Ganoderma lucidum Polysaccharides Promote Thymic Regeneration in Starvation Mice

Abstract

Background: Thymic functional decline is closely associated with immunosenescence. Ganoderma lucidum polysaccharides (GLP) are major immunoactive constituents of Ganoderma (Lingzhi, a well-known anti-aging herbs), but its effect on thymic regeneration remains limited. Method: An acute starvation-induced thymic involution model (induced by 72 h fasting) was established, female BALB/c mice were then refeeding with GLP (10/30/100 mg/kg, oral gavage) or metformin (100 mg/kg, i.p.) for 14 days. General behavior, spontaneous activity, thymus/spleen indices and thymic corticomedullary architecture was examined. The distribution of thymic epithelial cell (TEC) was assessed by immunofluorescence markers CK5/CK8, and thymic T-cell subsets (DN, DP, CD4⁺SP, CD8⁺SP) were quantified by flow cytometry. Results: A 72 h fast induced the thymic index decreasing from 0.17 ± 0.01% to 0.09 ± 0.03% (p < 0.05), and increasing to 0.18 ± 0.03% after refeeding, but its corticomedullary architecture and the distribution of T-cell subsets were not fully restored. Compared with the Regeneration group, GLP treatment nice have a clearer corticomedullary demarcation. Immunofluorescence indicated that GLP (particularly GLP-L/GLP-H) and metformin enhanced CK5- and CK8-positive cells and increased the density of the reticular network. Flow cytometry showed increased proportions of DN T cells and CD8⁺SP cells in the treatment groups relative to the spontaneous-regeneration group. Conclusion: GLP repairs the structure and function of thymus in acute starvation-induced thymic involution, indicating potential value for counteracting thymus-associated immunosenescence and enhancing thymic regeneration.