Antimicrobial and Anti-inflammatory Biological Activities of Royal Jelly

Royal jelly is a milky-white, pale yellow, or light orange paste-like substance secreted mainly by the hypopharyngeal and mandibular glands of worker bees aged 5-15 days. It is primarily used to feed the queen bee and bee larvae. As a highly complex bee product rich in nutrients such as proteins and fatty acids, royal jelly exhibits a wide range of biological activities. This article focuses on its antimicrobial and anti-inflammatory properties.

I. Anti-inflammatory Effects and Mechanisms of Royal Jelly

The anti-inflammatory effect of royal jelly is not mediated by a single component but results from the synergistic action of its rich content of lipids, proteins, amino acids, and peptides (KOCOT J et al., 2018). Modern research has revealed its significant efficacy and mechanisms in inhibiting inflammation at the molecular level and through various animal models.

1. Regulation of Key Pro-inflammatory Factors

Pro-inflammatory cytokines are core mediators of the body's inflammatory response, and their overexpression is closely related to various chronic inflammatory diseases. Tumor necrosis factor-alpha (TNF-α), as a crucial bioactive cytokine, plays a key role in initiating and amplifying inflammatory cascades. Its abnormal elevation is associated with the development of diseases such as colitis, arthritis, and tumors.

Multiple studies have confirmed that royal jelly can effectively inhibit the production of various pro-inflammatory factors. Research by Petelin A et al. (2019) showed that administering 300 mg of royal jelly orally for 14 consecutive days to rats with high serum levels of TNF-α and C-reactive protein (CRP, another important inflammatory marker) significantly reduced their serum TNF-α and CRP levels. This directly proves the systemic anti-inflammatory effect of royal jelly in living animals.

More in-depth mechanistic studies indicate that the anti-inflammatory effect of royal jelly exhibits a dose-dependent characteristic. Research by Kohno K et al. (2004) found that royal jelly significantly reduced the levels of core pro-inflammatory factors such as TNF-α, interleukin-1 (IL-1), and interleukin-6 (IL-6) in mice, and this process did not produce toxicity to any cells, indicating its good biosafety. This suggests that royal jelly curbs the excessive formation of an inflammatory "storm" at its source by directly regulating the signaling pathways of immune cells.

2. Application and Mechanistic Elucidation in Inflammatory Disease Models

The anti-inflammatory activity of royal jelly has been further validated in specific disease models, revealing its multi-target characteristics. The study by Karaca T (2012) on royal jelly improving colitis in rats provides strong evidence for this. The research elucidated two potential mechanisms of action:

Enhancing Antioxidant and Repair Capacity of the Intestinal Barrier: Royal jelly can promote the secretion of specific proteins by colonic epithelial cells, enhance their ability to resist oxidative stress, and accelerate the regeneration and repair of colon cells, thereby consolidating the intestinal physical barrier.

Inhibiting Macrophage-mediated Inflammatory Response: The study found that royal jelly reduced the proliferation of CD68+ cells in colon tissue. CD68 is a marker protein for macrophages, and an increase in its number signifies extensive macrophage infiltration in the tissue, a typical feature of chronic inflammation. By inhibiting the aggregation of such cells, royal jelly directly reduces local inflammation levels in the intestinal mucosa.

In summary, the anti-inflammatory mechanism of royal jelly can be summarized as: achieving multi-pathway, multi-target synergistic anti-inflammatory effects by systematically inhibiting the production of key pro-inflammatory factors such as TNF-α, IL-1, and IL-6, and, on this basis, enhancing tissue self-repair capacity and inhibiting excessive immune cell infiltration in local inflammatory tissues.

II. Antimicrobial Effects and Active Components of Royal Jelly

The antimicrobial effects of royal jelly entered researchers' study as early as the 1960s. Over the following decades, its antimicrobial spectrum, efficacy, and key active components have been gradually revealed.

1. Broad-spectrum Antimicrobial Activity

Numerous in vitro studies have confirmed that royal jelly has significant inhibitory or bactericidal effects on various Gram-positive and Gram-negative bacteria. Research by Li Lijun et al. (2008) indicated that royal jelly has strong inhibitory effects on common pathogenic bacteria such as Escherichia coli, Pseudomonas, and Salmonella, and this inhibitory effect increases with its concentration. Research by Huo Wei et al. further supplemented that royal jelly also has strong inhibitory effects on Staphylococcus aureus and Bacillus megaterium.

