaneously hypertensive rats. Phytother. Res., 2012, 26(9), 1272-1277.
[http://dx.doi.org/10.1002/ptr.3724] [PMID: 22228501]
[90]
Visnagri, A.; Adil, M.; Kandhare, A.D.; Bodhankar, S.L. Effect of naringin on hemodynamic changes and left ventricular function in renal artery occluded renovascular hypertension in rats. J. Pharm. Bioallied Sci., 2015, 7(2), 121-127.
[http://dx.doi.org/10.4103/0975-7406.154437] [PMID: 25883516]
[91]
Fallahi, F.; Roghani, M.; Moghadami, S. Citrus flavonoid naringenin improves aortic reactivity in streptozotocin-diabetic rats. Indian J. Pharmacol., 2012, 44(3), 382-386.
[http://dx.doi.org/10.4103/0253-7613.96350] [PMID: 22701251]
[92]
Saponara, S.; Testai, L.; Iozzi, D.; Martinotti, E.; Martelli, A.; Chericoni, S.; Sgaragli, G.; Fusi, F.; Calderone, V. (+/-)-Naringenin as large conductance Ca2+-activated K+ (BKCa) channel opener in vascular smooth muscle cells. Br. J. Pharmacol., 2006, 149(8), 1013-1021.
[http://dx.doi.org/10.1038/sj.bjp.0706951] [PMID: 17088866]
[93]
Ahmed, O.M.; Mahmoud, A.M.; Abdel-Moneim, A.; Ashour, M.B. Antidiabetic effects of hesperidin and naringin in type 2 diabetic rats. Diabetol. Croat., 2012, 41(2), 53-67.
[94]
Parmar, H.S.; Jain, P.; Chauhan, D.S.; Bhinchar, M.K.; Munjal, V.; Yusuf, M.; Choube, K.; Tawani, A.; Tiwari, V.; Manivannan, E.; Kumar, A. DPP-IV inhibitory potential of naringin: An in silico, in vitro and in vivo study. Diabetes Res. Clin. Pract., 2012, 97(1), 105-111.
[http://dx.doi.org/10.1016/j.diabres.2012.02.011] [PMID: 22410395]
[95]
Adebiyi, O.A.; Adebiyi, O.O.; Owira, P.M. Naringin reduces hyperglycemia-induced cardiac fibrosis by relieving oxidative stress. PLoS One, 2016, 11(3), e0149890.
[http://dx.doi.org/10.1371/journal.pone.0149890] [PMID: 26967518]
[96]
Mojzisová, G.; Sarisský, M.; Mirossay, L.; Martinka, P.; Mojzis, J. Effect of flavonoids on daunorubicin-induced toxicity in H9c2 Cardiomyoblasts. Phytother. Res., 2009, 23(1), 136-139.
[http://dx.doi.org/10.1002/ptr.2566] [PMID: 18803248]
[97]
Qin, C.X.; Chen, X.; Hughes, R.A.; Williams, S.J.; Woodman, O.L. Understanding the cardioprotective effects of flavonols: Discovery of relaxant flavonols without antioxidant activity. J. Med. Chem., 2008, 51(6), 1874-1884.
[http://dx.doi.org/10.1021/jm070352h] [PMID: 18307286]
[98]
Adebiyi, A.O.; Adebiyi, O.O.; Owira, P.M. Naringin mitigates cardiac hypertrophy by reducing oxidative stress and inactivating c-jun nuclear kinase-1 protein in type I diabetes. J. Cardiovasc. Pharmacol., 2016, 67(2), 136-144.
[http://dx.doi.org/10.1097/FJC.0000000000000325] [PMID: 26421421]
[99]
Pari, L.; Suman, S. Antihyperglycemic and antilipidperoxidative effects of flavanoid naringin in streptozotocinnicotinamide induced diabetic rats. Int. J. Biol. Med. Res., 2010, 1, 206-210.
[100]
Annadurai, T.; Muralidharan, A.R.; Joseph, T.; Hsu, M.J.; Thomas, P.A.; Geraldine, P. Antihyperglycemic and antioxidant effects of a flavanone, naringenin, in streptozotocin-nicotinamide-induced experimental diabetic rats. J. Physiol. Biochem., 2012, 68(3), 307-318.
[http://dx.doi.org/10.1007/s13105-011-0142-y] [PMID: 22234849]
[101]
Ortiz-Andrade, R.R.; Sánchez-Salgado, J.C.; Navarrete-Vázquez, G.; Webster, S.P.; Binnie, M.; García-Jiménez, S.; León-Rivera, I.; Cigarroa-Vázquez, P.; Villalobos-Molina, R.; Estrada-Soto, S. 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(11), 1097-1104.
[http://dx.doi.org/10.1111/j.1463-1326.2008.00869.x] [PMID: 18355329]
[102]
Tsai, S.J.; Huang, C.S.; Mong, M.C.; Kam, W.Y.; Huang, H.Y.; Yin, M.C. Anti-inflammatory and antifibrotic effects of naringenin in diabetic mice. J. Agric. Food Chem., 2012, 60(1), 514-521.
[http://dx.doi.org/10.1021/jf203259h] [PMID: 22117528]
[103]
Mulvihill, E.E.; Allister, E.M.; Sutherland, B.G.; Telford, D.E.; Sawyez, C.G.; Edwards, J.Y.; Markle, J.M.; Hegele, R.A.; Huff, M.W. Naringenin prevents dyslipidemia, apolipoprotein B overproduction, and hyperinsulinemia in LDL receptor-null mice with diet-induced insulin resistance. Diabetes, 2009, 58(10), 2198-2210.
