Skip to main content

Advertisement

SpringerLink
Log in

Royal jelly: a predictive, preventive and personalised strategy for novel treatment options in non-communicable diseases

  • Review
  • Published:
EPMA Journal Aims and scope Submit manuscript

Abstract

Royal jelly (RJ) is a bee product produced by young adult worker bees, composed of water, proteins, carbohydrates and lipids, rich in bioactive components with therapeutic properties, such as free fatty acids, mainly 10-hydroxy-trans-2-decenoic acid (10-H2DA) and 10-hydroxydecanoic acid (10-HDA), and major royal jelly proteins (MRJPs), as well as flavonoids, most flavones and flavonols, hormones, vitamins and minerals. In vitro, non-clinical and clinical studies have confirmed its vital role as an antioxidant and anti-inflammatory. This narrative review discusses the possible effects of royal jelly on preventing common complications of non-communicable diseases (NCDs), such as inflammation, oxidative stress and intestinal dysbiosis, from the viewpoint of predictive, preventive and personalised medicine (PPPM/3PM). It is concluded that RJ, predictively, can be used as a non-pharmacological therapy to prevent and mitigate complications related to NCDs, and the treatment must be personalised.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data availability

Not applicable.

Code availability

Not applicable.

References

  1. World Health Organization. Heads of state commit to noncommunicable disease global compact to save 50 million lives by 2030. 2022; Available from: https://www.who.int/news/item/21-09-2022-heads-of-state-commit-to-noncommunicable-disease-global-compact-to-save-50-million-lives-by-2030. Accessed 27 Jan 2023

  2. Wang Y, Wang J. Modelling and prediction of global non-communicable diseases. BMC Public Health. 2020;20:1–13.

    Article  Google Scholar 

  3. Furman D, Campisi J, Verdin E, Carrera-Bastos P, Targ S, Franceschi C, et al. Chronic inflammation in the etiology of disease across the life span. Nat Med Nature Res. 2019;25:1822–32.

    Article  CAS  Google Scholar 

  4. Soomro S. Oxidative stress and inflammation. Open J Immunol Scientific Research Publishing Inc. 2019;09:1–20.

    Article  CAS  Google Scholar 

  5. Mafra D, Borges NA, Lindholm B, Shiels PG, Evenepoel P, Stenvinkel P. Food as medicine: targeting the uraemic phenotype in chronic kidney disease. Nat Rev Nephrol. 2021;17:153–71.

  6. Câmara JS, Albuquerque BR, Aguiar J, Corrêa RCG, Gonçalves JL, Granato D, et al. Food bioactive compounds and emerging techniques for their extraction: polyphenols as a case study. Foods. 2021;10:1–34.

    Google Scholar 

  7. Sugiyama T, Takahashi K, Mori H. Royal jelly acid, 10-hydroxy-trans-2-decenoic acid, as a modulator of the innate immune responses Endocr Metab Immune Disord Drug Targets. United Arab Emirates. 2012;12:368–76.

    CAS  Google Scholar 

  8. Bogdanov S. The royal jelly book. Royal jelly and bee brood: harvest, composition, quality. Bee Prod Sci. 2017;1:1–13.

    Google Scholar 

  9. Kocot J, Kiełczykowska M, Luchowska-Kocot D, Kurzepa J, Musik I. Antioxidant potential of propolis, bee pollen, and royal jelly: possible medical application. Oxid Med Cell Longev. 2018;2018:7074209.

  10. Kanelis D, Tananaki C, Liolios V, Dimou M, Goras G, Rodopoulou MA, et al. A suggestion for royal jelly specifications. Arh Hig Rada Toksikol. 2015;66:275–84.

    Article  PubMed  Google Scholar 

  11. Abu-Serie MM, Habashy NH. Two purified proteins from royal jelly with in vitro dual anti-hepatic damage potency: major royal jelly protein 2 and its novel isoform X1. Int J Biol. 2019;128:782–95. https://doi.org/10.1016/j.ijbiomac.2019.01.210.

    Article  CAS  Google Scholar 

  12. Ali FEM, Saad Eldien HM, Mostafa NAM, Almaeen AH, Marzouk MRA, Eid KM, et al. The impact of royal jelly against hepatic ischemia/reperfusion-induced hepatocyte damage in rats: the role of cytoglobin, Nrf-2/HO-1/COX-4, and P38-MAPK/NF-κB-p65/TNF-α Signaling Pathways. Curr Mol Pharmacol. 2021;14:88–100.

    Article  CAS  PubMed  Google Scholar 

  13. Aslan A, Beyaz S, Gok O, Can MI, Parlak G, Ozercan IH, et al. Royal jelly abrogates flouride-induced oxidative damage in rat heart tissue by activating of the nrf-2/NF-κB and bcl-2/bax pathway. Toxicol Mech Methods. 2021;31:644–54. https://doi.org/10.1080/15376516.2021.1950249.

    Article  CAS  PubMed  Google Scholar 

  14. Miyata Y, Araki K, Ohba K, Mastuo T, Nakamura Y, Yuno T, et al. Oral intake of royal jelly improves anti-cancer effects and suppresses adverse events of molecular targeted therapy by regulating TNF-α and TGF-β in renal cell carcinoma: a preliminary study based on a randomized double-blind clinical trial. Mol Clin Oncol. 2020;13:1–8.

    Article  Google Scholar 

  15. Aslan A, Beyaz S, Gok O, Can MI, Parlak G, Ozercan IH, et al. Royal jelly abrogates flouride-induced oxidative damage in rat heart tissue by activating of the nrf-2/NF-κB and bcl-2/bax pathway. Toxicol Mech Methods. 2021;31:644–54.

    Article  CAS  PubMed  Google Scholar 

  16. Almeer RS, Soliman D, Kassab RB, AlBasher GI, Alarifi S, Alkahtani S, et al. Royal jelly abrogates cadmium-induced oxidative challenge in mouse testes: involvement of the Nrf2 pathway. Int J Mol Sci. 2018;19:3979.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Jenkhetkan W, Thitiorul S, Jansom C, Ratanavalachai T. Molecular and cytogenetic effects of Thai royal jelly: modulation through c-MYC, h-TERT, NRF2, HO-1, BCL2, BAX and cyclins in human lymphocytes in vitro. Mutagenesis. 2017;32:525–31.

    Article  CAS  PubMed  Google Scholar 

  18. Golubnitschaja O, Watson ID, Topic E, Sandberg S, Ferrari M, Costigliola V. Position paper of the EPMA and EFLM: a global vision of the consolidated promotion of an integrative medical approach to advance health care. EPMA J. 2013;4:12.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Denisow B, Denisow-Pietrzyk M. Biological and therapeutic properties of bee pollen: a review. J Sci Food Agric. 2016;96:4303–9.

    Article  CAS  PubMed  Google Scholar 

  20. Fratini F, Cilia G, Mancini S, Felicioli A. Royal Jelly: an ancient remedy with remarkable antibacterial properties. Microbiol Res. 2016;192:130–41. https://doi.org/10.1016/j.micres.2016.06.007.

    Article  CAS  PubMed  Google Scholar 

  21. Cao LF, Zheng HQ, Pirk CWW, Hu FL, Xu ZW. High royal jelly-producing honeybees (Apis mellifera ligustica) (Hymenoptera: Apidae) in China. J Econ Entomol. 2016;109:510–4.

    Article  CAS  PubMed  Google Scholar 

  22. Li X, Huang C, Xue Y. Contribution of lipids in honeybee (Apis mellifera) royal jelly to health. J Med Food. 2013;16:96–102.

