Anti-Allergic Effects of Dietary Caterpillar Mushroom Cordyceps militaris (Ascomycota) Derived from Eri Silkworm

Allergic disorders affect a substantial proportion of the global population, and current treatments often focus on symptom management rather than addressing the underlying immunological imbalances. <i>Cordyceps militaris</i> (L.) Fr. (<i>C. militaris</i>), an entomopathogenic fungus used in traditional East Asian medicine, contains bioactive compounds with potential immunomodulatory properties, including cordycepin and &beta;-glucans. However, the anti-allergic effects of eri silkworm-derived <i>C. militaris</i> remain largely unknown. Here, we show that dietary supplementation with <i>C. militaris</i> extract (CME) reduces allergen-specific immune responses in an ovalbumin-induced allergic mouse model, as evidenced by decreased OVA-specific IgG production and suppressed IL-4 secretion by splenocytes. We found that while both CME and purified cordycepin (CD) significantly reduced allergen-specific IL-4 production, CME had a more pronounced effect on OVA-specific antibody production, suggesting the synergistic effects of multiple bioactive compounds. Interestingly, these immunomodulatory effects were primarily observed in systemic rather than local intestinal immune responses, indicating a selective mechanism of action. Our findings provide a scientific basis for the potential use of CME as a dietary supplement for allergic conditions by modulating allergen-specific responses without general immunosuppression. This selective immunomodulatory effect presents advantages for therapeutic applications, as it preserves protective immune responses while suppressing harmful allergic inflammation. Future research should focus on identifying specific bioactive compounds in CME, beyond cordycepin, and elucidating their molecular mechanisms of action to develop optimized formulations for clinical application.