The Signature Compound of Royal Jelly – 10-HDA

Royal jelly is often called “liquid gold,”and its remarkable health benefits are largely attributed to a unique fatty acid—10‑hydroxy‑2‑decenoic acid (10‑HDA), also known as royal jelly acid. First discovered in the mandibular glands of worker bees by German scientist D. J. Lange in 1921, 10‑HDA was later isolated from royal jelly by Batendt in 1957. To date, this compound has not been found in any other natural substance, which is why it is regarded as the signature marker and quality indicator of genuine royal jelly.

1. Chemical Properties & Stability

10‑HDA accounts for approximately 50% of the total fatty acids in royal jelly, with a natural content of 1.4% – 2.0%. At room temperature, it appears as white crystals and exhibits excellent stability—its molecular structure remains intact even after prolonged storage at ambient or elevated temperatures. It is readily soluble in methanol, ethanol, and chloroform, slightly soluble in acetone, and poorly soluble in water. Its melting point is 64°C. 10‑HDA can be extracted from royal jelly or produced synthetically.

2. Biological Activities

2.1 Immune Modulation & Anti‑Inflammation

- Shi Jing (1990) demonstrated that 10‑HDA (at 50 and 100 mg/L) enhances macrophage phagocytic activity and promotes the production of anti‑tumor cytokines TNF and IL‑1, thereby boosting immune function.

- Vucevic et al. (2007) confirmed that 10‑HDA suppresses xenogeneic T‑cell proliferation by inhibiting IL‑2Rα expression and IL‑2 production in activated T cells.

- Gasic et al. (2007) and Sugiyama et al. (2013) showed that 10‑HDA inhibits IL‑12 production in splenic dendritic cells and suppresses LPS‑ and IFN‑β‑induced NO production in macrophages.

On the anti‑inflammatory front:

- Sugiyama et al. (2012) verified that 10‑HDA exerts its anti‑inflammatory effects by inhibiting LPS‑induced NF‑κB signaling pathway activation.

- Chen Yifan (2018) confirmed in both in vivo and in vitro models that 10‑HDA dose‑dependently suppresses the release of key inflammatory mediators, including IL‑1β, IL‑6, MCP‑1, and COX‑2.

- Wang et al. (2015) indicated that 10‑HDA inhibits rheumatoid arthritis fibroblast‑like synoviocytes, suggesting therapeutic potential in chronic inflammatory and degenerative diseases.

2.2 Anti‑Tumor & Anti‑Radiation

- Izuta et al. (2009) found that 10‑HDA promotes the growth of interleukin‑2 and lymphocyte subsets, exerting both anticancer and immunomodulatory effects.

- Pengpanich and Srisuparbh (2019) revealed that 10‑HDA not only reduces the viability of triple‑negative breast cancer cells but also significantly inhibits their invasion, adhesion, and migration—demonstrating anti‑metastatic activity against aggressive breast cancer.

 For radiation protection:

- Zheng et al. (2012) confirmed that 10‑HDA protects human skin fibroblasts by inhibiting UVA‑induced cytotoxicity and reactive oxygen species production, while stimulating collagen production and suppressing MMP‑1 and MMP‑3 expression at both transcriptional and protein levels.

- Park et al. (2011) found that 10‑HDA, in synergy with other fatty acids in royal jelly, upregulates type I collagen via UVB‑stimulated TGF‑β1 production, mediating protection against photoaging.

2.3 Anti‑Aging & Neuroprotection

- Honda et al. (2015) discovered that 10‑HDA extends lifespan and enhances heat and oxidative stress tolerance in C. elegans through dietary restriction and TOR kinase signaling.

- Koya‑Miyata et al. (2004) demonstrated that 10‑HDA promotes collagen synthesis in human skin fibroblasts.

- Yang et al. (2010) and Wang et al. (2012) found that 10‑HDA inhibits the release of MMP‑1, MMP‑3, and connective tissue growth factor from synovial fibroblasts by downregulating the JNK/p38 MAP kinase and AP‑1 transcription factor pathways.

 Neuroregulatory effects:

- Hattori et al. (2007) showed that 10‑HDA stimulates neuronal differentiation of rat embryonic neural stem cells, an effect similar to that of omega‑3 docosahexaenoic acid (DHA), but with a smaller molecular size that may facilitate blood‑brain barrier penetration.

- Terada et al. (2011) demonstrated that 10‑HDA is a potent agonist of human TRPA1 and TRPV1 receptors.

- Pyrzanowska et al. (2012) also confirmed that 10‑HDA increases neurogenesis.

 2.4 Metabolic Regulation & Antimicrobial Activity

- Takikawa et al. (2013) reported that 10‑HDA enhances insulin‑independent muscle glucose uptake via AMPK activation and GLUT4 translocation to the plasma membrane, thereby improving hyperglycemia and insulin resistance in obese/diabetic mice.