    Article  CAS  PubMed  Google Scholar 

  23. Khalifa SAM, Elashal MH, Yosri N, Du M, Musharraf SG, Nahar L, et al. Bee pollen: Current status and therapeutic potential. Nutrients. 2021;13:1–15.

    Article  Google Scholar 

  24. Chen Y-F, Wang K, Zhang Y-Z, Zheng Y-F, Hu F-L. In vitro anti-inflammatory effects of three fatty acids from royal jelly. Mediat Inflamm. 2016;2016:3583684.

    Article  Google Scholar 

  25. Yamaga M, Tani H, Yamaki A, Tatefuji T, Hashimoto K. Metabolism and pharmacokinetics of medium chain fatty acids after oral administration of royal jelly to healthy subjects. RSC Adv Royal Soc Chem. 2019;9:15392–401.

    Article  CAS  Google Scholar 

  26. Ramadan MF, Al-Ghamdi A. Bioactive compounds and health-promoting properties of royal jelly: a review. J Funct Foods. 2012;4:39–52. https://doi.org/10.1016/j.jff.2011.12.007.

    Article  CAS  Google Scholar 

  27. Melliou E, Chinou I. Chemistry and bioactivity of royal jelly from Greece. J Agric Food Chem. 2005;53:8987–92.

    Article  CAS  PubMed  Google Scholar 

  28. Isdorov VA, Bakier S, Grzech I. Gas chromatographic–mass spectrometric investigation of volatile and extractable compounds of crude royal jelly. J Chromatogr B. 2012;885–886:109–16.

    Article  Google Scholar 

  29. Uthaibutra V, Kaewkod T, Prapawilai P, Pandith H. Yingmanee Tragoolpua Inhibition of skin pathogenic bacteria, antioxidant and anti-inflammatory activity of royal jelly from northern Thailand. Molecules. 2023;28(3):28.

    Article  Google Scholar 

  30. Liu J-R, Yang Y-C, Shi L-S, Peng C-C. Antioxidant properties of royal jelly associated with larval age and time of harvest. J Agric Food Chem. 2008;56:11447–52.

    Article  CAS  PubMed  Google Scholar 

  31. Garcia-Amoedo LH, De Almeida-Muradian LB. Physicochemical composition of pure and adulterated royal jelly. Quim Nova. 2007;30:257–9.

    Article  CAS  Google Scholar 

  32. López-Gutiérrez N, Aguilera-Luiz MDM, Romero-González R, Vidal JLM, Garrido Frenich A. Fast analysis of polyphenols in royal jelly products using automated TurboFlowTM-liquid chromatography-Orbitrap high resolution mass spectrometry. J Chromatogr B. 2014;973:17–28.

    Article  Google Scholar 

  33. Kanbur M, Eraslan G, Silici S, Karabacak M. Effects of sodium fluoride exposure on some biochemical parameters in mice: evaluation of the ameliorative effect of royal jelly applications on these parameters. Food Chem Toxicol an Int J Publ Br Ind Biol Res Assoc. 2009;47:1184–9.

    Article  CAS  Google Scholar 

  34. Negri G, Teixeira EW, Alves MLTMF, De Camargo CarmelloMoreti AC, Otsuk IP, Borguini RG, et al. Hydroxycinnamic acid amide derivatives, phenolic compounds and antioxidant activities of extracts of pollen samples from Southeast Brazil. J Agric Food Chem. 2011;59:5516–22.

    Article  CAS  PubMed  Google Scholar 

  35. Durazzo A, Lucarini M, Plutino M, Lucini L, Aromolo R, Martinelli E, et al. Bee products: a representation of biodiversity, sustainability, and health. Life. 2021;11:1–32.

    Article  Google Scholar 

  36. Arct J, Pytkowska K. Flavonoids as components of biologically active cosmeceuticals. Clin Dermatol. 2008;26:347–57.

    Article  PubMed  Google Scholar 

  37. Manzo LP, De-Faria FM, Dunder RJ, Rabelo-Socca EA, Consonni SR, De Almeida ACA, et al. Royal jelly and its dual role in TNBS colitis in mice. Sci World J. 2015;2015:1–7.

    Article  Google Scholar 

  38. Kolayli S, Sahin H, Can Z, Yildiz O, Malkoc M, Asadov A. A member of complementary medicinal food: Anatolian royal jellies, their chemical compositions, and antioxidant properties. J Evidence-Based Complement Altern Med. 2016;21:43–8.

    Article  Google Scholar 

  39. Malekinejad H, Ahsan S, Delkhosh-Kasmaie F, Cheraghi H, Rezaei-Golmisheh A, Janbaz-Acyabar H. A cardioprotective effect of royal jelly on paclitaxel-induced cardio-toxicity in rats. Iran J Basic Med Sci. 2016;19:221–7.

    PubMed  PubMed Central  Google Scholar 

  40. Klaudiny J, Bachanová K, Kohútová L, Dzúrová M, Kopernický J, Majtán J. Expression of larval jelly antimicrobial peptide defensin1 in Apis mellifera colonies. Biologia. 2012;67:200–11.

    Article  CAS  Google Scholar 

  41. Khoshpey B, Djazayeri S, Amiri F, Malek M, Hosseini AF, Hosseini S, et al. Effect of royal jelly intake on serum glucose, apolipoprotein A-I (ApoA-I), apolipoprotein B (ApoB) and ApoB/ApoA-I ratios in patients with type 2 diabetes: a randomized, double-blind clinical trial study. Can J Diabetes. 2016;40:324–8. https://doi.org/10.1016/j.jcjd.2016.01.003.

    Article  PubMed  Google Scholar 

  42. ShakibKhoob M, Hosseini SM, Kazemi S. In vitro and in vivo antioxidant and anticancer potentials of royal jelly for dimethylhydrazine-induced colorectal cancer in Wistar rats. Oxid Med Cell Longev. 2022;2022:9506026.

    Google Scholar 

  43. Mostafa RE, Shaffie NM, Allam RM. Protective effects of royal jelly and Echinacea against moxifloxacin-induced renal and hepatic injury in rats. Drug Chem Toxicol. 2022;1–10.

  44. Viuda-Martos M, Ruiz-Navajas Y, Fernández-López J, Pérez-Álvarez JA. Functional properties of honey, propolis, and royal jelly. J Food Sci. 2008;73:117–24.

    Article  Google Scholar 

  45. Brazil. Regulamentos Técnicos de Identidade e Qualidade de apitoxina, cera de abelha, geléia real, geléia real liofilizada, pólen apícola, própolis e extrato de própolis. BRAZIL. 2001;97:11.

  46. Kocot J, Kiełczykowska M, Luchowska-Kocot D, Kurzepa J, Musik I. Antioxidant potential of propolis, bee pollen, and royal jelly: possible medical application. Oxid Med Cell Longev. 2018;2018:7074209.

    Article  PubMed  PubMed Central  Google Scholar 

  47. De Paula R, Rabalski I, Messia MC, Abdel-Aal E-SM, Marconi E. Effect of processing on phenolic acids composition and radical scavenging capacity of barley pasta. Food Res Int. 2017;102:136–43.

    Article  PubMed  Google Scholar 

  48. Guo H, Kouzuma Y, Yonekura M. Structures and properties of antioxidative peptides derived from royal jelly protein. Food. 2009;113:238–45. https://doi.org/10.1016/j.foodchem.2008.06.081.

    Article  CAS  Google Scholar 

  49. Mihajlovic D, Rajkovic I, Chinou I, Colic M. Dose-dependent immunomodulatory effects of 10-hydroxy-2-decenoic acid on human monocyte-derived dendritic cells. J Funct Foods. 2013;5:838–46.