[http://dx.doi.org/10.2337/db09-0634] [PMID: 19592617]
[104]
Priscilla, D.H.; Roy, D.; Suresh, A.; Kumar, V.; Thirumurugan, K. Naringenin inhibits α-glucosidase activity: A promising strategy for the regulation of postprandial hyperglycemia in high fat diet fed streptozotocin induced diabetic rats. Chem. Biol. Interact., 2014, 210, 77-85.
[http://dx.doi.org/10.1016/j.cbi.2013.12.014] [PMID: 24412302]
[105]
Yan, N.; Wen, L.; Peng, R.; Li, H.; Liu, H.; Peng, H.; Sun, Y.; Wu, T.; Chen, L.; Duan, Q.; Sun, Y.; Zhou, Q.; Wei, L.; Zhang, Z. Naringenin ameliorated kidney injury through Let-7a/TGFBR1 signaling in diabetic nephropathy. J. Diabetes Res., 2016, 2016, 8738760.
[http://dx.doi.org/10.1155/2016/8738760] [PMID: 27446963]
[106]
Kannappan, S.; Anuradha, C.V. Naringenin enhances insulin-stimulated tyrosine phosphorylation and improves the cellular actions of insulin in a dietary model of metabolic syndrome. Eur. J. Nutr., 2010, 49(2), 101-109.
[http://dx.doi.org/10.1007/s00394-009-0054-6] [PMID: 19727895]
[107]
Al-Rejaie, S.S.; Aleisa, A.M.; Abuohashish, H.M.; Parmar, M.Y.; Ola, M.S.; Al-Hosaini, A.A.; Ahmed, M.M. Naringenin neutralises oxidative stress and nerve growth factor discrepancy in experimental diabetic neuropathy. Neurol. Res., 2015, 37(10), 924-933.
[http://dx.doi.org/10.1179/1743132815Y.0000000079] [PMID: 26187552]
[108]
Ren, B.; Qin, W.; Wu, F.; Wang, S.; Pan, C.; Wang, L.; Zeng, B.; Ma, S.; Liang, J. Apigenin and naringenin regulate glucose and lipid metabolism, and ameliorate vascular dysfunction in type 2 diabetic rats. Eur. J. Pharmacol., 2016, 773, 13-23.
[http://dx.doi.org/10.1016/j.ejphar.2016.01.002] [PMID: 26801071]
[109]
Ke, J.Y.; Cole, R.M.; Hamad, E.M.; Hsiao, Y.H.; Cotten, B.M.; Powell, K.A.; Belury, M.A. Citrus flavonoid, naringenin, increases locomotor activity and reduces diacylglycerol accumulation in skeletal muscle of obese ovariectomized mice. Mol. Nutr. Food Res., 2016, 60(2), 313-324.
[http://dx.doi.org/10.1002/mnfr.201500379] [PMID: 26573879]
[110]
Jung, U.J.; Lee, M.K.; Jeong, K.S.; Choi, M.S. The hypoglycemic effects of hesperidin and naringin are partly mediated by hepatic glucose-regulating enzymes in C57BL/KsJ-db/db mice. J. Nutr., 2004, 134(10), 2499-2503.
[http://dx.doi.org/10.1093/jn/134.10.2499] [PMID: 15465737]
[111]
Reddy, T.K.; Nagaraju, I.; Kumar, K.H.; Lokanatha, V.; Reddy, C.D.; Jagetia, G.C. Cardioprotective effect of naringin in mice treated with doxorubicin. Planta Med., 2008, 74, 49.
[http://dx.doi.org/10.1055/s-2008-1075245]
[112]
Rajadurai, M.; Prince, P.S. Preventive effect of naringin on cardiac mitochondrial enzymes during isoproterenol-induced myocardial infarction in rats: A transmission electron microscopic study. J. Biochem. Mol. Toxicol., 2007, 21(6), 354-361.
[http://dx.doi.org/10.1002/jbt.20203] [PMID: 17994577]
[113]
Hayanga, J.A.; Ngubane, S.P.; Murunga, A.N.; Owira, P.M.O. Grapefruit juice improves glucose intolerance in streptozotocin-induced diabetes by suppressing hepatic gluconeogenesis. Eur. J. Nutr., 2016, 55(2), 631-638.
[http://dx.doi.org/10.1007/s00394-015-0883-4] [PMID: 25792078]
[114]
Jagetia, G.C.; Lalnuntluangi, V. The citrus flavanone naringin enhances antioxidant status in the albino rat liver treated with doxorubicin. Biochem. Mol. Biol. J., 2016, 2(2), 1-9.
[http://dx.doi.org/10.21767/2471-8084.100018]
[115]
M S, S.; C D, N. Influence of quercetin, naringenin and berberine on glucose transporters and insulin signalling molecules in brain of streptozotocin-induced diabetic rats. Biomed. Pharmacother., 2017, 94, 605-611.
[http://dx.doi.org/10.1016/j.biopha.2017.07.142] [PMID: 28783583]
[116]
Chtourou, Y.; Slima, A.B.; Makni, M.; Gdoura, R.; Fetoui, H. Naringenin protects cardiac hypercholesterolemia-induced oxidative stress and subsequent necroptosis in rats. Pharmacol. Rep., 2015, 67(6), 1090-1097.
