Authors : Mohammed Sohail; Narendra Pentu; Uma Maheshwara Rao

Volume/Issue : Volume 11 - 2026, Issue 1 - January

Google Scholar : https://tinyurl.com/mt2u4b73

Scribd : https://tinyurl.com/2x52jfum

DOI : https://doi.org/10.38124/ijisrt/26jan682

Note : A published paper may take 4-5 working days from the publication date to appear in PlumX Metrics, Semantic Scholar, and ResearchGate.

Abstract : Citrus fruits are rich in naringenin, a naturally occurring flavanone that has been thoroughly investigated for its diverse biological and pharmacological properties. This narrative review addresses the chemical structure, natural sources, metabolism, and medicinal properties of naringenin, focusing particularly on its anti-inflammatory, antioxidant, antidiabetic, hepatoprotective, neuroprotective, and anticancer effects. Experimental research suggests that these effects are mediated via the control of several molecular pathways. However, naringenin's low water solubility and restricted bioavailability prevent it from being used therapeutically. Novel drug delivery technologies, particularly nanocarriers, and recent advancements in extraction procedures have demonstrated promise in circumventing these constraints and improving its pharmacological efficacy. All things considered, this review emphasizes naringenin's increasing significance as a bioactive phytochemical and its potential for further advancement as a medicinal agent.

Keywords : Naringenin, Citrous Flavonoids, Bioavailability, Anti-Inflammatory, Cancer.

References :

