Cordyceps sinensis (CS) is a traditional Chinese medicine that is known for treating various diseases, and particularly for exerting therapeutic effects in immune disorders. The adaptive immunoregulatory effects of CS aqueous extract (CSAE) on γ‐irradiated mice have not been reported previously. The study aimed to evaluate the therapeutic effects of CSAE in mice immunosuppressed by irradiation. We observed that CSAE administration significantly increased body weight and spleen index, as well as the number of white blood cells, lymphocytes, and platelets in peripheral blood, T and B lymphocytes in spleen tissue, and total serum immunoglobulins in irradiated mice, whereas total serum pro‐inflammatory cytokine levels were decreased. Collectively, CSAE maintained the structural integrity of spleen tissue and repaired its damage in irradiated mice as shown by hematoxylin and eosin staining, and decreased the number of terminal deoxynucleotidyl transferase‐mediated dUTP nick end labeling‐positive splenocytes. Mechanistically, CSAE upregulated Bcl‐2, and downregulated Bax and cleaved caspase‐3 in spleen of irradiated mice. However, there were no significant differences in red blood cells and neutrophils in different groups. The results revealed that CSAE had protective effects against irradiation‐induced immunosuppression, which was likely associated with an antiapoptotic effect and the regulation of adaptive immunity.
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