The Immunomodulatory Effects of Royal Jelly: Mechanisms and Evidence

Royal jelly is renowned for its broad spectrum of biological activities, among which its immunomodulatory effect stands out as one of its most significant core functions. A substantial body of research indicates that royal jelly is not a simple immune "stimulant," but rather a natural substance capable of bidirectionally regulating the immune system, enhancing immune defense, and maintaining immune balance. Its mechanisms of action involve positive influences on various immune cells, cytokines, and immune organs, with its efficacy primarily attributed to the synergistic action of its multiple bioactive components.

I. Regulatory Effects on Immune Cells and Cytokines

Royal jelly can directly act on the core cellular components of the human immune system, enhancing their function and promoting the release of key signaling molecules.

Promotion of Immune Cell Proliferation and Activity: Components such as proteins, peptides, and amino acids in royal jelly effectively stimulate the activity of various immune cells. Studies have found that royal jelly significantly promotes the proliferation of peripheral blood mononuclear cells (PBMCs), an effect confirmed in both elderly and young individuals. Crucially, royal jelly treatment was able to reverse age-related immune function decline, restoring the proliferative capacity of PBMCs from elderly subjects to levels similar to those of young subjects (Bouamama et al., 2021). At the cellular subset level, royal jelly activates T lymphocytes and B lymphocytes, the key executors of adaptive immune responses.

Regulation of Cytokine Secretion: Cytokines are crucial messengers for communication between immune cells. Research shows that royal jelly promotes the release of cytokines such as interleukin-2 (IL-2), IL-4, and IL-6 from PBMCs (Bouamama et al., 2021). These interleukins play multiple roles in immune regulation: IL-2 is a core factor for T cell growth and activation; IL-4 promotes B cell differentiation and antibody class switching; IL-6 is involved in acute phase reactions and lymphocyte differentiation. By modulating the balance of these cytokines, royal jelly helps coordinate adaptive immune responses and maintain immune homeostasis. Furthermore, royal jelly has been found to alter the Th1/Th2 cytokine ratio, increase the production of interferon-gamma (IFN-γ), and induce the proliferation of healthy lymphocytes, providing a basis for its potential use in modulating immune states in autoimmune diseases such as hyperthyroidism (Erem C., et al., 2006).

Enhancement of Innate Immune Function: Beyond adaptive immunity, royal jelly also strengthens innate immune defenses. Animal experiments indicate that royal jelly enhances the phagocytic capacity of macrophages and increases serum hemolysin levels in immunocompromised mice (Yang et al., 2011), reflecting an improvement in non-specific phagocytic function and humoral immunity, respectively.

II. Protective and Restorative Effects on Immune Organs

Healthy immune organs are the structural foundation for normal immune function. Research shows that administering royal jelly via gavage to immunocompromised model mice for 30 days not only effectively boosts immunity but also exerts a restorative effect on the morphological structure of the spleen and thymus, key immunoregulatory organs (Li et al., 2022). This suggests that the immune-enhancing effect of royal jelly is partly due to its overall protection and nutritional support of immune organs.

III. Key Bioactive Components and Their Immunomodulatory Mechanisms

The immunomodulatory function of royal jelly results from the synergistic action of its various bioactive components. The main components and their mechanisms are as follows:

• Proteins and Peptides: Major Royal Jelly Proteins (MRJPs) and their hydrolysates are core active components. They may act as immunostimulants or signaling molecules, directly interacting with receptors on the surface of immune cells to initiate intracellular activation signaling pathways, thereby promoting cell proliferation and factor secretion.
• 10-HDA: As the signature and unique unsaturated fatty acid of royal jelly, 10-HDA possesses significant antibacterial and antiviral activities. Its immunomodulatory mechanisms include: stimulating the synthesis of cyclic adenosine monophosphate (cAMP), thereby regulating cellular metabolism and function; promoting the normalization of damaged cellular structures (e.g., due to tumors); restoring immune function suppressed by tumors or other factors; and modulating immune responses involving T lymphocytes (Guo, 1998).
• Taurine: Taurine, an organic acid abundant in royal jelly, has multiple physiological functions. It promotes lymphocyte proliferation and the production of interleukin-1 (IL-1) by macrophages, enhances the phagocytic and bactericidal activity of neutrophils, and facilitates the production of antiviral antibodies (Guo, 1996, 1999). Taurine can enhance both specific and non-specific immune functions without causing significant disruption to normal physiological processes.
• Vitamins:

1. Vitamin C: Essential for the effective functioning of the immune system. High levels of vitamin C are necessary for the phagocytic function of leukocytes; it is also an important component of lymphocytes and promotes the generation of antibody molecules.
2. Vitamin E: As a potent antioxidant, vitamin E protects immune cell membranes from lipid peroxidation damage. Studies have confirmed that it can enhance the activity of T lymphocytes and improve cellular immune function.
3. Trace Elements: Royal jelly contains various trace elements such as selenium, zinc, and iron. Selenium plays a clear role in improving immunity and promoting recovery. Zinc is a necessary cofactor for thymulin and various immune enzymes. These trace elements collectively form the basis of the active centers of immune-related enzymes and hormones.
4. Nucleic Acids: Nucleic acids (DNA and RNA) are the fundamental materials of life. Research has found that exogenous nucleic acids can stimulate the proliferation and accelerate the secretion of T and B lymphocytes, thus acting as a nutritional immune enhancer to improve overall immune capacity (Guo, 1998).

IV. Evidence from Clinical and Experimental Studies

The immunomodulatory effects of royal jelly have been validated not only in cellular and animal models but have also shown potential in some clinical observations:

A study on pediatric patients with systemic lupus erythematosus (SLE) found that a 3-month royal jelly treatment increased patients' CD4+ T lymphocyte levels and the CD4+/CD8+ ratio, accompanied by significant improvement in clinical symptoms (Zahran et al., 2016). This suggests that royal jelly may help modulate the disturbed immune balance in SLE patients.

As mentioned earlier, its role in regulating the Th1/Th2 balance in hyperthyroid patients hints at its potential value in adjunctive therapy for autoimmune diseases (Erem C., et al., 2006).

Conclusion

In summary, royal jelly is an effective natural immunomodulator. Its mechanism of action is multi-targeted and comprehensive: on one hand, components like proteins, 10-HDA, and taurine directly activate immune cells (T cells, B cells, macrophages, etc.), promoting their proliferation, phagocytosis, and secretory functions; on the other hand, by providing key nutrients such as vitamins, trace elements, and nucleic acids, it comprehensively nourishes and supports the immune system, repairs immune organs, and finely regulates the cytokine network, thereby restoring and maintaining immune balance. Current evidence supports the potential efficacy of royal jelly in enhancing immune defense, correcting immune imbalance, and delaying immunosenescence, providing a scientific basis for its application in health promotion and as an adjunctive aid for conditions related to immune dysregulation.

Reference

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