[http://dx.doi.org/10.1016/j.pharep.2015.04.002] [PMID: 26481526]
[117]
Krogh-Madsen, R.; Plomgaard, P.; Møller, K.; Mittendorfer, B.; Pedersen, B.K. Influence of TNF-alpha and IL-6 infusions on insulin sensitivity and expression of IL-18 in humans. Am. J. Physiol. Endocrinol. Metab., 2006, 291(1), E108-E114.
[http://dx.doi.org/10.1152/ajpendo.00471.2005] [PMID: 16464907]
[118]
Hotamisligil, G.S.; Shargill, N.S.; Spiegelman, B.M. Adipose expression of tumor necrosis factor-alpha: Direct role in obesity-linked insulin resistance. Science, 1993, 259(5091), 87-91.
[http://dx.doi.org/10.1126/science.7678183] [PMID: 7678183]
[119]
Dandona, P.; Aljada, A.; Bandyopadhyay, A. Inflammation: The link between insulin resistance, obesity and diabetes. Trends Immunol., 2004, 25(1), 4-7.
[http://dx.doi.org/10.1016/j.it.2003.10.013] [PMID: 14698276]
[120]
Terra, X.; Montagut, G.; Bustos, M.; Llopiz, N.; Ardèvol, A.; Bladé, C.; Fernández-Larrea, J.; Pujadas, G.; Salvadó, J.; Arola, L.; Blay, M. Grape-seed procyanidins prevent low-grade inflammation by modulating cytokine expression in rats fed a high-fat diet. J. Nutr. Biochem., 2009, 20(3), 210-218.
[http://dx.doi.org/10.1016/j.jnutbio.2008.02.005] [PMID: 18602813]
[121]
Lee, I.S.; Shin, G.; Choue, R. Shifts in diet from high fat to high carbohydrate improved levels of adipokines and pro-inflammatory cytokines in mice fed a high-fat diet. Endocr. J., 2010, 57(1), 39-50.
[http://dx.doi.org/10.1507/endocrj.K09E-046] [PMID: 19822999]
[122]
Punithavathi, V.R.; Anuthama, R.; Prince, P.S.M. Combined treatment with naringin and vitamin C ameliorates streptozotocin-induced diabetes in male Wistar rats. J. Appl. Toxicol., 2008, 28(6), 806-813.
[http://dx.doi.org/10.1002/jat.1343] [PMID: 18344197]
[123]
Ali, M.M.; El Kader, M.A. The influence of naringin on the oxidative state of rats with streptozotocin-induced acute hyperglycaemia. Z. Naturforsch. C J. Biosci., 2004, 59(9-10), 726-733.
[http://dx.doi.org/10.1515/znc-2004-9-1018] [PMID: 15540607]
[124]
Jeon, S.M.; Bok, S.H.; Jang, M.K.; Kim, Y.H.; Nam, K.T.; Jeong, T.S.; Park, Y.B.; Choi, M.S. Comparison of antioxidant effects of naringin and probucol in cholesterol-fed rabbits. Clin. Chim. Acta, 2002, 317(1-2), 181-190.
[http://dx.doi.org/10.1016/S0009-8981(01)00778-1] [PMID: 11814474]
[125]
Fuhrman, B.; Aviram, M. Flavonoids protect LDL from oxidation and attenuate atherosclerosis. Curr. Opin. Lipidol., 2001, 12(1), 41-48.
[http://dx.doi.org/10.1097/00041433-200102000-00008] [PMID: 11176202]
[126]
Naderi, G.A.; Asgary, S.; Sarraf-Zadegan, N.; Shirvany, H. Anti-oxidant effect of flavonoids on the susceptibility of LDL oxidation. Mol. Cell. Biochem., 2003, 246(1-2), 193-196.
[http://dx.doi.org/10.1023/A:1023483223842] [PMID: 12841362]
[127]
Oak, M.H.; El Bedoui, J.; Schini-Kerth, V.B. Antiangiogenic properties of natural polyphenols from red wine and green tea. J. Nutr. Biochem., 2005, 16(1), 1-8.
[http://dx.doi.org/10.1016/j.jnutbio.2004.09.004] [PMID: 15629234]
[128]
Choe, S.C.; Kim, H.S.; Jeong, T.S.; Bok, S.H.; Park, Y.B. Naringin has an antiatherogenic effect with the inhibition of intercellular adhesion molecule-1 in hypercholesterolemic rabbits. J. Cardiovasc. Pharmacol., 2001, 38(6), 947-955.
[http://dx.doi.org/10.1097/00005344-200112000-00017] [PMID: 11707699]
[129]
Sirovina, D.; Oršolić, N.; Gregorović, G.; Končić, M.Z. Naringenin ameliorates pathological changes in liver and kidney of diabetic mice: A preliminary study. Arh. Hig. Rada Toksikol., 2016, 67(1), 19-24.
[http://dx.doi.org/10.1515/aiht-2016-67-2708] [PMID: 27092635]
[130]
Song, Y.; Guo, B.; Ma, S.; Chang, P.; Tao, K. Naringin suppresses the growth and motility of hypertrophic scar fibroblasts by inhibiting the kinase activity of Akt. Biomed. Pharmacother., 2018, 105, 1291-1298.