The study by Sun Liangxian et al. (2005) used royal jelly subjected to different physical treatments for antibacterial experiments. They found that two of the treated royal jelly samples exhibited strong inhibitory effects on both bacteria and fungi. Based on this, the researchers inferred that antimicrobial components in royal jelly, particularly certain polypeptide substances, might play a key role.

Multiple studies collectively indicate that the antimicrobial effect of royal jelly is concentration-dependent: at low concentrations, it inhibits various bacteria and fungi such as Staphylococcus aureus, streptococci, Proteus, E. coli, Bacillus subtilis, Mycobacterium tuberculosis, as well as Trichophyton asteroides and Epidermophyton; at higher concentrations, it exhibits bactericidal action. Some research has quantified its antimicrobial potency, suggesting its strength is approximately one-fourth that of penicillin and one-fifth that of chloramphenicol (Xu Yaxiang et al., 2000; Song Weizhong et al., 2005; Guo Fangbin, 2003).

2. Discovery and Properties of the Key Antimicrobial Component – Royalisin

Research into the material basis of royal jelly's antimicrobial action has achieved important breakthroughs. Fujiwara et al. (1990) first isolated a protein with potent antimicrobial activity from the royal jelly of the Italian honeybee (Apis mellifera) through a series of protein purification techniques including acid extraction, gel filtration, and reverse-phase high-performance liquid chromatography. They named this protein "Royalisin."

Studies show that Royalisin belongs to the proline-rich antimicrobial peptide family. It exhibits strong antimicrobial activity against Gram-positive bacteria at very low concentrations. However, notably, Royalisin is ineffective against Gram-negative bacteria, which may be related to the structural characteristics of the outer membrane of Gram-negative bacteria, preventing Royalisin from accessing its inner membrane targets. Researchers speculate that Royalisin may specialize in defending against Gram-positive bacterial invasion in the social immunity of the bee colony, reflecting the work of natural selection.

3. Synergistic Effect in Promoting Wound Healing

The antimicrobial effect of royal jelly, combined with its ability to promote tissue regeneration, shows good application prospects in wound healing. A classic animal experiment directly compared the efficacy of royal jelly with an antibiotic: researchers infected rat wounds with a mixture of E. coli, Staphylococcus aureus, Proteus type N, and hemolytic streptococci. The experimental group was then treated with a 10% aqueous solution of royal jelly, while the control group was treated with 2000 units of penicillin.

The results showed that wounds in the royal jelly experimental group began to recover within 13 to 20 days, while those in the penicillin control group began to recover within 10 to 20 days (Xu Ju Ye et al., 2005). This result not only confirmed that royal jelly has effective antimicrobial effects comparable to penicillin but, more importantly, highlighted its unique advantage in promoting wound healing. This is likely due to the combined action of its antimicrobial components and nutrient-rich substances (such as vitamins, amino acids), providing a material basis for tissue repair while controlling infection (Yuan Zeliang et al., 2001).

Substantial clinical observations also support the above findings. For example, royal jelly shows good therapeutic effects on arthritis patients; patients receiving X-ray therapy experienced reduced inflammatory side effects and faster recovery of appetite and blood counts after taking royal jelly. Furthermore, research by Yoshifumi et al. (2003) provided evidence for the safety of royal jelly. They found that feeding royal jelly to mice with allergic inflammation significantly reduces the inflammation without any side effects. They also observed an increase in serum immunoglobulin levels in the mice, suggesting that royal jelly may have immunomodulatory effects.

III. Summary and Outlook

As a natural bioactive substance, the antimicrobial and anti-inflammatory effects of royal jelly have been fully supported by numerous in vitro studies and animal experiments. Regarding anti-inflammatory effects, royal jelly effectively alleviates systemic and local inflammation by downregulating key pro-inflammatory factors such as TNF-α and IL-6, combined with multiple mechanisms including enhancing tissue antioxidant defense and inhibiting macrophage infiltration. Regarding antimicrobial effects, royal jelly possesses broad-spectrum antimicrobial activity. Its core antimicrobial component, Royalisin, is particularly effective against Gram-positive bacteria. Furthermore, its overall antimicrobial efficacy demonstrates synergistic advantages beyond antibiotics in complex physiological processes such as promoting wound healing.

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