Propolis and its therapeutic effects on renal diseases: A review

Document Type : Review Article


1 Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

2 Department of Physiology, Faculty of Medicine, Gonabad University of Medical Sciences, Gonabad, Iran

3 Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

4 Department of Physiology, Faculty of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran

5 Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

6 Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran


Propolis is produced by bees using a mixture of bees wax and saliva. It contains several bioactive compounds that mainly induce anti-oxidant and anti-inflammatory effects. In this review, we aimed to investigate the effects of propolis on kidney diseases. We used “Kidney”, “Disease”, “Propolis”, “Renal”, “Constituent”, “Mechanism”, “Infection”, and other related keywords as the main keywords to search for works published before July 2023 in Google scholar, Scopus, and Pubmed databases. The search terms were selected according to Medical Subject Headings (MeSH). This review showed that propolis affects renal disorders with inflammatory and oxidative etiology due to its bioactive compounds, mainly flavonoids and polyphenols. There have been few studies on the effects of propolis on kidney diseases; nevertheless, the available studies are integrated in this review. Overall, propolis appears to be effective against several renal diseases through influencing mechanisms such as apoptosis, oxidative balance, and inflammation. 


Main Subjects

1. Siew ED, Davenport A. The growth of acute kidney injury: A rising tide or just closer attention to detail? Kidney Int 2015; 87:46-61.
2. Ozkok A, Edelstein CL. Pathophysiology of cisplatin-induced acute kidney injury. Biomed Res Int 2014; 2014.
3. Vervaet BA, D’Haese PC, Verhulst A. Environmental toxin-induced acute kidney injury. Clin Kidney J 2017; 10:747-758.
4. Sanz AB, Sanchez-Niño MD, Martin-Cleary C, Ortiz A, Ramos AM. Progress in the development of animal models of acute kidney injury and its impact on drug discovery. Expert Opin Drug Discov 2013; 8:879-895.
5. Andrassy KM. Comments on ‘KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease’. Kidney Int 2013; 84:622-623.
6. Barsoum RS. Chronic kidney disease in the developing world. N Engl J Med 2006; 354:997-999.
7. López-Hernández FJ, López-Novoa JM. Role of TGF-β in chronic kidney disease: an integration of tubular, glomerular and vascular effects. Cell Tissue Res 2012; 347:141-154.
8. Asada N, Takase M, Nakamura J, Oguchi A, Asada M, Suzuki N, et al. Dysfunction of fibroblasts of extrarenal origin underlies renal fibrosis and renal anemia in mice. J Clin Invest 2011; 121:3981-3990.
9. Souma T, Yamazaki S, Moriguchi T, Suzuki N, Hirano I, Pan X, et al. Plasticity of renal erythropoietin-producing cells governs fibrosis. J. Am. Soc. Nephrol 2013; 24:1599-1616.
10. Duffield JS. Cellular and molecular mechanisms in kidney fibrosis. J Clin Invest 2014; 124:2299-2306.
11. Bonventre JV, Yang L. Cellular pathophysiology of ischemic acute kidney injury. J Clin Invest 2011; 121:4210-4221.
12. Meng X-M, Nikolic-Paterson DJ, Lan HY. Inflammatory processes in renal fibrosis. Nat. Rev. Nephrol 2014; 10:493-503.
13. Kliem V, Johnson RJ, Alpers CE, Yoshimura A, Couser WG, Koch KM, et al. Mechanisms involved in the pathogenesis of tubulointerstitial fibrosis in 5/6-nephrectomized rats. Kidney Int 1996; 49:666-678.
14.Himmelfarb J, editor Poor nutritional status and inflammation: Linking oxidative stress and inflammation in kidney disease: which is the chicken and which is the egg? Semin Dial 2004: Wiley Online Library.
15. Hu Q, Jiang L, Yan Q, Zeng J, Ma X, Zhao Y. A natural products solution to diabetic nephropathy therapy. Pharmacol Ther 2022:108314.
16. Papa G, Maier R, Durazzo A, Lucarini M, Karabagias IK, Plutino M, et al. The honey bee Apis mellifera: An insect at the interface between human and ecosystem health. Biology 2022; 11:233.