[http://dx.doi.org/10.1016/j.biopha.2018.06.103] [PMID: 30021366]
[131]
National Center for Biotechnology Information. Available from: https://www.ncbi.nlm.nih.gov/gene/1374 (Accessed April 30, 2021).
[132]
Zygmunt, K.; Faubert, B.; MacNeil, J.; Tsiani, E. Naringenin, a citrus flavonoid, increases muscle cell glucose uptake via AMPK. Biochem. Biophys. Res. Commun., 2010, 398(2), 178-183.
[http://dx.doi.org/10.1016/j.bbrc.2010.06.048] [PMID: 20558145]
[133]
O’Neill, H.M.; Holloway, G.P.; Steinberg, G.R. AMPK regulation of fatty acid metabolism and mitochondrial biogenesis: Implications for obesity. Mol. Cell. Endocrinol., 2013, 366(2), 135-151.
[http://dx.doi.org/10.1016/j.mce.2012.06.019] [PMID: 22750049]
[134]
Mahmoud, A.; Ahmed, O.M.; Abdel-Moniem, A.; Ashour, M.B. Upregulation of PPARg mediates the antidiabetic effects of citrus flavanoids in type 2 diabetic rats. Int. J. Bioassays, 2013, 2, 756-761.
[135]
Ferré, P.; Foufelle, F. Hepatic steatosis: A role for de novo lipogenesis and the transcription factor SREBP-1c. Diabetes Obes. Metab., 2010, 12(Suppl. 2), 83-92.
[http://dx.doi.org/10.1111/j.1463-1326.2010.01275.x] [PMID: 21029304]
[136]
Li, J.M.; Che, C.T.; Lau, C.B.; Leung, P.S.; Cheng, C.H. Inhibition of intestinal and renal Na+-glucose cotransporter by naringenin. Int. J. Biochem. Cell Biol., 2006, 38(5-6), 985-995.
[http://dx.doi.org/10.1016/j.biocel.2005.10.002] [PMID: 16289850]
[137]
Mehraban, M.H.; Yousefi, R.; Panahi, F. 11th Iran Conference on Biophysical Chemistry; University of Medical Sciences: Ardabil, 2012.
[138]
Zhang, J.; Qiu, H.; Huang, J.; Ding, S.; Huang, B.; Wu, Q.; Jiang, Q. Naringenin exhibits the protective effect on cardiac hypertrophy via EETs-PPARs activation in streptozocin-induced diabetic mice. Biochem. Biophys. Res. Commun., 2018, 502(1), 55-61.
[http://dx.doi.org/10.1016/j.bbrc.2018.05.119] [PMID: 29778538]
[139]
Huang, H.; Wu, K.; You, Q.; Huang, R.; Li, S.; Wu, K. Naringin inhibits high glucose-induced cardiomyocyte apoptosis by attenuating mitochondrial dysfunction and modulating the activation of the p38 signaling pathway. Int. J. Mol. Med., 2013, 32(2), 396-402.
[http://dx.doi.org/10.3892/ijmm.2013.1403] [PMID: 23732220]
[140]
Chen, J.; Guo, R.; Yan, H.; Tian, L.; You, Q.; Li, S.; Huang, R.; Wu, K. Naringin inhibits ROS-activated MAPK pathway in high glucose-induced injuries in H9c2 cardiac cells. Basic Clin. Pharmacol. Toxicol., 2014, 114(4), 293-304.
[http://dx.doi.org/10.1111/bcpt.12153] [PMID: 24118820]
[141]
You, Q.; Wu, Z.; Wu, B.; Liu, C.; Huang, R.; Yang, L.; Guo, R.; Wu, K.; Chen, J. Naringin protects cardiomyocytes against hyperglycemia-induced injuries in vitro and in vivo. J. Endocrinol., 2016, 230(2), 197-214.
[http://dx.doi.org/10.1530/JOE-16-0004] [PMID: 27270899]
[142]
Roy, S.; Ahmed, F.; Banerjee, S.; Saha, U. Naringenin ameliorates streptozotocin-induced diabetic rat renal impairment by downregulation of TGF-β1 and IL-1 via modulation of oxidative stress correlates with decreased apoptotic events. Pharm. Biol., 2016, 54(9), 1616-1627.
[http://dx.doi.org/10.3109/13880209.2015.1110599] [PMID: 26928632]
[143]
Hirai, S.; Kim, Y.I.; Goto, T.; Kang, M.S.; Yoshimura, M.; Obata, A.; Yu, R.; Kawada, T. Inhibitory effect of naringenin chalcone on inflammatory changes in the interaction between adipocytes and macrophages. Life Sci., 2007, 81(16), 1272-1279.
[http://dx.doi.org/10.1016/j.lfs.2007.09.001] [PMID: 17915259]
[144]
Lin, C.Y.; Ni, C.C.; Yin, M.C.; Lii, C.K. Flavonoids protect pancreatic beta-cells from cytokines mediated apoptosis through the activation of PI3-kinase pathway. Cytokine, 2012, 59(1), 65-71.
[http://dx.doi.org/10.1016/j.cyto.2012.04.011] [PMID: 22579112]
[145]
Yoshida, H.; Takamura, N.; Shuto, T.; Ogata, K.; Tokunaga, J.; Kawai, K.; Kai, H. The citrus flavonoids hesperetin and naringenin block the lipolytic actions of TNF-α in mouse adipocytes. Biochem. Biophys. Res. Commun., 2010, 394(3), 728-732.