- Xu et al. (2002) found that this fatty acid ameliorates hyperlipidemia.

- Fang et al. (1994) observed that 10‑HDA protects rats against experimental gastric ulcers.

 Antimicrobial properties:

- Alreshoodi et al. (2015) confirmed that 10‑HDA exhibits potent antibacterial activity against Staphylococcus aureus, Escherichia coli, and other pathogens.

- Yousefi et al. (2012) found that it inhibits the adhesion of the oral pathogen Streptococcus mutans by interfering with the expression of glucosyltransferase genes gtfB and gtfC.

- Melliou et al. (2005) demonstrated strong antifungal activity against Candida tropicalis and Candida albicans.

Summary

10‑HDA stands out as a multifaceted bioactive compound with immune‑modulating, anti‑inflammatory, anti‑tumor, anti‑radiation, anti‑aging, neuroprotective, and metabolic‑regulating properties. Its wide‑ranging benefits make it a promising ingredient in functional foods, pharmaceuticals, and cosmetics.

Important Note: While 10‑HDA and royal jelly offer numerous health‑supporting activities, they are functional food ingredients and are not intended to replace medications for the treatment of any disease. Always consult your healthcare professional before adding new supplements to your routine.

Reference:

1. ALRESHOODI F M, SULTANBAWA Y. Antimicrobial activity of royal jelly[J]. Anti-Infective Agents, 2015, 13(1):50-59. Doi:10.2174/2211352513666150318234430.
2. BARKER S A, FOSTER A B, LAMB D C. Biological Origin and Configuration of 10-Hydroxy-Δ2-decenoic Acid[J]. Nature, 1959, 184(9):634. Doi:10.1038/184634a0.
3. CHEN Y F, YOU M M, LIU Y C, et al. Potential protective effect of trans-10-hydroxy-2-decenoic acid on the inflammation induced by Lipoteichoic acid[J]. Journal of Functional Foods, 2018, 45:491-498. Doi:10.1016/j.jff.2018.03.029.
4. FANG E L, ZHOU H Z, XU H L, et al. Antiulcer effects of 10-hydroxy-2-decenoic acid in rats[J]. Chinese Pharmacological Bulletin, 1994, 10:139-142.
5. GASIC S, VUCEVIC D, VASILIJIC S, et al. Evaluation of the Immunomodulatory Activities of Royal Jelly Components In Vitro[J]. Immunopharmacology and Immunotoxicology, 2007, 29(3-4):521-536. Doi:10.1080/08923970701690977.
6. HATTORI N, NOMOTO H, FUKUMITSU H, et al. Royal jelly and its unique fatty acid, 10-hydroxy-trans-2-decenoic acid, promote neurogenesis by neural stem/progenitor cells in vitro[J]. Biomedical Research, 2007, 28(5):261-266. Doi:10.2220/biomedres.28.261.
7. HIRAKAWA A, SHIMIZU K, FUKUMITSU H, et al. 2-Decenoic acid ethyl ester, a derivative of unsaturated medium-chain fatty acids, facilitates functional recovery of locomotor activity after spinal cord injury[J]. Neuroscience, 2010, 171(4):1377-1385. Doi:10.1016/j.neuroscience.2010.10.004.
8. HONDA Y, ARAKI Y, HATA T, et al. 10-Hydroxy-2-decenoic Acid, the Major Lipid Component of Royal Jelly, Extends the Lifespan of Caenorhabditis elegans through Dietary Restriction and Target of Rapamycin Signaling[J]. Journal of Aging Research, 2015, 2015:1-7. Doi:10.1155/2015/425261.
9. IZUTA H, NARAHARA Y, SHIMAZAWA M, et al. 1,1-Diphenyl-2-picrylhydrazyl Radical Scavenging Activity of Bee Products and Their Constituents Determined by ESR[J]. Biological and Pharmaceutical Bulletin, 2009, 32(12):1947-1951. Doi:10.1248/bpb.32.1947.
10. KOYA-MIYATA S, OKAMOTO I, USHIO S, et al. Identification of a Collagen Production-promoting Factor from an Extract of Royal Jelly and Its Possible Mechanism[J]. Bioscience, Biotechnology and Biochemistry, 2004, 68(4):767-773. Doi:10.1271/bbb.68.767.
11. MELLIOU E, CHINOU I. Chemistry and Bioactivity of Royal Jelly from Greece[J]. Journal of Agricultural and Food Chemistry, 2005, 53(23):8987-8992. Doi:10.1021/jf051550p.
12. MIHAJLOVIC D, RAJKOVIC I, CHINOU I, et al. Dose-dependent immunomodulatory effects of 10-hydroxy-2-decenoic acid on human monocyte-derived dendritic cells[J]. Journal of Functional Foods, 2013, 5(2):838-846. Doi:10.1016/j.jff.2013.01.031.
