Active medicinal-food homologous complex nutrients (AMCN) enhance immune systems in zebrafish

Abstract

Background: Immunosuppression, whether caused by disease, stress, or medical treatments, compromises host defense by disrupting both innate and adaptive immune responses. Natural compounds such as Ganoderma lucidum, polygonatum, and mulberry leaves have long been used in traditional medicine for their immune-enhancing properties, yet their efficacy is often limited by low bioavailability. Biotransformation offers a promising approach to enhance the bioactivity of these medicinal-food homologous substances, but its potential in restoring immune function has not been fully explored.

Objective: The objective of this study was to investigate whether active medicinal-food homologous complex nutrients (AMCN) formulation containing Ganoderma lucidum, polygonatum, and mulberry leaf could restore immune function in an immunodeficient zebrafish model. Specifically, we aimed to evaluate its effects on both innate and adaptive immune cell populations, including neutrophils, macrophages, and T cells, as well as its ability to modulate key immune-related cytokines.

Methods: AMCN was prepared by culturing Ganoderma lucidum mycelia, followed by enzymatic biotransformation with polygonatum and mulberry leaf powders and subsequent fermentation with Lactobacillus plantarum. Transgenic zebrafish larvae were used as an in vivo model to evaluate immunomodulatory effects. Immune suppression was induced using cyclophosphamide, and larvae were exposed to AMCN to assess immune recovery. Changes in innate and adaptive immune cell populations and key cytokine expression were analyzed to determine the efficacy of AMCN.

Results: AMCN treatment significantly restored immune cell populations in immunodeficient zebrafish, increasing neutrophils, macrophages, and T cells compared with the model group. It also upregulated key pro-inflammatory cytokines, including tnf-α, il-12a, and ifn-γ.

Conclusion: AMCN effectively restores both innate and adaptive immune cell populations in an immunodeficient zebrafish model, highlighting its potential as a natural immunomodulatory agent.

Novelty of the study: This study is the first to show that a biotransformed complex of AMCN can restore both innate and adaptive immune cell populations in an immunodeficient zebrafish model. AMCN exhibited broad immunostimulatory effects, upregulating key cytokines and highlighting biotransformation as a strategy to enhance the bioactivity of medicinal-food homologous substances for mitigating immunosuppression.

Keywords: AMCN, biotransformation, immunomodulation, zebrafish model.