[http://dx.doi.org/10.1016/j.bbrc.2010.03.060] [PMID: 20230793]
[146]
Lee, C.H.; Jeong, T.S.; Choi, Y.K.; Hyun, B.H.; Oh, G.T.; Kim, E.H.; Kim, J.R.; Han, J.I.; Bok, S.H. Anti-atherogenic effect of citrus flavonoids, naringin and naringenin, associated with hepatic ACAT and aortic VCAM-1 and MCP-1 in high cholesterol-fed rabbits. Biochem. Biophys. Res. Commun., 2001, 284(3), 681-688.
[http://dx.doi.org/10.1006/bbrc.2001.5001] [PMID: 11396955]
[147]
Xu, X.; Lei, T.; Li, W.; Ou, H. Enhanced cellular cholesterol efflux by naringenin is mediated through inhibiting endoplasmic reticulum stress - ATF6 activity in macrophages. Biochim. Biophys. Acta Mol. Cell Biol. Lipids, 2019, 1864(10), 1472-1482.
[http://dx.doi.org/10.1016/j.bbalip.2019.06.005] [PMID: 31176760]
[148]
Qin, W.; Ren, B.; Wang, S.; Liang, S.; He, B.; Shi, X.; Wang, L.; Liang, J.; Wu, F. Apigenin and naringenin ameliorate PKCβII-associated endothelial dysfunction via regulating ROS/caspase-3 and NO pathway in endothelial cells exposed to high glucose. Vascul. Pharmacol., 2016, 85, 39-49.
[http://dx.doi.org/10.1016/j.vph.2016.07.006] [PMID: 27473516]
[149]
Richard, A.J.; Amini-Vaughan, Z.; Ribnicky, D.M.; Stephens, J.M. Naringenin inhibits adipogenesis and reduces insulin sensitivity and adiponectin expression in adipocytes. Evid. Based Complement. Alternat. Med., 2013, 2013, 549750.
[http://dx.doi.org/10.1155/2013/549750] [PMID: 23983791]
[150]
Chen, S.; Ding, Y.; Tao, W.; Zhang, W.; Liang, T.; Liu, C. Naringenin inhibits TNF-α induced VSMC proliferation and migration via induction of HO-1. Food Chem. Toxicol., 2012, 50(9), 3025-3031.
[http://dx.doi.org/10.1016/j.fct.2012.06.006] [PMID: 22709785]
[151]
Choi, A.M.; Alam, J. Heme oxygenase-1: Function, regulation, and implication of a novel stress-inducible protein in oxidant-induced lung injury. Am. J. Respir. Cell Mol. Biol., 1996, 15(1), 9-19.
[http://dx.doi.org/10.1165/ajrcmb.15.1.8679227] [PMID: 8679227]
[152]
Hernández-Aquino, E.; Zarco, N.; Casas-Grajales, S.; Ramos-Tovar, E.; Flores-Beltrán, R.E.; Arauz, J.; Shibayama, M.; Favari, L.; Tsutsumi, V.; Segovia, J.; Muriel, P. Naringenin prevents experimental liver fibrosis by blocking TGFβ-Smad3 and JNK-Smad3 pathways. World J. Gastroenterol., 2017, 23(24), 4354-4368.
[http://dx.doi.org/10.3748/wjg.v23.i24.4354] [PMID: 28706418]
[153]
Yahfoufi, N.; Alsadi, N.; Jambi, M.; Matar, C. The immunomodulatory and anti-inflammatory role of polyphenols. Nutrients, 2018, 10(11), 1618.
[http://dx.doi.org/10.3390/nu10111618] [PMID: 30400131]
[154]
Zhao, Y.; Liu, S. Bioactivity of naringin and related mechanisms. Pharmazie, 2021, 76(8), 359-363.
[PMID: 34412734]
[155]
Mollace, V.; Sacco, I.; Janda, E.; Malara, C.; Ventrice, D.; Colica, C.; Visalli, V.; Muscoli, S.; Ragusa, S.; Muscoli, C.; Rotiroti, D.; Romeo, F. Hypolipemic and hypoglycaemic activity of bergamot polyphenols: From animal models to human studies. Fitoterapia, 2011, 82(3), 309-316.
[http://dx.doi.org/10.1016/j.fitote.2010.10.014] [PMID: 21056640]
[156]
Dow, C.A.; Going, S.B.; Chow, H.H.; Patil, B.S.; Thomson, C.A. The effects of daily consumption of grapefruit on body weight, lipids, and blood pressure in healthy, overweight adults. Metabolism, 2012, 61(7), 1026-1035.
[http://dx.doi.org/10.1016/j.metabol.2011.12.004] [PMID: 22304836]
[157]
Aptekmann, N.P.; Cesar, T.B. Long-term orange juice consumption is associated with low LDL-cholesterol and apolipoprotein B in normal and moderately hypercholesterolemic subjects. Lipids Health Dis., 2013, 12, 119.
[http://dx.doi.org/10.1186/1476-511X-12-119] [PMID: 23919812]
[158]
Kurowska, E.M.; Spence, J.D.; Jordan, J.; Wetmore, S.; Freeman, D.J.; Piché, L.A.; Serratore, P. HDL-cholesterol-raising effect of orange juice in subjects with hypercholesterolemia. Am. J. Clin. Nutr., 2000, 72(5), 1095-1100.
