A Review on the Pharmacokinetic Properties of Naringin and Its Therapeutic Efficacies in Respiratory Diseases

Author(s): Xuan Zeng, Weiwei Su, Buming Liu, Ling Chai, Rui Shi, Hongliang Yao*.

Journal Name: Mini-Reviews in Medicinal Chemistry

Volume 20 , Issue 4 , 2020

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Graphical Abstract:


Abstract:

Flavonoids are an important class of phytopharmaceuticals in plants. Naringin (naringenin- 7-O-rhamnoglucoside) is a flavanone glycoside isolated from folk herbal medicine Exocarpium Citri grandis (called Huajuhong in Chinese). Massive experimental works have been performed on naringin describing its phytochemical, pharmacokinetic, and bioactive properties. Naringin was found to possess multiple pharmacological activities in relieving inflammation, diabetes, neurodegeneration, cardiovascular disorders, and metabolic syndrome. Recently, it has been approved as a potential antitussive and expectorant for clinical trials. However, the pharmacokinetic aspects of naringin and its therapeutic potentials in respiratory diseases have not been comprehensively reviewed. The present review provides highlights of naringin with respect to its absorption, distribution, metabolism, excretion and its therapeutic effects on cough, phlegm, and pulmonary inflammation. This review would be helpful for the interpretation of pharmacokinetics and pharmacodynamics of naringin in clinical trials.

Keywords: Naringin, pharmacokinetics, therapeutic efficacies, antitussive, expectorant, anti-inflammation.

[1]
Wang, T.; Li, Q.; Bi, K. Bioactive flavonoids in medicinal plants: Structure, activity and biological fate. Asian J. Pharm. Sci, 2018, 13, 12-23.
[http://dx.doi.org/10.1016/j.ajps.2017.08.004]
[2]
Yang, B.; Liu, H.; Yang, J.; Gupta, V.K.; Jiang, Y. New insights on bioactivities and biosynthesis of flavonoid glycosides. Trends Food Sci. Technol., 2018, 79, 116-124.
[http://dx.doi.org/10.1016/j.tifs.2018.07.006]
[3]
Raffa, D.; Maggio, B.; Raimondi, M.V.; Plescia, F.; Daidone, G. Recent discoveries of anticancer flavonoids. Eur. J. Med. Chem., 2017, 142, 213-228.
[http://dx.doi.org/10.1016/j.ejmech.2017.07.034] [PMID: 28793973]
[4]
Guan, L.P.; Liu, B.Y. Antidepressant-like effects and mechanisms of flavonoids and related analogues. Eur. J. Med. Chem., 2016, 121, 47-57.
[http://dx.doi.org/10.1016/j.ejmech.2016.05.026] [PMID: 27214511]
[5]
Wan, L.; Jiang, J. Protective effects of plant-derived flavonoids on hepatic injury. J. Funct. Foods, 2018, 44, 283-291.
[http://dx.doi.org/10.1016/j.jff.2018.03.015]
[6]
Wu, W.Y.; Hou, J.J.; Long, H.L.; Yang, W.Z.; Liang, J.; Guo, D.A. TCM-based new drug discovery and development in China. Chin. J. Nat. Med., 2014, 12(4), 241-250.
[http://dx.doi.org/10.1016/S1875-5364(14)60050-9] [PMID: 24863348]
[7]
Zheng, Y.Y.; Zeng, X.; Peng, W.; Wu, Z.; Su, W.W. Characterisation and classification of Citri Reticulatae Pericarpium varieties based on UHPLC-Q-TOF-MS/MS combined with multivariate statistical analyses. Phytochem. Anal., 2019, 30(3), 278-291.
[http://dx.doi.org/10.1002/pca.2812] [PMID: 30588683]
[8]
Li, P.L.; Liu, M.H.; Hu, J.H.; Su, W.W. Systematic chemical profiling of Citrus grandis ‘Tomentosa’ by ultra-fast liquid chromatography/diode-array detector/quadrupole time-of-flight tandem mass spectrometry. J. Pharm. Biomed. Anal., 2014, 90, 167-179.