17. Cornara L, Biagi M, Xiao J, Burlando B. Therapeutic properties of bioactive compounds from different honeybee products. Front Pharmacol 2017; 8:412.
18. Araujo MA, Libério SA, Guerra RN, Ribeiro MNS, Nascimento FR. Mechanisms of action underlying the anti-inflammatory and immunomodulatory effects of propolis: a brief review. Rev Bras Farmacogn 2012; 22:208-219.
19. Cuevas A, Saavedra N, Salazar LA, Abdalla DS. Modulation of immune function by polyphenols: possible contribution of epigenetic factors. Nutrients 2013; 5:2314-2332.
20. Lan X, Wang W, Li Q, Wang J. The natural flavonoid pinocembrin: molecular targets and potential therapeutic applications. Mol Neurobiol 2016; 53:1794-1801.
21. Rasul A, Millimouno FM, Ali Eltayb W, Ali M, Li J, Li X. Pinocembrin: a novel natural compound with versatile pharmacological and biological activities. Biomed Res Int 2013; 2013.
22. Batista LLV, Campesatto EA, Assis MLBd, Barbosa APF, Grillo LAM, Dornelas CB. Comparative study of topical green and red propolis in the repair of wounds induced in rats. Rev Col Bras Cir 2012; 39:515-520.
23. Braakhuis A. Evidence on the health benefits of supplemental propolis. Nutrients 2019; 11:2705.
24. Bazmandegan G, Boroushaki MT, Shamsizadeh A, Ayoobi F, Hakimizadeh E, Allahtavakoli M. Brown propolis attenuates cerebral ischemia-induced oxidative damage via affecting antioxidant enzyme system in mice. Biomedicine & Pharmacotherapy 2017; 85:503-510.
25. Zulhendri F, Perera CO, Chandrasekaran K, Ghosh A, Tandean S, Abdulah R, et al. Propolis of stingless bees for the development of novel functional food and nutraceutical ingredients: A systematic scoping review of the experimental evidence. J Funct Foods 2022; 88:104902.
26. Yen C-H, Chiu H-F, Wu C-H, Lu Y-Y, Han Y-C, Shen Y-C, et al. Beneficial efficacy of various propolis extracts and their digestive products by in vitro simulated gastrointestinal digestion. LWT 2017; 84:281-289.
27. Anjum SI, Ullah A, Khan KA, Attaullah M, Khan H, Ali H, et al. Composition and functional properties of propolis (bee glue): A review. Saudi J Biol Sci 2019; 26:1695-1703.
28. Bueno-Silva B, Marsola A, Ikegaki M, Alencar SM, Rosalen PL. The effect of seasons on Brazilian red propolis and its botanical source: chemical composition and antibacterial activity. Nat Prod Res 2017; 31:1318-1324.
29. Patel S. Emerging adjuvant therapy for cancer: propolis and its constituents. J Diet Suppl 2016; 13:245-268.
30. Chiu H-F, Yang C-S, Chi H-I, Han Y-C, Shen Y-C, Venkatakrishnan K, et al. Cyclooxygenase-2 expression in oral precancerous and cancerous conditions and its inhibition by caffeic acid phenyl ester-enriched propolis in human oral epidermal carcinoma KB cells. Arch Biol Sci 2017; 69:83-91.
31. Hashemi JM. Biological effect of bee propolis: a review. Eur J Appl Sci 2016; 8:311-318.
32. Bae Y-J, Lee E-J, Kang M-H, Kwon OR, Kim M-K, Sung M-K. Effect of propolis intake on anti-oxidative capacity in rats fed high fat diet.  2010; 15:143-151.
33. Saad MA, Salam RMA, Kenawy SA, Attia AS. Pinocembrin attenuates hippocampal inflammation, oxidative perturbations and apoptosis in a rat model of global cerebral ischemia reperfusion. Pharmacolo Rep 2015; 67:115-122.
34. Yesiltas B, Capanoglu E, Firatligil-Durmus E, Sunay AE, Samanci T, Boyacioglu D. Investigating the in-vitro bioaccessibility of propolis and pollen using a simulated gastrointestinal digestion System. J Apic Res 2014; 53:101-108.