1. Zobeiri M, Belwal T, Parvizi F, Naseri R, Farzaei MH, Nabavi SF, Sureda A, Nabavi SM. Naringenin and its nano-formulations for fatty liver: cellular modes of action and clinical perspective. Current pharmaceutical biotechnology. 2018 Mar 1;19(3):196-205.
2. Patel K, Singh GK, Patel DK. A review on pharmacological and analytical aspects of naringenin. Chinese journal of integrative medicine. 2018 Jul;24(7):551-60.
3. Nouri Z, Fakhri S, El-Senduny FF, Sanadgol N, Abd-ElGhani GE, Farzaei MH, Chen JT. On the neuroprotective effects of naringenin: pharmacological targets, signaling pathways, molecular mechanisms, and clinical perspective. Biomolecules. 2019 Nov 3;9(11):690.
4. Karami MH, Abdouss M, Rahdar A, Pandey S. Graphene quantum dots: Background, synthesis methods, and applications as nanocarrier in drug delivery and cancer treatment: An updated review. Inorganic Chemistry Communications. 2024 Mar 1;161:112032.
5. Tripoli E, La Guardia M, Giammanco S, Di Majo D, Giammanco M. Citrus flavonoids: Molecular structure, biological activity and nutritional properties: A review. Food chemistry. 2007 Jan 1;104(2):466-79.
6. Galluzzo P, Ascenzi P, Bulzomi P, Marino M. The nutritional flavanone naringenin triggers antiestrogenic effects by regulating estrogen receptor α-palmitoylation. Endocrinology. 2008 May 1;149(5):2567-75.
7. Han X, Ren D, Fan P, Shen T, Lou H. Protective effects of naringenin-7-O-glucoside on doxorubicin-induced apoptosis in H9C2 cells. European journal of pharmacology. 2008 Feb 26;581(1-2):47-53.
8. Martin HJ, Kornmann F, Fuhrmann GF. The inhibitory effects of flavonoids and antiestrogens on the Glut1 glucose transporter in human erythrocytes. Chemico-biological interactions. 2003 Dec 15;146(3):225-35.
9. Erlund I. Review of the flavonoids quercetin, hesperetin, and naringenin. Dietary sources, bioactivities, bioavailability, and epidemiology. Nutrition research. 2004 Oct 1;24(10):851-74.
10. Gattuso G, Barreca D, Gargiulli C, Leuzzi U, Caristi C. Flavonoid composition of citrus juices. Molecules. 2007 Aug 3;12(8):1641-73.
11. Aherne SA, O’Brien NM. Dietary flavonols: chemistry, food content, and metabolism. Nutrition. 2002 Jan 1;18(1):75-81.
12. Joshi R, Kulkarni YA, Wairkar S. Pharmacokinetic, pharmacodynamic and formulations aspects of Naringenin: An update. Life sciences. 2018 Dec 15;215:43-56.
13. Kumar S, Pandey AK. Chemistry and biological activities of flavonoids: an overview. The scientific world journal. 2013;2013(1):162750.
14. Gattuso G, Barreca D, Gargiulli C, Leuzzi U, Caristi C. Flavonoid composition of citrus juices. Molecules. 2007 Aug 3;12(8):1641-73.
15. Den Hartogh DJ, Tsiani E. Antidiabetic properties of naringenin: A citrus fruit polyphenol. Biomolecules. 2019 Mar;9(3):99.
16. Chtourou Y, Kamoun Z, Zarrouk W, Kebieche M, Kallel C, Gdoura R, Fetoui H. Naringenin ameliorates renal and platelet purinergic signalling alterations in high- cholesterol fed rats through the suppression of ROS and NF-κB signaling pathways. Food & function. 2016;7(1):183-93.
17. Burke AC, Sutherland BG, Telford DE, Morrow MR, Sawyez CG, Edwards JY, Drangova M, Huff MW. Intervention with citrus flavonoids reverses obesity and improves metabolic syndrome and atherosclerosis in obese Ldlr−/− mice. Journal of Lipid Research. 2018 Sep 1;59(9):1714-28.
18. Hua YQ, Zeng Y, Xu J, Le Xu X. Naringenin alleviates nonalcoholic steatohepatitis in middle-aged Apoe−/− mice: role of SIRT1. Phytomedicine. 2021 Jan 1;81:153412.
19. Duda-Madej A, Kozłowska J, Krzyżek P, Anioł M, Seniuk A, Jermakow K, Dworniczek E. Antimicrobial O-alkyl derivatives of naringenin and their oximes against multidrug- resistant bacteria. Molecules. 2020 Aug 10;25(16):3642.
20. Choi J, Lee DH, Jang H, Park SY, Seol JW. Naringenin exerts anticancer effects by inducing tumor cell death and inhibiting angiogenesis in malignant melanoma. International journal of medical sciences. 2020 Oct 18;17(18):3049.
21. Rehman MU, Rahman Mir MU, Farooq A, Rashid SM, Ahmad B, Bilal Ahmad S, Ali R, Hussain I, Masoodi M, Muzamil S, Madkhali H. Naringenin (4, 5, 7‐ trihydroxyflavanone) suppresses the development of precancerous lesions via controlling hyperproliferation and inflammation in the colon of Wistar rats. Environmental toxicology. 2018 Apr;33(4):422-35.
22. Wang Q, Ou Y, Hu G, Wen C, Yue S, Chen C, Xu L, Xie J, Dai H, Xiao H, Zhang Y. Naringenin attenuates non‐alcoholic fatty liver disease by down‐regulating the NLRP3/NF‐κB pathway in mice. British journal of pharmacology. 2020 Apr;177(8):1806-21.