[http://dx.doi.org/10.1093/ajcn/72.5.1095] [PMID: 11063434]
[159]
Dallas, C.; Gerbi, A.; Elbez, Y.; Caillard, P.; Zamaria, N.; Cloarec, M. Clinical study to assess the efficacy and safety of a citrus polyphenolic extract of red orange, grapefruit, and orange (Sinetrol-XPur) on weight management and metabolic parameters in healthy overweight individuals. Phytother. Res., 2014, 28(2), 212-218.
[http://dx.doi.org/10.1002/ptr.4981] [PMID: 23554029]
[160]
Knekt, P.; Kumpulainen, J.; Järvinen, R.; Rissanen, H.; Heliövaara, M.; Reunanen, A.; Hakulinen, T.; Aromaa, A. Flavonoid intake and risk of chronic diseases. Am. J. Clin. Nutr., 2002, 76(3), 560-568.
[http://dx.doi.org/10.1093/ajcn/76.3.560] [PMID: 12198000]
[161]
Farook, V.S.; Reddivari, L.; Chittoor, G.; Puppala, S.; Arya, R.; Fowler, S.P.; Hunt, K.J.; Curran, J.E.; Comuzzie, A.G.; Lehman, D.M.; Jenkinson, C.P.; Lynch, J.L.; DeFronzo, R.A.; Blangero, J.; Hale, D.E.; Duggirala, R.; Vanamala, J. Metabolites as novel biomarkers for childhood obesity-related traits in Mexican-American children. Pediatr. Obes., 2015, 10(4), 320-327.
[http://dx.doi.org/10.1111/ijpo.270] [PMID: 25405847]
[162]
Russell, R.P. Side effects of calcium channel blockers. Hypertension, 1988, 11(3 Pt 2), II42-II44.
[PMID: 3280492]
[163]
Burnier, M.; Brunner, H.R. Angiotensin II receptor antagonists. Lancet, 2000, 355(9204), 637-645.
[http://dx.doi.org/10.1016/S0140-6736(99)10365-9] [PMID: 10696996]
[164]
Sowers, J.R.; Epstein, M. Diabetes mellitus and associated hypertension, vascular disease, and nephropathy. An update. Hypertension, 1995, 26(6 Pt 1), 869-879.
[http://dx.doi.org/10.1161/01.HYP.26.6.869] [PMID: 7490142]
[165]
Scalbert, A.; Williamson, G. Dietary intake and bioavailability of polyphenols. J. Nutr., 2000, 130(Suppl.), 2073S-2085S.
[http://dx.doi.org/10.1093/jn/130.8.2073S]
[166]
Beecher, G.R. Overview of dietary flavonoids: Nomenclature, occurrence and intake. J. Nutr., 2003, 133(Suppl.), 3248S-3254S.
[http://dx.doi.org/10.1093/jn/133.10.3248S]
[167]
Chun, O.K.; Chung, S.J.; Song, W.O. Estimated dietary flavonoid intake and major food sources of U.S. adults. J. Nutr., 2007, 137(5), 1244-1252.
[http://dx.doi.org/10.1093/jn/137.5.1244] [PMID: 17449588]
[168]
Lyons-Wall, P.; Autenzio, P.; Lee, E.; Moss, R.; Samman, S. Catechins are the major source of flavonoids in a group of Australian women. Asia Pac. J. Clin. Nutr., 2004, 13, S72.
[169]
Bai, Y.; Peng, W.; Yang, C.; Zou, W.; Liu, M.; Wu, H.; Fan, L.; Li, P.; Zeng, X.; Su, W. Pharmacokinetics and metabolism of naringin and active metabolite naringenin in rats, dogs, humans, and the differences between species. Front. Pharmacol., 2020, 11, 364.
[http://dx.doi.org/10.3389/fphar.2020.00364] [PMID: 32292344]
[170]
Hsiu, S.L.; Huang, T.Y.; Hou, Y.C.; Chin, D.H.; Chao, P.D. Comparison of metabolic pharmacokinetics of naringin and naringenin in rabbits. Life Sci., 2002, 70(13), 1481-1489.
[http://dx.doi.org/10.1016/S0024-3205(01)01491-6] [PMID: 11895099]
[171]
Liu, M.; Zou, W.; Yang, C.; Peng, W.; Su, W. Metabolism and excretion studies of oral administered naringin, a putative antitussive, in rats and dogs. Biopharm. Drug Dispos., 2012, 33(3), 123-134.
[http://dx.doi.org/10.1002/bdd.1775] [PMID: 22374702]
[172]
Ma, Y.; Li, P.; Chen, D.; Fang, T.; Li, H.; Su, W. LC/MS/MS quantitation assay for pharmacokinetics of naringenin and double peaks phenomenon in rats plasma. Int. J. Pharm., 2006, 307(2), 292-299.
[http://dx.doi.org/10.1016/j.ijpharm.2005.10.018] [PMID: 16289985]
[173]
Zeng, X.; Bai, Y.; Peng, W.; Su, W. Identification of naringin metabolites in human urine and feces. Eur. J. Drug Metab. Pharmacokinet., 2017, 42(4), 647-656.
[http://dx.doi.org/10.1007/s13318-016-0380-z] [PMID: 27744636]
[174]
Sun, H.; Dong, T.; Zhang, A.; Yang, J.; Yan, G.; Sakurai, T.; Wu, X.; Han, Y.; Wang, X. Pharmacokinetics of hesperetin and naringenin in the Zhi Zhu Wan, a traditional Chinese medicinal formulae, and its pharmacodynamics study. Phytother. Res., 2013, 27(9), 1345-1351.