35. Lotfy M. Biological activity of bee propolis in health and disease. Asian Pac J Cancer Prev 2006; 7:22-31.
36. Huang S, Zhang C-P, Wang K, Li GQ, Hu F-L. Recent advances in the chemical composition of propolis. Molecules 2014; 19:19610-19632.
37. Yin X, Zhang Y, Wu H, Zhu X, Zheng X, Jiang S, et al. Protective effects of Astragalus saponin I on early stage of diabetic nephropathy in rats. J Pharmacol Sci 2004; 95:256-266.
38. Yoshida M, Kimura H, Kyuki K, Ito M. Effect of combined vitamin E and insulin administration on renal damage in diabetic rats fed a high cholesterol diet. Biol Pharm Bull 2005; 28:2080-2086.
39. Okutan H, Ozcelik N, Yilmaz HR, Uz E. Effects of caffeic acid phenethyl ester on lipid peroxidation and antioxidant enzymes in diabetic rat heart. Clin Biochem 2005; 38:191-196.
40. Valadares B, Graf U, Spanó M. Inhibitory effects of water extract of propolis on doxorubicin-induced somatic mutation and recombination in Drosophila melanogaster. Food Chem Toxicol 2008; 46:1103-1110.
41. Abo-Salem OM, El-Edel RH, Harisa G, El-Halawany N, Ghonaim MM. Experimental diabetic nephropathy can be prevented by propolis: effect on metabolic disturbances and renal oxidative parameters. Pak J Pharm Sci 2009; 22:205-210.
42. Oktem F, Ozguner F, Sulak O, Olgar Ş, Akturk O, Yilmaz HR, et al. Lithium-induced renal toxicity in rats: protection by a novel antioxidant caffeic acid phenethyl ester. Mol Cell Biochem 2005; 277:109-115.
43. Wagh VD. Propolis: A wonder bees product and its pharmacological potentials. Adv Pharmacol Pharm Sci 2013; 2013:308249.
44. Arvouet-Grand A, Lejeune B, Bastide P, Pourrat A, Privat A, Legret P. Propolis extract. I. Acute toxicity and determination of acute primary cutaneous irritation index. J Pharm Pharmacol 1993; 48:165-170.
45. Mohammadzadeh S, Shariatpanahi M, Hamedi M, Ahmadkhaniha R, Samadi N, Ostad SN. Chemical composition, oral toxicity and antimicrobial activity of Iranian propolis. Food Chem 2007; 103:1097-1103.
46. Fuliang H, Hepburn H, Xuan H, Chen M, Daya S, Radloff S. Effects of propolis on blood glucose, blood lipid and free radicals in rats with diabetes mellitus. Pharmacol Res 2005; 51:147-152.
47. Granados-Pineda J, Uribe-Uribe N, García-López P, Ramos-Godinez MDP, Rivero-Cruz JF, Pérez-Rojas JM. Effect of pinocembrin isolated from Mexican brown propolis on diabetic nephropathy. Molecules 2018; 23:852.
48. Nna VU, Abu Bakar AB, Zakaria Z, Othman ZA, Jalil NAC, Mohamed M. Malaysian propolis and metformin synergistically mitigate kidney oxidative stress and inflammation in streptozotocin-induced diabetic rats. Molecules 2021; 26:3441.
49. Luan J, Wang N, Tian L. Study on the pharmacologic effect of propolis. Zhong Yao Cai 2000; 23:346-348.
50. Jasprica I, Mornar A, Debeljak Ž, Smolčić-Bubalo A, Medić-Šarić M, Mayer L, et al. In vivo study of propolis supplementation effects on antioxidative status and red blood cells. J Ethnopharmacol 2007; 110:548-554.
51. Kang M-K, Park S-H, Kim Y-H, Lee E-J, Antika LD, Kim DY, et al. Chrysin ameliorates podocyte injury and slit diaphragm protein loss via inhibition of the PERK-eIF2α-ATF-CHOP pathway in diabetic mice. Acta Pharmacol Sin 2017; 38:1129-1140.
