Emerging Renoprotective Role of Citrus Flavonoid Naringin: Current Pharmaceutical Status and Future Perspectives


Purpose of Review

This review provides a concise overview of emerging renoprotective role of citrus flavonoid naringin. In recent years, naringin has emerged as a therapeutic candidate of interest due to its renoprotective role. Very limited literature is available but still it is interesting to find the strong candidature of naringin in renal function improvements. This is the first review article presenting the recent studies and mechanisms dealing with the renoprotective effect of naringin.

Recent Findings

Naringin is an important flavonoid from citrus fruits which contributes bitter taste to citrus juices. Naringin is an important compound with vast array of biological activities and immense therapeutic role. Naringin is well-known for its various biological and therapeutic activities. It has been found effective even in neurological disorders. In recent years, it has been investigated for renoprotective effect and has been found a promising agent. It seems an important and emerging compound of interest for protecting the renal functions under various conditions. Also, cellular and physiological aspects have been investigated for naringin-mediated improvement in renal functions.


This review emphasizes on the emerging role of naringin as renoprotective compound with special emphasis on the pharmaceutical potential.

This is a preview of subscription content, access via your institution.

Fig. 1


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.

    Ghasemzadeh A, Jaafar HZE. Profiling of phenolic compounds and their antioxidant and anticancer activities in pandan (Pandanus amaryllifolius Roxb.) extracts from different locations of Malaysia. BMC Complement Altern Med. 2013;13:341. https://doi.org/10.1186/1472-6882-13-341.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  2. 2.

    • Chen R, Qi QL, Wang MT, Li QY. Therapeutic potential of naringin: an overview. Pharm Biol. 2016;54:3203–10. https://doi.org/10.1080/13880209.2016.1216131This article provides comprehensive review on therapeutic potential of naringin.

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Wang DM, Yang YJ, Zhang L, Zhang X, Guan FF, Zhang LF. Naringin enhances CaMKII activity and improves long-term memory in a mouse model of Alzheimer’s disease. Int J Mol Sci. 2013;14:5576–86. https://doi.org/10.3390/ijms14035576.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  4. 4.

    • Sehrawat N, Devi S, Devi A, Yadav M. Anti-diabetic and anti-cancerous potential of citrus flavonoid naringin: a review. Med Plants. 2018;10:171–5. https://doi.org/10.5958/0975-6892.2018.00028.XThis article reviewed the therapeutic, anti-diabetic, and anti-cancerous potential of naringin.

    Article  Google Scholar 

  5. 5.

    Singh R, Upadhyay SK, Rani A, Kumar P, Kumar A, Sharma P. Ethanobotanical study of Subhartipuram, Meerut, Uttar Pradesh, India. I. Diversity and pharmacological significance of trees. Int J Pharma Res. 2019;11(4):782–94.

    Google Scholar 

  6. 6.

    • Yadav M, Sehrawat N, Singh M, Upadhyay SK, Aggarwal D, Sharma AK. Cardioprotective and hepatoprotective potential of citrus flavonoid naringin: current status and future perspectives for health benefits. Asian J Biol Life Sci. 2020;9:1–5. https://doi.org/10.5530/ajbls.2020.9.1This article reviewed the recent findings on naringin’s therapeutic potential specifically involving the cardioprotective and hepatoprotective role.

    CAS  Article  Google Scholar 

  7. 7.

    Mahmoud M, Hamdan D, Wink M, El-Shazly A. Naringin and rutin prevent d-galactosamine-induced hepatic injury in rats via attenuation of the inflammatory cascade and oxidative stress. Eur Sci J. 2013;9:141–55. https://doi.org/10.19044/esj.2013.v9n30p%25p.

    Article  Google Scholar 

  8. 8.

    • Chandramohan Y, Parameswari CS. Therapeutic efficacy of naringin on cyclosporine (A) induced nephrotoxicity in rats: involvement of hemeoxygenase-1. Pharmacol Rep. 2013;65:1336–44. https://doi.org/10.1016/s1734-1140(13)71492-0This article reported the role of naringin on cyclosporine-induced nephrotoxicity and mechanism of renal function improvement through enzymatic and non-enzymatic candidate’s involvement.

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Jagetia GC, Reddy TK. The grape fruit flavonone naringin protects mice against doxorubicin-induced cardiotoxicity. J Mol Biochem. 2014;3:34–49.