[http://dx.doi.org/10.1016/j.jpba.2013.11.030] [PMID: 24370611]
[9]
Jiang, K.; Song, Q.; Wang, L.; Xie, T.; Wu, X.; Wang, P.; Yin, G.; Ye, W.; Wang, T. Antitussive, expectorant and anti-inflammatory activities of different extracts from Exocarpium Citri grandis. J. Ethnopharmacol., 2014, 156, 97-101.
[http://dx.doi.org/10.1016/j.jep.2014.08.030] [PMID: 25178947]
[10]
Li, P.B.; Ma, Y.; Wang, Y.G.; Su, W.W. Experimental studies on antitussive, expectorant and antiasthmatic effects of extract from Citrus grandis var. tomentosa. Zhongguo Zhongyao Zazhi, 2006, 31(16), 1350-1352.
[PMID: 17061559]
[11]
Li, P.; Wang, Y.; Wu, Z.; Peng, W.; Yang, C.; Nie, Y.; Liu, M.; Luo, Y.; Zou, W.; Liu, Y. The pre-clinical studies of naringin,an innovative drug,derived from Citri Grandis Exocarpium (Huajuhong). Acta Sci. Natur. Univ. Sunyatseni, 2015, 54, 1-5.
[12]
Yao, H.; Su, W.; Lin, L.; Pan, W.; Zeng, X.; Li, P. Comprehensive investigation into the interconversion of C-2 diastereomers of naringin. Chirality, 2018, 30(5), 652-660.
[http://dx.doi.org/10.1002/chir.22830] [PMID: 29443426]
[13]
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]
[14]
Gao, S.; Li, P.; Yang, H.; Fang, S.; Su, W. Antitussive effect of naringin on experimentally induced cough in Guinea pigs. Planta Med., 2011, 77(1), 16-21.
[http://dx.doi.org/10.1055/s-0030-1250117] [PMID: 20645246]
[15]
Lin, B.Q.; Li, P.B.; Wang, Y.G.; Peng, W.; Wu, Z.; Su, W.W.; Ji, H. The expectorant activity of naringenin. Pulm. Pharmacol. Ther., 2008, 21(2), 259-263.
[http://dx.doi.org/10.1016/j.pupt.2007.05.001] [PMID: 17664077]
[16]
Nie, Y.C.; Wu, H.; Li, P.B.; Luo, Y.L.; Long, K.; Xie, L.M.; Shen, J.G.; Su, W.W. Anti-inflammatory effects of naringin in chronic pulmonary neutrophilic inflammation in cigarette smoke-exposed rats. J. Med. Food, 2012, 15(10), 894-900.
[http://dx.doi.org/10.1089/jmf.2012.2251] [PMID: 22985397]
[17]
Li, P.; Wang, S.; Guan, X.; Liu, B.; Wang, Y.; Xu, K.; Peng, W.; Su, W.; Zhang, K. Acute and 13 weeks subchronic toxicological evaluation of naringin in Sprague-Dawley rats. Food Chem. Toxicol., 2013, 60, 1-9.
[http://dx.doi.org/10.1016/j.fct.2013.07.019] [PMID: 23871784]
[18]
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]
[19]
Zeng, X.; Su, W.; Liu, H.; Zheng, Y.; Chen, T.; Zhang, W.; Yan, Z.; Bai, Y.; Yao, H. Simultaneous determination of rosuvastatin, naringin and naringenin in rat plasma by RRLC-MS/MS and its application to a pharmacokinetic drug interaction study. J. Chromatogr. Sci., 2018, 56(7), 611-618.
[http://dx.doi.org/10.1093/chromsci/bmy034] [PMID: 29701749]
[20]
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]
[21]
Patel, K.; Singh, G.K.; Patel, D.K. A review on pharmacological and analytical aspects of naringenin. Chin. J. Integr. Med., 2018, 24(7), 551-560.
[http://dx.doi.org/10.1007/s11655-014-1960-x] [PMID: 25501296]
[22]
Orrego-Lagarón, N.; Martínez-Huélamo, M.; Vallverdú-Queralt, A.; Lamuela-Raventos, R.M.; Escribano-Ferrer, E. High gastrointestinal permeability and local metabolism of naringenin: Influence of antibiotic treatment on absorption and metabolism. Br. J. Nutr., 2015, 114(2), 169-180.
[http://dx.doi.org/10.1017/S0007114515001671] [PMID: 26083965]
[23]
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]
[24]
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.