52. Nadkarni GN, Rao V, Ismail-Beigi F, Fonseca VA, Shah SV, Simonson MS, et al. Association of urinary biomarkers of inflammation, injury, and fibrosis with renal function decline: The ACCORD trial. J Am Soc Nephrol  2016; 11:1343-1352.
53. Kanamori H, Matsubara T, Mima A, Sumi E, Nagai K, Takahashi T, et al. Inhibition of MCP-1/CCR2 pathway ameliorates the development of diabetic nephropathy. Biochem. Biophys Res Commun 2007; 360:772-777.
54. Banba N, Nakamura T, Matsumura M, Kuroda H, Hattori Y, Kasai K. Possible relationship of monocyte chemoattractant protein-1 with diabetic nephropathy. Kidney Int 2000; 58:684-690.
55. Silveira MAD, Teles F, Berretta AA, Sanches TR, Rodrigues CE, Seguro AC, et al. Effects of Brazilian green propolis on proteinuria and renal function in patients with chronic kidney disease: a randomized, double-blind, placebo-controlled trial. BMC Nephrol 2019; 20:1-12.
56. Ozkul Y, Silici S, Eroğlu E. The anticarcinogenic effect of propolis in human lymphocytes culture. Phytomedicine 2005; 12:742-747.
57. Ozkul Y, Eroglu H, Ok E. Genotoxic potential of Turkish propolis in peripheral blood lymphocytes. Die Pharmazie. Int J Pharm Pharm Sci 2006; 61:638-640.
58. Erhan Eroğlu H, Özkul Y, Tatlısen A, Silici S. Anticarcinogenic and antimitotic effects of Turkish propolis and mitomycin-C on tissue cultures of bladder cancer. Nat Prod Res 2008; 22:1060-1066.
59. Oršolić N, Šaranović AB, Bašić I. Direct and indirect mechanism (s) of antitumour activity of propolis and its polyphenolic compounds. Planta Medica 2006; 72:20-27.
60. Chen C-N, Weng M-S, Wu C-L, Lin J-K. Comparison of radical scavenging activity, cytotoxic effects and apoptosis induction in human melanoma cells by Taiwanese propolis from different sources. J Evid Based Complementary Altern Med 2004; 1:175-185.
61. Búfalo M, Candeias J, Sousa J, Bastos J, Sforcin J. In vitro cytotoxic activity of Baccharis dracunculifolia and propolis against HEp-2 cells.Nat Prod Res 2010; 24:1710-1718.
62. Elumalai P, Muninathan N, Megalatha ST, Suresh A, Kumar KS, Jhansi N, et al. An Insight into anticancer effect of propolis and its constituents: A review of molecular mechanisms. Evid Based Complementary Altern Med 2022; 2022:5901191.
63. Banskota AH, Nagaoka T, Sumioka LY, Tezuka Y, Awale S, Midorikawa K, et al. Antiproliferative activity of the Netherlands propolis and its active principles in cancer cell lines. J Ethnopharmacol 2002; 80:67-73.
64. Usia T, Banskota AH, Tezuka Y, Midorikawa K, Matsushige K, Kadota S. Constituents of Chinese propolis and their antiproliferative activities. J Nat Prod 2002; 65:673-676.
65. Kimoto T, Koya S, Hino K, Yamamoto Y, Nomura Y, Micallef MJ, et al. Renal carcinogenesis induced by ferric nitrilotriacetate in mice, and protection from it by Brazilian propolis and artepillin C. Pathol Int 2000; 50:679-689.
66. Valente MJ, Baltazar AF, Henrique R, Estevinho L, Carvalho M. Biological activities of Portuguese propolis: protection against free radical-induced erythrocyte damage and inhibition of human renal cancer cell growth in vitro. Food Chem Toxicol 2011; 49:86-92.
67. Freitas AS, Costa M, Pontes O, Seidel V, Proença F, Cardoso SM, et al. Selective cytotoxicity of Portuguese propolis ethyl acetate fraction towards renal cancer cells. Molecules 2022; 27:4001.