    Article  CAS  Google Scholar 

  50. Hayden MS, Ghosh S. Shared principles in NF-kappaB signaling. Cell. 2008;132:344–62.

    Article  CAS  PubMed  Google Scholar 

  51. Yang CH, Murti A, Pfeffer SR, Kim JG, Donner DB, Pfeffer LM. Interferon alpha /beta promotes cell survival by activating nuclear factor kappa B through phosphatidylinositol 3-kinase and Akt. J Biol. 2001;276:13756–61.

    Article  CAS  PubMed  Google Scholar 

  52. Sugiyama T, Takahashi K, Kuzumaki A, Tokoro S, Neri P, Mori H. Inhibitory mechanism of 10-hydroxy-trans-2-decenoic acid (royal jelly acid) against lipopolysaccharide- and interferon-β-induced nitric oxide production. Inflammation. 2013;36:372–8.

    Article  CAS  PubMed  Google Scholar 

  53. Inoue Y, Hara H, Mitsugi Y, Yamaguchi E, Kamiya T, Itoh A, et al. 4-Hydroperoxy-2-decenoic acid ethyl ester protects against 6-hydroxydopamine-induced cell death via activation of Nrf2-ARE and eIF2α-ATF4 pathways. Neurochem Int. 2018;112:288–96.

    Article  CAS  PubMed  Google Scholar 

  54. Koklesova L, Mazurakova A, Samec M, Kudela E, Biringer K, Kubatka P, et al. Mitochondrial health quality control: measurements and interpretation in the framework of predictive, preventive, and personalized medicine. EPMA J. 2022;13:177–93.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Videla LA, Marimán A, Ramos B, José Silva M, Del Campo A. Standpoints in mitochondrial dysfunction: underlying mechanisms in search of therapeutic strategies. Mitochondrion. 2022;63:9–22.

    Article  CAS  PubMed  Google Scholar 

  56. Rai SN, Singh C, Singh A, Singh MP, Singh BK. Mitochondrial dysfunction: a potential therapeutic target to treat Alzheimer’s disease. Mol Neurobiol. 2020;57:3075–88.

    Article  CAS  PubMed  Google Scholar 

  57. Eldeeb MA, Thomas RA, Ragheb MA, Fallahi A, Fon EA. Mitochondrial quality control in health and in Parkinson’s disease. Physiol Rev. 2022;102:1721–55.

    Article  CAS  PubMed  Google Scholar 

  58. Rovira-Llopis S, Bañuls C, Diaz-Morales N, Hernandez-Mijares A, Rocha M, Victor VM. Mitochondrial dynamics in type 2 diabetes: pathophysiological implications. Redox Biol. 2017;11:637–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Boengler K, Kosiol M, Mayr M, Schulz R, Rohrbach S. Mitochondria and ageing: role in heart, skeletal muscle and adipose tissue. J Cachexia Sarcopenia Muscle. 2017;8:349–69.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Takahashi Y, Hijikata K, Seike K, Nakano S, Banjo M, Sato Y, et al. Effects of royal jelly administration on endurance training-induced mitochondrial adaptations in skeletal muscle. Nutrients. 2018;10:1735.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Aslan A, Beyaz S, Gok O, Can MI, Parlak G, Gundogdu R, et al. Protective effect of royal jelly on fluoride-induced nephrotoxicity in rats via the some protein biomarkers signalling pathways: a new approach for kidney damage. Biomarkers. 2022;27:637–47.

    Article  CAS  PubMed  Google Scholar 

  62. Hashem KS, Elkelawy AMMH, Abd-Allah S, Helmy NA. Involvement of Mfn2, Bcl2/Bax signaling and mitochondrial viability in the potential protective effect of royal jelly against mitochondria-mediated ovarian apoptosis by cisplatin in rats. Iran J Basic Med Sci. 2020;23:515–26.

    PubMed  PubMed Central  Google Scholar 

  63. Ogurtsova K, da Rocha Fernandes JD, Huang Y, Linnenkamp U, Guariguata L, Cho NH, et al. IDF Diabetes Atlas: global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes Res Clin Pract. 2017;128:40–50.

    Article  CAS  PubMed  Google Scholar 

  64. Tinajero MG, Malik VS. An update on the epidemiology of type 2 diabetes: a global perspective. Endocrinol Metab Clin North Am. 2021;50:337–55.

  65. Ali O. Principles of diabetes mellitus: third edition. Princ Diabetes Mellit. 2017:1–1066.

  66. DeFronzo RA, Ferrannini E, Groop L, Henry RR, Herman WH, Holst JJ, et al. Type 2 diabetes mellitus. Nat Rev Dis Prim. 2015;1:15019.

    Article  PubMed  Google Scholar 

  67. Luc K, Schramm-Luc A, Guzik TJ, Mikolajczyk TP. Oxidative stress and inflammatory markers in prediabetes and diabetes. J Physiol Pharmacol an Off J Polish Physiol Soc. 2019;70:809–18.

    CAS  Google Scholar 

  68. Rohm TV, Meier DT, Olefsky JM, Donath MY. Inflammation in obesity, diabetes, and related disorders. Immunity. 2022;55:31–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Tan SY, Mei Wong JL, Sim YJ, Wong SS, Mohamed Elhassan SA, Tan SH, et al. Type 1 and 2 diabetes mellitus: a review on current treatment approach and gene therapy as potential intervention. Diabetes Metab Syndr. 2019;13:364–72.

    Article  PubMed  Google Scholar 

  70. Cao H, Ou J, Chen L, Zhang Y, Szkudelski T, Delmas D, et al. Dietary polyphenols and type 2 diabetes: human study and clinical trial. Crit Rev Food Sci Nutr. 2019;59:3371–9.

    Article  CAS  PubMed  Google Scholar 

  71. Pivari F, Mingione A, Brasacchio C, Soldati L. Curcumin and type 2 diabetes mellitus: prevention and treatment. Nutrients. 2019;11:1837.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Sharma S, Mandal A, Kant R, Jachak S, Jagzape M. Is cinnamon efficacious for glycaemic control in type-2 diabetes mellitus? J Pak Med Assoc. 2020;70:2065–9.

    PubMed  Google Scholar 

  73. Pourmoradian S, Mahdavi R, Mobasseri M, Faramarzi E, Mobasseri M. Effects of royal jelly supplementation on glycemic control and oxidative stress factors in type 2 diabetic female: a randomized clinical trial. Chin J Integr Med. 2014;20:347–52.

    Article  CAS  PubMed  Google Scholar 

  74. Yoshida M, Hayashi K, Watadani R, Okano Y, Tanimura K, Kotoh J, et al. Royal jelly improves hyperglycemia in obese/diabetic KK-Ay mice. J Vet Med Sci. 2017;79:299–307.

    Article  CAS  PubMed  Google Scholar 

  75. Maleki V, Jafari-Vayghan H, Saleh-Ghadimi S, Adibian M, Kheirouri S, Alizadeh M. Effects of royal jelly on metabolic variables in diabetes mellitus: a systematic review. Complement Ther Med. 2019;43:20–7.

    Article  PubMed  Google Scholar 

  76. Hu X, Liu Z, Lu Y, Chi X, Han K, Wang H, et al. Glucose metabolism enhancement by 10-hydroxy-2-decenoic acid via the PI3K/AKT signaling pathway in high-fat-diet/streptozotocin induced type 2 diabetic mice. Food Funct England. 2022;13:9931–46.

    Article  CAS  Google Scholar 

  77. Nohair SF. Al Antidiabetic efficacy of a honey-royal jelly mixture: biochemical study in rats. Int J Health Sci (Qassim). 2021;15:4–9.