[25]
Fang, T.; Wang, Y.; Ma, Y.; Su, W.; Bai, Y.; Zhao, P. A rapid LC/MS/MS quantitation assay for naringin and its two metabolites in rats plasma. J. Pharm. Biomed. Anal., 2006, 40(2), 454-459.
[http://dx.doi.org/10.1016/j.jpba.2005.07.031] [PMID: 16406442]
[26]
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]
[27]
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]
[28]
Mata-Bilbao, Mde.L.; Andrés-Lacueva, C.; Roura, E.; Jáuregui, O.; Escribano, E.; Torre, C.; Lamuela-Raventós, R.M. . Absorption and pharmacokinetics of grapefruit flavanones in beagles. Br. J. Nutr., 2007, 98(1), 86-92.
[http://dx.doi.org/10.1017/S0007114507707262] [PMID: 17391560]
[29]
Yang, C.P.; Liu, M.H.; Zou, W.; Guan, X.L.; Lai, L.; Su, W.W. Toxicokinetics of naringin and its metabolite naringenin after 180-day repeated oral administration in beagle dogs assayed by a rapid resolution liquid chromatography/tandem mass spectrometric method. J. Asian Nat. Prod. Res., 2012, 14(1), 68-75.
[http://dx.doi.org/10.1080/10286020.2011.632369] [PMID: 22263596]
[30]
Erlund, I.; Meririnne, E.; Alfthan, G.; Aro, A. Plasma kinetics and urinary excretion of the flavanones naringenin and hesperetin in humans after ingestion of orange juice and grapefruit juice. J. Nutr., 2001, 131(2), 235-241.
[http://dx.doi.org/10.1093/jn/131.2.235] [PMID: 11160539]
[31]
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]
[32]
Zeng, X.; Su, W.; Bai, Y.; Chen, T.; Yan, Z.; Wang, J.; Su, M.; Zheng, Y.; Peng, W.; Yao, H. Urinary metabolite profiling of flavonoids in Chinese volunteers after consumption of orange juice by UFLC-Q-TOF-MS/MS. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2017, 1061-1062, 79-88.
[http://dx.doi.org/10.1016/j.jchromb.2017.07.015] [PMID: 28711784]
[33]
Chen, R.; Shang, Y.; Li, Q.; Li, X.; Zhao, J. Study on the absorption characteristics of naringin in situ single-pass intestinal perfusion model of rats. China Pharm., 2018, 29, 47-50.
[34]
Tsai, Y-J.; Tsai, T-H. Mesenteric lymphatic absorption and the pharmacokinetics of naringin and naringenin in the rat. J. Agric. Food Chem., 2012, 60(51), 12435-12442.
[http://dx.doi.org/10.1021/jf301962g] [PMID: 23210543]
[35]
Chen, Z.; Zheng, S.; Li, L.; Jiang, H. Metabolism of flavonoids in human: A comprehensive review. Curr. Drug Metab., 2014, 15(1), 48-61.
[http://dx.doi.org/10.2174/138920021501140218125020] [PMID: 24588554]
[36]
Zeng, X.; Su, W.; Zheng, Y.; He, Y.; He, Y.; Rao, H.; Peng, W.; Yao, H. Pharmacokinetics, tissue distribution, metabolism, and excretion of naringin in aged Rats. Front. Pharmacol., 2019, 10, 34.
[http://dx.doi.org/10.3389/fphar.2019.00034] [PMID: 30761003]
[37]
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]
[38]
Zeng, X.; Su, W.; Bai, Y.; Peng, W.; Yao, H. HPLC-MS/MS method for simultaneous determination of naringin and naringenin in human plasma. Acta Sci. Natur. Univ. Sunyatseni, 2017, 56, 125-130.
[39]
Zhang, L.; Zuo, Z.; Lin, G. Intestinal and hepatic glucuronidation of flavonoids. Mol. Pharm., 2007, 4(6), 833-845.
[http://dx.doi.org/10.1021/mp700077z] [PMID: 17979245]
[40]
Liu, M.; Zou, W.; Fan, L.; Li, P.; Su, W. Comparative protein binding of naringin and its aglycone naringenin in rat, dog and human plasma. Afr. J. Pharm. Pharmacol., 2012, 6, 934-940.