68. Wang D, Xiang D-B, He Y-J, Li Z-P, Wu X-H, Mou J-H, et al. Effect of caffeic acid phenethyl ester on proliferation and apoptosis of colorectal cancer cells in vitro. World J Gastrointest Endosc 2005; 11:4008.
69. Jung JE, Lee HG, Cho IH, Chung DH, Yoon SH, Yang YM, et al. STAT3 is a potential modulator of HIF‐1‐mediated VEGF expression in human renal carcinoma cells. FASEB J 2005; 19:1296-1298.
70. Sutherland J, Parks J, Coe F. Recurrence after a single renal stone in a community practice. Miner Electrolyte Metab 1985; 11:267-269.
71. Khan SR, Kok DJ. Modulators of urinary stone formation. Front Biosci 2004; 9:1450-1482.
72. De Almeida E, Menezes H. Anti-inflammatory activity of propolis extracts: A review.  J Venom Anim Toxins 2002; 8:191-212.
73. Khayyal M, El-Ghazaly M, El-Khatib A. Mechanisms involved in the antiinflammatory effect of propolis extract. Drugs Exp Clin Res 1993; 19:197-203.
74. Kolankaya D, Selmanoǧlu G, Sorkun K, Salih B. Protective effects of Turkish propolis on alcohol-induced serum lipid changes and liver injury in male rats. Food Chem 2002; 78:213-217.
75. Ramaswamy K, Shah O. Metabolic syndrome and nephrolithiasis.Transl Androl Urol 2014; 3:285.
76. Holoch PA, Tracy CR. Antioxidants and self-reported history of kidney stones: the National Health and Nutrition Examination Survey. J Endourol 2011; 25:1903-1908.
77. Ozyurt H, Irmak MK, Akyol O, Söğüt S. Caffeic acid phenethyl ester changes the indices of oxidative stress in serum of rats with renal ischaemia-reperfusion injury. Cell Biochem Funct 2001; 19:259-263.
78. Yılmaz Aydoğan H, Fehmi Narter K, Sarıkaya Ş, Diren A, P Eronat A, Kafkaslı A, et al. Anatolian propolis prevents oxalate kidney stones: Dramatic reduction of crystal deposition in ethylene-glycol-induced rat model. Rec Nat Prod 2018; 12:445-459.
79. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). Jama 2016; 315:801-810.
80. Hotchkiss RS, Nicholson DW. Apoptosis and caspases regulate death and inflammation in sepsis. Nat Rev Immunol 2006; 6:813-822.
81. Messaris E, Memos N, Chatzigianni E, Kataki A, Nikolopoulou M, Manouras A, et al. Apoptotic death of renal tubular cells in experimental sepsis. Surg Infec 2008; 9:377-388.
82. Doğanyiğit Z, Yakan B, Okan A, Silici S. Antioxidative role of propolis on LPS induced renal damage. Eurobiotech J 2020; 4:156-160.
83. Teles F, da Silva TM, da Cruz Junior FP, Honorato VH, de Oliveira Costa H, Barbosa APF, et al. Brazilian red propolis attenuates hypertension and renal damage in 5/6 renal ablation model. PLoS One 2015; 10:e0116535.
84. Silveira MAD, Capcha JMC, Sanches TR, de Sousa Moreira R, Garnica MS, Shimizu MH, et al. Green propolis extract attenuates acute kidney injury and lung injury in a rat model of sepsis. Sci Rep 2021; 11:1-11.
85. Pei B, Sun J. Pinocembrin alleviates cognition deficits by inhibiting inflammation in diabetic mice. J Neuroimmunol 2018; 314:42-49.
86. de Faria JBL, Silva KC, de Faria JML. The contribution of hypertension to diabetic nephropathy and retinopathy: the role of inflammation and oxidative stress. Hypertens Res 2011; 34:413-422.
87. Parving H-H, Andersen AR, Hommel E, Smidt U. Effects of long-term antihypertensive treatment on kidney function in diabetic nephropathy. Hypertension 1985; 7:II114.