23. He W, Wang Y, Yang R, Ma H, Qin X, Yan M, Rong Y, Xie Y, Li L, Si J, Li X. Molecular mechanism of naringenin against high-glucose-induced vascular smooth muscle cells proliferation and migration based on network pharmacology and transcriptomic analyses. Frontiers in Pharmacology. 2022 Jun 9;13:862709.
24. Tutunchi H, Naeini F, Ostadrahimi A, Hosseinzadeh‐Attar MJ. Naringenin, a flavanone with antiviral and anti‐inflammatory effects: A promising treatment strategy against COVID‐19. Phytotherapy Research. 2020 Dec;34(12):3137-47.
25. Felgines C, Texier O, Morand C, Manach C, Scalbert A, Régerat F, Rémésy C. Bioavailability of the flavanone naringenin and its glycosides in rats. American Journal of Physiology-Gastrointestinal and Liver Physiology. 2000 Dec 1;279(6):G1148-54.
26. Singh S, Sharma A, Monga V, Bhatia R. Compendium of naringenin: Potential sources, analytical aspects, chemistry, nutraceutical potentials and pharmacological profile. Critical Reviews in Food Science and Nutrition. 2023 Oct 25;63(27):8868-99.
27. Kanaze FI, Bounartzi MI, Georgarakis M, Niopas I. Pharmacokinetics of the citrus flavanone aglycones hesperetin and naringenin after single oral administration in human subjects. European journal of clinical nutrition. 2007 Apr;61(4):472-7.
28. 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. The Journal of nutrition. 2001 Feb 1;131(2):235-41.
29. Meng Z, Zhao J, Duan H, Guan Y, Zhao L. Green and efficient extraction of four bioactive flavonoids from Pollen Typhae by ultrasound-assisted deep eutectic solvents extraction. Journal of Pharmaceutical and Biomedical Analysis. 2018 Nov 30;161:246- 53.
30. Wu Z, Wang W, He F, Li D, Wang D. Simultaneous enrichment and separation of four flavonoids from Zanthoxylum bungeanum leaves by ultrasound‐assisted extraction and macroporous resins with evaluation of antioxidant activities. Journal of Food Science. 2018 Aug;83(8):2109-18.
31. Vallverdú-Queralt A, Regueiro J, Martínez-Huélamo M, Alvarenga JF, Leal LN, Lamuela-Raventos RM. A comprehensive study on the phenolic profile of widely used culinary herbs and spices: Rosemary, thyme, oregano, cinnamon, cumin and bay. Food chemistry. 2014 Jul 1;154:299-307.
32. Yang Z, Kuboyama T, Tohda C. A systematic strategy for discovering a therapeutic drug for Alzheimer’s disease and its target molecule. Frontiers in Pharmacology. 2017 Jun 19;8:273886.
33. Alam MA, Subhan N, Rahman MM, Uddin SJ, Reza HM, Sarker SD. Effect of citrus flavonoids, naringin and naringenin, on metabolic syndrome and their mechanisms of action. Adv Nutr 5 (4): 404–417 [Internet]. 2014.
34. Shakeel S, Rehman MU, Tabassum N, Amin U. Effect of naringenin (a naturally occurring flavanone) against pilocarpine-induced status epilepticus and oxidative stress in mice. Pharmacognosy Magazine. 2017 Apr 7;13(Suppl 1):S154.
35. Iijima Y, Nakamura Y, Ogata Y, Tanaka KI, Sakurai N, Suda K, Suzuki T, Suzuki H, Okazaki K, Kitayama M, Kanaya S. Metabolite annotations based on the integration of mass spectral information. The Plant Journal. 2008 Jun;54(5):949-62.
36. Fan R, Pan T, Zhu AL, Zhang MH. Anti-inflammatory and anti-arthritic properties of naringenin via attenuation of NF-κB and activation of the heme oxygenase (HO)- 1/related factor 2 pathway. Pharmacological Reports. 2017 Sep;69(5):1021-9.
37. Hua FZ, Ying J, Zhang J, Wang XF, Hu YH, Liang YP, Liu Q, Xu GH. Naringenin pre- treatment inhibits neuroapoptosis and ameliorates cognitive impairment in rats exposed to isoflurane anesthesia by regulating the PI3/Akt/PTEN signalling pathway and suppressing NF-κB-mediated inflammation. International Journal of Molecular Medicine. 2016 Oct;38(4):1271-80.
38. Park S, Lim W, Bazer FW, Song G. Naringenin induces mitochondria-mediated apoptosis and endoplasmic reticulum stress by regulating MAPK and AKT signal transduction pathways in endometriosis cells. MHR: Basic science of reproductive medicine. 2017 Dec 1;23(12):842-54.
39. Liu X, Wang N, Fan S, Zheng X, Yang Y, Zhu Y, Lu Y, Chen Q, Zhou H, Zheng J. The citrus flavonoid naringenin confers protection in a murine endotoxaemia model through AMPK-ATF3-dependent negative regulation of the TLR4 signalling pathway. Scientific reports. 2016 Dec 22;6(1):39735.
40. Shan S, Zhang Y, Wu M, Yi B, Wang J, Li Q. Naringenin attenuates fibroblast activation and inflammatory response in a mechanical stretch-induced hypertrophic scar mouse model. Molecular Medicine Reports. 2017 Oct 1;16(4):4643-9.