    PubMed  Google Scholar 

  78. Yoneshiro T, Kaede R, Nagaya K, Aoyama J, Saito M, Okamatsu-Ogura Y, et al. Royal jelly ameliorates diet-induced obesity and glucose intolerance by promoting brown adipose tissue thermogenesis in mice. Obes Res Clin Pract. 2018;12:127–37.

    Article  PubMed  Google Scholar 

  79. GBD. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980–2017: a systematic analysis for the Global Burden of Disease Study. Lancet. 2017;2018(392):1736–88.

  80. GBD. Global, regional, and national disability-adjusted life-years (DALYs) for 359 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study. Lancet. 2017;2018(392):1859–922.

  81. Jain AK, Mehra NK, Swarnakar NK. Role of antioxidants for the treatment of cardiovascular diseases: challenges and opportunities. Curr Pharm Des. 2015;21:4441–55.

    Article  CAS  PubMed  Google Scholar 

  82. Frostegård J. Immunity atherosclerosis and cardiovascular disease. BMC Med. 2013;11:117.

    Article  PubMed  PubMed Central  Google Scholar 

  83. Lind L, Ingelsson M, Sundstrom J, Ärnlöv J. Impact of risk factors for major cardiovascular diseases: a comparison of life-time observational and Mendelian randomisation findings. Open Hear. 2021;8:e001735.

  84. Golubnitschaja O, Liskova A, Koklesova L, Samec M, Biringer K, Büsselberg D, et al. Caution, “normal” BMI: health risks associated with potentially masked individual underweight-EPMA Position Paper 2021. EPMA J. 2021;12:243–64.

    Article  PubMed  PubMed Central  Google Scholar 

  85. Badimon L, Chagas P, Chiva-Blanch G. Diet and cardiovascular disease: effects of foods and nutrients in classical and emerging cardiovascular risk factors. Curr Med Chem. 2019;26:3639–51.

    Article  CAS  PubMed  Google Scholar 

  86. Olas B. Bee products as interesting natural agents for the prevention and treatment of common cardiovascular diseases. Nutrients. 2022;14:2267.

  87. Matsui T, Yukiyoshi A, Doi S, Sugimoto H, Yamada H, Matsumoto K. Gastrointestinal enzyme production of bioactive peptides from royal jelly protein and their antihypertensive ability in SHR. J Nutr Biochem. 2002;13:80–6.

    Article  CAS  PubMed  Google Scholar 

  88. Tokunaga K, Yoshida C, Suzuki K, Maruyama H, Futamura Y, Araki Y, et al. Antihypertensive effect of peptides from royal jelly in spontaneously hypertensive rats. Biol Pharm Bull. 2004;27:189–92.

    Article  CAS  PubMed  Google Scholar 

  89. Takaki-Doi S, Hashimoto K, Yamamura M, Kamei C. Antihypertensive activities of royal jelly protein hydrolysate and its fractions in spontaneously hypertensive rats. Acta Med Okayama. 2009;63:57–64.

    CAS  PubMed  Google Scholar 

  90. Pan Y, Rong Y, You M, Ma Q, Chen M, Hu F. Royal jelly causes hypotension and vasodilation induced by increasing nitric oxide production. Food Sci Nutr. 2019;7:1361–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Liang Y, Kagota S, Maruyama K, Oonishi Y, Miyauchi-Wakuda S, Ito Y, et al. Royal jelly increases peripheral circulation by inducing vasorelaxation through nitric oxide production under healthy conditions. Biomed Pharmacother. 2018;106:1210–9.

    Article  CAS  PubMed  Google Scholar 

  92. Patel SA, Winkel M, Ali MK, Narayan KMV, Mehta NK. Cardiovascular mortality associated with 5 leading risk factors: national and state preventable fractions estimated from survey data. Ann Intern Med. 2015;163:245–53.

    Article  PubMed  Google Scholar 

  93. Virani SS, Alonso A, Benjamin EJ, Bittencourt MS, Callaway CW, Carson AP, et al. Heart Disease and Stroke Statistics-2020 update: a report from the American Heart Association. Circulation. 2020;141:e139-596.

    Article  PubMed  Google Scholar 

  94. Guo H, Saiga A, Sato M, Miyazawa I, Shibata M, Takahata Y, et al. Royal jelly supplementation improves lipoprotein metabolism in humans. J Nutr Sci Vitaminol. 2007;53:345–8.

    Article  CAS  PubMed  Google Scholar 

  95. Kamakura M, Moriyama T, Sakaki T. Changes in hepatic gene expression associated with the hypocholesterolaemic activity of royal jelly. J Pharm Pharmacol. 2006;58:1683–9.

    Article  CAS  PubMed  Google Scholar 

  96. Hadi A, Najafgholizadeh A, Aydenlu ES, Shafiei Z, Pirivand F, Golpour S, et al. Royal jelly is an effective and relatively safe alternative approach to blood lipid modulation: a meta-analysis. J Funct Foods. 2018;41:202–9.

    Article  CAS  Google Scholar 

  97. Kashima Y, Kanematsu S, Asai S, Kusada M, Watanabe S, Kawashima T, et al. Identification of a novel hypocholesterolemic protein, major royal jelly protein 1, derived from royal jelly. PLoS One. 2014;9:e105073.

    Article  PubMed  PubMed Central  Google Scholar 

  98. Torres Crigna A, Link B, Samec M, Giordano FA, Kubatka P, Golubnitschaja O. Endothelin-1 axes in the framework of predictive, preventive and personalised (3P) medicine. EPMA J. 2021;12:265–305.

    Article  PubMed  PubMed Central  Google Scholar 

  99. Abd El-Hakam FE-Z, Abo Laban G, Badr El-Din S, Abd El-Hamid H, Farouk MH. Apitherapy combination improvement of blood pressure cardiovascular protection, and antioxidant and anti-inflammatory responses in dexamethasone model hypertensive rats. Sci Rep. 2022;12:20765.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Bikbov B, Purcell C, Levey A, Smith M, Abdoli A, Abebe M. Global, regional, and national burden of chronic kidney disease, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2020;395:709–33.

  101. Ebert T, Pawelzik SC, Witasp A, Arefin S, Hobson S, Kublickiene K, et al. Inflammation and premature ageing in chronic kidney disease. Toxins. 2020;12:227.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Rysz J, Franczyk B, Ławiński J, Olszewski R, Ciałkowska-Rysz A, Gluba-Brzózka A. The impact of CKD on uremic toxins and gut microbiota. Toxins. 2021;13:252.

  103. Stenvinkel P, Chertow GM, Devarajan P, Levin A, Andreoli SP, Bangalore S, et al. Chronic inflammation in chronic kidney disease progression: role of Nrf2. Kidney Int Reports. 2021;6:1775–87.

    Article  Google Scholar 

  104. Pedruzzi LM, Cardozo LFMF, Daleprane JB, Stockler-Pinto MB, Monteiro EB, Leite MJ, et al. Systemic inflammation and oxidative stress in hemodialysis patients are associated with down-regulation of Nrf2. J Nephrol. 2015;28:495–501.

    Article  CAS  PubMed  Google Scholar 

  105. Mafra D, Borges NA, Lindholm B, Shiels PG, Evenepoel P, Stenvinkel P. Food as medicine: targeting the uraemic phenotype in chronic kidney disease. Nat Rev. 2021;17:153–71. https://doi.org/10.1038/s41581-020-00345-8.

