Royal Jelly: A Natural Functional Food with Promising Anticancer Potential

Royal jelly, a traditional and revered functional food produced by honeybees, has garnered significant scientific interest in recent decades for its broad spectrum of health-promoting properties. Among these, its potential antitumor activity has emerged as a compelling focus of contemporary research. A substantial body of evidence from in vitro, in vivo, and clinical observational studies indicates that royal jelly and its bioactive constituents may exert significant anticancer effects through multifaceted mechanisms. These include directly inhibiting cancer cell proliferation, inducing programmed cell death (apoptosis), modulating key cellular signaling pathways, and, notably, enhancing the body's own immune defenses. This article synthesizes current scientific understanding of royal jelly's anticancer properties, highlighting its key active components and their dual mechanisms of action.

Key Bioactive Components with Anticancer Potential

The anticancer activity of royal jelly is attributed to the synergistic interplay of its complex mixture of bioactive compounds. Research has identified several classes of components as primary contributors:

• Unique Fatty Acid: 10-Hydroxy-2-decenoic Acid (10-HDA)

10-HDA, often referred to as "royal jelly acid," is an unsaturated fatty acid unique to royal jelly and serves as a marker for authenticity. Constituting over 50% of its total fatty acids, 10-HDA is considered one of its most significant bioactive components, playing a central role in its documented antimicrobial, anti-radiation, immunomodulatory, and anticancer effects (Huang, 2010).

• Flavonoids and Polyphenols

Royal jelly contains various flavonoids, such as chrysin, naringenin, and kaempferol, which have been demonstrated to effectively inhibit the proliferation of multiple tumor cell lines (Abotaleb et al., 2018). Its polyphenol content also shows anticancer promise by enhancing systemic antioxidant capacity and regulating the expression of apoptosis-related proteins, thereby slowing tumorigenesis (Albalawi et al., 2022).

• Synergistic Supporting Nutrients

The broad nutritional profile of royal jelly—rich in 21 amino acids, organic acids, nucleic acids (RNA and DNA), proteinaceous substances (like insulin-like peptides, γ-globulin), vitamins (A, B2, B5, B12, C, E), and trace elements (selenium, iron, copper)—forms a crucial supportive foundation. These nutrients contribute to stimulating antibody production, enhancing liver detoxification functions, and boosting overall immunity, all of which play indirect yet vital roles in cancer defense (Guo, 1996; 1997; 1998).

 Direct Antitumor Action: Mechanisms of Proliferation Inhibition and Apoptosis Induction

Royal jelly and its isolated components can act directly on cancer cells, disrupting their cell cycle and activating apoptosis.

The Central Role of 10-HDA: Studies have elucidated 10-HDA's efficacy against various cancers. In human lung carcinoma A549 cells, 10-HDA induces cell cycle arrest at the G0/G1 phase and apoptosis by simultaneously regulating multiple signaling pathways (MAPK, STAT3, NF-κB, TGF-β) through a reactive oxygen species (ROS)-mediated mechanism (Lin et al., 2020). In lymphoma (SU-DHL-2) and hepatocellular carcinoma (HepG2) cells, 10-HDA suppresses cell viability in a dose-dependent manner. Against HepG2 cells, it works by upregulating pro-apoptotic proteins (Caspase-3, PARP, BAX) and downregulating the anti-apoptotic protein Bcl-2 (Kamiya et al., 2024).

Contribution of Flavonoids and Polyphenols: Flavonoids are widely reported for their antiproliferative effects on cancer cells (Abotaleb et al., 2018). Polyphenols from royal jelly exhibit systemic regulatory effects. Oral administration of royal jelly polyphenols (200mg/kg and 400mg/kg) in mice significantly boosted antioxidant enzyme activity, upregulated pro-apoptotic BAX, and downregulated liver inflammatory factor TNF-α and anti-apoptotic Bcl-2, providing strong experimental support for their therapeutic development (Albalawi et al., 2022).

In summary, royal jelly's active components synergistically target multiple cancer-related pathways to effectively inhibit cancer cell proliferation and metastasis (Bălan et al., 2020; Salama et al., 2022).

Indirect Antitumor Action: Potentiation of Host Immune Function

A cardinal feature of royal jelly's anticancer potential lies in its powerful immunomodulatory capacity, which empowers the body's innate defense systems against tumors.

Activation of Cellular Immunity: Cellular immunity is paramount in antitumor responses. Research by Zhang et al. (2000, 2001) confirmed that lyophilized royal jelly powder not only inhibited the growth of S180 tumors and prolonged the survival of EAC-bearing mice but also significantly enhanced their cellular immune function. This was evidenced by: 1) strengthening the phagocytic function of the mononuclear macrophage system, and 2) increasing the activity of Natural Killer (NK) cells, which are crucial first-line defenders capable of directly destroying tumor cells.

Stimulation of Lymphocytes and Antibody Production: Royal jelly stimulates lymphocyte mitosis, promoting cell transformation and proliferation. Its amino acids, nucleic acids, and proteinaceous substances (e.g., γ-globulin) can stimulate the production of antibodies, thereby enhancing humoral immunity (Guo, 1997).

Enhancement of Liver Detoxification and Antioxidant Defenses: The liver plays a vital role in metabolism and detoxification. Trace elements (e.g., selenium), vitamins (B2, C, E), active oxygen scavengers (e.g., superoxide dismutase), and taurine in royal jelly can significantly improve liver peroxidase activity and overall immune function. Vitamin B2, in particular, is a necessary cofactor for the liver to detoxify certain chemical carcinogens (Guo, 1998; Zhao, 1999). This function is significant for cancer prevention and adjunctive therapy.

Conclusion

Substantial evidence positions royal jelly as a natural functional food with remarkable anticancer potential, operating through multi-dimensional and multi-target mechanisms.

• Direct Cytotoxic Effects: Core components like 10-HDA, flavonoids, and polyphenols induce cancer cell cycle arrest and apoptosis by modulating key pathways such as ROS, MAPK, STAT3, and NF-κB.
• Indirect Immunoenhancement: Royal jelly comprehensively boosts the body's tumor surveillance and elimination capacity by activating macrophages and NK cells, stimulating lymphocyte and antibody production, and enhancing liver detoxification and antioxidant functions.

The convergence of these direct and indirect actions underscores royal jelly's promise as a supportive natural agent in holistic health strategies, warranting further focused clinical research to fully delineate its therapeutic applications.

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