[http://dx.doi.org/10.1002/ptr.4867] [PMID: 23148023]
[175]
Fuhr, U.; Kummert, A.L. The fate of naringin in humans: A key to grapefruit juice-drug interactions? Clin. Pharmacol. Ther., 1995, 58(4), 365-373.
[http://dx.doi.org/10.1016/0009-9236(95)90048-9] [PMID: 7586927]
[176]
Ishii, K.; Furuta, T.; Kasuya, Y. Determination of naringin and naringenin in human urine by high-performance liquid chromatography utilizing solid-phase extraction. J. Chromatogr. B Biomed. Sci. Appl., 1997, 704(1-2), 299-305.
[http://dx.doi.org/10.1016/S0378-4347(97)00474-X] [PMID: 9518163]
[177]
Lee, Y.S.; Reidenberg, M.M. A method for measuring naringenin in biological fluids and its disposition from grapefruit juice by man. Pharmacology, 1998, 56(6), 314-317.
[http://dx.doi.org/10.1159/000028215] [PMID: 9654218]
[178]
Terao, J.; Murota, K.; Kawai, Y. Conjugated quercetin glucuronides as bioactive metabolites and precursors of aglycone in vivo. Food Funct., 2011, 2(1), 11-17.
[http://dx.doi.org/10.1039/C0FO00106F] [PMID: 21773581]
[179]
Matsumoto, T.; Kaneko, A.; Koseki, J.; Matsubara, Y.; Aiba, S.; Yamasaki, K. Pharmacokinetic Study of bioactive flavonoids in the traditional Japanese medicine keigairengyoto exerting antibacterial effects against Staphylococcus aureus. Int. J. Mol. Sci., 2018, 19(2), E328.
[http://dx.doi.org/10.3390/ijms19020328] [PMID: 29360768]
[180]
Wang, M.; Chao, P.; Hou, Y.; Hsiu, S.; Wen, K.; Tsai, S. Pharmacokinetics and conjugation metabolism of naringin and naringenin in rats after single dose and multiple dose administrations. Yao Wu Shi Pin Fen Xi, 2006, 14, 247-253.
[181]
Walle, T. Absorption and metabolism of flavonoids. Free Radic. Biol. Med., 2004, 36(7), 829-837.
[http://dx.doi.org/10.1016/j.freeradbiomed.2004.01.002] [PMID: 15019968]
[182]
Felgines, C.; Texier, O.; Morand, C.; Manach, C.; Scalbert, A.; Régerat, F.; Rémésy, C. Bioavailability of the flavanone naringenin and its glycosides in rats. Am. J. Physiol. Gastrointest. Liver Physiol., 2000, 279(6), G1148-G1154.
[http://dx.doi.org/10.1152/ajpgi.2000.279.6.G1148] [PMID: 11093936]
[183]
Kanaze, F.I.; Bounartzi, M.I.; Georgarakis, M.; Niopas, I. Pharmacokinetics of the citrus flavanone aglycones hesperetin and naringenin after single oral administration in human subjects. Eur. J. Clin. Nutr., 2007, 61(4), 472-477.
[http://dx.doi.org/10.1038/sj.ejcn.1602543] [PMID: 17047689]
[184]
El Mohsen, M.A.; Marks, J.; Kuhnle, G.; Rice-Evans, C.; Moore, K.; Gibson, G.; Debnam, E.; Srai, S.K. The differential tissue distribution of the citrus flavanone naringenin following gastric instillation. Free Radic. Res., 2004, 38(12), 1329-1340.
[http://dx.doi.org/10.1080/10715760400017293] [PMID: 15763957]
[185]
Wilcox, L.J.; Borradaile, N.M.; Huff, M.W. Antiatherogenic properties of naringenin, a citrus flavonoid. Cardiovasc. Drug Rev., 1999, 17(2), 160-178.
[http://dx.doi.org/10.1111/j.1527-3466.1999.tb00011.x]
[186]
Bacanlı, M.; Başaran, A.A.; Başaran, N. The major flavonoid of grapefruit: Naringin. In: Polyphenols: Prevention and Treatment of Human Disease, 2nd ed; Watson, R.R.; Preedy, V.R.; Zibadi, S., Eds.; Academic Press: Cambridge, Massachusetts, 2018; pp. 37-44.
[187]
Liu, M.; Yang, C.; Zou, W.; Guan, X.; Zheng, W.; Lai, L.; Fang, S.; Cai, S.; Su, W. Toxicokinetics of naringin, a putative antitussive, after 184-day repeated oral administration in rats. Environ. Toxicol. Pharmacol., 2011, 31(3), 485-489.
[http://dx.doi.org/10.1016/j.etap.2011.01.006] [PMID: 21787720]
[188]
Li, P.; Wang, S.; Guan, X.; Cen, X.; Hu, C.; Peng, W.; Wang, Y.; Su, W. Six months chronic toxicological evaluation of naringin in Sprague-Dawley rats. Food Chem. Toxicol., 2014, 66, 65-75.
[http://dx.doi.org/10.1016/j.fct.2014.01.023] [PMID: 24462649]
[189]
Fuhr, U.; Klittich, K.; Staib, A.H. Inhibitory effect of grapefruit juice and its bitter principal, naringenin, on CYP1A2 dependent metabolism of caffeine in man. Br. J. Clin. Pharmacol., 1993, 35(4), 431-436.