    Article  Google Scholar 

  106. Kruse NT. Nutraceuticals as a potential adjunct therapy toward improving vascular health in CKD. Am J Physiol Regul Integr Comp Physiol. 2019;317:R719-32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Gobe GC, Wojcikowski K. Nontraditional (non-Western pharmaceutical) treatments for chronic kidney disease. Clin Nephrol. 2020;93:49–54.

    Article  PubMed  Google Scholar 

  108. Mafra D, Ugochukwu SA, Borges NA, Cardozo LFMF, Stenvinkel P, Shiels PG. Food for healthier aging: power on your plate. Crit Rev Food Sci Nutr. 2022;1–14.

  109. Ohba K, Miyata Y, Shinzato T, Funakoshi S, Maeda K, Matsuo T, et al. Effect of oral intake of royal jelly on endothelium function in hemodialysis patients: study protocol for multicenter, double-blind, randomized control trial. Trials. 2021;22:950.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Mostafa RE, El-Marasy SA, Abdel Jaleel GA, Bakeer RM. Protective effect of royal jelly against diclofenac-induced hepato-renal damage and gastrointestinal ulcerations in rats. Heliyon. 2020;6:e03330. https://doi.org/10.1016/j.heliyon.2020.e03330.

    Article  PubMed  PubMed Central  Google Scholar 

  111. Almeer RS, Kassab RB, AlBasher GI, Alarifi S, Alkahtani S, Ali D, et al. Royal jelly mitigates cadmium-induced neuronal damage in mouse cortex. Mol Biol Rep Netherlands. 2019;46:119–31.

    Article  CAS  Google Scholar 

  112. Aslan Z, Aksoy L. Anti-inflammatory effects of royal jelly on ethylene glycol induced renal inflammation in rats. Int Braz J Urol. 2015;41:1008–13.

    Article  PubMed  PubMed Central  Google Scholar 

  113. Grech G, Zhan X, Yoo BC, Bubnov R, Hagan S, Danesi R, et al. EPMA position paper in cancer: current overview and future perspectives. EPMA J. 2015;6:9.

    Article  PubMed  PubMed Central  Google Scholar 

  114. Bui TM, Wiesolek HL, Sumagin R. ICAM-1: a master regulator of cellular responses in inflammation, injury resolution, and tumorigenesis. J Leukoc Biol. 2020;108:787–99.

    Article  CAS  PubMed  Google Scholar 

  115. Hou J, Karin M, Sun B. Targeting cancer-promoting inflammation - have anti-inflammatory therapies come of age? Nat Rev Clin Oncol. 2021;18:261–79.

    Article  PubMed  PubMed Central  Google Scholar 

  116. Nabas Z, Haddadin MSY, Haddadin J, Nazer IK. Chemical composition of royal jelly and effects of synbiotic with two different locally isolated probiotic strains on antioxidant activities. Polish J Food Nutr Sci. 2014;64:171–80.

    Article  CAS  Google Scholar 

  117. Ponte LGS, Pavan ICB, Mancini MCS, Da Silva LGS, Morelli AP, Severino MB, et al. The hallmarks of flavonoids in cancer. Molecules. 2021;26:1–55.

    Article  Google Scholar 

  118. Huntington ND, Cursons J, Rautela J. The cancer-natural killer cell immunity cycle. Nat Rev Cancer. 2020;20:437–54.

    Article  CAS  PubMed  Google Scholar 

  119. Ikeda H, Togashi Y. Aging, cancer, and antitumor immunity. Int J Clin Oncol. 2022;27:316–22.

    Article  PubMed  Google Scholar 

  120. Wu S-Y, Fu T, Jiang Y-Z, Shao Z-M. Natural killer cells in cancer biology and therapy. Mol Cancer. 2020;19:120.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. El-Seedi HR, Eid N, Abd El-Wahed AA, Rateb ME, Afifi HS, Algethami AF, et al. Honey bee products: preclinical and clinical studies of their anti-inflammatory and immunomodulatory properties. Front Nutr. 2022;8:761267.

    Article  PubMed  PubMed Central  Google Scholar 

  122. Miyata Y, Sakai H. Anti-cancer and protective effects of royal jelly for therapy-induced toxicities in malignancies. Int J Mol Sci. 2018;19:3270.

  123. Yang Y-C, Chou W-M, Widowati DA, Lin I-P, Peng C-C. 10-hydroxy-2-decenoic acid of royal jelly exhibits bactericide and anti-inflammatory activity in human colon cancer cells. BMC Complement Altern Med. 2018;18:202.

    Article  PubMed  PubMed Central  Google Scholar 

  124. Zhang W, Borcherding N, Kolb R. IL-1 signaling in tumor microenvironment. Adv Exp Med Biol. 2020;1240:1–23.

    Article  CAS  PubMed  Google Scholar 

  125. Ibrahimi R, Ibrahimi M, Jamalzei B, Akbari ME, Navari M, Moossavi M, et al. Association between interleukin-1 receptor antagonist (IL-1ra) VNTR, gene polymorphism and breast cancer susceptibility in Iranian population: experimental and web-based analysis. Int J Immunogenet. 2022;49:254–9.

    Article  CAS  PubMed  Google Scholar 

  126. Rothenberger NJ, Somasundaram A, Stabile LP. The role of the estrogen pathway in the tumor microenvironment. Int J Mol Sci. 2018;19:611.

    Article  PubMed  PubMed Central  Google Scholar 

  127. Zhao Y, Wang X, Liu Y, Wang H-Y, Xiang J. The effects of estrogen on targeted cancer therapy drugs. Pharmacol Res. 2022;177:106131.

    Article  CAS  PubMed  Google Scholar 

  128. Liu G, Cai W, Liu H, Jiang H, Bi Y, Wang H. The association of bisphenol A and phthalates with risk of breast cancer: a meta-analysis. Int J Environ Res Public Health. 2021;18:2375.

  129. Engin AB, Engin A. The effect of environmental bisphenol A exposure on breast cancer associated with obesity. Environ Toxicol Pharmacol. 2021;81:103544.

    Article  CAS  PubMed  Google Scholar 

  130. Ahmad S, Campos MG, Fratini F, Altaye SZ, Li J. New insights into the biological and pharmaceutical properties of royal jelly. Int J Mol Sci. 2020;21:382.

  131. Wu S, Wei X, Jiang J, Shang L, Hao W. Effects of bisphenol A on the proliferation and cell cycle of HBL-100 cells. Food Chem Toxicol an Int J Publ Br Ind Biol Res Assoc. 2012;50:3100–5.

    Article  CAS  Google Scholar 

  132. Wang Q, Morris RJ, Bode AM, Zhang T. Prostaglandin pathways: opportunities for cancer prevention and therapy. Cancer Res. 2022;82:949–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Bincoletto C, Eberlin S, Figueiredo CAV, Luengo MB, Queiroz MLS. Effects produced by royal Jelly on haematopoiesis: relation with host resistance against Ehrlich ascites tumour challenge. Int Immunopharmacol. 2005;5:679–88.

    Article  CAS  PubMed  Google Scholar 

  134. Chi X, Liu Z, Wang H, Wang Y, Wei W, Xu B. Royal jelly enhanced the antioxidant activities and modulated the gut microbiota in healthy mice. J Food Biochem. 2021;45:e13701.

    Article  CAS  PubMed  Google Scholar 

  135. Yuno T, Miyata Y, Mukae Y, Otsubo A, Mitsunari K, Matsuo T, et al. Mechanisms underlying the inhibition of tyrosine kinase inhibitor-induced anorexia and fatigue by royal jelly in renal cell carcinoma patients and the correlation between macrophage colony stimulating factor and inflammatory mediators. Med Sci. 2020;8:43.