[41]
Zou, W.; Yang, C.; Liu, M.; Su, W. Tissue distribution study of naringin in rats by liquid chromatography-tandem mass spectrometry. Arzneimittelforschung, 2012, 62(4), 181-186.
[http://dx.doi.org/10.1055/s-0031-1299746] [PMID: 22270844]
[42]
Lin, S.P.; Hou, Y.C.; Tsai, S.Y.; Wang, M.J.; Chao, P.D. Tissue distribution of naringenin conjugated metabolites following repeated dosing of naringin to rats. Biomedicine (Taipei), 2014, 4, 16.
[http://dx.doi.org/10.7603/s40681-014-0016-z] [PMID: 25520929]
[43]
Wang, X.; Zhao, X.; Gu, L.; Lv, C.; He, B.; Liu, Z.; Hou, P.; Bi, K.; Chen, X. Simultaneous determination of five free and total flavonoids in rat plasma by ultra HPLC-MS/MS and its application to a comparative pharmacokinetic study in normal and hyperlipidemic rats. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2014, 953-954, 1-10.
[http://dx.doi.org/10.1016/j.jchromb.2014.01.042] [PMID: 24566333]
[44]
Zhang, J.; Brodbelt, J.S. Screening flavonoid metabolites of naringin and narirutin in urine after human consumption of grapefruit juice by LC-MS and LC-MS/MS. Analyst (Lond.), 2004, 129(12), 1227-1233.
[http://dx.doi.org/10.1039/b412577k] [PMID: 15565223]
[45]
Zou, W.; Luo, Y.; Liu, M.; Chen, S.; Wang, S.; Nie, Y.; Cheng, G.; Su, W.; Zhang, K. Human intestinal microbial metabolism of naringin. Eur. J. Drug Metab. Pharmacokinet., 2015, 40(3), 363-367.
[http://dx.doi.org/10.1007/s13318-014-0193-x] [PMID: 24935725]
[46]
Zeng, X.; Su, W.; Zheng, Y.; Liu, H.; Li, P.; Zhang, W.; Liang, Y.; Bai, Y.; Peng, W.; Yao, H. UFLC-Q-TOF-MS/MS-based screening and identification of flavonoids and derived metabolites in human urine after oral administration of Exocarpium Citri Grandis extract. Molecules, 2018, 23(4), 895.
[http://dx.doi.org/10.3390/molecules23040895] [PMID: 29649170]
[47]
Breinholt, V.M.; Offord, E.A.; Brouwer, C.; Nielsen, S.E.; Brøsen, K.; Friedberg, T. In vitro investigation of cytochrome P450-mediated metabolism of dietary flavonoids. Food Chem. Toxicol., 2002, 40(5), 609-616.
[http://dx.doi.org/10.1016/S0278-6915(01)00125-9] [PMID: 11955666]
[48]
Ishii, K.; Furuta, T.; Kasuya, Y. Mass spectrometric identification and high-performance liquid chromatographic determination of a flavonoid glycoside naringin in human urine. J. Agric. Food Chem., 2000, 48(1), 56-59.
[http://dx.doi.org/10.1021/jf9907992] [PMID: 10637051]
[49]
Pereira-Caro, G.; Borges, G.; van der Hooft, J.; Clifford, M.N.; Del Rio, D.; Lean, M.E.J.; Roberts, S.A.; Kellerhals, M.B.; Crozier, A. Orange juice (poly)phenols are highly bioavailable in humans. Am. J. Clin. Nutr., 2014, 100(5), 1378-1384.
[http://dx.doi.org/10.3945/ajcn.114.090282] [PMID: 25332336]
[50]
Pereira-Caro, G.; Ludwig, I.A.; Polyviou, T.; Malkova, D.; García, A.; Moreno-Rojas, J.M.; Crozier, A. Identification of plasma and urinary metabolites and catabolites derived from orange juice (poly)phenols: Analysis by high-performance liquid chromatography–high-resolution mass spectrometry. J. Agric. Food Chem., 2016, 64(28), 5724-5735.
[http://dx.doi.org/10.1021/acs.jafc.6b02088] [PMID: 27339035]
[51]
Feng, L.; He, Y.; Xu, G.; Hu, H.; Guo, L.; Wan, J. Determination of tyrosine and its metabolites in human serum with application to cancer diagnosis. Anal. Lett., 2014, 47, 1275-1289.
