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. 2023 Aug 2;28(15):5825.
doi: 10.3390/molecules28155825.

Immunomodulatory Effect of Flammulina rossica Fermentation Extract on Healthy and Immunosuppressed Mice

Yingdi Dai  1   2 , Sijia Ma  1   2 , Yanyan Zhu  1 , Andrey A Gontcharov  3 , Yang Liu  1   2 , Qi Wang  1
Affiliations

Immunomodulatory Effect of Flammulina rossica Fermentation Extract on Healthy and Immunosuppressed Mice

Yingdi Dai et al. Molecules. .

Abstract

Flammulina rossica fermentation extract (FREP) was obtained by ethanol precipitation of the fermentation broth. The molecular weight of FREP is 28.52 kDa, and it mainly contains active ingredients such as polysaccharides, proteins, reducing sugars, and 16 amino acids. Among them, the polysaccharides were mannose, glucose, galactose, arabinose, and fucose and possessed β-glycosidic bonds. Furthermore, the immunoregulatory activities of FREP were investigated in vivo. The results demonstrated that FREP could increase the counts of CD4+ T lymphocytes and the ratio of CD4+/CD8+ in a dose-dependent manner in healthy mice. In addition, FREP significantly increased serum cytokines, including IL-2, IL-8, IL-10, IL-12, IL-6, IL-1β, INF-γ, C-rection protein, and TNF-α, and promoted splenocyte proliferation in healthy mice. Finally, FREP could restore the counts of white blood cells, red blood cells, secretory immunoglobulin A, and antibody-forming cells and significantly promote the serum haemolysin level in mice treated with cyclophosphamide. The findings indicated that FREP possessed immunoregulatory activity in healthy mice and could improve the immune functions in immunosuppressive mice. Therefore, FREP could be exploited as an immunomodulatory agent and potential immunotherapeutic medicine for patients with inadequate immune function.

Keywords: Flammulina rossica; T lymphocytes; fermented extract; immunomodulatory; liquid fermentation.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Structural characterization of fermentation extract FREP. (A) Ion chromatogram of the standard; (B) FREP polysaccharides ion chromatogram; (C) FTIR spectra of FREP polysaccharides; and (D) molecular weight of FREP polysaccharides.
Figure 2
Figure 2
Effects of FREP on immune organ index in mice. (A) Spleen index in healthy mice; (B) thymus index in healthy mice; (C) spleen index in immunosuppressive mice; and (D) thymus index in immunosuppressive mice. The data were analyzed using a one-way ANOVA and they are expressed as means ± SEMs. ### p < 0.001 and #### p < 0.0001 in comparison with the control group (C,D); * p < 0.05, *** p < 0.001, and **** p < 0.0001 as compared with the control group (A,B). * p < 0.05, *** p < 0.001, and **** p < 0.0001 as compared with the model group (C,D). CTRL: normal control; Model: model group; AMP: Astragalus membranaceus polysaccharides; and FREP: Flammulina rossica fermentation extract.
Figure 3
Figure 3
Effect of FREP on splenocyte proliferation of healthy mice in vitro. The data were analyzed using a one-way ANOVA and they are expressed as means ± SEMs (n = 8). ** p < 0.01 as compared with the normal control group. CTRL: normal control; Con A: concanavalin A; FREP: Flammulina rossica fermentation extract.
Figure 4
Figure 4
Effects of FREP on serum cytokines. (A) IFN-γ levels in the serum of different groups of mice; (B) IL-2 levels in the serum of different groups of mice; (C) IL-8 levels in the serum of different groups of mice; (D) IL-10 levels in the serum of different groups of mice; (E) IL-12 levels in the serum of different groups of mice; (F) TNF-α levels in the serum of different groups of mice; (G) IL-1β levels in the serum of different groups of mice; and (H) IL-6 levels in the serum of different groups of mice. The data were analyzed using a one-way ANOVA and they are expressed as means ± SEMs. * p < 0.05 and ** p < 0.01 as compared with the control group. CTRL: normal control; AMP: Astragalus membranaceus polysaccharides; and FREP: Flammulina rossica fermentation extract.
Figure 5
Figure 5
Effect of FREP on the number of red blood cells (RBC, 1012/L) and white blood cells (WBC, 109/L) in Cy-treated mice. The data were analyzed using one-way ANOVA and are expressed as means ± SEMs (n = 8). ## p < 0.01 in comparison with the control group; * p < 0.05 and ** p < 0.01 as compared with the model group. CTRL: normal control; Model: model group; AMP: Astragalus membranaceus polysaccharides; and FREP: Flammulina rossica fermentation extract.
Figure 6
Figure 6
Effect of FREP on the number of antibody-forming cells in Cy-treated mice. The data were analyzed using one-way ANOVA and are expressed as means ± SEMs (n = 8). ## p < 0.01 in comparison with the control group; * p < 0.05 as compared with the model group. CTRL: normal control; Model: model group; AMP: Astragalus membranaceus polysaccharides; and FREP: Flammulina rossica fermentation extract.
Figure 7
Figure 7
Effect of FREP on the content of serum hemolysin. The data were analyzed using one-way ANOVA and are expressed as means ± SEMs (n = 8). ## p < 0.01 in comparison with the control group; * p < 0.05 and ** p < 0.01 as compared with the model group. CTRL: normal control; Model: model group; AMP: Astragalus membranaceus polysaccharides; and FREP: Flammulina rossica fermentation extract.
Figure 8
Figure 8
Effect of FREP on SIgA in intestinal contents. The data were analyzed using one-way ANOVA and are expressed as means ± SEMs (n = 8). #### p < 0.0001 in comparison with the control group; *** p < 0.001 and **** p < 0.0001 as compared with the model group. CTRL: normal control; Model: model group; AMP: Astragalus membranaceus polysaccharides; and FREP: Flammulina rossica fermentation extract.
Figure 9
Figure 9
Mouse modeling process.
See this image and copyright information in PMC

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