    CAS  Google Scholar 

  136. Münstedt K, Männle H. Using bee products for the prevention and treatment of oral mucositis induced by cancer treatment. Molecules. 2019;24:3023.

    Article  PubMed  PubMed Central  Google Scholar 

  137. Bolton L. Managing oral mucositis in patients with cancer. Wounds a Compend Clin Res Pract. 2021;33:136–8.

    Article  Google Scholar 

  138. Severo MLB, Thieme S, Silveira FM, Tavares RPM, Gonzaga AKG, Zucolotto SM, et al. Comparative study of royal jelly, propolis, and photobiomodulation therapies in 5-fluorouracil-related oral mucositis in rats. Support care cancer Off J Multinatl Assoc Support Care Cancer. 2022;30:2723–34.

    Google Scholar 

  139. Yamauchi K, Kogashiwa Y, Moro Y, Kohno N. The effect of topical application of royal jelly on chemoradiotherapy-induced mucositis in head and neck cancer: a preliminary study. Int J Otolaryngol. 2014;2014:974967.

    Article  PubMed  PubMed Central  Google Scholar 

  140. Erdem O, Güngörmüş Z. The effect of royal jelly on oral mucositis in patients undergoing radiotherapy and chemotherapy. Holist Nurs Pract. 2014;28:242–6.

    Article  PubMed  Google Scholar 

  141. Daugėlaitė G, Užkuraitytė K, Jagelavičienė E, Filipauskas A. Prevention and treatment of chemotherapy and radiotherapy induced oral mucositis. Medicina. 2019;55:25.

    Article  PubMed  PubMed Central  Google Scholar 

  142. Pasupuleti VR, Sammugam L, Ramesh N, Gan SH. Honey, propolis, and royal jelly: a comprehensive review of their biological actions and health benefits. Oxid Med Cell Longev. 2017;2017:1259510.

    Article  PubMed  PubMed Central  Google Scholar 

  143. Cornara L, Biagi M, Xiao J, Burlando B. Therapeutic properties of bioactive compounds from different honeybee products. Front Pharmacol. 2017;8:412.

    Article  PubMed  PubMed Central  Google Scholar 

  144. Borsini A, Nicolaou A, Camacho-Muñoz D, Kendall AC, Di Benedetto MG, Giacobbe J, et al. Omega-3 polyunsaturated fatty acids protect against inflammation through production of LOX and CYP450 lipid mediators: relevance for major depression and for human hippocampal neurogenesis. Mol Psychiatry. 2021;26:6773–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Rodríguez-Iglesias N, Nadjar A, Sierra A, Valero J. Susceptibility of female mice to the dietary omega-3/omega-6 fatty-acid ratio: effects on adult hippocampal neurogenesis and glia. Int J Mol Sci. 2022;23:3399.

    Article  PubMed  PubMed Central  Google Scholar 

  146. Bălan A, Moga MA, Dima L, Toma S, Elena Neculau A, Anastasiu CV. Royal jelly-a traditional and natural remedy for postmenopausal symptoms and aging-related pathologies. Molecules. 2020;25:3291.

    Article  PubMed  PubMed Central  Google Scholar 

  147. Kunugi H, Mohammed Ali A. Royal jelly and its components promote healthy aging and longevity: from animal models to humans. Int J Mol Sci. 2019;20:4662.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Botchway BOA, Moore MK, Akinleye FO, Iyer IC, Fang M. Nutrition: review on the possible treatment for Alzheimer’s disease. J Alzheimers Dis. 2018;61:867–83.

    Article  PubMed  Google Scholar 

  149. Wang Z, Zhu W, Xing Y, Jia J, Tang Y. B vitamins and prevention of cognitive decline and incident dementia: a systematic review and meta-analysis. Nutr Rev. 2022;80:931–49.

    Article  PubMed  Google Scholar 

  150. Mikkelsen K, Apostolopoulos V. B vitamins and ageing. Subcell Biochem United States. 2018;90:451–70.

    Article  CAS  Google Scholar 

  151. Sun Q, Zhang J, Li A, Yao M, Liu G, Chen S, et al. Acetylcholine deficiency disrupts extratelencephalic projection neurons in the prefrontal cortex in a mouse model of Alzheimer’s disease. Nat Commun England. 2022;13:998.

    Article  CAS  Google Scholar 

  152. Tsetlin VI. Acetylcholine and acetylcholine receptors: textbook knowledge and new data. Biomolecules. 2020;10:852.

  153. Kunugi H, Ali AM. Royal jelly and its components promote healthy aging and longevity: from animal models to humans. Int J Mol Sci. 2019;20:1–26.

    Article  Google Scholar 

  154. Calderón-Ospina CA, Nava-Mesa MO. B Vitamins in the nervous system: current knowledge of the biochemical modes of action and synergies of thiamine, pyridoxine, and cobalamin. CNS Neurosci Ther. 2020;26:5–13.

    Article  PubMed  Google Scholar 

  155. Scholefield M, Church SJ, Xu J, Patassini S, Hooper NM, Unwin RD, et al. Substantively lowered levels of pantothenic acid (vitamin B5) in several regions of the human brain in Parkinson’s disease dementia. Metabolites. 2021;11:569.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Athar T, Al Balushi K, Khan SA. Recent advances on drug development and emerging therapeutic agents for Alzheimer’s disease. Mol Biol Rep. 2021;48:5629–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Ab Hamid N, Abu Bakar AB, Mat Zain AA, Nik Hussain NH, Othman ZA, Zakaria Z, et al. Composition of royal jelly (RJ) and its anti-androgenic effect on reproductive parameters in a polycystic ovarian syndrome (PCOS) animal model. Antioxidants (Basel, Switzerland). Switzerland; 2020;9.

  158. Hattori N, Nomoto H, Fukumitsu H, Mishima S, Furukawa S. AMP N(1)-oxide, a unique compound of royal jelly, induces neurite outgrowth from PC12 cells via signaling by protein kinase A independent of that by mitogen-activated protein kinase. Evid Based Complement Alternat Med. 2010;7:63–8.

    Article  PubMed  Google Scholar 

  159. You M, Pan Y, Liu Y, Chen Y, Wu Y, Si J, et al. Royal jelly alleviates cognitive deficits and β-amyloid accumulation in APP/PS1 mouse model via activation of the cAMP/PKA/CREB/BDNF pathway and inhibition of neuronal apoptosis. Front Aging Neurosci. 2018;10:428.

    Article  CAS  PubMed  Google Scholar 

  160. Abdelnour SA, Abd El-Hack ME, Alagawany M, Taha AE, Elnesr SS, AbdElmonem OM, et al. Useful impacts of royal jelly on reproductive sides, fertility rate and sperm traits of animals. J Anim Physiol Anim Nutr. 2020;104:1798–808.

    Article  CAS  Google Scholar 

  161. Russell JK, Jones CK, Newhouse PA. The role of estrogen in brain and cognitive aging. Neurother J Am Soc Exp Neurother. 2019;16:649–65.

    CAS  Google Scholar 

  162. Borrás C, Ferrando M, Inglés M, Gambini J, Lopez-Grueso R, Edo R, et al. Estrogen replacement therapy induces antioxidant and longevity-related genes in women after medically induced menopause. Oxid Med Cell Longev. 2021;2021:8101615.

    Article  PubMed  PubMed Central  Google Scholar 

  163. Pascale A, Marchesi N, Marelli C, Coppola A, Luzi L, Govoni S, et al. Microbiota and metabolic diseases. Endocrine. 2018;61:357–71.

    Article  CAS  PubMed  Google Scholar 

  164. Kovatcheva-Datchary P, Tremaroli V, Backhed F. The prokaryotes: human microbiology. 4th ed. Prokaryotes Hum Microbiol. 2013;1–554.