    Google Scholar 

  10. 10.

    Singh R, Upadhyay SK, Rani A, Kumar P, Kumar A. Ethanobotanical study of Subhartipuram, Meerut, Uttar Pradesh, India. II. Diversity and pharmacological significance of shrubs and climbers. Int J Pharma Res. 2020a;12(2):383–93.

    Google Scholar 

  11. 11.

    Jagetia GC, Venkatesha VA, Reddy TK. Naringin, a citrus flavonone, protects against radiation-induced chromosome damage in mouse bone marrow. Mutagenesis. 2003;18:337–43. https://doi.org/10.1093/mutage/geg001.

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    Wei M, Yang Z, Li P, Zhang Y, Sse WC. Anti-osteoporosis activity of naringin in the retinoic acid-induced osteoporosis model. Am J Chin Med. 2007;35:663–7. https://doi.org/10.1142/S0192415X07005156.

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    Lauro MR, De Simone F, Sansone F, Iannelli P, Aquino RP. Preparations and release characteristics of naringin and naringenin gastro-resistant microparticles by spray-drying. J Drug Deliv Sci Technol. 2007;17:119–24.

    CAS  Article  Google Scholar 

  14. 14.

    Zhai YK, Niu YB, Pan YL, Li CR, Wu XL, Mei QB. Effects of naringin on proliferation, differentiation and maturation of rat calvarial osteoblasts in vitro. Zhongguo Zhong Yao Za Zhi. 2013;38:105–11.

    CAS  PubMed  Google Scholar 

  15. 15.

    Han B, Fang J, Yang Z, Kwon KK, Nimni M. Stimulatory effects of naringin on osteogenic differentiation and bone formation are BMP dependent. Poster No. 540, 55th Annual Meeting of the Orthopaedic Research Society, 2009.

  16. 16.

    Prakash A, Shur B, Kumar A. Naringin protects memory impairment and mitochondrial oxidative damage against aluminum-induced neurotoxicity in rats. Inter J Neurosci. 2013;123:636–45. https://doi.org/10.3109/00207454.2013.785542.

    CAS  Article  Google Scholar 

  17. 17.

    Jung UJ, Kim SR. Effects of naringin, a flavanone glycoside in grapefruits and citrus fruits, on the nigrostriatal dopaminergic projection in the adult brain. Neural Regen Res. 2014;9:1514–7. https://doi.org/10.4103/2F1673-5374.139476.

    Article  PubMed  PubMed Central  Google Scholar 

  18. 18.

    Leem E, Nam JH, Jeon MT, Shin WH, Won SY, Park SJ, et al. Naringin protects the nigrostriatal dopaminergic projection through induction of GDNF in a neurotoxin model of Parkinson’s disease. J Nutr Biochem. 2014;25:801–6. https://doi.org/10.1016/j.jnutbio.2014.03.006.

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    Jeong KH, Jung UJ, Kim SR. Naringin attenuates autophagic stress and neuroinflammation in kainic acid-treated hippocampus in vivo. Evid Based Complement Alternat Med. 2015;2015:354326–9. https://doi.org/10.1155/2015/354326.

    Article  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Kim YH, Tabata Y. Dual-controlled release system of drugs for bone regeneration. Adv Drug Deliv Rev. 2015;94:28–40. https://doi.org/10.1016/j.addr.2015.06.003.

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    Sun X, Fengbo L, Xinlong MA, Jianxiong MA, Zhao B, Zhang Y, et al. The effects of combined treatment with naringin and treadmill exercise on osteoporosis in ovariectomized rats. Sci Rep. 2015;5:13009.

    CAS  Article  Google Scholar 

  22. 22.

    Singh R, Upadhyay SK, Rani A, Kumar P, Sharma P, Sharma I, et al. Ethnobotanical study of weed flora at district Ambala, Haryana, India: comprehensive medicinal and pharmacological aspects of plant resources. Int J Pharma Res. 2020b;12(1SP):1941–56.

    Google Scholar 

  23. 23.

    • Adil M, Kandhare AD, Ghosh P, Venkata S, Raygude KS, Bodhankar SL. Ameliorative effect of naringin in acetaminophen induced hepatic and renal toxicity in laboratory rats: role of FXR and KIM-1. Ren Fail. 2016;38(6):1007–20. https://doi.org/10.3109/0886022x.2016.1163998In this article, protective role of naringin against the acetaminophen-induced hepatic and renal toxicity has been investigated. Also, the role of FXR and KIM-1 has been studied.