41. Hernández-Aquino E, Muriel P. Beneficial effects of naringenin in liver diseases: Molecular mechanisms. World journal of gastroenterology. 2018 Apr 28;24(16):1679.
42. Jin L, Zeng W, Zhang F, Zhang C, Liang W. Naringenin ameliorates acute inflammation by regulating intracellular cytokine degradation. The Journal of Immunology. 2017 Nov 15;199(10):3466-77.
43. Fouad AA, Albuali WH, Jresat I. Protective effect of naringenin against lipopolysaccharide-induced acute lung injury in rats. Pharmacology. 2016 Mar 1;97(5- 6):224-32.
44. Shi LB, Tang PF, Zhang W, Zhao YP, Zhang LC, Zhang H. Naringenin inhibits spinal cord injury-induced activation of neutrophils through miR-223. Gene. 2016 Oct 30;592(1):128-33.
45. Wang CC, Guo L, Tian FD, An N, Luo L, Hao RH, Wang B, Zhou ZH. Naringenin regulates production of matrix metalloproteinases in the knee-joint and primary cultured articular chondrocytes and alleviates pain in rat osteoarthritis model. Brazilian Journal of Medical and Biological Research. 2017;50(4):e5714.
46. Manchope MF, Calixto-Campos C, Coelho-Silva L, Zarpelon AC, Pinho-Ribeiro FA, Georgetti SR, Baracat MM, Casagrande R, Verri Jr WA. Naringenin inhibits superoxide anion-induced inflammatory pain: role of oxidative stress, cytokines, Nrf-2 and the NO− cGMP− PKG− KATPChannel signaling pathway. PloS one. 2016 Apr 5;11(4):e0153015.
47. Chtourou Y, Kamoun Z, Zarrouk W, Kebieche M, Kallel C, Gdoura R, Fetoui H. Naringenin ameliorates renal and platelet purinergic signalling alterations in high- cholesterol fed rats through the suppression of ROS and NF-κB signaling pathways. Food & function. 2016;7(1):183-93.
48. Al-Roujayee AS. Naringenin improves the healing process of thermally-induced skin damage in rats. Journal of International Medical Research. 2017 Apr;45(2):570-82.
49. Liang J, Halipu Y, Hu F, Yakeya B, Chen W, Zhang H, Kang X. Naringenin protects keratinocytes from oxidative stress injury via inhibition of the NOD2-mediated NF-κB pathway in pemphigus vulgaris. Biomedicine & Pharmacotherapy. 2017 Aug 1;92:796- 801.
50. Al-Rejaie SS, Aleisa AM, Abuohashish HM, Parmar MY, Ola MS, Al-Hosaini AA, Ahmed MM. Naringenin neutralises oxidative stress and nerve growth factor discrepancy in experimental diabetic neuropathy. Neurological research. 2015 Oct 1;37(10):924-33.
51. Al-Dosari DI, Ahmed MM, Al-Rejaie SS, Alhomida AS, Ola MS. Flavonoid naringenin attenuates oxidative stress, apoptosis and improves neurotrophic effects in the diabetic rat retina. Nutrients. 2017 Oct 24;9(10):1161.
52. Sandeep MS, Nandini CD. Influence of quercetin, naringenin and berberine on glucose transporters and insulin signalling molecules in brain of streptozotocin-induced diabetic rats. Biomedicine & Pharmacotherapy. 2017 Oct 1;94:605-11.
53. 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. European journal of pharmacology. 2016 Feb 15;773:13-23.
54. 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. Pharmaceutical biology. 2016 Sep 1;54(9):1616-27.
55. Sirovina D, Oršolić N, Končić MZ, Gregorović G. Naringenin ameliorates pathological changes in liver and kidney of diabetic mice: a preliminary study.
56. Chandrika BB, Steephan M, Kumar TS, Sabu A, Haridas M. Hesperetin and naringenin sensitize HER2 positive cancer cells to death by serving as HER2 tyrosine kinase inhibitors. Life sciences. 2016 Sep 1;160:47-56.
57. Arul D, Subramanian P. Naringenin (citrus flavonone) induces growth inhibition, cell cycle arrest and apoptosis in human hepatocellular carcinoma cells. Pathology & Oncology Research. 2013 Oct;19(4):763-70.
58. Ke JY, Banh T, Hsiao YH, Cole RM, Straka SR, Yee LD, Belury MA. Citrus flavonoid naringenin reduces mammary tumor cell viability, adipose mass, and adipose inflammation in obese ovariectomized mice. Molecular nutrition & food research. 2017
59. Lim W, Park S, Bazer FW, Song G. Naringenin‐induced apoptotic cell death in prostate cancer cells is mediated via the PI3K/AKT and MAPK signaling pathways. Journal of cellular biochemistry. 2017 May;118(5):1118-31.
60. Bouzaiene NN, Chaabane F, Sassi A, Chekir-Ghedira L, Ghedira K. Effect of apigenin-7- glucoside, genkwanin and naringenin on tyrosinase activity and melanin synthesis in B16F10 melanoma cells. Life sciences. 2016 Jan 1;144:80-5.