13. PARK H M, HWANG E, LEE K G, et al. Royal Jelly Protects Against Ultraviolet B-Induced Photoaging in Human Skin Fibroblasts via Enhancing Collagen Production[J]. Journal of Medicinal Food, 2011, 14(9):899-906. Doi:10.1089/jmf.2010.1363.
14. PENGPANICH S, SRISUPARBH D, UTHAISANGTANECHPONGTAMB W. Potential Role of Royal Jelly and 10-Hydroxy-2-Decenoic Acid as Metastasis Inhibitors in Triple-Negative Breast Cancer Cells[J]. Journal of the Medical Association of Thailand, 2019, 102:17-24.
15. PYRZANOWSKA J, PIECHAL A, BLECHARZ-KLIN K, et al. Long-term administration of Greek Royal Jelly improves spatial memory and influences the concentration of brain neurotransmitters in naturally aged Wistar male rats[J]. Journal of Ethnopharmacology, 2014, 155(1):343-351. Doi:10.1016/j.jep.2014.05.032.
16. SUGIYAMA T, TAKAHASHI K, KUZUMAKI A, et al. Inhibitory Mechanism of 10-Hydroxy-trans-2-decenoic Acid (Royal Jelly Acid) Against Lipopolysaccharide- and Interferon-β-Induced Nitric Oxide Production[J]. Inflammation, 2013, 36(2):372-378. Doi:10.1007/s10753-012-9556-0.
17. SUGIYAMA T, TAKAHASHI K, TOKORO S, et al. Inhibitory effect of 10-hydroxy-trans-2-decenoic acid on LPS-induced IL-6 production via reducing IκB-ζ expression[J]. Innate Immunity, 2012, 18(3):429-437. Doi:10.1177/1753425911416022.
18. TAKIKAWA M, KUMAGAI A, HIRATA H, et al. 10-Hydroxy-2-decenoic acid, a unique medium-chain fatty acid, activates 5'-AMP-activated protein kinase in L6 myotubes and mice[J]. Molecular Nutrition and Food Research, 2013, 57(10). Doi:10.1002/mnfr.201300041.
19. TERADA Y, NARUKAWA M, WATANABE T. Specific Hydroxy Fatty Acids in Royal Jelly Activate TRPA1[J]. Journal of Agricultural and Food Chemistry, 2011, 59(6):2627-2635. Doi:10.1021/jf1041646.
20. TOWNSEND G F, BROWN W H, FELAUER E E, et al. Studies on the in vitro antitumor activity of fatty acids. IV. The esters of acids closely related to 10-hydroxy-2-decenoic acid from royal jelly against transplantable mouse leukemia[J]. Canadian Journal of Biochemistry and Physiology, 1961, 39(1):1765. Doi:10.1139/o61-195.
21. VUCEVIC D, MELLIOU E, VASILIJIC S, et al. Fatty acids isolated from royal jelly modulate dendritic cell-mediated immune response in vitro[J]. International Immunopharmacology, 2007, 7(9):1219-1220. Doi:10.1016/j.intimp.2007.05.005.
22. WANG J G, RUAN J, LI C Y, et al. Connective tissue growth factor, a regulator related with 10-hydroxy-2-decenoic acid down-regulate MMPs in rheumatoid arthritis[J]. Rheumatology International, 2012, 32(9):2791-2799. Doi:10.1007/s00296-011-1960-5.
23. WANG J, ZHANG W, ZHOU H, et al. 10-Hydroxy-2-decenoic acid inhibiting the proliferation of fibroblast-like synoviocytes by PI3K-AKT pathway[J]. International Immunopharmacology, 2015, 28(1). Doi:10.1016/j.intimp.2015.05.036.
24. XU D H, MA X T, XU S B. The Research of 10-Hydroxy-2-Decenoic Acid on Experiment Hyperlipoidemic Rat[J]. Journal of Chinese Medicinal Materials, 2002.
25. YANG X Y, YANG D S, ZHANG W, et al. 10-Hydroxy-2-decenoic acid from Royal jelly: A potential medicine for RA[J]. Journal of Ethnopharmacology, 2010, 128(2):314-321. Doi:10.1016/j.jep.2010.01.055.
26. YOUSEFI B, GHADERI S, REZAPOOR-LACTOOYI A, et al. 10-Hydroxy-2-decenoic acid down regulates gtfB and gtfC expression and prevents Streptococcus mutans adherence to the cell surfaces[J]. Annals of Clinical Microbiology and Antimicrobials, 2012, 11:21. Doi:10.1186/1476-0711-11-21.
27. ZHENG J, LAI W, ZHU G, et al. 10-Hydroxy-2-decenoic acid prevents ultraviolet A-induced damage and matrix metalloproteinases expression in human dermal fibroblasts[J]. Journal of the European Academy of Dermatology and Venereology, 2013, 27(10):1269-1277. Doi:10.1111/j.1468-3083.2012.04707.x.