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Jaeschke H, McGill MR, Ramachandran A. Oxidant stress, mitochondria, and cell death mechanisms in drug induced liver injury: lessons learned from acetaminophen hepatotoxicity. Drug Metab Rev. 2012;44:88–106. https://doi.org/10.3109/03602532.2011.602688.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  25. 25.

    McGill MR, Williams CD, Xie Y, Ramachandran A, Jaeschke H. Acetaminophen-induced liver injury in rats and mice: comparison of protein adducts, mitochondrial dysfunction, and oxidative stress in the mechanism of toxicity. Toxicol Appl Pharmacol. 2012;264:387–94. https://doi.org/10.1016/j.taap.2012.08.015.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  26. 26.

    •• Amini N, Sarkaki A, Dianat M, Mard SA, Ahangarpour A, Badavi M. The renoprotective effects of naringin and trimetazidine on renal ischemia/reperfusion injury in rats through inhibition of apoptosis and downregulation of micoRNA-10a. Biomed Pharmacother. 2019;112:108568. https://doi.org/10.1016/j.biopha.2019.01.029This article revealed that naringin, trimetazidine, or their combination is renoprotective against renal ischemia-reperfusion injury. The protective activity was due to increasing antioxidant enzyme capacity, prevention of cell apoptosis, or reducing the miR-10a in the plasma.

    CAS  Article  PubMed  Google Scholar 

  27. 27.

    •• El-kott AF. Abd El-latif Abd El-karim M, Ismail MF. Chemoprotection of acute renal failure in rats by naringin. Egypt J Exp Biol (Zool.). 2009;5:383–8 This article reports the preventive role of naringin against acute renal failure. The study was conducted in a mice model of acute tubular necrosis.

    Google Scholar 

  28. 28.

    • Chen F, Wei G, Xu J, Ma X, Wang Q. Naringin ameliorates the high glucose induced rat mesangial cell inflammatory reaction by modulating the NLRP3 inflammasome. BMC Complement Altern Med. 2018;18:192 This article reports the protective role of naringin in high glucose-induced rat mesangial cell inflammatory reaction.

    Article  Google Scholar 

  29. 29.

    Chen FQ, Wang J, Liu XB, Ma XY, Zhang XB, Huang T, et al. Levels of inflammatory cytokines in type 2 diabetes patients with different urinary albumin excretion rates and their correlation with clinical variables. J Diabetes Res. 2013;2013:138969–6. https://doi.org/10.1155/2013/138969.

    Article  PubMed  PubMed Central  Google Scholar 

  30. 30.

    Chen FQ, Wang QY, Wei GZ, Ma XY, Ma DW, Deng WW, et al. Effects of mycophenolate mofetil on the expression of monocyte chemoattractant protein-1 and fibronectin in high glucose cultured human mesangial cells. Genet Mol Res. 2014;13:3154–61. https://doi.org/10.4238/2014.

    CAS  Article  PubMed  Google Scholar 

  31. 31.

    Madhumita JB, Marie EM, Hyunjin S, et al. Elevated proinflammatory cytokine production by a skewed T cell compartment requires monocytes and promotes inflammation in type 2 diabetes. J Immunol. 2011;186:1162–72.

    Article  Google Scholar 

  32. 32.

    Juan F, Navarro G, Carmen MF. The role of inflammatory cytokines in diabetic nephropathy. J Am Soc Nephrol. 2008;19(3):433–42. https://doi.org/10.1681/ASN.2007091048.

    CAS  Article  Google Scholar 

  33. 33.

    Ortiz-Muñoz G, Lopez-Parra V, Lopez-Franco O, Fernandez-Vizarra P, Mallavia B, Flores C, et al. Suppressors of cytokine signaling abrogates diabetic nephropathy. J Am Soc Nephrol. 2010;21(5):763–72. https://doi.org/10.1681/2FASN.2009060625.

    Article  PubMed  PubMed Central  Google Scholar 

  34. 34.

    Sridevi D, Jung MY, Catherine R, et al. Low vitamin D levels correlate with the proinflammatory state in type 1 diabetic subjects with and without microvascular complications. American Society for Clinical Pathology. 2011;135(3):429–33. https://doi.org/10.1309/AJCPJGZQX42BIAXL.