88. Ghosh SS, Krieg R, Massey HD, Sica DA, Fakhry I, Ghosh S, et al. Curcumin and enalapril ameliorate renal failure by antagonizing inflammation in ⅚ nephrectomized rats: Role of phospholipase and cyclooxygenase. Am J Physiol Renal Physiol  2012; 302:F439-F454.
89. Sameni HR, Ramhormozi P, Bandegi AR, Taherian AA, Mirmohammadkhani M, Safari M. Effects of ethanol extract of propolis on histopathological changes and anti‐oxidant defense of kidney in a rat model for type 1 diabetes mellitus. Journal of diabetes investigation 2016; 7:506-513.
90. Nagai T, Inoue R, Inoue H, Suzuki N. Preparation and antioxidant properties of water extract of propolis. Food Chem 2003; 80:29-33.
91. Boutabet K, Kebsa W, Alyane M, Lahouel M. Polyphenolic fraction of Algerian propolis protects rat kidney against acute oxidative stress induced by doxorubicin. Indian J Nephrol 2011; 21:101.
92. Zulhendri F, Lesmana R, Tandean S, Christoper A, Chandrasekaran K, Irsyam I, et al. Recent Update on the Anti-Inflammatory Activities of Propolis. Molecules 2022; 27:8473.
93. Bhadauria M. Propolis prevents hepatorenal injury induced by chronic exposure to carbon tetrachloride. Evid Based Complement Alternat Med 2012; 2012: 235358.
94. Izzularab BM, Megeed M, Yehia M. Propolis nanoparticles modulate the inflammatory and apoptotic pathways in carbon tetrachloride‐induced liver fibrosis and nephropathy in rats. Environ. Toxicol 2021; 36:55-66.
95. Ulusoy HB, Öztürk İ, Sönmez MF. Protective effect of propolis on methotrexate-induced kidney injury in the rat. Ren Fail 2016; 38:744-750.
96. Gonçalves ARR, Fujihara CK, Mattar AL, Malheiros DMAC, Noronha IL, De Nucci G, et al. Renal expression of COX-2, ANG II, and AT1 receptor in remnant kidney: strong renoprotection by therapy with losartan and a nonsteroidal anti-inflammatory. Am J Physiol Renal Physiol 2004; 286:F945-F954.
97. Aldahmash BA, El-Nagar DM, Ibrahim KE. Reno-protective effects of propolis on gentamicin-induced acute renal toxicity in swiss albino mice. Nefrología (Engl Ed) 2016; 36:643-652.
98. da Costa MFB, Libório AB, Teles F, da Silva Martins C, Soares PMG, Meneses GC, et al. Red propolis ameliorates ischemic-reperfusion acute kidney injury. Phytomedicine 2015; 22:787-795.
99. Chang J-F, Hsieh C-Y, Lu K-C, Chen Y-W, Liang S-S, Lin C-C, et al. Therapeutic targeting of aristolochic acid induced uremic toxin retention, SMAD 2/3 and JNK/ERK pathways in tubulointerstitial fibrosis: Nephroprotective role of propolis in chronic kidney disease. Toxins 2020; 12:364.
100. Bueno-Silva B, Kawamoto D, Ando-Suguimoto ES, Casarin RC, Alencar SM, Rosalen PL, et al. Brazilian red propolis effects on peritoneal macrophage activity: Nitric oxide, cell viability, pro-inflammatory cytokines and gene expression. J Ethnopharmacol  2017; 207:100-107.
101. Silveira M, Teles F, Melo E, Borges V, Miranda F, Dutra F, et al. editors. Effects of brazilian green propolis extract (EPP-AF) on inflammation in hemodialysis patients. Nephrol Dial Transplant 2020; 35:1894-1894
102. Tohamy AA, Abdella EM, Ahmed RR, Ahmed YK. Assessment of anti-mutagenic, anti-histopathologic and antioxidant capacities of Egyptian bee pollen and propolis extracts.  Cytotechnology  2014; 66:283-297.
103. Zhu W, Chen M, Shou Q, Li Y, Hu F. Biological activities of Chinese propolis and Brazilian propolis on streptozotocin-induced type 1 diabetes mellitus in rats. Evid Based Complement Alternat Med 2011; 2011: 468529.