  165. Rinninella E, Raoul P, Cintoni M, Franceschi F, Miggiano GAD, Gasbarrini A, et al. What is the healthy gut microbiota composition? A changing ecosystem across age, environment, diet, and diseases. Microorganisms. 2019;7:14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Allaband C, McDonald D, Vázquez-Baeza Y, Minich JJ, Tripathi A, Brenner DA, et al. Microbiome 101: studying, analyzing, and interpreting gut microbiome data for clinicians. Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc. 2019;17:218–30.

    Google Scholar 

  167. Conlon MA, Bird AR. The impact of diet and lifestyle on gut microbiota and human health. Nutrients. 2014;7:17–44.

    Article  PubMed  PubMed Central  Google Scholar 

  168. Cresci GA, Bawden E. Gut microbiome: what we do and don’t know. Nutr Clin Pract Off Publ Am Soc Parenter Enter Nutr. 2015;30:734–46.

    CAS  Google Scholar 

  169. Kim YS, Unno T, Kim BY, Park MS. Sex differences in gut microbiota. World J Mens Health. 2020;38:48–60.

    Article  PubMed  Google Scholar 

  170. Milani C, Duranti S, Bottacini F, Casey E, Turroni F, Mahony J, et al. The first microbial colonizers of the human gut: composition, activities, and health implications of the infant gut microbiota. Microbiol Mol Biol Rev. 2017;81:e00036–17.

    Article  PubMed  PubMed Central  Google Scholar 

  171. Nobre JG, Alpuim CD. “Sociobiome”: how do socioeconomic factors influence gut microbiota and enhance pathology susceptibility? - a mini-review. Front Gastroenterol. 2022;1:1–6.

    Article  Google Scholar 

  172. Mafra D, Borges N, Alvarenga L, Esgalhado M, Cardozo L, Lindholm B, et al. Dietary components that may influence the disturbed gut microbiota in chronic kidney disease. Nutrients. 2019;11:1–23.

    Article  Google Scholar 

  173. Eshraghi S, Seifollahi F. Antibacterial effects of royal jelly on different strains of bacteria. Iran J Public Health [Internet]. 2003;32:25–30. Available from: http://www.doaj.org/doaj?func=openurl&issn=22516085&date=2003&volume=32&issue=1&spage=25&genre=article. Accessed 27 Jan 2023

  174. Guo J, Ma B, Wang Z, Chen Y, Tian W, Dong Y. Royal jelly protected against dextran-sulfate-sodium-induced colitis by improving the colonic mucosal barrier and gut microbiota. Nutrients. 2022;14:2069.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Wang W, Li X, Li D, Pan F, Fang X, Peng W, et al. Effects of major royal jelly proteins on the immune response and gut microbiota composition in cyclophosphamide-treated mice. Nutrients MDPI. 2023;15:974.

    Article  CAS  Google Scholar 

  176. Wang W, Yan Y, Guo Z, Hou H, Garcia M, Tan X, et al. All around suboptimal health - a joint position paper of the suboptimal health study consortium and european association for predictive, preventive and personalised medicine. EPMA J. 2021;12:403–33.

    Article  PubMed  PubMed Central  Google Scholar 

  177. Lemke HU, Golubnitschaja O. Towards personal health care with model-guided medicine: long-term PPPM-related strategies and realisation opportunities within “Horizon 2020.” EPMA J. 2014;5:8.

    Article  PubMed  PubMed Central  Google Scholar 

  178. Golubnitschaja O, Baban B, Boniolo G, Wang W, Bubnov R, Kapalla M, et al. Medicine in the early twenty-first century: paradigm and anticipation - EPMA position paper 2016. EPMA J. 2016;2016(7):23.

    Article  Google Scholar 

  179. Lin XM, Liu S Bin, Luo YH, Xu WT, Zhang Y, Zhang T, et al. 10-HDA induces ROS-mediated apoptosis in A549 human lung cancer cells by regulating the MAPK, STAT3, NF-κB, and TGF-β1 signaling pathways. Biomed Res Int. 2020;3042636.

  180. Tsuchiya Y, Hayashi M, Nagamatsu K, Ono T, Kamakura M, Iwata T, et al. The key royal jelly component 10-hydroxy-2-decenoic acid protects against bone loss by inhibiting NF-κB signaling downstream of FFAR4. J Biol Chem. 2020;295:12224–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  181. You M, Miao Z, Sienkiewicz O, Jiang X, Zhao X, Hu F. 10-Hydroxydecanoic acid inhibits LPS-induced inflammation by targeting p53 in microglial cells. Int Immunopharmacol. 2020;84:106501. https://doi.org/10.1016/j.intimp.2020.106501.

    Article  CAS  PubMed  Google Scholar 

  182. Mohamed HK, Mobasher MA, Ebiya RA, Hassen MT, Hagag HM, El-Sayed R, et al. Anti-inflammatory, anti-apoptotic, and antioxidant roles of honey, royal jelly, and propolis in suppressing nephrotoxicity induced by doxorubicin in male albino rats. Antioxidants. 2022;11:1029.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  183. Nazar-Zadeh M, Jalili C, Nikgoftar Fathi A, Ghanbari A, Bakhtiari M. Royal-jelly-based apitherapy can attenuate damages to male reproductive parameter following nicotine administration. Anim Model Exp Med. 2022;5:133–40.

    Article  CAS  Google Scholar 

  184. Aksakal E, Ekinci D, Supuran CT. Dietary inclusion of royal jelly modulates gene expression and activity of oxidative stress enzymes in zebrafish. J Enzyme Inhib Med Chem. 2021;36:885–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  185. Azad F, Nejati V, Shalizar-Jalali A, Najafi G, Rahmani F. Antioxidant and anti-apoptotic effects of royal jelly against nicotine-induced testicular injury in mice. Environ Toxicol. 2019;34:708–18.

    Article  CAS  PubMed  Google Scholar 

  186. Fatmawati F, Erizka E, Hidayat R. Royal jelly (bee product) decreases inflammatory response in Wistar rats induced with ultraviolet radiation. Open access Maced J Med Sci North. 2019;7:2723–7.

    Article  Google Scholar 

  187. Ovchinnikov AN, Paoli A, Seleznev VV, Deryugina AV. Royal jelly plus coenzyme Q10 supplementation improves high-intensity interval exercise performance via changes in plasmatic and salivary biomarkers of oxidative stress and muscle damage in swimmers: a randomized, double-blind, placebo-controlled pilot t. J Int Soc Sports Nutr. 2022;19:239–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  188. Petelin A, Kenig S, Kopinč R, Deželak M, ČerneličBizjak M, Jenko Pražnikar Z. Effects of royal jelly administration on lipid profile, satiety, inflammation, and antioxidant capacity in asymptomatic overweight adults. Evid Based Complement Alternat Med. 2019;2019:4969720.

    Article  PubMed  PubMed Central  Google Scholar 

  189. Shidfar F, Jazayeri S, Mousavi SN, Malek M, Hosseini AF, Khoshpey B. Does supplementation with royal jelly improve oxidative stress and insulin resistance in type 2 diabetic patients? Iran J Public Health. 2015;44:797–803.

    PubMed  PubMed Central  Google Scholar 

  190. Ghanbari E, Nejati V, Khazaei M. Improvement in serum biochemical alterations and oxidative stress of liver and pancreas following use of royal jelly in streptozotocin-induced diabetic rats. Cell J. 2016;18:362–70.