[http://dx.doi.org/10.1111/j.1365-2125.1993.tb04162.x] [PMID: 8485024]
[190]
Allen, L.V.; Ansel, H.C. Ansel’s Pharmaceutical Dosage Forms and Drug Delivery Systems; Wolters Kluwer Health: Baltimore, MD, 2014.
[191]
Anselmo, A.C.; Mitragotri, S. An overview of clinical and commercial impact of drug delivery systems. J. Control. Release, 2014, 190, 15-28.
[http://dx.doi.org/10.1016/j.jconrel.2014.03.053] [PMID: 24747160]
[192]
Cassidy, A.; Minihane, A.M. The role of metabolism (and the microbiome) in defining the clinical efficacy of dietary flavonoids. Am. J. Clin. Nutr., 2017, 105(1), 10-22.
[http://dx.doi.org/10.3945/ajcn.116.136051] [PMID: 27881391]
[193]
Choi, J.S.; Shin, S.C. Enhanced paclitaxel bioavailability after oral coadministration of paclitaxel prodrug with naringin to rats. Int. J. Pharm., 2005, 292(1-2), 149-156.
[http://dx.doi.org/10.1016/j.ijpharm.2004.11.031] [PMID: 15725561]
[194]
Rivoira, M.A.; Rodriguez, V.; Talamoni, G.; Tolosa de Talamoni, N. New perspectives in the pharmacological potential of naringin in medicine. Curr. Med. Chem., 2021, 28(10), 1987-2007.
[http://dx.doi.org/10.2174/0929867327666200604171351] [PMID: 32496985]
[195]
Budel, R.G.; da Silva, D.A.; Moreira, M.P.; Dalcin, A.J.F.; da Silva, A.F.; Nazario, L.R.; Majolo, J.H.; Lopes, L.Q.S.; Santos, R.C.V.; Antunes Soares, F.A.; da Silva, R.S.; Gomes, P.; Boeck, C.R. Toxicological evaluation of naringin-loaded nanocapsules in vitro and in vivo. Colloids Surf. B Biointerfaces, 2020, 188, 110754.
[http://dx.doi.org/10.1016/j.colsurfb.2019.110754] [PMID: 31887647]
[196]
Bhia, M.; Motallebi, M.; Abadi, B.; Zarepour, A.; Pereira-Silva, M.; Saremnejad, F.; Santos, A.C.; Zarrabi, A.; Melero, A.; Jafari, S.M.; Shakibaei, M. Naringenin nano-delivery systems and their therapeutic applications. Pharmaceutics, 2021, 13(2), 291.
[http://dx.doi.org/10.3390/pharmaceutics13020291] [PMID: 33672366]
[197]
Rao, K.; Imran, M.; Jabri, T.; Ali, I.; Perveen, S.; Shafiullah, A.S.; Ahmed, S.; Shah, M.R. Gum tragacanth stabilized green gold nanoparticles as cargos for Naringin loading: A morphological investigation through AFM. Carbohydr. Polym., 2017, 174, 243-252.
[http://dx.doi.org/10.1016/j.carbpol.2017.06.071] [PMID: 28821064]
[198]
Santo, V.E.; Gomes, M.E.; Mano, J.F.; Reis, R.L. From nano- to macro-scale: Nanotechnology approaches for spatially controlled delivery of bioactive factors for bone and cartilage engineering. Nanomedicine (Lond.), 2012, 7(7), 1045-1066.
[http://dx.doi.org/10.2217/nnm.12.78] [PMID: 22846091]
[199]
Singh, R.; Lillard, J.W.J. Jr Nanoparticle-based targeted drug delivery. Exp. Mol. Pathol., 2009, 86(3), 215-223.
[http://dx.doi.org/10.1016/j.yexmp.2008.12.004] [PMID: 19186176]
[200]
Lavrador, P.; Gaspar, V.M.; Mano, J.F. Bioinspired bone therapies using naringin: Applications and advances. Drug Discov. Today, 2018, 23(6), 1293-1304.
[http://dx.doi.org/10.1016/j.drudis.2018.05.012] [PMID: 29747006]
[201]
Low, S.A.; Kopeček, J. Targeting polymer therapeutics to bone. Adv. Drug Deliv. Rev., 2012, 64(12), 1189-1204.
[http://dx.doi.org/10.1016/j.addr.2012.01.012] [PMID: 22316530]
[202]
Cordenonsi, L.M.; Bromberger, N.G.; Raffin, R.P.; Scherman, E.E. Simultaneous separation and sensitive detection of naringin and naringenin in nanoparticles by chromatographic method indicating stability and photodegradation kinetics. Biomed. Chromatogr., 2016, 30(2), 155-162.
[http://dx.doi.org/10.1002/bmc.3531] [PMID: 26053258]
[203]
Kim, Y.H.; Tabata, Y. Dual-controlled release system of drugs for bone regeneration. Adv. Drug Deliv. Rev., 2015, 94, 28-40.
[http://dx.doi.org/10.1016/j.addr.2015.06.003] [PMID: 26079284]
[204]
Zeng, X.; Yao, H.; Zheng, Y.; He, Y.; He, Y.; Rao, H.; Li, P.; Su, W. Tissue distribution of naringin and derived metabolites in rats after a single oral administration. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2020, 1136, 121846.
[http://dx.doi.org/10.1016/j.jchromb.2019.121846] [PMID: 31821965]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy