| Sign up

PDF (11.9 MB)

Cite

EndNote(RIS) BibTeX

Collect

Collect

Submit Manuscript

Show Outline

Figures (10)

Fig. 1

Fig. 2

Fig. 3

Fig. 4

Fig. 5

Fig. 6

Fig. 7

Fig. 8

Fig. 9

Article | Open Access

Royal jelly modulates serum lipid metabolism and improves brain lipid profiles in natural aging mice

Lili Chen^{^a^,^b^,^c}, Li Zhao^{^b}, Gaowei Zhang^{^c}, Zhuozhen Li^{^a}, Huihui Ming^{^c}, Liangliang Qu^{^c}, Fangjian Ning^{^a}, Liping Luo^{^a^,^d}()

a

College of Food and Health, Beijing Technology and Business University, Beijing 100048, China

b

School of Life Science, Jiangxi Science & Technology Normal University, Nanchang 330013, China

c

School of Life Sciences, Nanchang University, Nanchang 330031, China

d

Key Laboratory of Geriatric Nutrition and Health Ministry of Education, Beijing Technology and Business University, Beijing 100048, China

Peer review under responsibility of Tsinghua University Press.

Show Author Information

Highlight

• Royal jelly (RJ) can modulate serum lipid metabolism in natural aging mice.

• RJ effectively improves the natural aging mice brain lipid profile.

• The specific antioxidant ether lipids level is increased after RJ intervention.

• RJ raises the ratio of monounsaturated fatty acids to polyunsaturated fatty acids.

Graphical Abstract

View original image Download original image

Abstract

Royal jelly (RJ) is rich in various nutrients with multiple health-promoting properties. This study aims to evaluate whether RJ can modulate related metabolite in the natural aging mice. Male C57BL/6J mice drank RJ solution daily for 9 months. Determination of serum lipids and pathological analysis exhibited that triglycerides, serum cholesterol, and low-density lipoprotein cholesterol were decreased by 31.15%, 9.96%, and 22.58%, respectively, the morphology of brain nerve cells was also effectively recovered after RJ intervention. Lipidomic analysis showed that RJ could improve the levels of different kinds of lipids in aging mice brain, especially by increasing the content of antioxidant ether ester, and that the ratio of monounsaturated fatty acid to polyunsaturated fatty acid was up by 23.46%, which could alleviate oxidative stress. Moreover, the metabolism of glycerol phospholipids, glycerols, and fatty acids in aging mice could be regulated by RJ. RJ intervention can effectively improve lipid metabolism disorders caused by aging.

Keywords

Royal jelly Natural aging Brain Lipidomic Fatty acids

Electronic Supplementary Material

Download File(s)

fshw-14-3-9250071_ESM.docx (2.2 MB)

References

[1]

Y.S. Cai, W. Song, J.M. Li, et al., The landscape of aging, Sci. China Life Sci. 65 (2022) 2354-2454. https://doi.org/10.1007/s11427-022-2161-3.

Crossref Google Scholar

[2]

S. Srivastava, Emerging insights into the metabolic alterations in aging using metabolomics, Metabolites 9 (2019) 301. https://doi.org/10.3390/metabo9120301.

Crossref Google Scholar

[3]

M.B. Cavalcante, T.D. Saccon, A.D.C. Nunes, et al., Dasatinib plus quercetin prevents uterine age-related dysfunction and fibrosis in mice, Aging 12 (2020) 2711-2722. https://doi.org/10.18632/aging.102772.

Crossref Google Scholar

[4]

D.R. Gómez-Linton, S. Alavez, A. Alarcón-Aguilar, et al., Some naturally occurring compounds that increase longevity and stress resistance in model organisms of aging, Biogerontology 20 (2019) 583-603. https://doi.org/10.1007/s10522-019-09817-2.

Crossref Google Scholar

[5]

D.E. Harrison, R. Strong, Z.D. Sharp, et al., Rapamycin fed late in life extends lifespan in genetically heterogeneous mice, Nature 460 (2009) 392-395. https://doi.org/10.1038/nature08221.

Crossref Google Scholar

[6]

D.E. Harrison, R. Strong, S. Alavez, et al., Acarbose improves health and lifespan in aging HET3 mice, Aging Cell 18 (2019) e12898. https://doi.org/10.1111/acel.12898.

Crossref Google Scholar

[7]

J.Y. Wang, S.Q. Li, J. Wang, et al., Spermidine alleviates cardiac aging by improving mitochondrial biogenesis and function, Aging 12 (2020) 650-671. https://doi.org/10.18632/aging.102647.

Crossref Google Scholar

[8]

H.B. Zhang, D. Ryu, Y.B. Wu, et al., NAD⁺ repletion improves mitochondrial and stem cell function and enhances life span in mice, Science 352 (2016) 1436-1443. https://doi.org/10.1126/science.aaf2693.

Crossref Google Scholar

[9]

J. Campisi, P. Kapahi, G.J. Lithgow, et al., From discoveries in ageing research to therapeutics for healthy ageing, Nature 571 (2019) 183-192. https://doi.org/10.1038/s41586-019-1365-2.

Crossref Google Scholar

[10]

D.G. le Couteur, S.M. Solon-Biet, B.L. Parker, et al., Nutritional reprogramming of mouse liver proteome is dampened by metformin, resveratrol, and rapamycin, Cell Metab. 33 (2021) 2367-2379. https://doi.org/10.1016/j.cmet.2021.10.016.

Crossref Google Scholar

[11]

N. Collazo, M. Carpena, B. Nuñez-Estevez, et al., Health promoting properties of bee royal jelly: food of the queens, Nutrients 13 (2021) 543. https://doi.org/10.3390/nu13020543.

Crossref Google Scholar

[12]

M. Kamakura, Royalactin induces queen differentiation in honeybees, Nature 473 (2011) 478-483. https://doi.org/10.1038/nature10093.

Crossref Google Scholar

[13]

H. Kunugi, A. Mohammed Ali, Royal jelly and its components promote healthy aging and longevity: from animal models to humans, Int. J. Mol. Sci. 20 (2019) 4662. https://doi.org/10.3390/ijms20194662.

Crossref Google Scholar

[14]

J. Ding, J. Ji, Z. Rabow, et al., A metabolome atlas of the aging mouse brain, Nat. Commun. 12 (2021) 6021. https://doi.org/10.1038/s41467-021-26310-y.

Crossref Google Scholar

[15]

Z.W. Gong, E. Tas, S. Yakar, et al., Hepatic lipid metabolism and non-alcoholic fatty liver disease in aging, Mol. Cell. Endocrinol. 455 (2017) 115-130. https://doi.org/10.1016/j.mce.2016.12.022.

Crossref Google Scholar

[16]

R. Pasha, S. Azmi, M. Ferdousi, et al., Lipids, lipid-lowering therapy, and neuropathy: a narrative review, Clin. Ther. 44 (2022) 1012-1025. https://doi.org/10.1016/j.clinthera.2022.03.013.

Crossref Google Scholar

[17]

L.L. Chen, F.J. Ning, L. Zhao, et al., Quality assessment of royal jelly based on physicochemical properties and flavor profiles using HS-SPME-GC/MS combined with electronic nose and electronic tongue analyses, Food Chem. 403 (2023) 134392. https://doi.org/10.1016/j.foodchem.2022.134392.

Crossref Google Scholar

[18]

H. Chang, How to eat fresh royal jelly, J. Bee 4 (2004) 33. https://doi.org/10.3969/j.issn.1003-9139.2004.04.029.

Crossref Google Scholar

[19]

J.H. Huang, X.J. Huang, Z.Y. Chen, et al., Dose conversion among different animals and healthy volunteers in pharmacological study, J. Clinical Pharm. Ther. 9 (2004) 1069-1072. https://doi.org/10.3969/j.issn.1009-2501.2004.09.026.

Crossref Google Scholar

[20]

H.H. Chen, Q.X. Nie, J.L. Hu, et al., Glucomannans alleviated the progression of diabetic kidney disease by improving kidney metabolic disturbance, Mol. Nutr. Food Res. 63 (2019) 1801008. https://doi.org/10.1002/mnfr.201801008.

Crossref Google Scholar

[21]

I. Lambrinoudaki, A. Augoulea, D. Rizos, et al., Greek-origin royal jelly improves the lipid profile of postmenopausal women, Gynecol. Endocrinol. 32 (2016) 835-839. https://doi.org/10.1080/09513590.2016.1188281.

Crossref Google Scholar

[22]

H.F. Chiu, B.K. Chen, Y.Y. Lu, et al., Hypocholesterolemic efficacy of royal jelly in healthy mild hypercholesterolemic adults, Pharm. Biol. 55 (2017) 497-502. https://doi.org/10.1080/13880209.2016.1253110.

Crossref Google Scholar

[23]

I. Almeida, S. Magalhães, A. Nunes, Lipids: biomarkers of healthy aging, Biogerontology 22 (2021) 273-295. https://doi.org/10.1007/s10522-021-09921-2.

Crossref Google Scholar

[24]

I. Diegoa, S. Pelega, B. Fuchs. The role of lipids in aging-related metabolic changes, Chem. Phys. Lipids 222 (2019) 59-69. https://doi.org/10.1016/j.chemphyslip.2019.05.005.

Crossref Google Scholar

[25]

V. Gonzalez-Covarrubias, Lipidomics in longevity and healthy aging, Biogerontology 14 (2013) 663-672. https://doi.org/10.1007/s10522-013-9450-7.

Crossref Google Scholar

[26]

K.W. Chung, Advances in understanding of the role of lipid metabolism in aging, Cells 10 (2021) 880. https://doi.org/10.3390/cells10040880.

Crossref Google Scholar

[27]

J.M. Dean, I.J. Lodhi, Structural and functional roles of ether lipids, Protein Cell 9 (2018) 196-206. https://doi.org/10.1007/s13238-017-0423-5.

Crossref Google Scholar

[28]

D.V. Kruining, Q. Luo, G. Echten-Deckert, et al., Sphingolipids as prognostic biomarkers of neurodegeneration, neuroinflammation, and psychiatric diseases and their emerging role in lipidomic investigation methods, Adv. Drug Deliver. Rev. 159 (2020) 232-244. https://doi.org/10.1016/j.addr.2020.04.009.

Crossref Google Scholar

[29]

J. Tu, Y.D. Yin, M.M. Xu, et al., Absolute quantitative lipidomics reveals lipidome-wide alterations in aging brain, Metabolomics 14 (2017) 5. https://doi.org/10.1007/s11306-017-1304-x.

Crossref Google Scholar

[30]

M. Jové, A. Naudıí, J. Gambini, et al., A stress-resistant lipidomic signature confers extreme longevity to humans, J. Gerontol. A 72 (2017) 30-37. https://doi.org/10.1093/gerona/glw048.

Crossref Google Scholar

[31]

T. Yu, J. Guo, S. Zhu, et al., Protective effects of selenium-enriched peptides from Cardamine violifolia on D-galactose-induced brain aging by alleviating oxidative stress, neuroinflammation, and neuron apoptosis, J. Funct. Foods 75 (2020) 104277. https://doi.org/10.1016/j.jff.2020.104277.

Crossref Google Scholar

[32]

A. Zia, A.M Pourbagher-Shahri, T. Farkhondeh, et al., Molecular and cellular pathways contributing to brain aging, Behav. Brain Funct. 17 (2021) 6. https://doi.org/10.1186/s12993-021-00179-9.

Crossref Google Scholar

[33]

Y.C. Yang, W.M. Chou, D.A. Widowati, et al., 10-hydroxy-2-decenoic acid of royal jelly exhibits bactericide and anti-inflammatory activity in human colon cancer cells, BMC Complem. Alterne. M. 18 (2018) 202. https://doi.org/10.1186/s12906-018-2267-9.

Crossref Google Scholar

[34]

M.M. You, Z.N. Miao, J. Tian, et al., Trans-10-hydroxy-2-decenoic acid protects against LPS-induced neuroinflammation through FOXO1-mediated activation of autophagy, Eur. J. Nutr. 59 (2020) 2875-2892. https://doi.org/10.1007/s00394-019-02128-9.

Crossref Google Scholar

[35]

A. Hadi, A. Najafgholizadeh, E.S. Aydenlu, et al., Royal jelly is an effective and relatively safe alternative approach to blood lipid modulation: a meta-analysis, J. Funct. Foods 41 (2018) 202-209. https://doi.org/10.1016/j.jff.2017.12.005.

Crossref Google Scholar

[36]

M. Kamakura, T. Moriyama, T. Sakaki. Changes in hepatic gene expression associated with the hypocholesterolaemic activity of royal jelly, J. Pharm. Pharmacol. 58 (2006) 1683-1689. https://doi.org/10.1211/jpp.58.12.0017.

Crossref Google Scholar

[37]

Y. Kashima, S. Kanematsu, S. Asai, et al., Identification of a novel hypocholesterolemic protein, major royal jelly protein 1, derived from royal jelly, Plos One 9 (2014) e105073. https://doi.org/10.1371/journal.pone.0105073.

Crossref Google Scholar

[38]

G. Sighinolf, S. Clark, L. Blanc, et al., Mass spectrometry imaging of mice brain lipid profile changes over time under high fat diet, Sci. Rep. 11 (2021) 19664. https://doi.org/10.1038/s41598-021-97201-x.

Crossref Google Scholar

[39]

F. Mesa-Herrera, L. Taoro-González, C. Valdés-Baizabal, et al., Lipid and lipid raft alteration in aging and neurodegenerative diseases: a window for the development of new biomarkers, Int. J. Mol. Sci. 20 (2019) 3810. https://doi.org/10.3390/ijms20153810.

Crossref Google Scholar

[40]

S. Zhang, N. Zhu, J. Gu, et al., Crosstalk between lipid rafts and aging: new frontiers for delaying aging, Aging Dis. 13 (2022) 1042-1055. https://doi.org/10.14336/AD.2022.0116.

Crossref Google Scholar

[41]

N. Kawanishi, Y. Kato, K. Yokozeki, et al., Effects of aging on serum levels of lipid molecular species as determined by lipidomics analysis in Japanese men and women, Lipids Health Dis. 17 (2018) 135. https://doi.org/10.1186/s12944-018-0785-6.

Crossref Google Scholar

[42]

N. Fabelo, V. Martín, G. Santpere, et al., Severe alterations in lipid composition of frontal cortex lipid rafts from Parkinson’s disease and incidental Parkinson’s disease, Mol. Med. 17 (2011) 1107-1118. https://doi.org/10.2119/molmed.2011.00119.

Crossref Google Scholar

[43]

J.H. Huang, H. Park, J. Iaconelli, et al., Unbiased metabolite profiling of schizophrenia fibroblasts under stressful perturbations reveals dysregulation of plasmalogens and phosphatidylcholines, J. Proteome Res. 16 (2017) 481-493. https://doi.org/10.1021/acs.jproteome.6b00628.

Crossref Google Scholar

[44]

M. Jové, N. Mota-Martorell, I. Pradas, et al., The lipidome fingerprint of longevity, Molecules 25 (2020) 4343. https://doi.org/10.3390/molecules25184343.

Crossref Google Scholar

[45]

L.S. Haddad, L. Kelbert, A.J. Hulbert. Extended longevity of queen honey bees compared to workers is associated with peroxidation-resistant membranes, Exp. Gerontol. 42 (2007) 601-609. https://doi.org/10.1016/j.exger.2007.02.008.

Crossref Google Scholar

[46]

A. Sanz, M. Soikkeli, M. Portero-Otín, et al., Expression of the yeast NADH dehydrogenase Ndi1 in Drosophila confers increased lifespan independently of dietary restriction, PNAS 107 (2010) 9105-9110. https://doi.org/10.1073/pnas.0911539107.

Crossref Google Scholar

[47]

R.J. Shmookler Reis, L. Xu, H. Lee, et al., Modulation of lipid biosynthesis contributes to stress resistance and longevity of C. elegans mutants, Aging (2011) 125-147. https://doi.org/10.18632/aging.100275.

Crossref Google Scholar

[48]

Z.R. Jarrell, M.R. Smith, X. Hu, et al., Plasma acylcarnitine levels increase with healthy aging, Aging 12 (2020) 13555-13570. https://doi.org/10.18632/aging.103462.

Crossref Google Scholar

[49]

X.J. Yu, Y.C. Li, X.H. Mu. Effect of quercetin on PC12 Alzheimer’s disease cell model induced by Aβ25-35 and its mechanism based on sirtuin1/Nrf2/HO-1 pathway, BioMed. Res. Int. 2020 (2020) 8210578. https://doi.org/10.1155/2020/8210578.

Crossref Google Scholar

[50]

Q.H. Zeng, W.C. Lian, G.Z. Wang, et al., Pterostilbene induces Nrf2/HO-1 and potentially regulates NF-κB and JNK-Akt/mTOR signaling in ischemic brain injury in neonatal rats, Biotech. 10 (2020) 192. https://doi.org/10.1007/s13205-020-02167-8.

Crossref Google Scholar

[51]

A. Loboda, M. Damulewicz, E. Pyza, et al., Role of Nrf2/HO-1 system in development, oxidative stress response and diseases: an evolutionarily conserved mechanism, Cell Mol. Life Sci. 73 (2016) 3221-3247. https://doi.org/10.1007/s00018-016-2223-0.

Crossref Google Scholar

[52]

H.Q. Zhang, K.J.A. Davies, H.J. Forman, Oxidative stress response and Nrf2 signaling in aging, Free Radical Bio. Med. 88 (2015) 314-336. https://doi.org/10.1016/j.freeradbiomed.2015.05.036.

Crossref Google Scholar

Food Science and Human Wellness

Volume 14 Issue 3,
March 2025

Article number: 9250071

DOI: 10.26599/FSHW.2024.9250071

Cite this article:

Chen L, Zhao L, Zhang G, et al. Royal jelly modulates serum lipid metabolism and improves brain lipid profiles in natural aging mice. Food Science and Human Wellness, 2025, 14(3): 9250071. https://doi.org/10.26599/FSHW.2024.9250071

Fig. 1 Chemical composition, biological activity and application of RJ in different species. (A) A schematic diagram of chemical composition and biological activity of RJ; (B) RJ and its constituents improve health and prolong life in different species.
Fig. 2 (A) Effects of RJ on serum lipids metabolism and (B) histopathological observations of the brain tissue among three groups (200×). n = 8. Different lowercase letters indicate significant differences between samples (P < 0.05).
Fig. 3 RJ alters lipid profile in aging mice brain tissue. (A) A total of 1490 lipid molecules and primary class and secondary classification of lipids in brain tissue. (B) The Venn diagram showed the common and specific number of metabolites in different groups. Each circle represents a pairwise comparison between different groups. (C) Score plots of PCA. (D) PLS-DA for lipid profiles among the three groups (n = 6). PC, phosphatidylcholine; PE, phosphatidylethanolamine; PE-P, phosphatidylethanolamine-vinyl ether bond; PG, phosphatidylglycerol; PS, phosphatidylserine; PI, phosphatidylinositol; PE-O, phosphatidylethanolamine-ether bond; PA, phosphatidate; LPC, lysophosphatidylcholine; PC-O, phosphatidylcholine-ether bond; LPE, lysophosphatidyl ethanolamine; BMP, bis(monoacylglycero) phosphate; LNAPE, N-acyl-lysophosphatidyl ethanolamine; LPC-O, lysophosphatidylcholine-ether bond; LPG, lysophosphatidylglycerol; LPI, lysophosphatidyl inositol; LPS, lysophosphatidylserine; PMeOH, phosphatidyl methanol; LPE-P, lysophosphatidylethanolamine-enether bond; LPA, lysophosphatidic acid; TG, triglycerides; DG, diglyceride; MGDG, monogalactosyl diglyceride; DG-O, diglyceride-ether bond; MG, monoglyceride; DGDG, disaccharide glycerol diester; Cer, ceramide; SM, sphingomyelin; HexCer, hexose ceramide; Cert, phytoceramide; CerP, ceramide phosphate; SPH, sphingosine; Car, carnitine; FFA, free fatty acids; EI, eicosanoid; CE, cholesterol ester; Cho, cholesterol; CoQ, co-enzyme Q.
Fig. 4 Comparison of lipid relative contents of different classes (A) and sub-classes (B-F) in the brain tissues among the three groups (n = 6). (B) GPs; (C) GLs; (D) SPs; (E) FAs; (F) STs. Different lowercase letters indicate significant differences between samples (P < 0.05).
Fig. 5 The change of FAs with different chain lengths and saturations in the three groups (n = 6). (A) The ratio differences of MUFA/PUFA in the brain tissues among the three groups. (B) The intensity of different chain lengths and different saturated fatty acyls changes in the brain tissues among the three groups. (B₁) FFA (17:1); (B₂) FFA (19:2); (B₃) Car (C_14:1); (B₄) Car (C_20:3). *P < 0.05; **P < 0.01; ***P < 0.001; n.s. P > 0.05.
Fig. 6 Differences in ether lipids with different chain lengths of the brain tissues among the three groups (n = 6). (A) PC (O-18:1_24:1); (B) PE (O-16:1_21:1); (C) PE (O-16:1_22:1); (D) PE (O-22:1_18:1); (E) PE (O-20:1_18:1); (F) PE (O-18:1_21:1). *P < 0.05; **P < 0.01; ***P < 0.001; n.s. P > 0.05.
Fig. 7 The intensity of different lipid molecules in the YC, OC, and RJ groups (n = 6). SPs are subclassified as (A) HexCer, (B) Cer, and (C) SM; STs are subclassified as (D) CE; GPs are subclassified as (E) PS (15:1_22:5), (F) PS (16:0_25:0), (G) PS (18:0_24:0), and (H) PS (20:0_16:1). (I) Heatmap of different GPs molecules. The colors of the heatmap indicate the level of lipids across different samples. Different lowercase letters indicate significant differences between samples (P < 0.05).
Fig. 8 K-means clustering trend of brain lipid molecules in the YC, OC, and RJ groups (n = 6). (A) Sub-class 3; (B) Sub-class 5; (C) Sub-class 7; (D) Sub-calss 8. The sub-class represents the number of metabolites with the same changing trend, and the total represents the number of metabolites in this category.
Fig. 9 Classification and pathway enrichment analysis of differential metabolites between OC and RJ groups. (A) The annotation results are classified according to the type of the KEGG pathway. (B) KEGG pathway enrichment analysis for differential lipid metabolites.
Fig. 10 (A) The relationship between Nrf2/HO-1 pathway and aging. Age-related changes in the Nrf2 regulatory system, increasing Keap1 lead to the inhibition of Nrf2 activity and downstream effects. (B₁) Nrf2, (B₂) HO-1, (B₃) Gpx1, (B₄) SOD, (B₅) IL-6, and (B₆) IL-1β expression levels in brain tissue of the three groups. *P < 0.05, **P < 0.01, ***P < 0.001; n.s. P > 0.05.

About Us

Learn about Open Access

Tsinghua University Press

Publish with Us

Peer Review Policy

Copyright and Licensing

Article Processing Charge

Contact Us

Journal Collaboration: Yao Meng (Ms.)✉️ +86-10-83470574

Technical Support: Kuo Zhao (Mr.)✉️ +86-10-83470507

Media Contact: Hao Jin (Mr.)✉️ +86-10-83470559

Address: Floor 6, Tower B, Xueyan Building, Shuangqing Road, Haidian District, Beijing 100084, China.

SciOpen——中国科技期刊卓越行动计划支持项目

Copyright © 2025 Tsinghua University Press Ltd.

京ICP备 10035462号-42 京公网安备11010802044758号