[http://dx.doi.org/10.1080/00032719.2013.871549]
[52]
Pero, R.W. Health consequences of catabolic synthesis of hippuric acid in humans. Curr. Clin. Pharmacol., 2010, 5(1), 67-73.
[http://dx.doi.org/10.2174/157488410790410588] [PMID: 19891605]
[53]
Jenner, A.M.; Rafter, J.; Halliwell, B. Human fecal water content of phenolics: The extent of colonic exposure to aromatic compounds. Free Radic. Biol. Med., 2005, 38(6), 763-772.
[http://dx.doi.org/10.1016/j.freeradbiomed.2004.11.020] [PMID: 15721987]
[54]
Chen, T.; Su, W.; Yan, Z.; Wu, H.; Zeng, X.; Peng, W.; Gan, L.; Zhang, Y.; Yao, H. Identification of naringin metabolites mediated by human intestinal microbes with stable isotope-labeling method and UFLC-Q-TOF-MS/MS. J. Pharm. Biomed. Anal., 2018, 161, 262-272.
[http://dx.doi.org/10.1016/j.jpba.2018.08.039] [PMID: 30172881]
[55]
Su, W.; Wang, Y.; Fang, T.; Peng, W.; Wu, Z. Uses of naringenin, naringin and salts thereof as expectorants in the treatment of cough, and compositions thereof. Europ. Pat., 1591123,. 2009.
[56]
Widdicombe, J. Neuroregulation of cough: Implications for drug therapy. Curr. Opin. Pharmacol., 2002, 2(3), 256-263.
[http://dx.doi.org/10.1016/S1471-4892(02)00152-2] [PMID: 12020466]
[57]
Luo, Y.L.; Zhang, C.C.; Li, P.B.; Nie, Y.C.; Wu, H.; Shen, J.G.; Su, W.W. Naringin attenuates enhanced cough, airway hyperresponsiveness and airway inflammation in a guinea pig model of chronic bronchitis induced by cigarette smoke. Int. Immunopharmacol., 2012, 13(3), 301-307.
[http://dx.doi.org/10.1016/j.intimp.2012.04.019] [PMID: 22575871]
[58]
Luo, Y.L.; Li, P.B.; Zhang, C.C.; Zheng, Y.F.; Wang, S.; Nie, Y.C.; Zhang, K.J.; Su, W.W. Effects of four antitussives on airway neurogenic inflammation in a guinea pig model of chronic cough induced by cigarette smoke exposure. Inflamm. Res., 2013, 62(12), 1053-1061.
[http://dx.doi.org/10.1007/s00011-013-0664-6] [PMID: 24085318]
[59]
Jiao, H.Y.; Su, W.W.; Li, P.B.; Liao, Y.; Zhou, Q.; Zhu, N.; He, L.L. Therapeutic effects of naringin in a guinea pig model of ovalbumin-induced cough-variant asthma. Pulm. Pharmacol. Ther., 2015, 33, 59-65.
[http://dx.doi.org/10.1016/j.pupt.2015.07.002] [PMID: 26169899]
[60]
Chen, Y.; Wu, H.; Nie, Y.C.; Li, P.B.; Shen, J.G.; Su, W.W. Mucoactive effects of naringin in lipopolysaccharide-induced acute lung injury mice and beagle dogs. Environ. Toxicol. Pharmacol., 2014, 38(1), 279-287.
[http://dx.doi.org/10.1016/j.etap.2014.04.030] [PMID: 24998504]
[61]
Nie, Y.C.; Wu, H.; Li, P.B.; Xie, L.M.; Luo, Y.L.; Shen, J.G.; Su, W.W. Naringin attenuates EGF-induced MUC5AC secretion in A549 cells by suppressing the cooperative activities of MAPKs-AP-1 and IKKs-IκB-NF-κB signaling pathways. Eur. J. Pharmacol., 2012, 690(1-3), 207-213.
[http://dx.doi.org/10.1016/j.ejphar.2012.06.040] [PMID: 22766066]
[62]
Rowe, S.M.; Miller, S.; Sorscher, E.J. Cystic fibrosis. N. Engl. J. Med., 2005, 352(19), 1992-2001.
[http://dx.doi.org/10.1056/NEJMra043184] [PMID: 15888700]
[63]
Shi, R.; Xiao, Z.T.; Zheng, Y.J.; Zhang, Y.L.; Xu, J.W.; Huang, J.H.; Zhou, W.L.; Li, P.B.; Su, W.W. Naringenin regulates CFTR activation and expression in airway epithelial cells. Cell. Physiol. Biochem., 2017, 44(3), 1146-1160.
[http://dx.doi.org/10.1159/000485419] [PMID: 29179179]
[64]
Liu, Y.; Wu, H.; Nie, Y.C.; Chen, J.L.; Su, W.W.; Li, P.B. Naringin attenuates acute lung injury in LPS-treated mice by inhibiting NF-κB pathway. Int. Immunopharmacol., 2011, 11(10), 1606-1612.
[http://dx.doi.org/10.1016/j.intimp.2011.05.022] [PMID: 21640201]
[65]
Chen, Y.; Nie, Y.C.; Luo, Y.L.; Lin, F.; Zheng, Y.F.; Cheng, G.H.; Wu, H.; Zhang, K.J.; Su, W.W.; Shen, J.G.; Li, P.B. Protective effects of naringin against paraquat-induced acute lung injury and pulmonary fibrosis in mice. Food Chem. Toxicol., 2013, 58, 133-140.
[http://dx.doi.org/10.1016/j.fct.2013.04.024] [PMID: 23603004]
[66]
Liu, Y.; Su, W.W.; Wang, S.; Li, P.B. Naringin inhibits chemokine production in an LPS-induced RAW 264.7 macrophage cell line. Mol. Med. Rep., 2012, 6(6), 1343-1350.
[http://dx.doi.org/10.3892/mmr.2012.1072] [PMID: 22965302]
[67]
Wei, D.; Ci, X.; Chu, X.; Wei, M.; Hua, S.; Deng, X. Hesperidin suppresses ovalbumin-induced airway inflammation in a mouse allergic asthma model. Inflammation, 2012, 35(1), 114-121.
[http://dx.doi.org/10.1007/s10753-011-9295-7] [PMID: 21287361]
[68]
Seyedrezazadeh, E.; Kolahian, S.; Shahbazfar, A.A.; Ansarin, K.; Pour Moghaddam, M.; Sakhinia, M.; Sakhinia, E.; Vafa, M. Effects of the flavanone combination hesperetin-naringenin, and orange and grapefruit juices, on airway inflammation and remodeling in a murine asthma model. Phytother. Res., 2015, 29(4), 591-598.
[http://dx.doi.org/10.1002/ptr.5292] [PMID: 25640915]
[69]
Fernando, W.; Rupasinghe, H.P.V.; Hoskin, D.W. Regulation of hypoxia-inducible factor-1α and vascular endothelial growth factor signaling by plant flavonoids. Mini Rev. Med. Chem., 2015, 15(6), 479-489.
[http://dx.doi.org/10.2174/1389557515666150414152933] [PMID: 25873069]
[70]
Johnson, J.L.; de Mejia, E.G. Flavonoid apigenin modified gene expression associated with inflammation and cancer and induced apoptosis in human pancreatic cancer cells through inhibition of GSK-3β/NF-κB signaling cascade. Mol. Nutr. Food Res., 2013, 57(12), 2112-2127.
[http://dx.doi.org/10.1002/mnfr.201300307] [PMID: 23943362]
[71]
Li, C.Z.; Jin, H.H.; Sun, H.X.; Zhang, Z.Z.; Zheng, J.X.; Li, S.H.; Han, S.H. Eriodictyol attenuates cisplatin-induced kidney injury by inhibiting oxidative stress and inflammation. Eur. J. Pharmacol., 2016, 772, 124-130.
[http://dx.doi.org/10.1016/j.ejphar.2015.12.042] [PMID: 26723515]
[72]
Ma, H.; Feng, X.; Ding, S. Hesperetin attenuates ventilator-induced acute lung injury through inhibition of NF-κB-mediated inflammation. Eur. J. Pharmacol., 2015, 769, 333-341.
[http://dx.doi.org/10.1016/j.ejphar.2015.11.038] [PMID: 26610718]


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