61. Stompor M, Uram Ł, Podgórski R. In vitro effect of 8-prenylnaringenin and naringenin on fibroblasts and glioblastoma cells-cellular accumulation and cytotoxicity. Molecules. 2017 Jun 30;22(7):1092.
62. Zhang F, Dong W, Zeng W, Zhang L, Zhang C, Qiu Y, Wang L, Yin X, Zhang C, Liang W. Naringenin prevents TGF-β1 secretion from breast cancer and suppresses pulmonary metastasis by inhibiting PKC activation. Breast Cancer Research. 2016 Apr 1;18(1):38.
63. Pannu A, Goyal RK, Ojha S, Nandave M. Naringenin: a promising flavonoid for herbal treatment of rheumatoid arthritis and associated inflammatory disorders. InBioactive Food as Dietary Interventions for Arthritis and Related Inflammatory Diseases 2019 Jan 1 (pp. 343-354). Academic Press.
64. Wang H, He Y, Hou Y, Geng Y, Wu X. Novel self-nanomicellizing formulation based on Rebaudioside A: A potential nanoplatform for oral delivery of naringenin. Materials Science and Engineering: C. 2020 Jul 1;112:110926.
65. Hernández-Aquino E, Muriel P. Beneficial effects of naringenin in liver diseases: Molecular mechanisms. World journal of gastroenterology. 2018 Apr 28;24(16):1679.
66. Karami MH, Abdouss M. Cutting-edge tumor nanotherapy: Advancements in 5- fluorouracil Drug-loaded chitosan nanoparticles. Inorganic Chemistry Communications. 2024 Jun 1;164:112430.
67. Karami MH, Abdouss M. Assessing particle size and surface charge in drug carrier nanoparticles for enhanced cancer treatment: a comprehensive review utilizing DLS and zeta potential characterization. PSPRJ. 2024;5(3):000615.
68. Zaidun NH, Thent ZC, Abd Latiff A. Combating oxidative stress disorders with citrus flavonoid: Naringenin. Life sciences. 2018 Sep 1;208:111-22.
69. Al-Roujayee AS. Naringenin improves the healing process of thermally-induced skin damage in rats. Journal of International Medical Research. 2017 Apr;45(2):570-82.
70. Yilma AN, Singh SR, Morici L, Dennis VA. Flavonoid naringenin: a potential immunomodulator for Chlamydia trachomatis inflammation. Mediators of inflammation. 2013;2013(1):102457.
71. Coelho RC, Hermsdorff HH, Bressan J. Anti-inflammatory properties of orange juice: possible favorable molecular and metabolic effects. Plant foods for human nutrition. 2013 Mar;68(1):1-0.
72. Vafeiadou K, Vauzour D, Lee HY, Rodriguez-Mateos A, Williams RJ, Spencer JP. The citrus flavanone naringenin inhibits inflammatory signalling in glial cells and protects against neuroinflammatory injury. Archives of Biochemistry and Biophysics. 2009 Apr 1;484(1):100-9.
73. Rani N, Bharti S, Krishnamurthy B, Bhatia J, Sharma C, Amjad Kamal M, Ojha S, Singh Arya D. Pharmacological properties and therapeutic potential of naringenin: a citrus flavonoid of pharmaceutical promise. Current pharmaceutical design. 2016 Aug 1;22(28):4341-59.
74. Ali F, Khan AQ, Khan R, Sultana S. Trichloroethylene-mediated cytotoxicity in human epidermal keratinocytes is mediated by the rapid accumulation of intracellular calcium: Interception by naringenin. Human & Experimental Toxicology. 2016 Feb;35(2):147-61.
75. Kanno SI, Tomizawa A, Hiura T, Osanai Y, Shouji A, Ujibe M, Ohtake T, Kimura K, Ishikawa M. Inhibitory effects of naringenin on tumor growth in human cancer cell lines and sarcoma S-180-implanted mice. Biological and Pharmaceutical Bulletin. 2005;28(3):527-30.
76. Harmon AW, Patel YM. Naringenin inhibits glucose uptake in MCF-7 breast cancer cells: a mechanism for impaired cellular proliferation. Breast Cancer Research and Treatment. 2004 May;85(2):103-10.
77. Gao K, Henning SM, Niu Y, Youssefian AA, Seeram NP, Xu A, Heber D. The citrus flavonoid naringenin stimulates DNA repair in prostate cancer cells. The Journal of nutritional biochemistry. 2006 Feb 1;17(2):89-95.
78. Qin L, Jin L, Lu L, Lu X, Zhang C, Zhang F, Liang W. Naringenin reduces lung metastasis in a breast cancer resection model. Protein & cell. 2011 Jun;2(6):507-16.
79. Zaidun NH, Thent ZC, Abd Latiff A. Combating oxidative stress disorders with citrus flavonoid: Naringenin. Life sciences. 2018 Sep 1;208:111-22.
80. Karami MH, Abdouss M. Recent advances of carbon quantum dots in tumor imaging. Nanomedicine Journal. 2024 Jan 1;11(1).
81. Karami MH, Abdouss M, Maleki B. The state of the art metal nanoparticles in drug delivery systems: A comprehensive review. Nanomedicine Journal. 2024 Jul 1;11(3).
82. Jung HA, Paudel P, Seong SH, Min BS, Choi JS. Structure-related protein tyrosine phosphatase 1B inhibition by naringenin derivatives. Bioorganic & Medicinal Chemistry Letters. 2017 Jun 1;27(11):2274-80.