    Article  Google Scholar 

  35. 35.

    Zehra O, Tahseen AC. Vitamin D deficiency and type 2 diabetes. Postgrad Med J. 2010;86:18–25. https://doi.org/10.1136/pgmj.2009.078626.

    CAS  Article  Google Scholar 

  36. 36.

    Kayaniyil S, Vieth R, Retnakaran R, Knight JA, Qi Y, Gerstein HC, et al. Association of vitamin D with insulin resistance and β-cell dysfunction in subjects at risk for type 2 diabetes. Diabetes Care. 2010;33:1379–81. https://doi.org/10.2337/dc09-2321.

    Article  PubMed  PubMed Central  Google Scholar 

  37. 37.

    Hypponen E, Boucher BJ, Berry DJ, Power C. 25-hydroxyvitamin D,IGF-1,and metabolic syndrome at 45 years of age: a cross sectional study in the 1958 British birth cohort. Diabetes. 2008;57(2):298–305. https://doi.org/10.2337/db07-1122.

    CAS  Article  PubMed  Google Scholar 

  38. 38.

    •• Abd Elmonem AT, Khalifa MMA, Abdel-Salam MI. Nephroprotective role of naringin against cisplatin-induced nephrotoxicity. Malaysian J Med Res. 2018;29:139–47 This article revealed the protective role of naringin against cisplatin-induced nephrotoxicity in mice. Decrease in the renal contents of TNF-α, COX-2, NO, and MPO enzyme activity has been reported. Also, naringin improved Bcl-2 gene expression.

    Google Scholar 

  39. 39.

    • Visnagri A, Adil M, Kandhare AD, Bodhankar SL. Effect of naringin on hemodynamic changes and left ventricular function in renal artery occluded renovascular hypertension in rats. J Pharm Bioallied Sci. 2015;7:121–7. https://doi.org/10.4103/0975-7406.154437This article deals with the antihypertensive potential of naringin in renal artery occlusion (RAO)–actuated hypertension in mice model.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  40. 40.

    •• Said Elshama S, Osman HH, El-Kenawy AE. Renoprotective effects of naringenin and olive oil against cyclosporine-induced nephrotoxicity in rats. IJT. 2016;10:27-37. This article discussed combined protective effect of naringenin and olive oil against the nephrotoxicity. .

  41. 41.

    Guerrero-Hue M, Rayego-Mateos S, Vázquez-Carballo C, Palomino-Antolín A, García-Caballero C, Opazo-Rios L, et al. Protective role of Nrf2 in renal disease. Antioxidants (Basel). 2020;10(1):39. https://doi.org/10.3390/antiox10010039.

    CAS  Article  PubMed Central  Google Scholar 

  42. 42.

    Kulasekaran G, Ganapasam S. Neuroprotective efficacy of naringin on 3-nitropropionic acid-induced mitochondrial dysfunction through the modulation of Nrf2 signaling pathway in PC12 cells. Mol Cell Biochem. 2015;409:199–211. https://doi.org/10.1007/s11010-015-2525-9.

    CAS  Article  PubMed  Google Scholar 

  43. 43.

    Jiang M, Bai M, Lei J, Xie Y, Xu S, Jia Z, et al. Mitochondrial dysfunction and the AKI-to-CKD transition. American J Renal Physiol-Renal Physiol. 2020;319:F1105–16. https://doi.org/10.1152/ajprenal.00285.2020.

    CAS  Article  Google Scholar 

Download references


The authors would like to express their gratitude to the Head of the Department of Biotechnology, Maharishi Markandeshwar (Deemed to be University) Mullana-Ambala (Haryana), India.

Author information



Corresponding author

Correspondence to Mukesh Yadav.

Ethics declarations

Conflict of Interest

The authors declare no conflict of interest.

Human and Animal Rights and Informed Consent

This is a review article and does not contain any experimental studies involving use of animals or humans.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Clinical Pharmacology

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Sehrawat, N., Upadhyay, S.K., Sharma, A.K. et al. Emerging Renoprotective Role of Citrus Flavonoid Naringin: Current Pharmaceutical Status and Future Perspectives. Curr Pharmacol Rep (2021). https://doi.org/10.1007/s40495-021-00256-7

Download citation


  • Flavonoid
  • Naringin
  • Pharmaceuticals
  • Biological activity
  • Renoprotective