Immunomodulatory effects of Yang He decoction on cyclophosphamide-induced immunosuppression in mice: restoration of immune organ integrity and cytokine balance

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Abstract
Objective: To evaluate the protective effects and potential mechanisms of Yang He decoction (YHD), a classic traditional Chinese medicine formula, against cyclophosphamide (CTX)-induced immunosuppression in mice. Methods: An immunosuppression model was established in Kunming mice via intraperitoneal injection of CTX (80 mg/kg). The mice were then treated with low, medium, or high doses of YHD (50, 100, or 200 mg/kg) or Astragalus polysaccharide (APS, 24 mg/kg) as a positive control for 15 consecutive day. Body weight changes, immune organ (spleen and thymus) index and histopathology, splenic lymphocyte proliferation and cell cycle distribution, and serum levels of cytokines (IL-1β, IFN-γ, TNF-α, IL-6, and IL-10) were systematically assessed. Results: YHD treatment significantly ameliorated CTX-induced immunosuppression. The medium dose (100 mg/kg) increased body weight by 58.5% (vs. 17.3% in the APS group), restored the spleen index to 9.41 ± 0.94 (0.52-fold vs. Model group 1.8 ± 0.3), and enhanced ConA-stimulated lymphocyte proliferation (27.03% ± 0.92% vs. Model group 10.60% ± 4.78%, P < 0.01). Cell cycle analysis revealed that the percentage of S-phase cells increased from 4.13% to 13.47% in the YHDH group. YHD also rebalanced cytokines: the concentration of IL-1β increased from 25.73 to 77.10 pg/mL, while IL-10 decreased from 222.83 to 20.77 pg/mL. Histopathology confirmed restoration of organ integrity without necrosis. Conclusion: The multiherbal formula YHD confers substantial protection against CTX-induced immunosuppression. Its mechanisms are associated with the restoration of immune organ integrity, promotion of lymphocyte activity, and rebalancing of the cytokine profile. These findings provide a pharmacological basis for the traditional use of YHD and support its potential as an adjuvant therapy for managing chemotherapy-related immunosuppression.

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