    PubMed  PubMed Central  Google Scholar 

  191. Fan P, Han B, Feng M, Fang Y, Zhang L, Hu H, et al. Functional and proteomic investigations reveal major royal jelly protein 1 associated with anti-hypertension activity in mouse vascular smooth muscle cells. Sci Rep. 2016;6:30230.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  192. Feng M, Fang Y, Han B, Xu X, Fan P, Hao Y, et al. In-depth N-glycosylation reveals species-specific modifications and functions of the royal jelly protein from western (Apis mellifera) and eastern honeybees (Apis cerana). J Proteome Res. 2015;14:5327–40.

    Article  CAS  PubMed  Google Scholar 

  193. Escamilla KIA, Ordóñez YBM, Sandoval-Peraza VM, Fernández JJA, Ancona DAB. Anti-hypertensive activity in vitro and in vivo on royal jelly produced by different diets. Emirates J Food Agric. 2022;34:9–15.

    Google Scholar 

  194. Fujisue K, Yamamoto E, Sueta D, Arima Y, Hirakawa K, Tabata N, et al. A randomized, double-blind comparison study of royal jelly to augment vascular endothelial function in healthy volunteers. J Atheroscler Thromb. 2022;29:1285–94.

    Article  CAS  PubMed  Google Scholar 

  195. Chiu H-F, Chen B-K, Lu Y-Y, Han Y-C, Shen Y-C, Venkatakrishnan K, et al. Hypocholesterolemic efficacy of royal jelly in healthy mild hypercholesterolemic adults. Pharm Biol. 2017;55:497–502.

    Article  PubMed  Google Scholar 

  196. Lambrinoudaki I, Augoulea A, Rizos D, Politi M, Tsoltos N, Moros M, et al. Greek-origin royal jelly improves the lipid profile of postmenopausal women. Gynecol Endocrinol. 2016;32:835–9.

    Article  PubMed  Google Scholar 

  197. Pourmobini H, Kazemi Arababadi M, Salahshoor MR, Roshankhah S, Taghavi MM, Taghipour Z, et al. The effect of royal jelly and silver nanoparticles on liver and kidney inflammation. Avicenna J Phytomedicine. 2021;11:218–23.

    CAS  Google Scholar 

  198. Salahshoor MR, Jalili C, Roshankhah S. Can royal jelly protect against renal ischemia/reperfusion injury in rats? Chin J Physiol. 2019;62:131–7.

    Article  CAS  PubMed  Google Scholar 

  199. Osama H, Abdullah A, Gamal B, Emad D, Sayed D, Hussein E, et al. Effect of honey and royal jelly against cisplatin-induced nephrotoxicity in patients with cancer. J Am Coll Nutr. 2017;36:342–6.

    Article  CAS  PubMed  Google Scholar 

  200. Filipič B, Gradišnik L, Rihar K, Šooš E, Pereyra A, Potokar J. The influence of royal jelly and human interferon-alpha (HuIFN-αN3) on proliferation, glutathione level and lipid peroxidation in human colorectal adenocarcinoma cells in vitro. Arh Hig Rada Toksikol. 2015;66:269–74.

    Article  PubMed  Google Scholar 

  201. Albalawi AE, Althobaiti NA, Alrdahe SS, Alhasani RH, Alaryani FS, Binmowyna MN. Antitumor activity of royal jelly and its cellular mechanisms against Ehrlich solid tumor in mice. Biomed Res Int. 2022:7233997.

  202. Sirinupong N, Chansuwan W, Kaewkaen P. Hydrolase-treated royal jelly attenuates H(2)O(2)- and glutamate-induced SH-SY5Y cell damage and promotes cognitive enhancement in a rat model of vascular dementia. Int J food Sci. 2021;2021:2213814.

    Article  PubMed  PubMed Central  Google Scholar 

  203. Zhang X, Yu Y, Sun P, Fan Z, Zhang W, Feng C. Royal jelly peptides: potential inhibitors of β-secretase in N2a/APP695swe cells. Sci Rep. 2019;9:168.

    Article  PubMed  PubMed Central  Google Scholar 

  204. Ghorbanpour AM, Saboor M, Panahizadeh R, Saadati H, Dadkhah M. Combined effects of royal jelly and environmental enrichment against stress-induced cognitive and behavioral alterations in male rats: behavioral and molecular studies. Nutr Neurosci. 2022;25:1860–71. https://doi.org/10.1080/1028415X.2021.1909205.

    Article  CAS  PubMed  Google Scholar 

  205. de Guardia Souza Silva ET, de Val Paulo MEF, da Silva JRM, da Silva Alves A, Britto LRG, Xavier GF, et al. Oral treatment with royal jelly improves memory and presents neuroprotective effects on icv-STZ rat model of sporadic Alzheimer’s disease. Heliyon. 2022;6:e03281.

    Article  Google Scholar 

  206. Pan Y, Xu J, Jin P, Yang Q, Zhu K, You M, et al. Royal jelly ameliorates behavioral deficits, cholinergic system deficiency, and autonomic nervous dysfunction in ovariectomized cholesterol-fed rabbits. Molecules. 2019;24:1149.

    Article  PubMed  PubMed Central  Google Scholar 

  207. Mohamed AAR, Galal AAA, Elewa YHA. Comparative protective effects of royal jelly and cod liver oil against neurotoxic impact of tartrazine on male rat pups brain. Acta Histochem. 2015;117:649–58.

    Article  CAS  PubMed  Google Scholar 

  208. Asama T, Matsuzaki H, Fukushima S, Tatefuji T, Hashimoto K, Takeda T. Royal jelly supplementation improves menopausal symptoms such as backache, low back pain, and anxiety in postmenopausal Japanese women. Evid Based Complement Alternat Med. 2018;2018:4868412.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This work was supported by Conselho Nacional de Pesquisa (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ).

Author information

Authors and Affiliations

  1. Graduate Program in Medical Sciences, Fluminense Federal University (UFF), Niterói, RJ, Brazil

    Beatriz G. Baptista & Denise Mafra

  2. Graduate Program in Biological Sciences – Physiology, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil

    Ligia S. Lima, Marcia Ribeiro, Isadora K. Britto, Livia Alvarenga & Denise Mafra

  3. Graduate Program in Nutrition Sciences, Fluminense Federal University (UFF), Niterói, RJ, Brazil

    Livia Alvarenga, Julie A. Kemp, Ludmila FMF Cardozo & Denise Mafra

  4. Research, Development, and Innovation Department, Apis Flora Indl. Coml. Ltda, Ribeirão Preto, SP, Brazil

    Andresa A. Berretta

  5. Unidade de Pesquisa Clínica, UPC, Rua Marquês de Paraná, 303/4 Andar, Niterói, RJ, 24033-900, Brazil

    Denise Mafra

Authors
  1. Beatriz G. Baptista
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ligia S. Lima
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marcia Ribeiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Isadora K. Britto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Livia Alvarenga
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Julie A. Kemp
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ludmila FMF Cardozo
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Andresa A. Berretta
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Denise Mafra
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the review conception and design. The first draft of the manuscript was written by Beatriz Germer Baptista, Márcia Ribeiro, Livia Alvarenga Ligia Lima, Isadora Britto and Julie Kemp; and Ludmila Cardozo, Andresa A. Berretta and Denise Mafra corrected the versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Denise Mafra.

Ethics declarations

Consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher's note

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

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Baptista, B.G., Lima, L.S., Ribeiro, M. et al. Royal jelly: a predictive, preventive and personalised strategy for novel treatment options in non-communicable diseases. EPMA Journal 14, 381–404 (2023). https://doi.org/10.1007/s13167-023-00330-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13167-023-00330-8

Keywords

Search

Navigation